To operate successfully in the industry, you will need to understand the language of biopharmaceutical manufacturing. 

BioProcess Engineering Glossary

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3Rs Principles

Replacement, Reduction, Refinement: Ethical guidelines to minimize animal use in research and testing.

483 Observation

A documented finding issued by the FDA during an inspection to highlight potential non-compliance or deficiencies.

6 Sigma (6σ)

Six sigma is a methodology for process improvement used in multiple industries. Six sigma is a statistical quality control tool. It is based on a 5-steps process called DMAIC: Define, Measure, Analyze, Improve, Control. Six sigma methodology focuses on the reduction of defects and errors.

A

Abbreviated Inspection

A focused regulatory inspection that targets specific systems, processes, or areas rather than a full facility review. It is often conducted to verify corrective actions, or support follow-up regulatory assessments at trusted manufacturers with good history of regulatory compliance.

Abbreviated New Drug Application (ANDA)

A submission to the FDA for approval of a generic drug product. It demonstrates bioequivalence and quality without requiring full clinical trial data from scratch.

Absorption, Distribution, Metabolism, Excretion (ADME)

ADME refers to the pharmacokinetic properties of a drug.

Acceptable Quality Level

A statistical threshold defining the maximum number of defects allowed within a batch or lot. It serves as a key quality control parameter to ensure consistency in product acceptance and compliance with regulatory and contractual requirements.

Acceptable Quality Level (AQL)

A statistical threshold defining the maximum number of allowable defects within a batch. It is used during quality control inspections to determine whether a lot meets acceptance standards.

Acceptance Criteria

Predetermined standards or limits that a process, material, or product must meet to be approved. These criteria ensure that manufacturing and testing results are consistent, reliable, and compliant with regulatory expectations.

Access Control

A security framework designed to restrict physical or digital access to authorized personnel only. It protects sensitive environments and data by preventing unauthorized entry or system usage, supporting compliance and product integrity.

Accuracy

The term accuracy is used in the context of analytical method to describes the trustworthiness of a testing method. It represents how close the results of a test are compared to the known result of a reference sample. (See precision)

ACH (Air Changes Per Hour)

A measure of how often the air in a controlled environment is replaced within one hour. Maintaining proper ACH rates is critical in cleanrooms to control particle levels and reduce contamination risk.

Active Pharmaceutical Ingredient (API)

The biologically active component. API is usually used in small molecules drugs. Drug substance is the word used in biologics.

Adeno-Associated Virus

An AAV (Adeno-Associated Virus) is a non-pathogenic viral vector commonly used in gene therapy for delivering genetic material into human cells. AAV are also used in vaccines.

Adjuvant

A compound added to a vaccine to enhance the body’s immune response to the antigen. Adjuvants help reduce the required antigen dose and improve the duration or strength of protection.

Advanced Therapy Medicinal Product (ATMP)

A category of innovative therapies including gene therapies, cell-based products, and tissue-engineered treatments. These products are regulated under specialized frameworks.

Adventitious Agent Testing

Adventitious agent testing designates analytical testing performed to detect unexpected or unintended viruses, bacteria, or other microorganisms in raw materials, intermediates, or finished products.

Affinity Chromatography

A purification method that isolates target molecules based on specific binding interactions, such as antigen-antibody or receptor-ligand recognition. It is widely used in the production of vaccines, antibodies, and therapeutic proteins.

Air Shower

An enclosed chamber that uses high-velocity, filtered air to remove loose particles from personnel or materials entering a controlled area. It minimizes contamination risk when transitioning into cleanroom environments.

Airborne Particle Monitoring

The continuous or periodic measurement of particle levels in controlled environments. Monitoring helps ensure cleanroom compliance with regulatory classification and early detection of deviations.

Airlock

A controlled access chamber that separates areas with different cleanliness levels. Airlocks reduce contamination risks by maintaining proper pressure differentials and controlling personnel and material movement.

Alarm System

An automated monitoring and notification system that alerts operators to deviations in process conditions, environmental parameters, or equipment performance. Prompt notification enables timely corrective actions and maintains process control.

ALCOA

Principles defining data integrity requirements: Attributable, Legible, Contemporaneous, Original, and Accurate. These standards ensure all recorded data can be traced, read, verified, and relied upon during audits and regulatory reviews.

ALCO-CCEA

A variation of ALCOA that emphasizes Complete, Consistent, Enduring, and Available data attributes. It is used to further reinforce regulatory compliance and data reliability.

Alternate Therapeutic Products

Biological or advanced therapies that differ from conventional drugs, such as gene or cell-based treatments. These products often follow distinct regulatory and manufacturing pathways due to their complexity.

Aluminum Vial Cap

A crimped metal closure used to secure stoppers on vials, maintaining container closure integrity. It ensures sterility and prevents contamination during handling and storage.

American Society for Testing and Materials (ASTM)

The ASTM is an American standards organization that develops and publishes technical standards for materials, products, systems, and services.

American Society of Mechanical Engineers BioProcess Equipment (ASME BPE)

The ASME BPE is a set of standards for bioprocessing equipment design.

AMSF (Active Substance Master File)

A regulatory document detailing the manufacturing, quality, and control of an active substance. It supports marketing authorizations by allowing confidential submission of proprietary data to authorities.

Anaerobic Product

A product manufactured under oxygen-free conditions to protect sensitive components or processes. Such conditions are critical for specific biologics and microbial cultures.

Analytical Instrument Validation (AIV)

Analytical Instrument Validation is the documented process of confirming that an analytical instrument performs according to predefined specifications. It ensures accuracy, reliability, and compliance with regulatory standards. (See Analytical Method Validation)

Analytical Method Qualification

A documented demonstration that an analytical method is suitable for its intended purpose. It evaluates parameters such as precision, accuracy, and robustness before use in testing.

Analytical Method Transfer

The structured process of transferring a validated analytical method from one laboratory or site to another. It ensures the receiving laboratory can reproduce accurate and reliable results.

Analytical Method Validation (AMV)

Analytical method validation is the process of proving that an analytical method is reliable, accurate, and reproducible for its intended application. It is a regulatory requirement before the method can be used for release or stability testing. Full analytical method validation is required for Phase III and commercial manufacturing while qualification is often sufficient for earlier stage, Phase I and II.

Analytical SOP

An analytical SOP is a Standard Operating Procedure for analytical testing.

Animal Derived Raw Materials (ADRM)

ADRM are materials obtained from animal sources used in the manufacture of biologics and vaccines. They are strictly controlled due to potential contamination risks and must meet regulatory standards for safety and traceability.

Annex 1

EU GMP guideline for sterile medicinal products.

Annex 11

EU GMP guideline for computerized systems.

Annual Product Quality Review (APQR)

APQR is a yearly evaluation of product quality and process performance. Performing APQR is a mandatory in most pharmaceutical regulations.

Antibody

A protein produced by the immune system to neutralize a foreign pathogen.

Antibody-Dependent Enhancement (ADE)

A biological phenomenon where certain antibodies facilitate, rather than neutralize, infection, potentially worsening disease severity. It is closely monitored during vaccine and therapeutic development to ensure product safety.

Antigen

A component in a vaccine that stimulates an immune response in the body. It is typically a protein that trains the immune system to recognize a pathogen.

Antigenicity Testing

Assessing a substances ability to provoke an immune response.

Approver

In a GMP environment, an approver is a person who is authorized, under a certain quality management system, to review and formally approve a controlled document.

Aseptic Connector

A device that allows the aseptic transfer of fluids between two systems while maintaining sterility during the connection of silicon tubes.

Aseptic Disconnector

A device that allows the disconnect two systems while maintaining sterility during the disconnection of silicon tubes.

Aseptic Gowning Qualification / Requalification

Training and assessment program ensuring that personnel can properly gown and maintain aseptic technique. Requalification is performed periodically to sustain compliance and minimize contamination risks.

Aseptic Process Simulation (APS)

A test run designed to simulate aseptic manufacturing conditions and verify the robustness of aseptic techniques. It demonstrates that personnel, processes, and environments can maintain sterility under actual production conditions. Also referred to as Media Fill Test. The process that is classified as aseptic (final filtration and vial filling) is reproduced using a soy media (bacterial growth promoter) instead of the product. The filled vials are then incubated and visually inspected to detect bacterial growth.

Aseptic Processing

Manufacturing under sterile conditions to prevent contamination.

Aseptic Processing Area (APA)

An APA is a controlled area for sterile manufacturing.

Aseptic Technique Challenge

A test that evaluates personnel’s ability to perform aseptic tasks without introducing contamination. It is often part of training and qualification for operators working in sterile environments.

Assessor

Person evaluating compliance or performance during audits.

At Line Analysis

At line analysis refers to tests performed adjacent to the production line to provide rapid in process information.

Atypical Event

An atypical event refers to an unexpected occurrence requiring investigation.

Audit Closing Meeting

An audit closing meeting is a meeting taking place at the end of an inspection to discuss the audit findings.

Audit Readiness

Preparedness for regulatory or internal audits. (see Inspection Readiness)

Audit Trail

A secure record that shows who performed actions, when, and what changes were made on a system or an equipment.

Audit Trail Review

Periodic review of audit trails for compliance.

Author

A person responsible for writing a controlled document. An author is neither a reviewer of an approver of a document.

Autoclave

An autoclave is an equipment used to perform sterilization of equipment and materials by steam injection.

Automated Sampling

Automated sampling refers to the use of automated systems to collect samples. In biomanufacturing, automated sampling is not frequent in drug substance manufacturing but is usual in Fill and Finish activities to remove vials for testing for example. Automated sampling systems are also used in R&D activities.

Automation

Use of machines, programs and regulation loops to control manufacturing processes with minimal human intervention.

Automation Architecture

Automation Architecture refers to the design of the system controlling
manufacturing system or process.

B

Back Pressure Valve

A valve designed to maintain a specific upstream pressure within fluid handling systems.

Bacterial Retention Test

A qualification test verifying a filter’s ability to retain bacteria under defined conditions. It confirms that the filter is suitable for sterile filtration processes.

Baculovirus

Baculovirus is a virus used in biotechnology for recombinant protein expression in insect cell systems through the Baculovirus Expression Vector System (BEVS).

Ballroom

A cleanroom designed to accommodate multiple unit operations or flexible manufacturing setups. In a ball room, buffer solutions are located outside of the main process area (ex: Grade D) and delivered through wall transfer port. Main process operation such as fermentation and purification is kept within the ball room. It allows for smaller footprint in Grade C areas, easy handling of equipment and flexibility of configuration.

Basic Design Package

Collection of documents generated throughout the basic design studies for a new facility construction project or a revamping project. The BD package includes layouts, P&ID and functional descriptions. BD package is the start of detailed design and execution.

Batch Production

The manufacturing of a defined quantity of product in a single production cycle. The opposite of batch production is continuous manufacturing.

Batch Record

Document detailing production and control of a batch. The batch record is used for batch release. It shall detail each production operations performed, raw materials and consumables used and IPCs.

Batch Record Review

Review of the batch record by the quality assurance department prior to releasing the batch.

Batch Release

The formal approval of a batch for market distribution following review of batch record and quality control results.

Batch Slot Reservation

Often applicable at CDMO or multiproduct facilities. The manufacturing line shall be made available for a specific product to manufacture at a specific date. For that, no other production shall be made on the line to be used and operators shall be available.

Bill Of Materials (BOM)

A BOM is a list of materials required for production.

Binding Capacity

The binding capacity is a measure of the quantity of a desired molecule per unit of volume a chromatography column can retain.

Bio-Availability

The rate and extent to which a drug is absorbed and becomes available in systemic circulation. It is a critical parameter for determining dosing and therapeutic effectiveness.

Bioassay Potency

A test measuring the biological activity or effectiveness of a drug or vaccine component.

Bioassay Validation

The documented process of proving that a bioassay produces reliable, accurate, and reproducible results.

Bioburden

The total number of viable microorganisms present in a product, material, or environment.

Bioburden Control

Controls implemented to minimize risk of microbial contamination during manufacturing. It includes clean room classification, filtration, cleaning and sterilization operations.

Biofilm

A biofilm is a microbial film formed when there is an accumulation of microorganisms within a pipe or on the surface of an equipment. Usually, biofilms form on poorly designed facilities or hard to clean pipe sections.

Biological Indicator (BI)

A Biological indicator is an indicator containing a known population of a microorganism used to verify performance of sterilization processes.

Biologics

Biologics refers to pharmaceutical drugs manufactured using ​biological organisms. In some cases, vaccines are considered separately from biologics. The two categories are commonly mentioned as Biologics and Vaccines.

Biologics License Application (BLA)

After completion of Phase 3 clinical trials on a biologic or a vaccine, the sponsors must submit a BLA to the FDA to obtain market authorization.

Biomanufacturing

Biomanufacturing refers to the production of biological products using biological organisms.

Bioprocesses

Manufacturing processes using biological agents to manufacture drugs.

Bioreactor

A bioreactor is a vessel used for culture of mammalian cells (plant and insect as well). A bioreactor is agitated, has temperature control system and often a sparging system to feed the cells with oxygen. A bioreactor can be reusable (stainless steel) or can be single use.

Biosafety

Biosafety included all the measures to protect against biological hazards. These measures are in place to protect operators as well as the environment.

Biosafety Cabinet (BSC)

Enclosed workspace protecting the operators when handling biohazardous materials. A unidirectional laminar airflow is applied in the chamber of a BSC to avoid suspension of particles. BSC are equipped with air supply and return filters.

Biosafety Level (BSL)

Biosafety level is a classification established for laboratories and manufacturing facilities handling hazardous biological agents. For each level, several safety procedures must be followed to ensure that biological risks are controlled.

Black Utilities

Black utilities designate utilities that are not in contact with the product and
do not have quality impact.

Block Flow Diagram (BFD)

Simplified diagram describing a process in a succession of steps represented into several blocks. Materials flow are also represented. BFD are used by process engineers to describe a complex process into smaller and simpler operations.

Booster

A booster is an additional dose of a vaccine to boost an immune response and enhance vaccine efficacy.

Bovine Serum Albumin (BSA)

BSA is a protein of bovine origin used in bioprocessing.

Bracketing

Risk based approach often used in process validation and cleaning validation to reduce the scope of validation when there are too many combinations to be tested. Bracketing consists in validating the extremes of a range instead of testing all points of the range. If the extremes are validated, the intermediate will also be validated. Bracketing is different from Matrix approach.

Breakthrough Therapy Designation

FDA status for expedited drug development. This status is given to drugs that addresses disease where there is not yet any solution available. Getting the designation give priority over other product in its review by FDA. The goal of the designation is to shorten the time taken by regulatory reviews.

British Pharmacopoeia (BP)

BP is the pharmacopoeia applicable for medicinal products in the United Kingdom.

BSL-1

BSL-1 is the lowest biosafety level for low-risk agents that are not harmful but that should not be released to the outside (ex: Genetically Modified Organisms).

BSL-2

BSL-2 is a biosafety level for moderate-risk agents that can harm the environment or cause disease to human for which they are prevention vaccines or treatment drugs.

BSL-3

BSL-3 is a biosafety level for serious-risk agents that can cause serious harm to humans and the environment.

BSL-4

BSL-4 is the highest biosafety level for life-threatening biological agents.  Biosafety level for severe-risk agents that can be lethal to humans and for which there are no vaccines or treatment.

Bubble Point Test

Test performed before and after use of a filter to verify its integrity.

Buffer

In the context of bioprocessing a buffer is a solution used to stabilize pH during downstream unit operations.

Buffer Capacity

Buffer capacity defines the ability of a buffer to resist pH changes during addition of acid or bases.  The main purpose of buffer usage in biomanufacturing is their ability to stabilize pH.

Buffer Preparation

All the operations required to prepare buffers to be used for the manufacturing process of a drug (Chromatography, UF/DF, Formulation). Buffer preparation starts with weighing of powders, dissolution into water, pH adjustment, filtration and storage. Buffers can be prepared for one or for multiple batches in one set.

Building Information Modeling (BIM)

A BIM is a digital tool to enable a 3D representation of a facility. BIM are generally used by engineering companies during construction projects.

Bulk

Usually refers to the product that has not yet been formulated into a drug product. The term drug substance bulk if often used in vaccine to refer to the antigen prior the formulation and filling stage.

C

Calibration

Ensuring that instruments on equipment are accurate for consistent measurements during production operations.

Calibration Certificate

Certificate attesting that an instrument has been calibrated and is suitable for use in a GMP environment.

CAPA Effectiveness Check

After implementation of CAPA, it is necessary to conduct a CAPA effectiveness check to confirm if the implemented procedures actually resolved the issue.

CAPA Team Leader

Person overseeing CAPA implementation. In small organization, the role is included in the scope of a QA staff. For larger organizations, it is not rare to have Capa Teams that are overseeing CAPA on multiple facilities.

Capacity Modeling

When running a manufacturing facility, how much product, how many doses shall be manufactured by the facility is a crucial question. For that, the manufacturing capacity shall be estimated and the resources shall be allocated to sustain the desired level of production. This process is referred to capacity modeling or capacity planning.

Capital Expenditure (CAPEX)

When building a new facility, a company uses cash to invest in new equipment and infrastructure. The infrastructure becomes part of the capital asset of the company. Such investment is referred to as a Capex. The opposite is an Opex, an operating expense that is the cost of running a facility.

Capsid

A capsid is the shell of a virus.

Carryover

Residual material from a previous batch. Cleaning procedures shall ensure that carryover is kept as low as acceptable.

Case Report Form (CRF)

A Case Report Form is a document used during clinical trial by a sponsor to collect data from participants.

Cell

A cell is the basic functional unit of an organism.

Cell Bank

A reserve of cells with identical characteristic to be used as starting material for multiple batches of cell culture or fermentation.

Cell Bank Characterization

All the test required to confirm the properties of a cell bank prior being used in manufacturing operation.

Cell Bank Qualification

The purpose of qualifying cell banks is to demonstrate their suitability for use in vaccines or biologics production. Various tests are conducted on the cell bank to verify that it meets the defined acceptance criteria.

Cell Bank Release

Upon characterization and qualification, the cell bank can be used for manufacturing. The authorization to use to cell bank is referred to as release.

Cell Bank Storage

Cell banks are stored at typically stored below -130°C using liquid nitrogen.

Cell Counting

Cell counting is measuring the viability of cells in a sample, i.e. measuring live cell numbers.

Cell Culture

Growing cells under controlled conditions. Cell culture in vaccines and biologics manufacturing is an operation that aims to increase a population of cells under controlled conditions (pH, O2, °C).

Cell Density

Cell density refers to the concentration of cells in a culture.

Cell Harvesting

After completion of the cell culture, the cultivate cells shall be collected. This operation is called harvest.

Cell Host Protein

Cell Host Proteins are residual proteins from host cells that must be removed from the product during purification of the drug substance.

Cell line

A cell line is a population of cells carefully selected that can be maintained in culture indefinitely without cell senescence and that keep the same properties.

Cell Line Authentication

Cell line authentication consists in a verification of the cell line identity and purity.

Cell Line Development

Creating stable cell lines for production of multiple batches of a biological drug.

Center For Biologics Evaluation And Research (CBER)

CBER is the FDA division for biologics regulation. Vaccines are in the jurisdiction of CBER.

Center For Drug Evaluation And Research (CDER)

CDER is the FDA division for drug regulation. Small molecules drugs are in the jurisdiction of CDER.

Centrifugal Pump

Centrifugal pumps are pumps using rotation to move fluids. Centrifugal pumps are found in water recirculation loop or CIP system for example. They are rarely used to transfer product to the shear stress they induce that can damage cells or proteins.

Centrifugation

Centrifugation is a separation technic based on the use of centrifugal force to separate elements by weight. From laboratory to large scale manufacturing, centrifugation is found in various type of equipment.

Centrifuge

A separation equipment that works on the principle of centrifugation.

Certificate of Analysis (CoA)

A Certificate of Analysis is a document generated by the QC laboratory to confirm that all tests were conducted on the product and that the product meets the expected quality attributes. The CoA is approved by the QA department.

Certificate of Conformity (CoC)

A Certificate of Conformity is a document generated by the QA department to confirm that a batch was manufactured in compliance with applicable quality standards and regulatory requirements. Usually, the CoC is generated after the CoA once all events and deviations have been closed and when all quality control results have been approved.

Certified Reference Material (CRM)

Reference material that is has been tested and that can be used as a standard for calibration or analytical method validation activities.

Change Control (CC)

When implementing a change in a GMP manufacturing environment, evaluating the impacts of the change and the potential risk is necessary prior the implementation. Upon implementation, a review is performed to confirm that the change was conducted as expect. This process for managing a change is called a change control.

Change Owner

The person responsible for implementing a change is the change owner.

Chemical Equivalence

In Pharmacology, chemical equivalent refers to drug products containing the same active compound in the same amount, with possible variations in excipients composition.

Chemical Sanitization

Sanitization refers to the use pf NaOH, HNO3 or other chemical agents to clean an equipment. Sanitization differs from CIP. We speak of sanitization of chromatography column or TFF membranes for example.

Chemistry, Manufacturing, and Controls (CMC)

Abbreviation for Chemistry, Manufacturing, and Controls. CMC refers to all the activities surrounding analytical methods and manufacturing ensuring that a drug can be consistently manufactured and delivered at the same level of quality and safety.

CHO Cells

Chinese Hamster Ovary (CHO) cells are widely used in the biomanufacturing industry for cell culture, recombinant protein expression, and monoclonal antibody (mAb) production, in a manner similar to Human Embryonic Kidney (HEK) cells.

Chromatography (XTO)

Chromatography is a separation technique based on differential interactions such as ion exchange, hydrophobic interactions, size exclusions… Chromatography is found in almost all biologics manufacturing processes for protein, antibody of virus purification.

Chromatography Skid

A chromatography skid is a term used to refer to a chromatography equipment used to run large scale chromatography operations.

CIP Cycle

A CIP cycle is a sequence to clean an equipment from initial rinse, NaOH wash to final rinse.

CIP Return Line

Often, CIP are performed in recirculation mode, i.e. the cleaning solution is supplied to the vessel to be cleaned and the return waters are recirculated back to the CIP tank. It allows for reduction of water consumption. Piping for returning cleaning solutions is the CIP return line.

CIP Skid

A CIP skid is a system usually composed of a tank for solution preparation, a detergent addition system, a temperature control system and a pump to deliver solutions to the equipment to be cleaned. CIP skids are automated equipment.

CircRNA

Circular RNA is a type of messenger RNA that has the particularity of being circular.

Clarification

Unit operations often found in biomanufacturing. Clarification consists in removing large impurities from a solution (e.g. cell debris)

Clean Bench

A clean bench is workspace with laminar airflow used to conduct open process operations. A clean bench is used to protect the product from external contamination.

Clean Hold Time (CHT)

After an equipment is cleaned, the duration of storage of the equipment until it is used in manufacturing process is referred to as Clean Hold Time. CHT has to be validated through Hold Time Study to demonstrate that during the CHT equipment does not get contaminated.

Clean Steam

Clean steam is purified steam used for sterilization in place and autoclaving. Condensate from clean steam have the same quality as WFI.

Clean Steam Generator

Clean steam is generated by a cleans team generator.

Clean Utility

Clean utilities designate utilities in contact with the product and which can impact the quality of the product.

Cleaning-In-Place (CIP)

Cleaning in place is an automated cleaning of equipment without having to displace it. Cleaning solutions are prepared in a separate vessel, CIP tank, and delivered to the equipment through pipes.

Cleaning Validation (CLV)

Document demonstration that cleaning procedure consistently removes contaminants below a safe level. Generally, cleaning validation requires extensive testing (endotoxin, bioburden, TOC, conductivity, concentration) to demonstrate on several cleaning cycle the performance of the cleaning procedure.

Cleaning Verification

Cleaning verification purpose is to demonstrate that equipment is clean and proper to be used in manufacturing. In cleaning verification, cleaning cycle can be repeated indefinitely until satisfactory results are obtained. Verification does not mean validation as it does not focus on consistency.

Cleanroom

A clean room, is an environment in which the level of micro-organisms and particle in the air is controlled to ensure low level of contamination.

Cleanroom Classification

Clean rooms are classified by level of cleanliness from A to D. Zone classification, also called Cleanroom classification refers to the grade of the clean room.

Cleanroom Zoning

Zoning is a term used in urban planning to define areas for specific activities in a city (industry, housing, commercial building). Cleanroom zoning refers to the division of the production room into several distinct clean rooms.

Clinical Study Report (CSR)

The CSR is a document, submitted to the FDA, that summarize the methods and the results of a clinical study.

Clinical Supply Manufacturing

Manufacturing of clinical trial material. Usually differs from routine commercial manufacturing.

Clinical Trial

A clinical trial is a collection of studies involving human subjects to test the safety and efficacy of a new drug.

Clinical Trial Application (CTA)

A Clinical Trial Application is the submission to the health authorities to obtain authorization to conduct a clinical trial on humans. No trial can be started without a CTA.

Closed Process

Opposite of an open process, a closed process is a process where the product is not exposed to the clean room air. It reduces the risk of contamination. A closed process requires the use of aseptic connection.

Code of Federal Regulations (CFR)

The Code of Federal Regulations is the collection of regulations applicable in the United States.  The CFR is divided into 50 titles, among which Title 21 governs the Food and Drugs.

Cold Chain

The term cold chain covers all the storage and distribution operations of a product where temperature requires to be controlled.

Cold Chain Validation

Cold chain validation is the documented demonstration that throughout the distribution of a pharmaceutical product, that requires low temperature storage, the product temperature can be consistently controlled within the expected temperatures.

Cold Room Qualification

Pharmaceutical facilities are generally equipped with cold rooms to store intermediate and final product at cold temperature. Cold room qualification is demonstrating that the cold room meets its expected performance and ensure proper temperatures throughout all points in the room.

Colony-Forming Unit (CFU)

CFU is a unit used in microbiology to count the number of viable microbes on a plate.

Column Packing

Most chromatography operations are performed using resin as material to separate the product of interest from the impurities (e.g. proteins, mRNA, Virus). Resins are generally stored in liquid then transferred into chromatography column to serve as separation media. To ensure the product does not by pass the resin within the column, the resin has to be made into a very tight cake. This process is called packing a chromatography column.

Column Sanitization

Chromatography columns, especially once filled with resin, are not suitable for CIP. Column are typically sanitized chemically using NaOH.

Commercial Supply Agreement

Once a pharmaceutical company and a CDMO decide to work together for the manufacturing of a drug, the two companies engage in a contract called a commercial supply agreement.

Commissioning

Commissioning is a major step in the construction of a new pharmaceutical facility. Once a system is introduced into in a new facility, the system has to be installed, integrate with other systems, test and calibrated. These operations are referred to as commissioning activities. The term comes from the chemical industry where prior starting a routine production in a chemical plant, the equipment had to be tested for functionality and safety. In the pharmaceutical industry, after commissioning comes the Qualification. The two are often referred to as C&Q.

Commissioning and Qualification (C&Q)

C&Q refers to all the activities to install and to verify that facilities and equipment meet the intended specifications and expected performance.

Commissioning Plan

The commissioning plan is a document outlining how the commissioning activities will be performed. Often, the plan is combined with the qualification activities in a document generally called the C&Q Plan.

Common Technical Document (CTD)

After competition of clinical trials, a pharmaceutical company can submit a new drug application. All the information required for the submission will be collected in a Dossier called a Common Technical Document, CTD. The CTD format has been harmonized between the US, the Europe and Japan. CTD can be submitted electronically, eCTD.

Comparability

The documented demonstration that two manufacturing processes or two products are equivalent despite possible gaps in the manufacturing process or location of manufacturing for example.

Comparability Study

To demonstrate the comparability, a comparability study is performed.

Compendial Method

Compendial methods are analytical test method that have been standardized in pharmacopoeias. Instead of having each manufacturer conduct a test in a different manner, it is better to have one standard method used all over the industry.

Compliance Audit

Pharmaceutical are required to comply with GMP. Inspection to verify regulatory compliance are regularly performed by health authorities.

Compressed Air (CA)

Compressed air is usually air at a pressure of 7 or 6 bars used for industrial processes. Compressed air is for example used to activate pneumatic valves.

Computerized System Validation (CSV)

CSV is the documented demonstration that a software is reliable enough to be used in pharmaceutical manufacturing.

Conceptual Design (CD)

Engineering studies to design a pharmaceutical facility are split into different stages. Among them, conceptual design during which the preliminary design of a facility or a process is performed.

Conductivity Meter

A conductivity meter is an instrument used to measure the conductivity f solutions (e.g. water, buffers).

Conjugate Vaccine

A conjugate vaccine is a type of vaccine on which an antigen, not sufficiently immunogenic by itself, is chemically conjugated with a carrier to enhance the immune response and improve protection. Polysaccharides based vaccines are often conjugate vaccines. CRM 187 and tetanus toxoid are proteins used are carriers.

Conjugation

Conjugation refers to the chemically linking of an antigen with a carrier.

Constructability Review

Upon completion of the basic design of a new facility, a constructability review is conducted to assess the feasibility of construction plans.

Consultation

A consultation is typically a meeting with the regulatory authority to obtain guidance or advice.

Consumable

Consumables are items required for the manufacturing process thar are not raw materials and that are disposable. Single use bags, tubes, filters and membranes are consumable. Gloves and gowning are also consumables.

Contact Plates

Contact plates are agar plated used for microbial surface testing.

Container Closure Integrity Test (CCIT)

After the filling of drug product into its final container, vial or syringe, to ensure that the product is not exposed to the outside environment, a container closure integrity is performed.

Container Closure Integrity Test (CCIT)

CCIT is a test performed on sterile drug product to confirm that a drug product container remains sealed and ensures the sterility of the product during its shelf life. Commonly used methods are vacuum decay and helium leak test.

Containment

Containment refers to the measures in place within a manufacturing facility to prevent the release of hazardous biological agents.

Contaminant

A contaminant is an unwanted substance that may compromise the quality and safety of a product.

Contamination Control Strategy (CCS)

A contamination control strategy is high level document that describes the procedures to be implemented to prevent product contamination. Very often, CCS is prepared at beginning of the conceptual design and further detailed prior starting manufacturing activities.

Continuous Centrifuge

Centrifuge operating in a continuous mode. The term often refers to conical plate centrifuge and in contrast with laboratory centrifuge.

Continuous Manufacturing (CM)

The opposite of batch production. In continuous manufacturing, a process is run continuously for several days without the notion of batch.

Continuous Monitoring

Real-time tracking of process parameters.

Continuous Process Verification (CPV)

CPV is the third stage of process validation. CPV consist in an ongoing verification of the performance of a process. In the past, process validation used to be a onetime event. Once a process was validated, it was not supposed to change and remains as it is for year without any verification of the actual performance. The practice was change with the introduction of CPV.

Contract Development Manufacturing Organization (CDMO)

A CDMO is an organization that has a factory but no pharmaceutical product of its own. A CDMO develops and manufactures drugs for Biotech and Pharmaceutical companies that want or need to externalize manufacturing.

Contract Manufacturing Organization (CMO)

Contract Manufacturing Organization. A CMO conduct manufacturing on behalf of companies looking to externalize manufacturing. A CMO, does not offer development services. (see CDMO)

Contract Research Organization (CRO)

A CRO is a Contract Research Organization that conduct research activities on behalf of a pharmaceutical company. CROs are the equivalent of CDMO but for the pre-clinical activities.

Control Measure

Control measures are actions taken to mitigate a risk to an acceptable level.

Control Sample

In QC testing, control samples are taken to serve as references. For example, during cleaning validation, a sample of water taken from the loop or the water container prior entering the equipment is taken to serve as baseline for pH, conductivity and TOC measurement with samples of water taken after the equipment to be cleaned.

Control Space

A control space is a range within which if a process parameter is controlled, the process performance and the product quality will meet the expected requirements. The control space is the operating range validated for GMP manufacturing. It is demonstrated during process performance qualification. Control space is narrower than the design space. (see Design Space)

Controlled Area

A controlled area is an area with regulated conditions of temperature and humidity.

Controlled Non-Classified (CNC)

CNC areas are Controlled Non-Classified areas in which temperature humidity are controlled but for which no clean room level is expected. CNC areas are below Grade D areas in terms of cleanliness.

COP (Cleaning-Out-Of-Place)

Cleaning-Out-Of-Place, as opposite to CIP, refers to equipment that are dismantled and displaced to be cleaned. For example, mobile stainless- steel vessels can be transferred to a COP station to be cleaned. Small material can be washed in a washing machine located in a different clean room.

Corrective Action

When a non-conformity occurs in a process or in any activities, actions must be implemented to correct the non-conformity and to prevent it from happening it in the future. These actions are called CAPAs for, Corrective Actions Preventive Action. Corrective Actions are the controls put in place immediately to correct the occurring issues. (See CAPA)

Corrective Action Preventive Action (CAPA)

When a non-conformity occurs in a process or in any activities, actions must be implemented to correct the non-conformity and to prevent it from happening it in the future. These actions are called CAPAs for, Corrective Actions Preventive Action. The actions to be implemented are described in a CAPA Plan.

Corynebacterium diphtheriae Mutant 197 (CRM-197)

CRM-197 is non-toxic diphtheria toxin variant used in conjugate vaccines
as carrier.

Cost Of Goods Sold (COGS)

COGS is the total cost of producing a pharmaceutical drug. COGs include direct labor, manufacturing overhead, raw materials, as well as other quality related activities.

Crimping

The term crimping is used for vial crimping in Fill and finish activities. It means sealing a vial with an aluminum cap. Crimping ensure the container closure integrity.

Critical Alarm

A critical alarm is an alarm for a significant process deviation.

Critical Material Attribute (CMA)

Critical material attribute are the attributes of raw materials used in a manufacturing process that have an impact on the product quality.

Critical Path

The term critical path is used in project management to define the sequence of tasks determining the duration of a project.

Critical Process Parameters (CPP)

Critical Process Parameters are parameters that impact the quality of the product.

Critical Quality Attribute (CQA)

A CQA is Critical Quality Attribute, i.e.an attribute that has an effect on the efficacy or the safety of a drug.

Cross-Contamination

A cross contamination is an unintended transfer of contaminants between different products or materials. For example, in a multiproduct facility, traces of product A were found in product B. This would be referred to as a cross-contamination. It can come from operators or equipment.

Cryogenic Vial

Cryogenic vials are vials suitable for cryogenic storage, i.e. storage below -130C. Master cell bank are usually stored in cryo vials.

Cryogenic Shipper

A cryogenic shipper is a type of container used for transporting frozen materials.

Cryogenic Storage

Storage at ultra-low temperatures. Usually in liquid nitrogen below -130C.

Cryopreservation

Preserving cells by freezing them at ultra-low temperatures.

Cryoprotectant

A cryoprotectant is any substance added into a product to protect it during freezing.  Cryoprotectant are necessary for cells that could be damaged by a freezing process.

Current Good Manufacturing Practice (cGMP)

cGMP refers the GMP regulatory standards enforced by the Food and Drug Administration (FDA) to ensure safety and quality of pharmaceuticals.

Cytoplasm

The cytoplasm is the cell’s internal fluid.

D

Data Integrity

Data Integrity refers to all the procedures and controls to ensure that data is accurate, complete, and reliable.

Data Logger

A data logger is a device used for recording data over long period of time. Data loggers are used for environment monitoring (temperature, humidity).

Deactivation

A deactivation is an operation that consists in neutralizing the activity of a biological agent or a chemical agent. Deactivations are typically achieved via chemical reactions.

Dead Leg

A dead leg is a section of a pipe where liquid might stagnate.

Decontamination Cycle

A decontamination cycle is a sequence of steps and or procedure followed to decontaminate a product or a waste.

Decontamination Station

A decontamination station, is a stainless-steel automated system typically composed of a collection tank, a temperature control system, and that is used to treat hazardous biological waste prior rejecting them to the waste waters. Most of the time, decontaminations are done thermally.

Dedicated Equipment

A dedicated equipment, contrary to share equipment, is a piece of equipment used for a single product.

Dedicated Suite

A dedicated suite is a process area use for the manufacturing of a single product.

Depth Filtration

A depth filtration, also sometime referred to as a clarification, is unit operation consisting of a filtering particle using a porous medium. Generally, depth filtrations take place after harvest and centrifugation.

Depyrogenation

Pyrogens are contaminant that if found in the final product can cause fever in the patient. Removing pyrogens from equipment or products is referred to as depyrogenation. Depyrogenation is performed at high temperature (250C). For example, glass vials used to fill injectable drug product, are depyrogeneted prior to filling. Endotoxins are pyrogens.

Design of Experiments (DoE)

According to EMA, DoE is a structured, organized method for determining the relationship between factors affecting a process and the output of that process.

Design Qualification (DQ)

At the end of a design, it is required to verify that the design meets user requirements. This verification is called DQ.

Design Requirements

Design requirements are all the specifications that shall be taken into account in the design of an equipment or a system to ensure it meets its intended function.

Design Space

The term design space is used in the Quality by design (QbD) approach. ICH Q8 defines design space as “the multidimensional combination and interaction of input variables (e.g., material attributes) and process parameters that have been demonstrated to provide assurance of quality." During process development, inputs are tested on broader control ranges to see how far can a process parameter can deviate from its set point. A design space is generated by conducting design of experiments (DoE).

Detailed Design Package

At the end of the detailed design studies, a detailed design package is generated and serves as the basis for execution studies by vendors and for construction activities.

Detergent Residue

Cleaning procedures generally make use of detergent to remove proteins and lipids or other insoluble matters. At the end of the cleaning procedure, the remaining cleaning agent are referred to as detergent residue.

Deviation

A deviation occurs when a process or an activity deviate from the approved procedures.

Deviation Log

A deviation log is any system used to keep a record of all deviations that occurred in a GMP facility. It can be a paper-based record or an electronic record.

Deviation Management

It is part of the GMP to have a procedure in place to manage deviations, investigate them, assess their impacts and implement the necessary CAPAs.

Deviation Report

Once a deviation occurs, it is documented into deviation report.

Diafiltration

A diafiltration is a purification process used to remove small molecules. A solution containing the product of interest, often a larger molecule, is continuously passed over a tangential flow filtration membrane. The small molecules pass through while the larger ones remain in the retentate. During diafiltration, a buffer solution is continuously supplied to maintain the solution at a constant concentration and volume. A diafiltration is also called a buffer exchange.

Diaphragm Pump

A diaphragm pump is a type of hygienic pump used in pharmaceutical processes. Using flexible membrane to generate fluid displacement, they are low shear pump, making them suitable for handling of fragile product. Typically, diaphragm pumps are used in TFF systems.

Differential Pressure (∆P)

A differential pressure is the pressure difference between two points or two areas. Clean rooms are kept under specific differential pressures to control the flow of contaminants from cleaner area to less clean area.

Diffusion Test

Filter integrity test using gas diffusion.

Dirty Hold Time (DHT)

After an equipment is used, the duration of storage of the dirty equipment until it is cleaned is referred to as Dirty Hold Time. DHT has to be validated through Hold Time Study to demonstrate that even after a dirty hold time, the cleaning procedures is still sufficient to ensure proper cleaning of the equipment.

Disposition

When a product does not meet its quality specification it has to be disposed.

DNA

Deoxyribonucleic acid (DNA) is a double-helix-shaped molecule that carries and stores genetic information. DNA is found in all living organisms.

Document Change

A document change is a modification to a document that was previously approved and effective.

Document Change Request

Prior making a change to an approved document, a request shall be made.

Document Owner

A document owner is the person responsible for a document.

Document Retention

GMP dictates that documents (e.g. Batch Records) must be retained for an appropriate duration depending on the type of document. A manufacturer must establish and follow a document retention procedure.

Dose

The term dose refers to the amount of product administered in an injection of a drug.

Dose Titration

Dose titration is conducted during clinical trials and consists in adjusting a drug dosage to obtain an optimal efficacy without adverse effects.

Downstream Process (DSP)

In biomanufacturing of drug substance, unit operations are often split into two categories, Upstream Process (USP) and Down Stream Process (DSP). DSP includes all unit operation related to the purification of the drug substance (Chromatography, UF/DF, filtration, dispensing).

Drug Master File (DMF)

According to the FDA, Drug master files (DMFs) are documents submitted to the FDA used to provide confidential, detailed information about facilities, processes, or articles used in the manufacturing, processing, packaging, and storing of human drug products

Drug Product (DP)

The drug product is the final formulated product ready for administration.

Drug Substance (DS)

In biomanufacturing, the term API is usually not used. Instead, the term Drug Substance is used. The DS can be the bacteria, the virus or the protein of interest.

Dynamic Light Scattering (DLS)

DSL is a technique used for measuring particle size. DLS is widely used in LNP manufacturing processes.

E

Efficacy

Efficacy is the ability of a vaccine to prevent disease or the ability of a drug to cure a disease or treat symptoms.

Electronic Batch Record

Also referred to as an eBR, an electronic batch record is a digital record of batch production.

Electronic Common Technical Document (eCTD)

eCTD is the digital format for of the Common Technical document. (see CTD).

Electroporation

Electroporation is a technique used to trans infect cells. It uses electric pulses to introduce materials into cells.

ELISA

Enzyme-Linked Immunosorbent Assay is a test assay for detecting proteins.

Eluate

After binding the product to separate on a chromatography column, the product has to be collected from the column. This operation is called elution. The collected product is called the eluate.

EMA

European Medicines Agency is the European regulatory body that has authority on medicines for human use.

Emergency Power Supply (EPS)

EPS is a backup power supplying critical systems during power outages.

Encapsulation

Encapsulation consists in enclosing a drug in a protective coating to enable its delivery to the target cell. mRNA vaccines are based on the encapsulation of mRNA in Lipid Nano Particles (LNP). The LNPs protect the mRNA from degradation up until the release of the mRNA into the cells.

End Of Hold Time (EOH)

End of hold time corresponds the end of product storage and the start of the next unit operations.

Endotoxin

An endotoxin is a lipopolysaccharide (LPS) secreted from the membrane of a bacteria. Endotoxins are pyrogen. They can trigger strong immune response (e.g. fever).

Endotoxin Challenge

Endotoxin challenge is a test to confirm endotoxin removal. It is used to validate depyrogenation cycles.

Endotoxin Units (EU)

Endotoxin levels are measured in EU/mL.

Engineering Procurement Construction Management (EPCM)

EPCM is a project management method for engineering and construction projects. In EPCM, a contractor is engaged by a sponsor to manage the engineering design studies, the procurement of the equipment and the construction of the facility. EPCM contractors are generally large engineering companies with multidomain expertise from civil engineering to bioprocess engineering.

Engineering Run

It is common practice to perform one or multiple engineering runs to ensure that the process is well established and lock prior manufacturing a batch of product that will be used for clinical trials or for commercial release.

Enveloped Virus

An enveloped virus is a virus capsid is enveloped in a lipid bilayer membrane.

Environmental Monitoring (EM)

Environmental monitoring consists in continuously tracking environmental conditions in clean rooms (temperature, humidity, differential pressure).

Environmental Trend Analysis

EM trends shall be analyzed at a defined frequency.

Enzyme

An enzyme is a protein that plays the role of a catalyst for biochemical reactions.

EU Marketing Authorization

Approval to market a drug in the EU.

EudraLex

EudraLex designates the collection of European legislations regulating medicinal products in the European market.

European Pharmacopoeia (EP)

EP is the European standards for medicines. It is also abbreviated as Ph.Eur. (see Pharmacopeia)

European Public Assessment Report (EPAR)

When reviewing a medicine prior market approval, the EMA publishes a report on its evaluation of the medicine.

European Union Good Manufacturing Practice (EU GMP)

The EU GMPs are the European set of standard practices to be followed to ensure compliant manufacturing operations and ensure product quality.

Excipient

An excipient is a non-active compound added in the formulation of a drug.

Excursion

An excursion is a deviation of a parameter during environmental monitoring (e.g. a temperature above or below the specified limits).

Expression System

An expression system is a host cell used for protein expression.

Expression Vector

An expression vector is a plasmid DNA or a virus genetically modified to express a gene in cells.

External Manufacturer

An external manufacturer is a third-party that performs production on behalf of a customer.

External Manufacturing Oversight

A sponsor has to manage its CDMOS. The practice is called external manufacturing oversight.

Extractables

Extractables are chemical substances released from plastic-based container under extreme conditions.

Extractables And Leachable Study (E&L)

An E&L study is a set of tests to identify the chemical substances released by a plastic-based material in contact with product.

F

Facility Layout

The layout of a manufacturing facility is the arrangement of the production rooms.

Factory Acceptance Test (FAT)

When ordering a complex equipment from a vendor, upon completion of the equipment construction and prior shipping to the customer site, the equipment shall be inspected to ensure that it meets the expected specifications. This inspection is performed at the constructor factory, hence the term Factory Acceptance Test. While the equipment is still at the factory, is it easier for the constructor to do modifications.

Failed Run

A failed run is a production run that was aborted or did not meeting specifications.

Failure Mode and Effects Analysis (FMEA)

An FMEA is a risk assessment tool that evaluates for each process parameters the impact of a deviation from the operating range.

Fast Track Designation

The fast-track designation is status given by the FDA to certain investigational drugs. Its purpose is to accelerate the regulatory review of a drug that meet certain criteria.

FDA Adverse Event Reporting System (FAERS)

FAERS is the system used in the USA to report adverse event related to the usage of a drug.

FDA Form 483

Officially titled "Inspectional Observations," is a document issued by the FDA at the end of an inspection. It highlights observations made by the FDA investigators.

Fed-Batch Culture

A fed batch is a cell culture in which nutrient addition is done periodically during throughout the culture. In regular batch culture, all the nutrients are loaded at the start of the culture and will get depleted as the number of cells increases. Fed-batch generally allows to obtain higher production yields in cell cultures of fermentations.

Fermentation

A fermentation consists in growing micro-organisms under controlled conditions to manufacture a product of interest expressed by the micro-organisms.

Fill and Finish (F&F)

In liquid drug manufacturing, F&F regroups the formulation of the drug product, the filling in vial or syringes, the inspection and the packaging activities.

Filter Challenge Study

A filter challenge test is a test during which a filter is exposed to a known population of bacteria to test its ability to remove the bacteria.

Filter Integrity Test (FIT)

After a filter is used, to ensure that the filter was not damaged before or during the filtration, a filter integrity test is performed. If the filter does not pass the FIT, there is no guaranty that the product was filtered. Contaminants could have passed the filter through holes or other defects in the filter.

Filter Validation

Filter validation is the document demonstration that a filtration process meets its expected performance.

Final Rinse

During a cleaning cycle, the final cleaning step is usually to rinse the equipment with WFI. This step is called the final rinse. During final rinse, conductivity on the return line is measured to ensure that no detergent remains.

Finished Pharmaceutical Product (FPP)

FFP designates the final packaged drug product.

First Expired First Out (FEFO)

FEFO is and inventory method prioritizing earliest expiration.

First In First Out (FIFO)

FIFO is inventory method prioritizing earliest received. For a drug manufacturer, usually the FIFO is the applicable method.

First in Human

The first clinical testing of an investigational drug on humans is referred to as First in Human. FIH comes after preclinical studies on animals.

Floor scale

A floor scale is a large-scale balance for weighing that is on the floor as opposed to a bench scale. Mobile vessels are load on floor scales.

Flux

Rate of material flow through a membrane.

Food and Drug Administration (FDA)

The U.S. Food and Drug Administration is the American administration in charge of regulating the pharmaceutical products on the American market.

Foreign Particulate Matter (FPM)

Foreign Particulate Matters are unintended particles found in a product. If FPM are found in a drug product vial, it is not suitable for injection.

Formulation

Formulation refers to one or multiple unit operations to transform the drug substance into the final product to be injected to the patient.

Fourier transform infrared spectroscopy (FT-IR)

FT-IR, is a method to obtain a spectrum of emission or absorption of a
molecule. FT-IR is widely used to identify molecules during raw material acceptance tests.

Freeze-Drying Cycle

A freeze-drying cycle is a lyophilization process that enable longer storage of a product. Some vaccines are freeze-dried.

Functional Assay

A functional assay of a molecule is a test measuring the biological activity of the molecule, i.e. what is does to an animal or a human when injected. It is a measure of the biological response of the body to the product.

G

Gantt Chart

A Gantt chart is visual tool for project scheduling invented by an American industrial engineer, Henry Gantt, in beginning of the 20th century. In a Gantt chart, a project schedule is displayed in the form of a bar chart.

Gap Analysis

A gap analysis is a detail review of all the differences between a system or a process and the evaluation of the impacts these gaps could have on the manufacturing of a product or on the testing of it. A technology transfer between a sending unit and a receiving unit often starts with a gap analysis of the equipment available at both sites.

Gas Chromatography (GC)

Gas chromatography is an analytical separation technique.

GMP Inspection

A GMP inspection if a regulatory audit to assess the level of GMP compliance of a manufacturing site.

Good Automated Manufacturing Practice (GAMP)

GAMP is a set of guidelines on how automated systems used in pharmaceutical
manufacturing should be designed and operated.

Good Distribution Practice (GDP)

GDP are guidelines for proper product distribution. Ensuring proper distribution is necessary to guarantee that a product is not deteriorated during its distribution.

Good Documentation Practices

Set of standards to be followed for accurate record-keeping.

Good Engineering Practice (GEP)

Good engineering practice are a set of standards for engineering activities. GEP are not laws as the GMP but serve as industry standards to ensure good execution of engineering projects.

Good Laboratory Practice (GLP)

Set of standard practice to be followed to ensure compliant laboratory operations.

Good Manufacturing Practice (GMP)

GMP are a set of standard practices to be followed to ensure compliant manufacturing operations and ensure product quality. GMP are country or region specific. (See EU GMP and cGMP)

Gowning

Gowning refers to the clothing appropriate to clean rooms operations to avoid contamination of product by the operators.

Gowning Qualification

Operators have to be trained for proper gowning procedures and evaluated periodically.

Grade A

Grade A is the highest cleanliness level in clean rooms. Grade A is the level for aseptic processing. Vial and syringes filling are performed in Grade A environment.

Grade B

Grade B is the second highest cleanliness level in clean rooms. Grade B are areas supporting Grade A operations.

Grade C

Grade C areas are clean room for less critical operation. Most of drug substance manufacturing operations are performed under grade C areas.

Grade D

Grade D is the lowest cleanliness level in clean rooms. Grade D areas are areas for non-critical processes like cleaning operations.

GxP

GxP is a general term to describe good practices to be followed in the pharmaceutical industry. GxP includes GMP, GLP, GDP.

H

Hardware Design Specification (HDS)

HDS is a detailed specification of hardware and mechanical components of a system. The opposite is an FDS, functional design specifications that describes how a system shall function.

Harmonized Monograph

A harmonized monograph is a pharmacopoeia standard that has been harmonized between the USP, Ph.Eur and JP.

HAZOP

Hazard and Operability Study is a risk assessment method to assess the safety impact of failures and mitigate the risks associated.

Health Authority Inspection

Regulatory audit by health authorities.

Health Canada

Health Canada is the regulatory authority in charge of medicines for human use in Canada.

Heat Exchanger

A heat exchanger is a device used in process engineering to heat or cool down a fluid.

Heavy Metals

Heavy metals refer to toxic metallic impurities that could be found in traces amount in pharmaceutical products (e.g. lead, mercury, arsenic).

Height equivalent to a theoretical plate (HEPT)

HETP describes a chromatography column separation efficiency.

HEK Cells

Human Embryonic Kidney cells are cells widely used in the biomanufacturing industry for cell culture, recombinant protein expression, and monoclonal antibody (mAb) production.

HEPA Filter

High-Efficiency Particulate Air filters are high efficiency filters used to remove particle from air supplied to cleanrooms.

HIC

Chromatography based on the principle of hydrophobic Interaction.

High-Performance Liquid Chromatography (HPLC)

HPLC is a chromatography technique used mainly for QC test. HPLC is not used for large scale separation of molecules.

Historian

A historian is a system used for recording data critical for manufacturing. Process parameters or environmental monitoring data are recorded on a historian for long term storage.

Historical Data

Historical data refers to past data that can be used for analysis.

Hold Time

The notion of hold time describes the duration of storage of a product in between two unit operations.

Hold Time Study

A hold time study is a study conduct to evaluate the stability of a product or an intermediate that is stored for a certain time in between two unit operations.

Hold-Up Volume

Hold up volume refers to the volume of product lost during a manufacturing operation due to the volumes that remain on the surface of equipment and within pipes. For example, during a filtration step, the final volume of product passing in the filter may not be recovered. For skid, like a TFF or a chromatograph equipment, the hold-up volume is a characteristic given by the equipment manufacturer and represents the total volume of product remaining inside the equipment piping.

Host Cell Protein

The term host cell protein refers to the undesired protein that belong to the host cell used to express a protein of interest. This protein shall be removed during purification and host cell protein testing is usually performed to assess residual protein content in the drug substance.

Human Machine Interface (HMI)

An HMI is an interface for operator to interact with equipment. An HMI can be a computer, a tablet or a touch panel.

HVAC (Heating, Ventilation, and Air Conditioning)

System used to control the quantity of air supplied to a room, its temperature, its humidity and its overall air quality. HVAC are what allows to have clean room with controlled atmosphere.

I

ICH

The International Council for Harmonization (ICH) is an initiative to establish global pharmaceutical standards.

ICH Guideline

The ICH guidelines are the standards that have been harmonized to be applicable globally.

ICH Q1

ICH guideline for stability testing.

ICH Q2

ICH guideline for analytical method validation.

ICH Q3

ICH guideline for impurities.

ICH Q4

ICH guideline for pharmacopoeia harmonization.

ICH Q5

ICH guideline for biotechnological products.

ICH Q6

ICH guideline for specifications.

ICH Q7

ICH guideline for API GMP.

ICH Q8

ICH guideline for pharmaceutical development.

ICH Q9

ICH guideline for quality risk management.

ICH Q10

ICH guideline for pharmaceutical quality systems.

ICH Q11

ICH guideline for API development.

ICH Q12

ICH guideline for lifecycle management.

ICH Q13

ICH guideline for continuous manufacturing.

ICH Q14

ICH guideline for analytical procedure development.

Idle Time

An idle time is a period during which an equipment is not used.

Immune Response

An immune response is the body’s natural reaction to defend itself from a foreign pathogen.

Immunization

Immunization is the act of protecting a person against a disease through vaccination.

Immunoassay

An immunoassay is a biochemical test to measure the presence of a molecule using a specific antibody.

Immunogenicity

Immunogenicity is the ability of a vaccine to provoke an immune response.

Immunogenicity Study

An immunogenicity study consists in an evaluation of the immune response triggered by a drug.

In Silico

In Silico is a fairly recent expression meaning experiments made in silicon,
i.e. simulated on a computer. In silico experiments are used to replace certain tests on animals.

In Vitro

Latin expression meaning in the glass, used to designate experiments not conducted in a human or an animal but on cell models.

In Vitro Transcription (IVT)

IVT is an enzymatic reaction used to synthesize mRNA from a DNA template.

In Vivo

Latin expression meaning in the living, used to designate experiments conducted within a living organism.

Inactivated Vaccine

An inactivated vaccine is a vaccine made from a killed virus that cannot replicate.

Inactivation

Inactivation consists in neutralizing the activity of a biological substance either thermally or chemically.

Incubation

An incubation is an operation commonly found in biomanufacturing to grow cells in under controlled conditions. Usually, the term incubation is used for small culture volume such as a flash in an incubator. For larger volumes, bioreactors or fermentors are used.

Inoculation

Inoculation refers to the introducing a vaccine or pathogen into the body. It also refers to the loading of a virus into a cell culture step.

Inoculum

The term inoculum is used to refer to the starting material (cells, or virus) used to start a culture. Once the inoculum is loaded in the media, the culture starts.

Inspection Readiness

Manufacturer are regularly inspected by health authorities. Inspection readiness covers all the activities established to ensure that a manufacturing organization is prepared for an audit.

Installation Qualification (IQ)

The document verification that equipment installation meets the expected specifications.

Institutional Review Board (IRB)

IRB is a committee that review clinical studies on humans to ensure that they are conducted in compliance with ethical and regulatory requirements.

Intermediate Precision

Also called within-in laboratory reproducibility, assess the ability of an analytical method to give the same result under different conditions (operators, time of testing). Intermediate precision is an indication of the robustness of a method. Intermediate precision is evaluated during analytical method validation.

International Conference on Harmonization (ICH)

ICH is a collaborative initiative to align pharmaceutical regulatory requirements among several countries.

International Federation of Pharmaceutical Manufacturers (IFPMA)

An industry association that gathers the major pharmaceutical manufacturers.

International Society for Pharmaceutical Engineering (ISPE)

International Society for Pharmaceutical Engineering is an organization that promotes engineering standards in the pharmaceutical industry. It originated from the US and is now a global organization.

Inventory Management

Inventory management consisting in controlling stock of materials used in manufacturing of QC.

Investigation

When a process parameter, an IPC, a release test or an environmental monitoring result is out of specification, an investigation shall be conducted to assess it cause, its impact and its potential CAPA.

Investigational Medicinal Product (IMP)

The European equivalent of an Investigational New Drug (IND). An IMP shall be submitted to the EMA to start clinical trials.

Investigational Medicinal Product Dossier (IMPD)

IMPD is regulatory document submitted to the EMA to obtain authorization to conduct clinical trials.

Investigational New Drug (IND)

An IND is regulatory document submitted to the FDA application to obtain the authorization to conduct clinical trials on an unapproved drug. It is the equivalent of the IMP in Europe.

Ion Exchange Chromatography (IEX)

(IEX) is a type of chromatography separation based on ionic interactions. IEX are frequently used in biomanufacturing.

ISO

International Organization for Standardization.

ISO 9000

International standards for quality management systems.

ISO 9001

International standard for quality management certification.

Isolator

An isolator is a system used to conduct aseptic filling of vials or syringes within a Grade A environment. Isolator enable a physical separation of the environment in which product is filled and the surrounding environment where operators are present, minimizing contamination risks during critical aseptic operations.

J

Jacket

Vessels and reactors often require temperature control. In the chemical industry is it not rare to have internal heat exchange within the reactor. In the pharmaceutical industry, to reduce risk of contaminations and for cleaning purposes, such internal heat exchanger are not common practice. A heating or cooling fluid circulates in an outer layer of the reactor to exchange heat with the inside of the reactor. This outside layer is referred to a jacket. Such vessels are referred to as jacketed vessels.

Japanese Pharmacopoeia (JP)

JP refers to the Japanese Pharmacopeia, which define the standards for medicines, testing and raw materials used in drugs to be market in Japan.

JIS

Japanese Industrial Standards.

K

Kanban

A kanban is a Japanese word meaning a "board". It was made popular in Japanese manufacturing plant (automobile) and is now used around the word as visual tools to manage work tasks.

Key Performance Indicator (KPI)

A KPI is a metric to evaluate the performance of a process, of a group or a company.

Key Process Parameter (KPP)

Parameters that have an impact on the performance or the process (e.g. yield.)

Kick Off

The first meeting when launching a project is a called a kick-off. The term is analogy to the beginning of a football game.

kLa

Certain cell cultures or fermentation are aerobic, i.e. require oxygen to grow cells. In such case, oxygen is supplied as a gas that has to be dissolved into the culture medium to be consumed by cells. The transfer of gaseous to aqueous is expressed by the kLa, also called Oxygen Transfer Coefficient.

L

Label

A label is a sticker on the primary container on which product information are described (product, manufacturer, expiry, lot number).

Labeling

Labeling is a unit operation in Fill and finish oh pharmaceutical product. It consists in applying labels to products.

Laboratory Information Management System (LIMS)

Laboratory Information Management System (LIMS) is a digital tool used to manage a quality control laboratory data. A LIMS is a substitute to a paper-based system for reagent inventory, test records and samples management.

Laminar Airflow (LAF)

A LAF is a piece of equipment providing a unidirectional flow of air filtered by an HEPA filter. A LAF is used for example when handling powders to avoid spreading powders on operators or all around the room.

Laminar Flow

A laminar flow is a unidirectional airflow for contamination control. Laminar means without turbulence.

LD50

The LD50, lethal dose 50, is the dose of a substance that is sufficient to cause a 50% mortality rate within a test population. The LD50 is used in toxicology studies.

Leachable

Leachable are chemical substances released from plastic-based container under normal conditions.

Lead Time

The lead time of an article is the duration it takes to receive the product once it has been ordered.

Leak

A leak, or a leakage is an unintended release of material.

Lean Manufacturing

Lean manufacturing is methodology used in manufacturing industries (e.g. automobile) to reduce waste in production. It is less relevant in the biomanufacturing industry than in other industries focusing on mass production. I am personally crusading against having people with the word "lean" in their job titles. Most of them do not understand biomanufacturing and do nothing but stating the obvious. My apology for the hard language.

Less Than (LT)

Less than is equivalent to strictly inferior to (<). Inferior or equal is equivalent to No more than (≤).

Level Switch (LS)

A switch is a captor that does not provide a continuous measure but a 1 or 0 measure. A level switch detects if the level of a solution contained in a vessel. Level switches are generally used for safety purposes. Is the tank full or not. Is it reaching a low level or not.

Lifecycle Documents

A drug is an evolving product from the time it is developed to the time is taken out from commercialization. Regulatory landscape changes, new data are obtained, better technologies are developed.

Limit Of Detection (LOD)

The LOD is a measure of the lowest detectable analyte concentration. LOD is evaluated during the validation of an analytical method.

Limit Of Quantification (LOQ)

The LOQ is the lowest quantifiable analyte concentration for an analytical method. LOQ is evaluated during the validation of an analytical method.

Line Clearance

Some facilities are used to manufacture several products in a campaign mode. After the completion of a campaign on a product, a line clearance is necessary to ensure that the production line is free of residual from previous campaign. The Line clearance refers to all the procedure in place to ensure no contamination occurs in between manufacturing campaigns.

Linear-DNA (L-DNA)

Linear DNA, is a DNA that has been linearize and is used as starting material in an IVT reaction for mRNA production. L-DNA is generated by linearization of plasmid DNA by use of an enzyme.

Linearity

Linearity is the ability of an analytical method to produce proportional results. Linearity is verified during analytical method validation.

Lipid Nanoparticle (LNP)

LNP are Lipid Nanoparticles composed of several lipids with different functions. LNP are used as drug delivery system for mRNA vaccines. LNP are generated by mixing lipid dissolved in ethanol with an aqueous solution containing mRNA. The mixing of the aqueous solution and the organic solution encapsulates the mRNA within a spherical particle made of lipids.

Lipids

Lipids are organic substance that are insoluble in water but soluble in organic solutions. Lipids include fats, oil and waxes. Lipids are used in RNA based therapeutics and vaccines to encapsulate the genetic material in Lipid Nano Particle for drug delivery (See LNP).

Liposome

A liposome is a lipid vesicle used for drug delivery.

Live Attenuated Vaccine (LAV)

A Live attenuated vaccine is a vaccine containing a weakened live pathogen triggering an immune response and a protection against future exposition. Live attenuated vaccines were the first vaccines developed.

Load Testing

When testing an autoclave or a washing machine, it is necessary to test the equipment by loading material in it to be as close as routine manufacturing conditions. The opposite is referred to as empty testing. Usually, the first tests are performed without any loading.

Log Reduction Value (LRV)

The LRV is a measure on a logarithmic scale of the microbial reduction. It is used to measure the performance of a filter or a sterilization process. The minimal LRV for a sterile filter is 7.

Long Lead Item

The term long lead item refers to any material, equipment, consumables that has a long lead duration of procurement. The duration is dependent on the type of item. For a raw material or a consumable, above 6 month is considered long. For an equipment, above 12 month is considered long. In certain projects, long lead items are ordered at risk to accelerate timelines.

Lot

A lot describes a quantity of product with a common manufacturing history. Usually, the word lot is used in Drug Product while batch is used for Drug Substance. One batch of DS is often split into several lots of DP. Multiple lots of DP have a common history as they originate from one batch of DS.

Lot Release

The lot release refers to the approval of a product lot for distribution. Lot release comes after completion of all QC testing and after verification that all results are within specification. A manufactured lot stays under quarantine within the manufacturer facility until is it release. Then it can be shipped for distribution.

Lot Traceability

Knowing when a lot was manufactured and how is important. Being able to identify from which lot a vial or a syringe originate is important in case of product default. Traceability means being able to track a lot through its supply chain from drug substance manufacturing, drug product and all the way to distribution.

Lyophilized Cake Appearance

After lyophilization of a drug product in a vial, a cake like solid product is obtained. The visual appearance of the cake is a quality attributes of the product.

Lyophilizer

A lyophilizer, also called a freeze-dryer, is an equipment used to remove the water contained in a product (drug or food) to extend its shelf life. Astronaut mostly consume lyophilized food during space missions.
A regular drying process would be done by heating a product to evaporate the water it contains. But such process is not suitable for heat sensitive substances. For such substances, freeze drying is used. Product is frozen by a temperature decrease followed by a sublimation of the water by a pressure decrease. This allows the removal of the water without breaking the product. Lyophilized vaccines are more stable thus more advantageous for distribution in countries where a robust cold chain cannot be maintained.

M

Maintenance

There are two types of maintenance, corrective and preventive maintenance. Corrective maintenance happens after an equipment failure and consists in bringing back the equipment to a working state as quickly as possible to not impact manufacturing. Preventive maintenance consists in keeping equipment under proper conditions to avoid failure during production. Each organization need to have a procedure in place that describes its overall plan for maintenance of equipment. This plan is referred to as maintenance program. Generally, maintenance is done annually. Frequency is facility dependent.

Management Review

Quality is the responsibility of all, not just QA, QC and the manufacturing team. Management is responsible for the proper implementation and operation of the quality management system and for providing the adequate resources to meet quality objectives. Periodically, the management of a manufacturing organization joins a meeting called Management Review consisting in an evaluation of the quality system.

Manual Cleaning

Manual cleaning refers to cleaning operation that are not automated. Nowadays, manual cleaning tends to be avoided as it is ultimately operator dependent and harder to validate compared to an automated cleaning process.

Manual Inspection

After the drug product is filled into its primary container (vials or syringes), visual defects are checked in an operation called inspection. Visual inspection can be automated by an inspection machine or done manually by operators checking one container at a time.

Manufacturing Execution System (MES)

An MES is a software for managing production. MES can include the batch record, the management of raw materials and consumables as well as samples.

Manufacturing Process Controls

Manufacturing process controls are all the measures implemented in a manufacturing process to ensure consistent production.

Marketing Authorization Application (MAA)

MAA refers to the submission for drug approval to the European Medicine Agency.

Marketing Authorization Holder (MAH)

The Marketing Authorization Holder is the entity responsible for the commercialization of a drug and the associated pharmacovigilance. It is frequent to see an MAH that does not conduct any manufacturing activities. For example, if the MAH uses a CDMO or if the MAH has simply acquired the distribution rights for a specific country.

Mass Flow Meter

Measuring flowrate is an important parameter in biomanufacturing. Various type of sensors exists to measure flowrate. Among them, mass flow rate enables a measure of the flowrate in a unit of mass per unit of time, which have the advantage of not being a variable of the temperature or the density of the fluid transferred. Mass flow meters are found on water circulation loops.

Mass Spectrometry (MS)

Mass spectrometry is a common analytical technique used for molecular analysis.

Master Batch Record

The Master Batch Record is probably the most important document in biomanufacturing. It is the primary document describing all operations to be conducted in the production of a batch. The Master Batch Record is a template document. At the start of a new batch, an empty MBR is emitted by the QA department and used by the manufacturing team to take records of all operations and materials used in the execution of a manufacturing batch.

Master Cell Bank (MCB)

Once a cell clone has been selected, it is multiplied into a stock of cells that have the same characteristics. This stock is referred to as Master Cell Bank. Within this reserve of cells, some cells are taken to be further multiplied into another stock of cells with the same characteristics. This stock is referred to as Working Cell Bank. At the beginning of a new manufacturing batch, cryo vials from the working bank will be taken to start a cell culture. The Master Cell bank is only used to product working cell bank.

Master flow diagram (MFD)

A master flow diagram is a flow diagram used in process engineering to describe main process equipment used in a manufacturing process. A master flow diagram gives a simplified representation of a process compared to a process flow diagram.

Master Production Schedule (MPS)

Biomanufacturing requires planning to ensure that material, facility and personal are available for the manufacturing of drug to be distributed. The annual production schedule that plans the production over a year is the Master Production Schedule.

Master Seed Lot (MSL)

The Master Seed Lot (MSL) is the initial characterized stock of a microorganism used to produce biological products, from which working seed lots are prepared for routine manufacturing. The MSL in bacterial fermentation is the equivalent to the MCB in cell culture.

Master Service Agreement (MSA)

MSA are very common in the biomanufacturing industry. A Master Service Agreement is a contract that defines the conditions of how an ongoing services shall be delivered by a service provider like a CDMO or a CRO. If it is a one-time service, a regular contract is sufficient and an MSA is not needed. This is the case for manufacturing of clinical lots by a CDMO. In the case of the manufacturing of a commercial product in routine by a CDMO, an MSA is recommended. It avoids having to renegotiate a contract every year.

Material Airlock (MAL)

A Material airlock is a chamber used for transferring materials from one clean room to another. Usually, material airlocks are found in between areas of different cleanliness to reduce risk of contaminations.

Material Attribute

A material attribute refers to a characteristic of a raw material used in a manufacturing process that could have an impact on the quality of the product. (see Critical Material Attribute)

Material Resource Planning (MRP)

System for managing material needs.

Matrix Approach

In process and cleaning validation, a matric approach is often taken to reduce the number of tests to be executed to perform a validation activity. For example, in cleaning validation, if there are multiple vessels to be cleaned, testing all vessels several time might be hard to do with the available resources.  In such case, vessels can be sorted into families based on their size, complexity of design and contact product. Within one category, the wors case vessel is identified and selected to be representative of all other. If the cleaning validation is demonstrated on this vessel, i.e. all results are within the acceptance criteria, and with the appropriate scientific rational, the results can be extrapolated to other vessels of the same family. A matrix approach shall always be based on risk assessment and a strong scientific rational.

Maximum Allowable Carryover (MACO)

The term Maximum Allowable Carryover is used in cleaning validation to estimate the acceptable limit for residual material from the previous batch carried into the next manufacturing batch. MACO is calculated based on toxicology data.

Media Fill

A test run designed to simulate aseptic manufacturing conditions and verify the robustness of aseptic techniques. It demonstrates that personnel, processes, and environments can maintain sterility under actual production conditions. Also referred to as Aseptic Process Simulation (APS), during Media fill test, an aseptic process (final filtration and vial filling) is reproduced using a soy media (bacterial growth promoter) instead of the product. The filled vials are then incubated and visually inspected to detect bacterial growth.

Media Preparation

Media preparation refers to all the operations performed to prepare media that are used for cell cultures. Most often, media and buffer preparation are separated activities even though they are very similar. Some media can be harder to clean than salt solution or even contains animal derived substances.

Media Supplementation

Media supplementation refers to the action of adding nutrients to culture media during a cell culture. After a certain time of culture, the nutrients contained in the media get depleted and cell culture growth rate can decrease. Adding fresh media increase the cell culture.

Medical Representative (MR)

A Medical Rep is a sales representative in the pharmaceutical industry. Their role is to meet with healthcare professionals, introduce them drugs and provide them with the relevant information.

Membrane Valve

Also called a diaphragm valve, a membrane valve is a valve controlling the fluid flow by mean of flexible membrane. The valve actuator pushes the membrane onto the body of the valve to restrict the flow of fluid. This type of valves is the most used in the pharmaceutical industry as they are the most hygienic valves.

Memorandum of Understanding (MOU)

The term MOU is often used in business deal to designate a preliminary agreement before working out the details of a final contract.

Messenger RNA (mRNA)

mRNA is single strand molecule obtained by transcription of a double strand molecule of DNA. The role of the mRNA is to transfer the genetic information contained in the DNA and be translated into proteins.

Method Qualification

(See analytical method qualification)

Method Transfer

(See analytical method transfer)

MHRA

The Medicines and Healthcare products Regulatory Agency (MHRA) regulates medicines, medical devices and blood components for transfusion in the UK.

Microbial Enumeration Test (MET)

The MET is a test performed to count the number of viable microorganisms present in a sample.

Microbial Limit Test

MLT is a test performed on a non-sterile product and raw material to evaluate if it meets the specified limits for Total Aerobic Microbial Count (TAMC), Total Combined Yeast and Mold Count (TYMC), and specified microorganisms.

Microbial Monitoring

Microbial monitoring refers to the activity of tracking microbial presence in environments.

Milestone

A milestone is a term used in project management to indicate a key project stage. A project can be split in several milestones which can be used for tracking the progress of the project. It is an analogy with milestone on the side of a road.

Mixing Study

In biomanufacturing, mixing operations are commonly found. A mixing study is a process validation activity that aims to demonstrate the consistent performance of a mixing operation, i.e. that after mixing the product concentration is homogeneous in all points of the vessel.

Mixing System

A mixing system is an equipment used for blending two or more materials together.

MLHW

Ministry of Health, Labour and Welfare is a regulatory body in Japan. MHLW is the agency that delivers marketing authorizations.

Mock Inspection

A mock inspection is a training audit conduct internally or by a third party to prepare for a regulatory inspection. Mock inspection is essential to inspection readiness.

Module 1

Module 1 is the section of a CTD that focuses on administrative data.

Module 2 (Summaries)

Module 2 is the section of a CTD that focuses on summary data.

Module 3 (Quality)

Module 3 is the section of a CTD that focuses on quality data.

Module 4 (Nonclinical)

Module 4 is the section of a CTD that focuses on non-clinical data.

Module 5 (Clinical)

Module 5 is the section of a CTD that focuses on clinical data.

Moist Heat Sterilization

Sterilization using pure steam. It is an alternative method to dry heat sterilization. Moist heat sterilization requires lower temperature (121°C) than dry heat (250 °C).

Monoclonal Antibody

Very often referred to as mAb, a monoclonal antibody is an antibody manufactured from a single clone of cells. mAbs are widely used as therapeutics. The opposite of mAbs are polyclonal antibodies made using different cell clones.

Monograph

Monograph are standardized product specifications that are collected in pharmacopoeias.

More Than (MT)

MT is equivalent to strictly superior.

mRNA Vaccine

mRNA vaccines are vaccines using messenger RNA to deliver genetic information into the cells, which results in the production of proteins and generates an immune response.

Multi-Product Facility

A multi-product facility is a manufacturing facility that is used for the production of different drugs. CDMO facilities are usually multi-product facilities. Fill and finish building are also generally multi-product facilities. For commercial products, internally manufactured, the model is usually to have dedicated single product facilities. However, with the growing single use adoption and the intensifications of process yields, there is a shift towards multi-product facility even at large pharmaceutical companies.

Mycoplasma Testing

Testing for mycoplasma contamination. Mycoplasma are bacteria that do not present a cell wall around their membrane. These bacteria are resistant to antibiotics targeting cell walls. Mycoplasma can pose safety risks in case of contamination.

N

Net Positive Suction Head (NPSH)

A centrifugal pump, by its rotation, creates a low pressure at its suction which generates a fluid displacement from higher to low pressure points. If the suction pressure is too low, vapor bubble in the liquid form. When going high to low pressure areas in the pump, vapor bubbles collapse causing vibrations that can damage the pump. This phenomenon is called cavitation. The limit for the suction pressure is the liquid's vapor pressure. To avoid cavitation, the critical factor to consider is the Net Positive Suction Head. The NPSH measure the difference between the pressure of the liquid at the suction point and the liquid's vapor pressure.
(see NPSHa; see NPSHr; see suction head)

Neutralizing Antibody

The Nucleus is the core of a cell containing its genetic material.

Neutralizing Antibody Assay

Test for antibodies neutralizing a biological activity. For example, for an inactivated virus vaccine, neutralizing antibody would refer to the antibody generated by the immune response that would block the target antigen from infecting cells.

New Drug Application (NDA)

An NDA designates the submission of a new drug to the FDA.

Next-Generation Sequencing (NGS)

NGS is DNA sequencing technology. It is used for example in mRNA vaccine manufacturing for identification tests on DNA.

No Action Indicated (NAI)

NAI is the mention on reports from inspections conducted by the FDA, where no issue was identified.

No More Than (NMT)

NMT is equivalent to inferior or equal to.

No Observed Adverse Effect Level (NOAEL)

NOAEL is a term used in pharmaco-toxicology studies. NOAEL is evaluated to assess the safety profile of a drug during pre-clinical and clinical studies. NOAEL is the maximal dosage of a product for which no adverse effect was detected. NOAEL value is used in cleaning validation to estimate the MACO. (see MACO)

No Observed Effect Level (NOEL)

NOEL is term used in pharmaco-toxicology studies. NOEL is the maximal dosage of a product for which no effect was observed. In the case of NOEL, the focus in not only on adverse effect but all physiological effects possible. NOEL is always below NOEAL.

Non-Disclosure Agreement (NDA)

In business, an NDA is a contract signed by two parties before sharing of confidential information. The party that will receive the information signed an NDA as a promise that it will not disclose the obtained information.

Non-conformity

A non-conformity is any test or parameters that did not meet its expected specification.

Non-GMP

By non-GMP are designated activities that are not under GMP regulations. For example, in a manufacturing facility, the civil engineering and the electrical installations are not under GMP even though they sustain GMP production. The designation is also used when referring to manufacturing that is not performed under GMP.

Normal Operating Range (NOR)

A Normal Operating Range designates the range within which a process parameter shall be controlled. NOR must be validated during process performance qualification (see PPQ).

NPSH Available (NPSHa)

The NPSH available is the NPSH calculated for the pump installed in its actual working environment. NPHSa is calculated and compared to NPSHr to ensure that the pump can operate without cavitation. If NPSHa < NPSHr, cavitation will occur.

NPSH Required (NPSHr)

The NPSH required is a specified value measured by the pump manufacturer under controlled test conditions. It indicates the minimal suction head the pump requires to operate without cavitation at a given flowrate.

Nucleus

The core of a cell containing its genetic material.

O

Occurrence

The term occurrence is frequently used in risk analysis to designated the frequency of a risk event.

Off-Line

Testing performed away from the production line. Off-line testing is the contrary to in-line testing. Off-line measurements require to take a sample and test it outside the production environment.

OOS (Out of Specification)

An OOS is a result outside of acceptable limits.

Open Process

An open process is a process in which the product can be exposed to the environment at certain operations. Open processes shall be performed in adequate clean room to control contamination risks.

Open System

An open system in biomanufacturing, refers to equipment that at some point in the manufacturing process has its inner surfaces exposed to the external environment. The opposite is a closed system. The term can also be used to describe a software.

Operational Qualification (OQ)

The documented verification that equipment meets the expected functional specifications. Operational Qualification comes after Installation Qualification (see IQ).

Operator Qualification

Operator qualification refers to the training of operators for specific tasks under GMP environment.

Original Document

The original document is the primary version of a record.

Orphan Drug Designation

Orphan Drug refers to rate disease for which there are no currently available treatment. The FDA gives the Orphan Drug Status.

Osmolality

Osmolality is a measure of dissolved particles (osmoles) per kilogram of solution. Osmolality is often an important quality attribute of injectable drugs. (see Osmole)

Osmole

An osmole designates one mole of particle dissolved in any solution.

Osmotic Shock

Cells have permeable membranes for molecules exchange by diffusion.  An excessive difference in solute concentration outside and inside the cell, creates a rapid flow of water across the membrane to equilibrate the solute concentration on both side which can cause the rupture of the membrane. This phenomenon is known as osmotic shock.

Outsourced Manufacturing

Outsourced manufacturing is equivalent to external manufacturing, i.e. the use of third party CDMO or CMOs for manufacturing.

Oxidation

An oxidation is a chemical reaction consisting in the addition oxygen atoms to a molecule or removing electrons from a molecule.

P

Package Insert

The package insert is a document slipped in the secondary container of a drug product (vial or syringe). It contains information relative to the drug usage information.

Packaging Operations

Packaging operations refers to the activities of labelling and boxing of drug product. Everything that concerns the secondary container of a drug product falls within the packaging operations.

Parenteral

In the context of medicinal products, parenteral refers to drugs that are administered to a patient by injection via a needle. All vaccines except oral vaccines are parenteral drugs. Parenteral drugs require higher level of control compared to oral solid dosage.

Part 11

Part 11 is an abbreviated way to refer to 21 CFR Part 11 regulating electronic records (see 21 CFR Part 11).

Particle Counter

Particle counters are devices use for measuring airborne particles. Particle counters are indispensable for clean room monitoring activities.

Particle Distribution Index (PDI)

The PDI is measure of how tight is a particle size distribution on a given sample. PDI is between 0 to 1, the closure to 0, the more the particles have similar size.

Particle Size Analyzer

Particle size analyzer is an instrument for measuring particle size distribution.

Particle Size Distribution

In a sample containing particles, not all particles have the same size. Two metrics are used to described the particles mixture, the average particle size and the distribution. Distribution is a curve that describes the proportion of particles on different ranges of size.

Pathogen

A pathogen is a microorganism that causes a disease.

PCR

PCR is molecular biology laboratory technique used to amplify DNA.

PDCA

Plan-Do-Check-Act (PDCA) is a methodology for continuous improvement. It was made famous by Deming and is also called Deming cycle. Its basic principle is planning an action, implementing the action, checking its results and acting depending on the result. PDCA has greatly contributed to quality improvement in manufacturing industry.

pDNA

Plasmid DNA is a type of DNA obtained from bacterial fermentation and used in nucleic acid vaccines and gene therapy.

Performance Qualification (PQ)

The documented verification that equipment meets the expected performance under load. Performance Qualification comes after Operation Qualification (see OQ).

Perfusion Culture

As opposed to batch culture where all nutrients are loaded at once until depletion, perfusion culture allows for continuous supply of fresh media, removal of waste and used media to achieve higher culture yield.

Peristalsis

The word peristalsis refers to the motion of a fluid pushed within a tube by repeated contractions and relaxations. In the human body, digested food moves through our intestines via a peristaltic motion.

Peristaltic Pump

Refers to pumps, widely used in biomanufacturing for liquid transfer, based on the principle of peristalsis. A flexible tube is compressed by rotating rollers generating a peristaltic motion. The main advantage of peristaltic pumps is the absence of product contact.

Permeate

The term permeate refers to any material passing through a membrane. The term is most often used in ultrafiltration and diafiltration operation.

Permeate Flux

Refers to the flowrate of permeate per unit of surface area of membrane.

Permissible Daily Exposure (PDE)

The Permissible Daily Exposure is a term used in toxicology to describe the maximal daily dose of a product a human can be exposed to with negligible safety risk.

Personalized Cancer Vaccine (PCV)

Personalized Cancer Vaccine (PCV) are vaccines that are individualized to a patient specific tumor. These vaccines are still under development but have made great progress with the adoption of the mRNA modality.

Personnel Airlock (PAL)

A PAL is a separation chamber used by production operators when moving between two clean rooms of different level of cleanliness. The main purpose of a PAL is to control risk of contamination related to personal flux.

pH

Measure of acidity or alkalinity. pH is logarithmic measure of the concentration of H+ cation in a solution.

pH Inactivation

Pathogens encountered in biomanufacturing processes can be neutralized by undergoing strongly acidic or basis pH conditions. Viral inactivation is often performed by pH inactivation.

Pharmaceutical Inspection Convention and Pharmaceutical Inspection Co-operation Scheme (PIC/S)

PIC/S is a set of international standards and guidelines that harmonized GMP inspections among several regulatory authorities.

Pharmaceutical-Grade Compound

A pharmaceutical grade-compound is a compound that is suitable for GMP manufacturing. It meets the regulatory standards applicable to the compound. The opposite is research grade compound which are suitable for process development activities or trials runs but not GMP manufacturing.

Pharmaceuticals and Medical Devices Agency (PMDA)

PMDA is Japan’s regulatory agency for pharmaceutical products.

Pharmacovigilance

Pharmacovigilance refers to all the activities to monitor drug safety after its market authorization.

Pharmacovigilance System Master File (PSMF)

The pharmacovigilance system master file (PSMF) is a detailed description of the pharmacovigilance system used by the Marketing Authorization Holder (MAH) of a certain drug.

Phase I

A Phase I trial is a small-scale trial to test the safety and dosage of a drug or a vaccine (typically less than a hundred participants).

Phase II

A Phase II trial is a trial to test the efficacy and further assess safety of a drug or a vaccine on a representative population of people (typically several hundred participants).

Phase III

A Phase III trial is a large-scale trial to confirm the efficacy and safety of a drug or a vaccine in a broad and representative population (typically several thousand participants).

Pilot Scale

The pilot scale is a manufacturing scale in between the laboratory a scale and large commercial scale. This intermediate-scale is used to further develop a process before moving to larger volumes. Sometime, the pilot scale is used for early clinical phase.

Piping & Instrumentation Diagram (P&ID)

Piping & Instrumentation Diagram (P&ID) are detailed schematic of an equipment. Vessels, valves, sensors, piping diameters, connectors and all other component on the equipment are represented on a P&ID. Originally, P&ID came from the chemical engineering industry and were used to represent equipment and chemical process. P&IDs are more detailed than PFDs and serve as basis to elaborate construction drawings (see PFD).

Piping and Instrumentation Diagram (P&ID)

P&ID originated from the chemical engineering industry and were used to describe process equipment with all their piping, instrument and components.  I highly recommend anyone working at a biomanufacturing plant to be familiar with reading and creating P&IDs.

Placebo

A placebo is an inactive substance used as a control in clinical trials. A placebo does not contain any drug substance but should look similar to the real product.

Plant Steam

Plant steam is a steam used for non-product-contact utilities in
manufacturing. Plant steam is a black utility used to supply heat exchangers. It is not suitable for SIP.

Pneumococcal conjugate vaccines (PCV)

Pneumococcal conjugate vaccines (PCV) are vaccines against pneumococcal infections. PCV are based on the conjugation of polysaccharides to a carrier protein for an enhanced immune response.

Point of Use (POU)

A POU is a point on a water loop where purified water or WFI is accessible.

Polymerase Chain Reaction (PCR)

Polymerase Chain Reaction (PCR) is a laboratory technique used to amplify a DNA sequence. PCR became widely known during the COVID-19 pandemic, as RT-PCR (Reverse Transcription PCR), was used to detect the presence of COVID-19 virus in sample.

Polysaccharide

A polysaccharide is a carbohydrate polymer made up of monosaccharide (sugar) units. Polysaccharides are found on the surface of certain bacteria and can be used as antigens for vaccines.

Pooling

In biomanufacturing, pooling refers to combining multiple liquid samples into one solution. For example, multiple batches of drug substance can be pooled together at the drug product stage. Or different drug substances can be pooled together at the formulation stage of a multivalent vaccine. Sublot in a manufacturing batch can be pooled together.

Post Approval Change Management Protocol (PACMP)

A Post-Approval Change Management Protocol (PACMP: EU and ICH Q12) also referred to as Comparability Protocol (US) is a comprehensive plan for assessing the effect of a proposed post-approval change on the quality of a product (identity, strength, purity, potency, performance and stability).

Post-Inspection Letter (PIL)

Upon completion of an inspection by a regulatory agency, the findings identified during the inspection are listed and communicated to the manufacturer in a Post-Inspection Letter.

Post-Marketing Surveillance (PMS)

Any Marketing Authorization Holder (MAH) is required to monitor the safety of the drug after its release to the market. This practice is called post-market surveillance. It is part of Pharmacovigilance (PV).
(See Pharmacovigilance)

Post-Use Integrity Test

Refers to testing the integrity of a filter after use.

Potency

Potency is a term used in pharmacology to describe intensity of the effect produced by a product for a given dose. A drug with intense effect at low concentration is highly potent. A low potency drug gives a response at higher concentration.

Potency Assay

A potency assay is a quantitative test measuring the biological activity of a product. (See Potency)

Pre-Approval Inspection (PAI)

Before the commercial approval of a product and its manufacturing site, regulatory agencies conduct site inspection. In the case of the FDA, this inspection is called Pre-Approval Inspection (PAI).

Pre-Filled Syringe (PFS)

Pre-Filled Syringes (PFS) are common containers for injectable drugs. The required quantity of a drug product is aseptically filled in a syringe by an automated filling machine under an isolator. The main advantage of PFS is its easiness of use for the medical professional in charge of the administration of the drug to the patient.

Precision

The term precision is used in the context of analytical method to describes the consistency of repeated measurements. It represents how close are the results when performing repeated measures of a sample under the same and different operating conditions. (See accuracy)

Preclinical Study

A preclinical study refers to a study performed on animals before human trials to evaluate the toxicity of a candidate drug or vaccine.

Prescription Drug User Fee Act (PDUFA)

The PDUFA is U.S. law passed in 1992 that enable the FDA to collect fees from pharmaceutical companies to fund the drug review activities managed by the agency. It is one source of revenue among others for the FDA. Other health agencies also operate in a similar manner.

Pressure Cascade

A pressure cascade refers to the having pressure differences between clean room to control the flow of contaminants.

Pressure Gauge

A pressure gauge is an analogue pressure indicator. All pressurized vessels must be equipped with a pressure gauge for safety reason.

Pressure Loss

A pressure loss refers to a reduction in pressure during flow of a fluid. Also called pressure drop, pressure loss can be due to frictions inside a pipe, obstacles, valves, reductions and angles. Pumps must be selected with the proper height to offset the pressure loss in a piping installation.

Pressure Safety Valve (PSV)

A PSV is a valve for pressure relief. It is usually found on compressed air piping. If pressure goes above a certain safety threshold, the valve opens and release the gas which reduces the pressure.

Preventive Action

When a non-conformity occurs in a process or in any activities, actions must be implemented to correct the non-conformity and to prevent it from happening it in the future. These actions are called CAPAs for, Corrective Actions Preventive Action. Preventive Actions are the controls put in place to avoid future issues from occurring. (See CAPA)

Preventive Maintenance Plan

Preventive Maintenance Plan is the program that describes how equipment shall be regularly maintained. (See Maintenance Program)

Primary Packaging

A container directly in contact with the drug product is referred to as primary packaging. For most biological drugs, primary packaging is in vials or syringes. Primary packaging must be aseptic for sterile medicine. (See Secondary Packaging)

Priority Review

A priority review is a favorable treatment granted by the FDA to conduct a drug application review within 6 months instead of the typical 10 months period.

Probe

In the context of instruments, a probe is a device used to access the location where a measurement is done. A probe includes a sensor.

Procedure

A procedure is a set of documented instructions followed to perform a process.

Process Analytical Technology (PAT)

PAT refers to analytical instruments and technologies that can be used for real-time process monitoring. PAT is a new trend in biomanufacturing. Off-line measurement performed by QC is the normal practice for most analytical testing. Yet, off-line measurements are often time consuming and provide information on the past status of the process. With the new techniques available, the goal is to measure in-line and have a real time monitoring of a manufacturing process.

Process Bottleneck

A process bottleneck refers to the step in a manufacturing process that limits the production. This term comes from industrial engineering. Usually in biomanufacturing, the bottleneck is the step with the longer duration. For example, a 3 days cell culture could be the bottleneck of a biological process. If higher production rate is needed, adding bioreactors can be considered.

Process Characterization

Process Characterization refers to the study of a manufacturing process, its critical process parameters and their impact on the quality attributes and the performance of the process. Process characterization is an important activity to ensure a robust manufacturing process and successful PPQs. The process control strategy is based on the outcomes of the process characterization. Process characterization is part of the Process Design, which the first stage of the process validation lifecycle. (See Process Validation)

Process Control Strategy (PCS)

The process control strategy is a plan that describes how a manufacturing process is operated to ensure consistent production. The PCS includes the critical process parameters (CPP), Key process parameters (KPP) and the In-Process Controls to monitor the process. The PCS is a key document in the establishment of a new manufacturing process.

Process Control System (PCS)

A PCS is a centralized automation system controlling manufacturing equipment.

Process cycle Time

Process cycle time and batch duration are distinct concepts. Batch duration is how many days it takes to manufacture an entire batch from start to finish. For example, a process composed of 5 days of fermentation and 4 days of purification has a batch duration of 9 days. In this case the process cycle time can be as low as 5 days if one batch of fermentation is started every 5 days. Here the lowest process cycle time will be defined by the bottleneck operation. Process cycle time is the minimal time between two consecutive batches.

Process Development (PD)

Process Development refers to the activities aiming to optimize a manufacturing process. PD is required to move a process from the laboratory scale to factory scale.

Process Flow Diagram (PFD)

Process Flow Diagram are simplified schematic of a manufacturing process or a manufacturing system. Principal equipment, certain auxiliary equipment and piping are represented on a PFD. Originally, PFD came from the chemical engineering industry and were used to represent equipment and chemical process. PFDs are less detailed than P&IDs but serve as the basis to elaborate P&IDs (see P&ID).

Process Gap Assessment

When transferring a product from one facility to another during a technology transfer to a CDMO or for a scale up, it is important to verify that the two processes remain equivalent and ensure the manufacturing of a product of the same quality. To do that, a process gap assessment is required. The gap assessment compared all factors that could have an effect on the manufacturing process such as equipment, process parameters, raw materials, consumables, utilities and facilities. The potential impacts and their criticality of each identified gap must be evaluated and if needed mitigated. A process gap assessment is a risk analysis focusing on comparing manufacturing processes in multiple facilities.

Process Intensification

Certain manufacturing processes designed at the laboratory scale do not deliver sufficient yields at commercial scale to be economically viable and technically feasible. In such cases, process development teams have to work on how to increase the yield of product manufactured while maintaining the current scale of the process. This activity is referred to as process intensification. In vaccines or biologics, process intensification is often focused on increasing the quantity of bacteria or protein at the fermentation or cell culture step. The increase of quantity of product of interest at Upstream stage has to be balanced with the purification capabilities at the Downstream stage.

Process Mapping

A manufacturing process is a complex sequence of multiple unit operations with process parameters, input raw materials, output products and byproducts and in process controls. A process mapping is visual way of describing the entire process with all its operations input and outputs. It is an important process knowledge document that serves as reference for many other activities during a technology transfer, a scale up or during routine operations.

Process Performance Qualification (PPQ)

Second stage of the Process Validation Life cycle, Process Performance Qualification refers to all the activities implemented to validate a manufacturing process, i.e.to establish the documented proof that a manufacturing process consistently meets its expected performance and ensure the manufacturing of a product that meets quality requirements. PPQ are conducted after engineering batches once the process is locked, equipment fully qualified, procedure and Master batch records approved and personal trained. for a long time, the rule of thumb was to conduct at least three consecutive successful PPQ batches to demonstrate that process is controlled. Nowadays, some agencies expect the number of PPQ batches to be based on a risk analysis and statistical methods. If successful, the product obtained from PPQ batches can be commercialized. During PPQ batches, mixing validation, hold time validation, filter validation, membrane lifetime studies, E&L studies are conducted.

Process Scale-Down Study

Before implementing a change into a process, it is beneficial to replicate the process at a smaller scale and evaluate the impacts of the change. For example, when changing a filter from one vendor to another, to evaluate material compatibility and filtration performance, a scale-down study can be performed as part of risk mitigation.

Process Scale-Up

The life cycle of a drug manufacturing process starts with the design of the process at small scale. Once the process is established in the laboratory, it can be transferred to a GMP Facility for Phase I clinical material manufacturing. At this stage, process is at a small scale and only a few thousands of doses are required. The further the product move forward in clinical trials, Phase II, Phase III, more doses are required. Increasing the scale of the process becomes necessary. This activity is referred to as process scale up.

Process Validation (PV)

Process validation as defined by the FDA is establishing the scientific evidence that a manufacturing process consistently delivers a product that meets the expected quality criteria. Process validation consists of three stages, Process Design, Process Qualification and Continuous Process Verification. The first stage focuses on the establishment of the process, the generation of process knowledge and the definition of the process control strategy. The second step focuses on the qualification of the utilities and equipment and on the execution of Process Performance Qualification activities to demonstrate the process delivers the expected quality product. The last stage is a continuous activity that cover the entire life time of the process. Its purpose is to increase process knowledge and to continuously track its performance.

Programmable Logic Controller (PLC)

A PLC is an industrial computer used for automating actions in a manufacturing process. Actuators and sensors on a process equipment are connected to the PLC.

Project Charter

A project charter is a project management document. Its purpose is to formally authorize the project, defines its context, its objectives and its scope. The project charter shall not be confused with a project execution plans which has a deeper level of details on how the project shall be conducted.

Project Execution Plan

A project execution plan is a project management document. Its purpose is quite similar to the Project Charter but with more details on when, who and how to implement a project. The PEP described the purpose, the timeline, the different phases of the project, the important deliverables and the roles of the different stakeholders. Initiating a project with a project charter is a good project management practice. Running a project without a PEP is a recipe for disaster.

Project Management

Project Management refers to the activities related to planning and controlling the execution of a project.

Project Management Office (PMO)

A PMO is a team coordinating project management activities.

Project Risk Register

A project risk register is a project management document. Its purpose is to identify all risk surrounding a project, evaluate them and define a mitigation plan. The larger the project, the more complex it can become and the more risk of failures appears.

Proof of Concept (POC)

A POC is a demonstration of feasibility of an idea. Before making a large investment to develop a product, a smaller, less elaborate and cheaper version is made and tested. If the results are satisfactory, the product can be developed for commercialization.

Protein

In the context of pharmaceutical drugs, proteins are large molecules formed by multiple chains of amino acids. Proteins are expressed by microorganisms during cell cultures and undergo various purifications processes to be used as therapeutics.

Protein A Resin

Protein A is a surface protein on the Staphylococcus aureus bacterium. It has high affinity with Immunoglobulin G (IgG) antibodies. For that reason, it is widely used for purifications by chromatography. Protein A resin is a chromatography resin with protein A on the surface of beads used for separation of antibodies.

Proven Acceptable Range (PAR)

A Proven Acceptable Range designates a range that expands beyond a Normal Operating Range without impacting product quality of process performance. A PAR allows a broader range of control for a process parameter. It can be seen as safety margin on both sides of the NOR. (see NOR).

Pure Steam

Pure Steam is a clean utility used in steam sterilization operations. SIP as well as autoclaving are performed using pure steam. Pure steam is obtained from Water for Injection, WFI.

Purified Water (PW)

Purified Water is a water of certain quality that is used in pharmaceutical production. It is usually obtained by the following operations: water softening, particle filtration, activated carbon, reverse osmosis and electro deionization.

Purity

Purity refers to the absence of impurities and contaminants in a product.

Q

Qualified Person (QP)

In the European Union, a drug product lot can only be released to the market if it has been reviewed, approved and released by a certified person. This person is referred to as Qualified Person (QP) and is the legal person responsible for lot release in the EU.

Quality Agreement

A Quality agreement is a formal document, a contract defining quality responsibilities of the various parties involved in a project. For example, a drug developer transfers a manufacturing process to a CDMO through a technology transfer. Both, the drug developer and the CDMO quality assurance teams are responsible for the quality of the product. How do they interact and what are the roles expected on each party are described in the Quality Agreement.

Quality Assurance (QA)

Quality Assurance refers to all the activities and practices in place throughout the manufacturing process to ensure product quality. It should not be confused with Quality Control (QC) which focuses on testing product to ensure that quality attributes are met. Quality assurance is built into the manufacturing process and all the procedures to make sure that even if all products are not tested, they will be manufactured in a manner that ensure the final product meets its quality specifications. In all manufacturing facility, there is a Quality Assurance department in charge of running the quality management system of an organization. All personnel involved in manufacturing and the management are responsible for quality assurance.

Quality by Design (QbD)

Quality by Design is a proactive quality approach that consist of ensuring the quality of a product by embedding quality within the facility, the manufacturing process and within the product. By integrating QbD, a more robust process can be implemented which by extension enable an improved quality assurance. Extensive process knowledge is required to implement QbD. QbD starts with the definition of the Quality Target Product Profile (QTTP) and then evaluating how Critical Process Parameters (CPP) and Critical Materials Attributes (CMA) affect the product Critical Quality Attributes (CQA). QbD enables the definition of an effective process control strategy.

Quality Management Review

Manufacturers are expected to periodically review their quality system and their quality performance. The Quality Management Review usually occurs once per year. Senior management must participate to the period review.

Quality Management System (QMS)

A Quality Management System (QMS) is framework of policies and procedures established within a manufacturing organization to consistently ensure that product meets it quality specifications. Quality Assurance procedures fall within the QMS.

Quality Overall Summary (QOS)

The QOS is a section of the Common Technical Document (CTD) of a drug application that summarizes the data related to the quality of the drug. QOS is part of the Module 2 of a CTD.

Quality Risk Management (QRM)

Quality Risk Management is a risk-based quality approach used in the pharmaceutical industry. Quality risks are identified, evaluated and mitigated based on scientific and process knowledge available. Its purpose is to ensure drug efficacy and safety.

Quality Target Product Profile (QTPP)

A Quality Target Product Profile is a document used in QbD to define the desired drug quality attributes that ensure drug efficacy and safety. The QTTP serves as the basis for designing the drug and the manufacturing process and the associated process control strategy.

R

Range

A range refers to the acceptable limits for a parameter. For example, a cell culture with a set point of 37 C usually have a +/-1 C tolerance, which is equivalent to a range from 36 - 38 C. Outside of the range, is considered a deviation that could impact product quality and/or performance.

Reagent

The term reagent is used to designate any substance used in chemical reactions. In the pharmaceutical industry it is also used to refer to raw materials used for buffer preparation as well as ingredients used for QC testing.

Recall

When a defective product has been released, it must be removed from the market to ensure that not patient is harmed. This practice is called recall.

Receiving Unit (RU)

In a technology transfer from one manufacturing site to another, the facility that receives the process is referred to as the receiving unit. Similarly, the facility that receives a drug substance or a drug product is called the receiving unit.

Recombinant Protein

A recombinant protein is a protein produced by genetically engineered cells. The cell genetic material has been modified by recombination with a DNA sequence coding for the expression of a protein of interest.

Recombinant Vaccine

A recombinant vaccine is a vaccine using a recombinant protein as its antigen.

Record Retention

The manufacturing of a drug and the actual use by a patient can span across several years. For that matter, all data related to a batch must be kept for long period. This period of data storage is called record retention.

Recovery

The term recovery is often used in downstream processes to designate the percentage of product retrieved from a process. If a chromatography process has a recovery of 90%, 10% of the product is lost.

Reference Standard (RS)

A reference standard (RS) is a sample of product that have already been tested and for which characteristics are known. It can then be used as a reference for other testing. For example, during a technology transfer of analytical methods from one facility to another, once analytical procedures are established at the receiving unit, a reference standard must be tested and if the test results are the same as the sending unit test results, the method transfer can be considered successful.

Reference Standard Qualification

Reference standard qualification refers to all the testing and characterization done on a material to ensure it can be used as a reference standard.

Regulatory Audit

A regulatory audit is an inspection to ensure that a manufacturer is compliant with the applicable regulations.

Regulatory Authority

A regulatory authority is an agency (e.g., FDA, EMA) overseeing pharmaceutical drug approval and release in a specific country or region.

Regulatory Dossier

A regulatory dossier is a large document that contains all the data to support the submission of a new drug.

Regulatory Filing

Regulatory filing refers to the submission of a drug application to a health agency.

Regulatory Filing Strategy

A regulatory filing strategy is a plan that lays out how a manufacturer will obtain regulatory approval for a new drug. The regulatory filing strategy must be considered early on at the start of the drug lifecycle. Key components of filing strategy are among others: the market of registration, the product classification, the pre-clinical and clinical data to be submitted, the key milestone and consultations with regulatory agencies.

Reject

A product that is non-compliant must be discarded. This practice is called reject. All manufacturers must have a reject procedure in place to manage such eventualities.

Rejection Rate

The rejection rate is the percentage of rejected product within a certain period of time or during a manufacturing campaign. The rejection rate is an important quality metric for a manufacturer.

Rejection Threshold

The rejection threshold is the limit of non-conform samples that would lead to the rejection of a lot. This notion is not used in drug substance manufacturing but in drug product manufacturing and especially during visual inspection of filled vials or syringes. For example, if 3% of all tested vials are non-conform, an entire lot can be rejected. The threshold must be defined using statistical methods.

Related Batch/Related Lot

Related batches or lots are all the batches or lots that have a common history. For example, one batch of drug substance can be used for several lots of drug product. In such case, each of the lot of drug product are related to one batch of drug substance. If the drug product is composed of several drug substances, then each lot of drug product is related to the various batches of drug substance. Keeping traceability of the relation is important for product recalls.

Release

Release refers to the approval for product distribution. Prior to batch release, batch records and quality control records must be verified by the Quality Assurance and product must meet quality standards. In EU, release can only be done by a certified person called a QP, Qualified Person.

Release Criteria

Release criteria are all the standards a product must meet to approve its release.

Reliability

The term reliability in drug manufactured if often used to refer to analytical methods. Reliability refers to the accuracy and precision of an analytical method. Accuracy is how close are the results compared to a reference measure. Precision is how close are the results when performing repeated measures under the same and different operating conditions. (See accuracy; See precision).

Representative Sample

A representative sample is a sample taken from a certain material that reflects the characteristics of a larger volume of the same material. Homogeneity of the liquid to be sample is necessary to ensure that the sample taken is representative. In some cases, such as a lot of filled vials, multiple vials are required to make a representative sample.

Request For Information (RFI)

A request for information is a document written by a customer to a vendor to obtain information on the price for a service or a product. RFI require less detail than RFQ and are often used for building cost estimate at early stage of a project or too short list vendors.

Request For Proposal (RFP)

A request for proposal is a formal document written by a customer to multiple vendors to obtain a solution and its associated cost. Generally, an RFP is sent to 3 or more vendors. The response is a proposal that lays out how the approach to the solution, the timeline and the cost. Each proposal is then compared during the vendor selection stage. A drug developer will usually send an RFP to a CDMO to outsource the manufacturing of a drug under development.

Request For Quotation (RFQ)

A request for quotation is a formal document written by a customer to multiple vendors to obtain quotations for a well-defined service or a specific product. The term RFP and RFQ are often used interchangeably. However, they do have slightly different purposes. The RFQ focuses on the cost for a well-known product or service while RFP aims at the solution and its cost. A manufacturer will usually send an equipment constructor a request for quotation for a piece of equipment that has been detailed in a technical specification sheet.

Reservation Fee

A reservation fee is a cost that a customer pays to a CDMO for reserving a production line for a certain period even though it may or may not use this slot. From the CDMO standpoint, agreeing to keep a manufacturing slot for a sponsor and getting a cancellation is considered an opportunity loss. The reservation fee is here to counterbalance it.

Residual DNA

In biomanufacturing processes, bacteria are used to produce proteins. During purification, residual by-products are removed through various unit operations. Host cell DNA is one of the residual impurities that can be found in the product of interest. Processes must be design to ensure removal of residual DNA to a satisfactory level.

Residual Moisture

Certain drug products are lyophilized product. The residual water content in such products is referred to as residual moisture. Residual moisture can impact lyophilized product stability and must meet acceptance criteria.

Residual Solvent

Various solvents can be used throughout a manufacturing process. These solvents are removed during purification steps. Residual solvent can be found in the final product which can impact product safety. Residual solvent must meet acceptance criteria.

Residue Limit

The purpose of a cleaning process is to remove the product that remains on the internal surface of an equipment after use to avoid contamination of the next batch. Residue limit refers to the maximum allowable residue after cleaning.

Restricted Access Barrier System (RABS)

Aseptic filling of vials or syringes must be done under a Grade A environment to ensure product sterility. Two system can be used to provide a grade A air, an isolator or a RABS. A RABS is a system that ensures a grade A environment during filling operation with a physical separation from the room environment. RABS are not fully sealed which is why they are not recommended nowadays. Isolators are preferred as they are gas-tight and ensure a better contamination control.

Retain Sample

Retain samples are samples kept for future testing. They are just in case samples for future investigations. Retain samples can come from any material used in manufacturing, drug substance, drug product, intermediate or raw material storage.

Retentate

Retentate designates the material that is retained by a filter. In tangential flow filtration, the retentate designates the liquid and product that does not pass the membrane and that gets recirculated within the vessel. (See permeate).

Retention Sample

Retention samples are samples of final drug product stored for regulatory purposes. They are representative samples of lot released to the market. Retention samples and retain samples are two different notions. (See retain sample).

Retest Period

A retest period is a defined period of time after which a product must be retested to verify that its quality attribute did not change over time.

Revalidation

Revalidation consists in repeating validation to confirm performance of a system, a process or an analytical method.

Reynolds Number

The Reynolds number is an adimensional number used in chemical engineering and fluid dynamic to predict the flow regime. Low Re < 2000 indicates a laminar flow. High Re > 4000 indicates a turbulent flow. In between is a transitional flow. Laminar flows are not recommended for water circulating into a water distribution loop as such flow pattern favors microbial contamination and biofilm formation. Reynolds is calculated by the following formula: Re = ρ.v.D/μ where ρ = fluid density (kg/m³), v = fluid velocity (m/s), D = characteristic length/diameter (m), and μ = dynamic viscosity (Pa.s).

Ribosome:

A ribosome is a cellular structure that translates mRNA into proteins.

Rinse

Rinses are performed during cleaning in place to remove product that remains from previous use. It is also use for removal of detergent used for cleaning. At the end of a cleaning in place cycle, a final water rinse is conducted. During this final rinse, the conductivity of the rinse water is measured on the return line to check that all detergent has been removed. If conductivity does not fall below conductivity limit of purified water or WFI, the cleaning is non-conform. An additional rinse can be conducted. There is usually a limit on how many final rinses are permitted before declaring a cleaning cycle non conform.

Rinse Sampling

To test how clean a vessel is after a cleaning operation, the rinse water exiting from the vessel are collected for testing. Such sampling is referred to as rinse sampling.

Rinsing Water

Rinsing water refers to the water used during cleaning in place operations.

Risk Assessment

A risk assessment is a methodic approach often used in the pharmaceutical industry to evaluating potential risks and mitigate them if needed.

Risk Management Plan (RMP)

A risk management plan is a high-level document written by a drug developer to define how risk management will be conducted throughout the development of a new drug. It usually described what methodology will be used and each party’s responsibilities. RMP are also required by certain regulatory agencies post-marketing approval.

Risk Minimization Action Plan (RiskMAPs)

A risk minimization action plan is a structured set of actions to reduce identified risks. It can also be referred to as a risk mitigation plan. The FDA requires that drug developers have RiskMAPs to minimize risk of adverse events.

Risk Mitigation

A risk mitigation is the set of measures taken to reduce the potential impacts associated to an identified risk.

Risk Priority Number (RPN)

When doing a risk assessment, the probability of occurrence (P), the severity (S) and the detectability (D) are scored. The final score, referred to as Risk Priority Number is calculated by the following formula:
RPN = P x S x D. The higher the RPN the higher the risk. High RPN are unacceptable risks that must be mitigated. Medium RPN may require mitigation. Low RPN are acceptable risks. Scoring criteria for probability, severity and detectability are usually taken from 1 - 5.

Risk Register

A risk register is a document used to identify all risk surrounding a drug development project, evaluate them and define a mitigation actions.

Risk/Benefit Analysis

All drugs present risks. A risk/benefit analysis aims at weighing risks against benefits. If the benefits are superior to the risk, a drug can be used.

Robustness

The robustness of a manufacturing process refers to its ability to withstand variations of inputs while maintaining satisfactory performance and quality. Robustness of a process goes hand in hand with QbD. The robustness of an analytical methods refers to its capability to be reliable even under small variations in method parameters.

Rolling Submission

A rolling submission is strategy of filling where a drug developer submits regulatory data incrementally to the health agency while other data are still being generated. The purpose is to accelerate the submission process by anticipating review by health agency professionals.

Root Cause Analysis (RCA)

Root cause analysis is a methodology to identify the source of deviations and non-conformances in manufacturing operations. Several methods for conducting RCA exist among which 5 whys and Fishbone Diagram are the most widely used. RCA enables the implementation of CAPAs.

Routine Inspection

A routine inspection is a regular regulatory audit conducted by health authorities at a manufacturer site.

S

Safety Data Sheet

Chemical substances used as raw materials in biomanufacturing processes usually come with what is called a Safety Data Sheet (SDS), a detailed description of the hazards linked to the material.

Safety Data Sheet (SDS)

An SDS is a document detailing the safety risks of a material. SDS originated from the chemical industry where hazardous materials are used. Similarly, in the biomanufacturing industry, biological agents and chemical agents that could be harmful to humans and the environment are used. Vendors of such materials provide SDS to their customers.

Safety Interlock

A safety interlock is a mechanism preventing unsafe operations. For example, the door of a hot chamber may be locked until the temperature within the chamber is below a certain temperature. In such case, the door opening is interlocked with a value measured by a temperature sensor.

Sample Traceability

It is important to know when a sample was taken, where and by who. If not the associated results it worthless in a GMP environment. For that, sample traceability must be kept at all stages of the manufacturing process.

Sampling Plan

A sampling plan is a document listing all the samplings to be performed during manufacturing activities or validation activities.

Sampling Procedure

A sampling procedure is a detailed instruction of how a sample shall be collected to ensure that it is representative and avoid contamination.

Sampling Record

A sampling record is a document that keeps a record all the sample made during manufacturing operations.

Sampling Valve

Opening a vessel or a piping to collect a sample is not recommended as it can be dangerous for the operator and can lead to contamination. Dedicated valves are installed on pipes and vessels to allow sample collection in a safe and sanitary manner. Certain valves are designed to enable aseptic sampling.

Sanitary

The term sanitary is used to refer to the design of an equipment or a component in ways that prevent contaminations and ensure high cleanability. Sanitary is often used to refer to fittings, connections, pipes and gaskets.

Sanitization

Certain equipment cannot be sterilized in place by use of pure steam. In such cases, chemical sanitization is used. NaOH is the most commonly used detergent. Chromatography columns are sanitized by NaOH contact for several hours. TFF membranes are also sanitized with NaOH.

Scale-Down

A scale down consists in reducing the scale of a manufacturing process to conduct various tests or changes without impacting commercial production. (See Process scale-down study)

Scale-Down Model

A scale-down model is small scale representation of a larger scale process.

Scale-Out

Scaling out is a way to increase production capacity, without changing the scale of the process, by adding several production lines running in parallel. For example, a 1000 L fermentation process can be scale out by adding another 1000 L fermenter, doubling the fermentation capacity. Process wise, the risk is decreased compared to a scale-up

Scale-Up

A scale-up is in increase in the manufacturing scale of a process. For example, taking a fermentation of 100 L to 1000 L is scale-up by a factor 10. Scaling up is generally necessary when moving from process development to commercial manufacturing.

Science-Based Approach

A science-based approach is a decision-making process based on scientific evidence rather than assumptions or opinions.

Scientific Advice Meeting

Scientific advice meeting refers to any meeting or consultation to get scientific advice from a regulatory agency during the development of a new drug. It is recommended to be pro-active and regularly meet with full openness to the regulator to ensure smooth regulatory review and avoid bad surprises.

Scope Change Request

While in the middle of its execution, the scope of a project can change. If so, the management team shall establish a scope change request and submit it to the project sponsor to authorize the modification of the project scope. Scope change request is good project management practice.

Scope Of Work (SOW)

The term Scope of Work refers to the tasks to be delivered through a project. A customer and a service provider when negotiating a contract for a service must fully agree on the service to be provided. The service is often broken down into several SOWs.

Secondary Packaging

A container not in contact with the drug product is referred to as secondary packaging. A box in which a syringe is contained is a secondary packaging. There is no sterility requirement for secondary packaging. Therefore, it is usually done in non-classified areas. (See Primary Packaging)

Seed Culture:

A seed culture is a small-scale cell culture used to start a larger culture.

Seed Lot

Seed lots are used as starting inoculum to initiate a microbial or viral process. (See Master Seed Lot; See Working Seed Lot)

Seed Train

During a fermentation or a cell culture, before reaching the main culture step which can be a couple of thousand liters, smaller volume cultures steps are required. All these steps are conducted in different bioreactors or fermenter of gradually increasing volumes. This sequence of cultures is referred to as seed train.

Self-Inspection

Manufacturers regularly conduct internal audit for compliance to ensure that their quality management system is up to the current regulatory standards.

Self-amplifying mRNA (Sa-mRNA)

Self-amplifying mRNA is an mRNA that contains additional genes making it capable of replicating itself. It is used in vaccines as it enables to lower the antigen concentration per dose while increasing the protein expression and the immune response.

Sending Unit (SU)

In a technology transfer from one manufacturing site to another, the facility that transfers the process is referred to as the sending unit. Similarly, the facility that ships a drug substance or a drug product is called the sending unit.

Sensor

A sensor is a device used to detect a signal and transform it into a measure of a physical property such as temperature, pressure or pH.

Serotype

A serotype is a distinct subtype of a pathogen.

Service Level Agreement (SLA)

A Service Level Agreement is a contract between a customer and a vendor that define the terms of a service to be delivered by a service provider. It defines the scope of the service, the performance expected, the conditions of the delivery, each party’s responsibilities and the consequences if service does not go according to plan.

Settle Plates

Settle plates are petri dishes used for monitoring of airborne microorganism during environmental monitoring. A settle plate is loaded in a device that passes clean room air onto the plate at a certain flowrate and for a certain duration. The plate is then incubated to check for bacterial growth. Settle plates contain a culture medium providing nutrient to airborne microbes during the incubation of the plates. After incubation, the number of colony-forming unit is counted and compared to the limit associated to the corresponding clean room grade.

Sever

A server is a computer system used for storage and data management.

Severity

Severity is a term used in risk analysis to designate the impact level of a risk. Usually, severity is classified as low, moderate, major or critical. It can also be scored from 1 to 5 with 5 being the highest.

Sf9 cells

Sf9 cells are insect cells derived from Spodoptera frugiperda ovaries, fall armyworm, widely used in the Baculovirus Expression Vector System (BEVS) for the production of recombinant proteins and virus-like particles.

Shared Manufacturing Facility

A shared manufacturing facility is a facility that is used for the manufacturing of multiple products. The opposite is single product facility. Such facilities require increase contamination control strategy and stricter cleaning procedures.

Shelf Life

The self-life of a drug is the time a drug remains safe and effective under proper storage conditions.

Shut Down

A shut down is a temporary stop of manufacturing facility for maintenance.

Sigma (σ)

Sigma in the context of statistics, is a unit representing the standard deviation.

Single-Use Bioreactor

A single use bioreactor is a bioreactor in which the product instead of being in contact with the stainless-steel surface of the bioreactor, is maintained in a disposable plastic bag that is hold by the stainless-steel frame. Doing so, the bioreactor does not require a cleaning step post use. The bag and all its associated components are discarded after use.

Single-Use System (SUS)

A single use system is any process equipment using disposable technology. The equipment in itself is not disposable the plastic tubes, bags or filters that composes the fluid path are disposable. Single-use technology allow for a rapid switch in between products and batches as sterilization and cleaning are not required. Parts in contact with product come already clean, often sterilized by gamma irradiation and ready to be used.

Single-Use Technology (SUT)

The term Single-Use Technology is used to designate bioprocess equipment using disposable consumables such as single use bioreactors or single use bags.

SIP Skid

An SIP Skid is a system to which mobile vessels are connected to undergo a sterilization in place. The SIP system manages the supply of steam and the temperature control.

Site Acceptance Test (SAT)

When buying a vessel or a process equipment from a vendor, at some point the equipment is delivered to the site and installed by the vendor. Upon completion of the installation, while the vendor is present, verification of the installation is conducted to ensure that it meets expectations. Upon completion of SAT, IQOQ can start. SAT is usually for complex systems that required connections with utilities and automation infrastructure. For simple systems, it is not rare to skip SAT and to conduct directly IQOQ with the vendor.

Site Master File (SMF)

A Site Master File is a document written by a drug manufacturer that describes an overview of its manufacturing operations, its facilities, its quality management system, and quality control operations.

Site Master Plan

A site master plan is a document that outlines the long-term development plan of a manufacturing site. Planned future expansions or constructions are described in the site master plan.

Skid

A skid is a term that is often used when referring to a process equipment. TFF skid or chromatography skid are common terms in biomanufacturing. Originally, the term skid comes from the physical skid or platform on which a machine is mounted.

Software Design Specification (SDS)

SDS in the context of a software or an automated equipment refers to the detailed software requirements. Customer and vendor agree on the SDS prior to the development of the software to ensure that the final solution meets the expected specifications.

Solubility Testing

Solubility testing is a test performed on a solid product to assess its solubility.

Special Protocol Assessment (SPA)

In the context of drug development, a Special Protocol Assessment (SPA) is a process in which a sponsor requests the FDA to review clinical study protocols to ensure that they meet regulatory requirements.

Specificity

Specificity in the context of analytical method, is the ability of a test to target a specific analyte without interference from other analytes. For example, a test method was developed to measure a certain protein concentration. A highly specific method is required to ensure that other protein concentration is not measure and given as the result of the concentration of the target protein.

Stability Study

Drugs are usually administered to patients long after their date of manufacture. A drug must have a certain shelf life during which it was demonstrated that the drug retains its efficacy and safety. To demonstrate that, a stability study is conducted. Such study consists in storing multiple samples of the drug for various months (12, 24, 36 or 60 months) at various temperatures and measure critical quality attributes at each point such as visual appearance, pH, concentration, purity, sterility and potency.

Stability Study Plan

A Stability Study Plan is a document that describes the conditions in which a stability study is performed. The study plan includes the temperature of storage of the samples to be tested, the duration of the experiment and the test to be performed.

Stabilizer

A stabilizer designates a substance entering into the formulation of a drug to enhance its stability. Stabilizers are, for example, used in vaccine formulations.

Stainless Steel Bioreactor

A stainless-steel bioreactor is a bioreactor whose main material of construction is stainless steel. Such reactor can be used multiple times and is compatible with sterilization in place by steam injection. The opposite is a single-use bioreactor.

Standard Curve

In the context of analytical methods, a standard curve, also called a calibration curve is a graph representing the measured attribute for several samples of known concentrations. Such plot is used for calibration of an analytical instrument.

Standard deviation

The standard deviation designates the variation of a set of data around its average. A low standard deviation means that values are close to each other. High standard deviation indicates a large dispersion of the data. In quality control, analytical methods shall have low standard deviation to be reliable.

Standard Operating Procedure (SOP)

A Standard Operating Procedure is a document that provides detailed instructions on how to conduct an operation. In the biomanufacturing industry, SOP related to manufacturing and testing operations are critical documents that instruct operators on how to operate equipment and manufacture a certain product.

Start Of Hold Time (SOH)

SOH refers to the beginning of a product hold period. The start of hold time corresponds to the time at which a product is put under storage until it is used in the next unit operation.

Sterilization-In-Place (SIP)

Sterilization-In-Place is a common operation in biomanufacturing which consist in the sterilization of equipment using clean steam. Steam is injected into a vessel and the inside temperature is held at 121C or more for a certain duration to remove microorganisms to a certain level. This operation is also often referred to as Steam-In-Place.

Sterile Boundary

The filling of a parenteral drug requires sterility to ensure patient safety. Within the manufacturing process of such drug, not all process is conducted under sterile conditions. Most of the time, only the final filtration and filling are done in aseptic manner. The sterile boundary designates the operations that are performed in sterile conditions. What is within the sterile boundary requires stricter cleanliness conditions.

Sterile Filtration

A sterile filtration is performed using a filter with a pore size below 0.22 µm, which ensures removal of all microorganisms. A sterile filtration does not remove viruses. A nanofiltration is required for viral clearance.

Sterility Assurance

Sterility assurance regroups all the activities and procedures in place within a manufacturing facility to ensure that the manufactured product is sterile. Sterility assurance is, in most cases, found in drug product manufacturing and less commonly in drug substance manufacturing.

Sterility Assurance Level (SAL)

The Sterility Assurance Level is a unit representing the probability of finding a viable microorganism in a product after sterilization. A SAL of 10⁻⁶ is an industry standard in biomanufacturing and is equivalent to one-in-a-million chance of finding a viable microorganism after sterilization.

Sterility Test

A sterility test is a test confirming the total absence of microbes in a certain product. A sterility test can be done on water for injection as well as on the final drug product. A sample of product is disposed on a petri dish containing a nutrient rich medium and incubated at 20°C for 7 days, followed by an incubation 30°C for 7 days. If no microbial growth is observed the product can be considered sterile.

Sterilization

Sterilization refers to the reduction of viable microbes to a sterility assurance level (SAL) of 10⁻⁶. (See Sterility Assurance level)

Sterilization Temperature

The sterilization temperature is the temperature at which a vessel is held during an SIP cycle.

Sterilizing-Grade Filter

A sterilizing grade filter is a filter, with a pore size below 0.22 µm, that enables the sterile filtration of a product.

Stopper

The term stopper is exclusively found in drug product manufacturing and more precisely in Filling. Once a vial is filled, it has to be closed to protect the internal product from the external contaminations. The rubber component that closes a vial is referred to as a stopper.

Storage Areas

Storage areas are designated spaces used for material storage.

Strain

A strain is a specific variant of a pathogen.

Subunit Vaccine

A subunit vaccine is a vaccine using only a part of a pathogen as its antigen to induce immunity.

Suction Head

The suction head of a pump is the height between the free surface of the liquid and the pump inlet. The suction head is dependent on the configuration of the tank, piping and location of the pump. The suction head is used for NPSH calculation. (see NPSH)

Supervisory Control and Data Acquisition (SCADA)

Supervisory Control and Data Acquisition, system for monitoring and controlling a process and equipment.

Surface Area

The term surface area can be used in various context in biomanufacturing. It is often used in relation to filtration surface areas as well an equipment internal surface area to calculate maximum allowable carry over in cleaning validation.

Surface Sampling

Surface sampling simply refers to the collection of samples from surfaces. For example, during cleaning validation of a vessel, the internal surface of the vessel as swabbed to measure the potential residue post cleaning. Similarly, to measure the degree of cleanliness of a surface in a clean room, contact plates are used for surface sampling.

Swab Recovery

The swab recovery is a measure of the efficiency of the swab method to collect product on a surface of swabbing. A known quantity of a reference product is spread on a specified surface. By swabbing the surface and measuring the quantity of product recovered, the recovery rate can be calculated. A swab recovery above 50% is recommended.

Swabbing

Swabbing is a sampling method with consist in collecting surface samples with swabs. Swabbing is widely used in cleaning validation for evaluating the amount of residue on equipment internal surface post cleaning.

Syringe

A syringe is a pumping device consisting of a plunger that fits tightly within a cylindrical tube called a barrel. In the context of drugs, the term syringe designates a device, including a needle, for drug administration by injection.

System Impact Assessment (SIA)

A System Impact Assessment is an evaluation of the potential impact of a change on a specific system. An SIA is the first step to be conducted prior implementation any changes on a GMP system.

T

Tangential Flow Filtration (TFF)

Tangential Flow Filtration is a filtration method for concentration and buffer exchange. Contrary to frontal filtration, during a TFF operation, the liquid is recirculated in a flow parallel to the filtration membrane. Particles smaller than the membrane pore size pass the membrane while others flow back as the retentate. By not doing a frontal filtration, buildup of particle and filter clogging is avoided. A product being recirculated on a TFF membrane can be concentrated and has its buffer exchanged. TFF is almost always present in vaccines and biologics manufacturing.

Target Product Profile (TTP)

The TPP is a regulatory document that described the characteristics of a pharmaceutical product. For example, physico-chemical properties of the drug substance, as well concentration, microbial characteristics, and stability duration, are listed in the TPP.

Technology Transfer

A technology transfer refers to any transfer of theoretical or technical knowledge from one unit to another. In the pharmaceutical industry, Tech Transfer occurs at all stages and consist of transferring a manufacturing process and or analytical methods form a sending unit to a receiving unit.

Technology Transfer Agreement

A TT agreement is a formal document contract signed between a sending unit and a receiving unit to lay out the terms of the technology transfer.

Technology Transfer Package

A TT package refers to a technical dossier containing detailed technical documentation to be used for a project. A technology transfer starts with the preparation of a technical dossier by the sending unit for the receiving unit to share the process knowledge.

Technology Transfer Readiness

Prior initiating a technology transfer, a multiple of activities are required. Preparedness for technology transfer is referred to as readiness.

Technology Transfer Plan

A technology transfer starts with a plan referred to as a Technology Transfer Plan. A TT Plan lays out the strategy and activities to transfer a process and its associated analytical methods from one manufacturing site to another.

Technology Transfer Plan

A technology Transfer Plan is a document describing how a process will be transferred from the sending unit to the receiving unit. The TT Plan serves as the basis for the management of a technology transfer.

Technology Transfer Report

Upon completion of a technology transfer from one manufacturing site to another, it is important to close the project with a document that summarizes all the activities conducted during the TT and the obtained results. This document is referred to as Technology Transfer Report.

Temperature Mapping

Temperature mapping consists in verifying the temperature uniformity within a temperature control system such as a refrigerator, an autoclave, a cold room, a clean room or a warehouse. Let's take the example of a cold room or a warehouse. The closer to the cooling system, the colder the temperature. The further, the higher the temperature. Temperature mapping is necessary to demonstrate that whatever the position of the product in the chamber, it will be within the target range of temperature.

Temperature Probe

A temperature probe is a device used to measure temperature. It contains a temperature sensor in an insulating housing.

Term

In the context of a written contract, a term is a contractual condition or definition explicitly mentioned in the document.

Terms And Conditions

“Terms and conditions” is an expression often used when writing a contract. The expression is used to designate all the details of a contract. If the party signs, it agrees to the terms and conditions of the contract

TFF Membrane

A TFF membrane is a type of filtration membrane used for tangential flow filtration. Two types of TFF membranes exist, flat sheet and hollow fiber.

Thawing

When a raw material, a drug substance or a drug product stored in a frozen condition, it has to be placed at a temperature above 0 C to return to liquid state. This unfreezing operation is referred to as thawing.

Thermostability

Thermostability in the context of a drug refers to its ability to remain stable at higher temperatures (room temperature).

Third-Party Audit

A third-party audit refers to an audit conducted by an external independent organization. For example, to obtain an ISO certification, a third-party audit is required.

Throughput

Throughput refers to the rate of production output. It is used to describe the production capacity of a manufacturing facility. It can also be used to refer to the capacity of an equipment to process a material.

Titer

In the context of vaccines and drugs, titer refers to the measurement of the antibody or antigen concentration in blood.

TOC Analyzer

A TOC analyzer is an instrument used for TOC measurement.

Total Aerobic Microbial Count (TAMC)

Total Aerobic Microbial Count, TAMC refers to the total number of aerobic bacteria a sample. TAMC is part of a Microbial Enumeration Test (MET).

Total Organic Carbon (TOC)

TOC, Total Organic Carbon is the measure of organic carbon in a sample. The carbon measured is coming from organic sources, i.e. proteins, DNA, RNA or bacteria. This measure is useful to measure the level of contaminants in a sample. It is used for water quality monitoring as well as cleaning verification tests.

Total Yeast and Mold Count (TYMC)

TYMC refers to the total number of yeast and mold present in a sample. TYMC is part of a Microbial Enumeration Test (MET).

Toxin

A toxin is a poisonous substance, in most cases a protein, released by a microorganism.

Toxoid

A toxoid is an inactivated toxin used in vaccines.

Traceability

Traceability refers to the ability to track the history of a material or a product throughout its lifecycle. Traceability is a critical element in quality assurance for pharmaceutical product. Without traceability, there is no way to guaranty the quality and safety of a product.

Traceability Matrix

A traceability matrix in the context of equipment qualification, is a document, usually a table, that lists the requirements and the qualification tests to be performed to verify that each requirement is met.

Training

Training is an important aspect of GMP manufacturing. It ensures that personnel are trained to conduct specific operations. If an operator fails a training, he is not allowed to conduct the operation which relates to the training. Training is not a onetime activity. Periodical training is required to ensure that operators maintain their capabilities to conduct manufacturing operations.

Transfection

Transfection is an operation that consists in introducing a genetic material into a cell.

Transfer Line

A transfer line is a pipe, usually stainless steel, used to transfer a liquid from one process equipment to another.

Transmembrane Pressure (TMP)

Transmembrane pressure refers to the pressure difference across a membrane. TMP is an important process parameter in a UF/DF operation. The TMP dictates the flow rate of permeate flowing through the membrane. The higher the TMP, the greater the pressure difference between the retentate side and the permeate side, and the greater the flux through the membrane. An excessive TMP can lead to membrane clogging.

Transmitter

A transmitter, in process engineering, is a device used to send a raw signal measured by a sensor to a controls system. A pressure sensor is associated to a transmitter. In such case the whole is referred to as a pressure transmitter (PT).

Trend Analysis

Trend analysis refers to the evaluation of data patterns over a certain period of time. Multiple data points are required to obtain a relevant data trend. Trend analysis is used to detect if a parameter is slowly deviating from its normal operating range. Evaluating trends is used in quality assurance to detect potential deviations before their occurrence.

Trial Master File (TMF)

The Trial Master File is a general document that documents major information on clinical trial.

Trial Run

A trial run is a run executed with product to establish a manufacturing process within a new production line. Purpose of the trial run is testing the implementation of the process prior moving into GMP manufacturing. Trial runs are used to test equipment, train operators and prepare MBR and SOPs. Trial runs are usually followed by Engineering runs to lock the process prior PPQ runs.

Turnover Package (TOP)

At the end of a construction project, the engineering, procurement and construction company contracted hands over all documents to the facility owner. Design, construction and qualification documents are gathered in what we call the Turnover Package.

Type C Meeting

A Type C meeting is a meeting with the FDA to discuss development issues of an investigational new drug.

U

UF Water

Ultrafiltered water used in certain manufacturing operations obtained by passing purified water through Ultrafiltration membranes. UF water is not suitable for injectable drugs formulation.

Ultra violet (UV)

Ultraviolet refers to lights with a wavelength below the visible spectrum limit of 400 nm.

Ultra-Low Freezer

An ultra-low freezer is storage unit below -60C.

Ultracentrifugation

Ultracentrifugation is a separation technique used in biomanufacturing and analysis based on the principle of high-speed centrifugation.

Ultracentrifuge

Separations by ultracentrifugation are performed on specific equipment referred to as ultracentrifuge.

Ultrafiltration

An ultrafiltration designates a filtration conducted using fine membranes with pore sizes in the range of nanometers. Most often, the term is used to designate a unit operation in a bioprocess which consists in recirculating a product over a tangential flow filtration membrane to remove impurities and concentrate the product. This operation is often followed by a diafiltration. The whole is referred to as UF/DF, ultrafiltration-diafiltration.

Ultrafiltration/Diafiltration (UF/DF)

UF/DF is common unit operation in biomanufacturing to concentrate a product and remove impurities vial buffer exchange.

Uninterrupted Power Supply (UPS)

UPS is a system to protect equipment from micro power failure that could be harmful to computer systems and lead to data loss.

United States Pharmacopeia (USP)

USP refers to the American Pharmacopeia, which define the standards for medicines, testing and raw materials used in drugs to be market in the United States. (See Pharmacopeia)

Upstream Process (USP)

In biomanufacturing of drug substance, unit operations are often split into two categories, Upstream Process (USP) and DownStream Process (DSP). USP includes all unit operation related to the culture and harvest of the cells (Inoculation, Pre-culture, Culture, Harvest, Lysis).  The term upstream is an analogy with a river stream. The upstream is the higher altitude stream and the downstream is the lower altitude stream.

User Requirement Brief (URB)

A URB is a written document at the beginning of a project to describe the expected outcomes of a project. A URB is less detailed than a URS. URB serves as the basis for the feasibility studies and the conceptual design when designing a new facility.

User Requirement Specification (URS)

A URS is a written document that lists the user needs that a system has to meet. A URS is the starting point to design any system or equipment in biomanufacturing. Without URS, there is no technical nor functional requirement and by extension no qualification no validation. I have seen many projects turn south due to the lack of importance put on the writing of URS. URS documents are the starting point for engineering studies. Without URS, an engineer team should refuse to conduct a basic design study.

Utilities

Utilities are all the fluid and energy systems used to support a manufacturing facility and a process. Water, pure steam, HVAC, compressed air, gases are utilities. Two categories of utilities are distinguished, clean utilities that directly impact product quality and black utilities with no quality impact.

UV Sensor

A UV sensor is a device used for measuring UV light. UV sensors can be used for concentration measurement.

V

Vaccination

Vaccination is the act of administering a vaccine to induce immunity.

Vaccine

A vaccine is a biological product, bacteria, virus, protein, nucleic acid, that, when administered to a human or an animal is able to generate an immune response that provides an immunity against a specific disease.

Vaccine Hesitancy

Vaccine Hesitancy refers to the reluctance or refusal to vaccinate despite the availability of vaccines.

Validated System

A validated system is a system that proven to consistently meet its specifications.

Validation

Validation is the documented demonstration that a system or process consistently meets its expected quality and performance requirements.

Validation Lifecycle

Validation lifecycle refers to all the ongoing validation throughout a system's life to ensure that the system continues to meets its expected quality and performance requirements.

Validation Master Plan (VMP)

A Validation Master Plan, often referred to as VMP is a central document that lays out the overall strategy to conduct validation activities. It is not rare to have multiple VMP for a project. On major VMP to cover the entire project, one focusing on the qualification of utilities and equipment, one for the process, one for the analytical methods and one for cleaning.

Validation Master Plan (VMP)

A VMP is a document written, during new facility construction or technology transfer projects, that lays out how validation activities on a facility or a process will be conducted. With the VMP are found information about the cleaning validation, the process validation as well as analytical method validation.

Validation Protocol

A validation protocol is a written document describing how to perform a validation activity.

Validation Report

A validation report is a written document summarizing validation results.

Vapor pressure

A liquid is always associated to its vapor phase that sits on top of the liquid surface. At a given temperature, the pressure exerted by the vapor phase on the liquid phase is called vapor pressure. For example, for water, at 100°C, the vapor pressure is 1 atm.

Vendor Audit

A vendor audit is an inspection of a supplier that provides materials or services that could have an impact on product quality. For example, raw materials and consumables vendors are audited by drug manufacturers to ensure quality compliance of the input materials.

Verification

Verification designates the documented confirmation that a system or process meets requirements. Verification is different from validation. Verification does not include the notion of consistency that is the basis of validation.

Vero Cells

Vero Cells are monkey kidney cells widely used to produce viral vaccines.

Viability

Viability refers to the ability of cells to remain alive and metabolically active under given conditions. It is commonly expressed as the percentage of live cells within a population and is a critical parameter for cell growth and product yield in biomanufacturing.

Vial

A vial is a container used for injectable drugs and vaccines. Unlike syringes, vials can be used to store multiple doses in one container.

Viral Clearance

Virus clearance designated all the procedures and operations in a manufacturing process that are conducted to reduce the viral concentration to a desired level. For example, nano filtrations for viral clearance are typically found in processes using viral vectors to express proteins.

Viral Vector Vaccine

A viral vector vaccine is a type of vaccine using a virus to deliver genetic
material into a patient’s cells to generate an immune response.

Visual Cleanliness

One of the acceptance criteria of a successful cleaning of an equipment is the visual cleanliness verification at the end of the cleaning procedure. Usually, presence of residual water and stains is checked by operators.

Visual Inspection

After the drug product is filled into its primary container (vials or syringes), visual defects are checked in an operation called inspection. Visual inspection can be automated by an inspection machine or done manually by operators checking one container at a time.

VLP

A Virus-Like Particle is a particle with a similar structure as a virus made of structural proteins without the genetic materials of a virus necessary for its replication. In vaccines, VLPs can be used to deliver genetic materials or to present antigenic surface proteins.

W

Warning Letter

A warning letter is a notice delivered by the FDA after an inspection in the case of major regulatory non compliances.

Water Run

When starting a new production line, instead of directly running equipment with costly materials, it is advised to conduct initial trials with water. These tests are referred to as Water Runs.

Western Blot

Western blot is molecular biology technique used to detect proteins in a sample. Western blot is commonly used in the industry.

WFI (Water for Injection)

WFI is the highest quality of water found in the pharmaceutical industry. Drugs to be injected to a patient must be formulated using WFI to ensure low levels of endotoxin and microbial contamination.

WFI Loop

After generation WFI is stored in a tank. Distribution from the tank to the different point of use in production areas is done via the WFI loop. Having a loop enable continuous recirculation to avoid microbial growth.

WHO

The World Health Organization (WHO) is the branch of the United Nation (UN) in charge of matters related to health on a global level. Vaccines procurement for low- and middle-income countries is done through the WHO grouped procurement system.

WHO Prequalification

Developing countries with pharmaceutical regulation not yet up to global guideline usually follow the WHO guidelines. For that reason, vaccine manufacturers from developing countries aiming to supply doses to population in low- and middle-income countries have to be certified by the WHO to prove their quality compliance. WHO prequalification is equivalent to be WHO approved.

Work Breakdown Structure (WBS)

WBS is a term used in project management. Large complex projects have to be broken down into smaller manageable activities in a hierarchical manner, called WBS.

Working Cell Bank (WCB)

The working cell bank is stock of cells derived from the master bank and used as starting material for each new manufacturing lot.

Working Seed Lot (WSL)

The WSL is derived from the MSL and is used for routine manufacturing. The WSL in bacterial fermentation is the equivalent to the WCB in cell culture.

Worst Case Product

A worst-case product is a product considered to be the most challenging. The notion of worst-case product is often taken in risk-based validation approaches. For example, in cleaning validation, instead of look for residues of all products, targeting the product that is the most difficult to clean allows for a reduction of the tests to perform.

Y

Yield

The yield is defined as the ratio of the quantity of product recovered at the end of the process compared to quantity of product available at the start of the process. The yield is equivalent to efficiency of the purification process. The higher the yield, the less product is lost during the upstream recovery and the downstream purification operations.

End