Glossary

This glossary provides common terms and definitions used throughout the Center for Regenerative Biotherapeutics, including at our biomanufacturing sites and in our quality management system. The source of the definitions is provided where applicable.

Sources include:

  • Code of Federal Regulations (CFR)
  • EudraLex
  • European Union directives (EC directives)
  • Foundation for the Accreditation of Cellular Therapy (FACT) and the Joint Accreditation Committee of the International Society for Cell and Gene Therapy (ISCT) and the European Society for Blood and Marrow Transplantation (EBMT) (FACT-JACIE)
  • International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH)
  • International Society for Pharmaceutical Engineering (ISPE)
  • Mayo Clinic Biosafety
  • Medicines and Healthcare products Regulatory Agency (MHRA)
  • U.S. Food and Drug Administration (FDA)
Active pharmaceutical ingredient (API)
Any substance or mixture of substances intended to be used in manufacturing of a drug (medicinal) product and that, when used in the production of a drug, becomes an active ingredient of the drug product. (ICH Q7)
Advanced therapy medicinal product (ATMP)
Gene therapy medicinal products, somatic cell therapy medicinal products and tissue engineered products. (EudraLex, volume 4, part IV)
Adverse event (AE)
Drug reaction, also known as a side effect, is any undesirable experience associated with the use of a medicine in a patient. Adverse events can range from mild to severe. Serious adverse events are those that can cause disability, are life-threatening, result in hospitalization or death, or are birth defects. (FDA glossary)
Any unintended or unfavorable sign, symptom, abnormality or condition temporally associated with an intervention that may or may not have a causal relationship with the intervention, medical treatment or procedure. Adverse reaction is a type of adverse event. (FACT-JACIE International Standards, Eighth edition — version 8.1)
Adventitious agents
Microorganisms — including bacteria, fungi, mycoplasma or spiroplasma, myocobacteria, rickettsia, viruses, protozoa, parasites and transmissible spongiform encephalopathy agents — that are inadvertently introduced into the production of biological products. (FDA cell substrate guidance)
ALCOA+
Acronym used for the attributes that characterize data reliability, which is the foundation of achieving Good Practice data integrity. The attributes apply to both paper and electronic records. The attributes describe data that are:
  • Attributable.
  • Legible.
  • Contemporaneous.
  • Original.
  • Accurate.
  • Complete.
  • Consistent.
  • Enduring.
  • Available.
(MHRA; ISPE GAMP)
Allogenic
The biologic relationship between genetically distinct individuals of the same species. (FACT-JACIE International Standards, Eighth edition — version 8.1)
Aseptic personnel process qualification
The assessment of an individual’s ability to handle sterile materials and perform critical operations without contaminating the process. May be demonstrated through direct challenges of critical steps via risk assessment.
Autologous materials
Materials or products containing cells or tissues derived from and intended for the same individual. In other words, the donor and recipient are the same individual. (Adapted from FACT-JACIE International Standards, Eighth edition — version 8.1)
Biological safety level (BSL)
A set of guidelines and containment principles established by various organizations, including the National Institutes of Health in the United States and the FDA, to ensure safe handling of biological agents and materials in laboratory settings. BSL levels are ranked from 1 to 4 with increasing levels of containment and safety measures. The Center for Regenerative Biotherapeutics does not handle or manufacture BSL-3 or BSL-4 products. Therefore, those definitions are not included here.
  • BSL-1. BSL-1 is the lowest containment level. It is suitable for work with well-characterized agents that are not known to cause disease in healthy people. Basic laboratory practices, such as hand-washing and the use of personal protective equipment (PPE), are required. Labs at this level are typically used for teaching and introductory research.
  • BSL-2. BSL-2 is appropriate for work involving moderate-risk agents that can cause diseases in humans but have available treatments. Additional safety precautions include restricted access, biohazard warning signs and the use of PPE. Labs at this level typically handle pathogens such as Staphylococcus aureus and salmonella.
  • BSL-2+. BSL-2+ is appropriate for work involving moderate-risk agents that could normally be handled as BSL-2. However, there are certain conditions that necessitate increased precautions. For example, oncogenes in lentivirus that have been attenuated have the potential to mutate or recombine and become active. Additional safety precautions include use of biological safety cabinets or containment for any open manipulations. Labs at this level typically handle viral vectors such as lentivirus or oncolytic viruses. (Mayo Clinic Biosafety)
Biological starting material or biological material
Any substance of biological origin, such as microorganisms, organs and tissues of either plant or animal origin, cells or fluids of human or animal origin including blood and plasma, and biotechnological cell constructs — that is, cell substrates, whether they are recombinant or not, including primary cells. (EC directive 2001/83/EC)
Cell bank
Vials of cells of uniform composition — although not necessarily clonal — that are derived from a single tissue or cell, aliquoted into appropriate storage containers, and stored under appropriate conditions, such as the vapor phase of liquid nitrogen. (FDA cell substrate guidance)
Cell line
Cells that have been propagated in culture since establishment of a primary culture and have survived through crisis and senescence. Such surviving cells are immortal and will not senesce. Diploid cell strains have been established from primary cultures and expanded into cell banks but have not passed through crisis and are not immortal. The American Type Culture Collection uses the abbreviation CCL to signify certified cell lines. (FDA cell substrate guidance)
Cellular therapy product
A product based on somatic cells — for example, hematopoietic progenitor cells, mononuclear cells, cord blood cells, immune effector cells, genetically modified cells and others — that is procured from a donor and intended for processing and administration. (FACT-JACIE International Standards, Eighth edition — version 8.1)
Certificate of analysis (CoA)
A document signed by an authorized representative of the Center for Regenerative Biotherapeutic’s quality management team attesting that a specific batch meets the product specifications. The document includes test results and analytic data references necessary for traceability to results found upon testing of the representative sample.
Certificate of compliance or certificate of conformance (CoC)
A document signed by an authorized representative of the Center for Regenerative Biotherapeutic’s quality management team attesting that a product or batch complies with applicable law. (FDA Current Good Manufacturing Practice guidance)
Clean area or clean room
A room or area designated, maintained and controlled to prevent particle and microbiological contamination of products. Such a room is assigned and reproducibly meets an appropriate air cleanliness classification. (EudraLex, volume 4, glossary and part IV; FDA, ISO 14644-1)
Colony-forming unit (CFU)
A microbiological term that describes the formation of a single macroscopic colony after the introduction of one or more organisms to microbiological growth media. One colony-forming unit is expressed as 1 CFU. (FDA guidance for industry)
Controlled classified area
An area constructed and operated in such a manner that some attempt is made to control the introduction of potential contamination and the consequences of accidental release of living organisms. The level of control exercised should reflect the nature of the organism used in the process. At a minimum, the area should be maintained at a pressure negative to the immediate external environment and allow for the efficient removal of small quantities of airborne contaminants. (ISPE glossary)
Controlled document
A document that is managed and maintained under a formal system to ensure that it remains accurate, up-to-date and in compliance with regulatory requirements. Controlled documents are subject to version control, approval processes and recordkeeping procedures.
Cord blood
Whole blood, including hematopoietic progenitor cells, collected from placental and umbilical cord blood vessels after the umbilical cord has been clamped. (FACT-JACIE International Standards, Eighth edition — version 8.1)
Current Good Manufacturing Practice (CGMP)
Regulations enforced by the FDA that assure proper design, monitoring and control of manufacturing processes and facilities. CGMP is the main regulatory standard for ensuring safety and pharmaceutical quality for the manufacture of medicinal products.
Donor
A person who is the source of cells or tissue for a cellular therapy product. (FACT-JACIE International Standards, Eighth edition — version 8.1)
Drug product
The product manufactured by the Center for Regenerative Biotherapeutics on behalf of the sponsor, in its final container closure in the agreed dosage form, whether labeled or unlabeled. (ICH Q7)
The finished dosage form that contains a drug substance, generally but not necessarily in association with other active or inactive ingredients. (FDA)
Drug substance
Any API or mixture of API that is intended to be used in the manufacture of a medicinal drug product and that, when used in the production of a drug, becomes an active ingredient of the drug product. Such substances are intended to furnish pharmacological or biological activity or other direct effect in the diagnosis, cure, mitigation, treatment or prevention of disease or to affect the structure and function of the body. (ICH Q7)
Gene therapy active substance
A substance consisting of one or more nucleic acid sequences or genetically modified microorganisms or viruses, or of cells genetically modified by a product containing one or more nucleic acid sequences or genetically modified microorganisms or viruses. (EC directive 2009/120/EC, annex, part IV)
Genetically modified cell
A cell that has been modified by replacing a disease-causing gene with a healthy copy of the gene, inactivating a disease-causing gene that is not functioning properly or introducing a new or modified gene into the body to help treat a disease. (FACT-JACIE International Standards, Eighth edition — version 8.1)
Genotoxic
Substances or agents that have the potential to cause damage to an organism’s genetic material, such as DNA, which can lead to mutations or other genetic alterations.
Hematopoietic progenitor cell (HPC)
A cellular therapy product that contains self-renewing or multipotent stem cells capable of maturing into any of the hematopoietic lineages, lineage-restricted pluripotent progenitor cells or committed progenitor cells regardless of tissue source — bone marrow, umbilical cord blood, peripheral blood or other tissue.
Human cell tissue/product (HTC/P)
Articles containing or consisting of human cells or tissues that are intended for implantation, transplantation, infusion or transfer into a human recipient. HCT/Ps that are minimally manipulated are regulated under section 361 of the Public Health Services (PHS) Act. HCT/Ps that are more than minimally manipulated are regulated under section 351 of the PHS as a drug, device or biologic product. (21 CFR 1271.3(d))
Immune effector cell (IEC)
A cell that has differentiated into a form capable of modulating or effecting a specific immune response. (FACT-JACIE International Standards, Eighth edition — version 8.1)
A cell that plays a role in the immune response in various diseases, including cancer. These cells can be natural, such as T cells and natural killer cells, or may be genetically modified to enhance their ability to target and destroy specific cells or pathogens. IECs are central to cellular therapies such as chimeric antigen receptor (CAR)-T cell therapy and are obtained to harness the body’s immune system to treat diseases.
Institutional review board (IRB) or ethics committee
Any board, committee or other group formally designated by an institution to review, to approve the initiation of and to conduct periodic review of biomedical research involving human participants. The primary purpose of such review is to assure the protection of the rights and welfare of human participants. (21 CFR Part 56)
A board or committee established by an institution in accordance with the regulations of the relevant governmental agency to review biomedical and behavioral research that involves human participants and is conducted at or supported by that institution. (FACT-JACIE International Standards, Eighth edition — version 8.1)
Investigation device exemption (IDE)
An IDE allows an investigational device to be used in a clinical study to collect safety and effectiveness data.
Investigation new drug (IND)
A drug or biological drug that has not been approved for general use by the FDA. It is used in a clinical trial to investigate its safety and efficacy. The term also includes biological products that are used in vitro for diagnostic purposes.
Information Standard for Blood and Transplant (ISBT) 128
A global standard for the identification, labeling and information transfer of human blood, cell, tissue and organ products published and maintained by the International Council for Commonality in Blood Banking Automation (ICCBBA). (FACT-JACIE International Standards, Eighth edition — version 8.1)
Manipulation, minimal
Processing that does not alter the relevant biological characteristics of cells or tissues. For structural tissue, processing that does not alter the original relevant characteristics of the tissue relating to the tissue’s utility for reconstruction, repair or replacement. (FACT-JACIE International Standards, Eighth edition — version 8.1)
Manipulation, more than minimal
Processing that does alter the relevant biological characteristics of cells or tissues. For structural tissue, processing that does alter the original relevant characteristics of the tissue relating to the tissue’s utility for reconstruction, repair or replacement. Products that are more than minimally manipulated are referred to as advanced therapy medicinal products in the European Union. (FACT-JACIE International Standards, Eighth edition — version 8.1)
Master services agreement (MSA)
An agreement with specific terms between two or more persons or entities in which there is a promise to provide services in return for a monetary fee or benefit.
Master cell bank
An aliquot of a single pool of cells that generally has been prepared from the selected cell clone under defined conditions, dispensed into multiple containers and stored under defined conditions. The master cell bank is used to derive all working cell banks. The testing performed on a new master cell bank — from a previous initial cell clone, master cell bank or working cell bank — should be the same as for the master cell bank unless otherwise justified. (ICH Q5A (R1))
Master viral bank
A viral seed of a selected virus from which all future viral production will be derived either directly or via working virus banks. (FDA cell substrate guidance)
Mesenchymal stem cell (MSC)
A type of multipotent stem cell that can differentiate into various cell types, including bone, cartilage and fat cells. MSCs are often used in cell therapy for their potential to promote tissue repair and regulate the immune response. They can be derived from various sources, including bone marrow, adipose tissue and umbilical cord tissue.
Quality agreement
A formal document between two parties involved in the manufacture, testing or distribution of pharmaceutical or related products. It outlines the responsibilities, expectations and requirements for ensuring product quality and regulatory compliance.
Site master file
A document that is prepared by the pharmaceutical manufacturer and that contains specific information about the quality management policies and activities of the site, the production, or the quality control of pharmaceutical manufacturing operations carried out at the named site and any closely integrated operations at adjacent and nearby buildings. (EudraLex, volume 4, part III)
Somatic cell
All cells within the developing or developed organism with the exception of egg and sperm cells. Sometimes referred to as adult cells.
Working cell bank
A working cell bank is prepared from aliquots of a homogeneous suspension of cells obtained from culturing a master cell bank under defined culture conditions. (ICH Q5A (R1))
Working viral bank
A viral seed derived by propagation of virus from a master viral bank under defined conditions and used to initiate production cell cultures lot-by-lot. (FDA cell substrate guidance)