Description
We, FDA, are providing you, manufacturers of viral vaccines, guidance for the characterization and qualification of cell substrates, viral seeds, and other biological materials used for the production of viral vaccines for human use.
Scope & Applicability
Product Classes
6Preventive and therapeutic medicinal products intended to elicit immune responses; Vaccines for infectious disease indications produced using cell substrates.; Production of viral vaccines for infectious disease indications; All licensed viral vaccines produced in cell substrates should be tested to ensure the absence of mycoplasma; Prophylactic viral vaccines produced using cell substrates.; Guidance focuses on the production of viral vaccines for infectious disease indications
WHO guidelines for quality, safety and efficacy
Produced using cell substrates.
Vaccine type that often cannot be purified as rigorously as subunits
Highly purified vaccine products
Vaccines where the inactivation process must be validated
Stakeholders
4Responsible for declaring acceptable market names on labels.
Animal model used for tumorigenicity testing due to T-cell deficiency.
Entity responsible for submitting NDINs
Entity responsible for submitting applications under section 524B
Regulatory Context
Attributes
10Property of cell substrates that must be tested; The process by which immortalized cells form tumors when inoculated into animals.
Requirement for devices provided sterile or non-sterile
Property tested at the End of Production (EOP) stage
The property of biological agents capable of immortalizing cells and forming tumors.
Tumor-producing dose in 50% of animals used to define tumorigenic phenotype.
means of assessing virus replication in cell-culture tests
specifications for the purity, strength, and composition of dietary supplements
Assessment for MVS derived from wild type viruses
Measurement of cell growth and life expectancy.
Recommended testing for gene inserts in EOP cells
Identified Hazards
Hazards
10Transmission of adventitious agents is a key issue in human- and animal-derived materials.; Human- and animal-derived materials increase the risk of introducing adventitious agents
A virus present in a cell without active replication but with potential to reactivate.
Retrovirus whose genome is part of the germ line of the species of origin.
Potential presence of exogenous agents in tumorigenic cells.
Adventitious agent requiring testing on cell culture harvest.
hazard associated with animal food facilities
exogenous retrovirus to be excluded in avian cells
Cell banks made from continuous cell lines should be tested for adventitious viruses.
detected in HAP, RAP, and MAP tests
Extraneous infectious organisms to be excluded
Related CFR Sections (7)
- 21CFR610.18§ 610.18 Cultures.
(a) Storage and maintenance. Cultures used in the manufacture of products shall be stored in a secure and orderly manner, at a temperature and by a method that will retain the initial characteristics of the organisms and insure freedom from contamination and deterioration.Read full regulation →
- 21CFR211.160§ 211.160 General requirements.
(a) The establishment of any specifications, standards, sampling plans, test procedures, or other laboratory control mechanisms required by this subpart, including any change in such specifications, standards, sampling plans, test procedures, or other laboratory control mechanisms, shall be drafted Read full regulation →
- 21CFR610.9§ 610.9 Equivalent methods and processes.
Modification of any particular test method or manufacturing process or the conditions under which it is conducted as required in this part or in the additional standards for specific biological products in parts 620 through 680 of this chapter shall be permitted only under the following conditions:Read full regulation →
- 21CFR610.12§ 610.12 Sterility.
(a) The test. Except as provided in paragraph (h) of this section, manufacturers of biological products must perform sterility testing of each lot of each biological product's final container material or other material, as appropriate and as approved in the biologics license application or supplemenRead full regulation →
- 21CFR610.15§ 610.15 Constituent materials.
(a) Ingredients, preservatives, diluents, adjuvants. All ingredients used in a licensed product, and any diluent provided as an aid in the administration of the product, shall meet generally accepted standards of purity and quality. Any preservative used shall be sufficiently nontoxic so that the amRead full regulation →
- 21CFR610.13§ 610.13 Purity.
Products shall be free of extraneous material except that which is unavoidable in the manufacturing process described in the approved biologics license application. In addition, products shall be tested as provided in paragraphs (a) and (b) of this section.Read full regulation →
- 21CFR600.3§ 600.3 Definitions.
As used in this subchapter:Read full regulation →
Related Warning Letters (10)
- 2025-12-23
CGMP/Finished Pharmaceuticals/Adulterated
SV Labs Corporation
- 2025-12-23
CGMP/Finished Pharmaceuticals/Adulterated
Guangdong Renhe Guozhuang Biotechnology Co., Ltd.
- 2025-12-23
CGMP/Finished Pharmaceuticals/Adulterated
Medinatura New Mexico, Inc.
- 2025-12-16
CGMP/Finished Pharmaceuticals/Adulterated
Sklar Personal Care Inc.
- 2025-12-16
CGMP/Deviations/Biologics License Application (BLA)
Microvascular Tissue, Inc.
- 2025-12-11
CGMP/Finished Pharmaceuticals/Adulterated
Catalent Indiana, LLC
- 2025-12-09
CGMP/Finished Pharmaceuticals/Adulterated
DeVere Manufacturing Inc.
- 2025-12-09
CGMP/Finished Pharmaceuticals/Adulterated
CDL Services, Inc. DBA Technichem
- 2025-12-09
CGMP/Finished Pharmaceuticals/Adulterated
Seaway Pharma Inc.
- 2025-12-02
Compounding Pharmacy/Adulterated Drug Products
PQ Pharmacy, LLC
See Also (8)
- Use of Nucleic Acid Tests on Pooled and Individual Samples From Donors of Whole Blood and Blood Components, Including Source Plasma, to Reduce the Risk of Transmission of Hepatitis B Virus: Final Guidance for Industry (Status: Final)
- Determining Donor Eligibility for Autologous Donors of Blood and Blood Components Intended Solely for Autologous Use - Compliance Policy: Guidance for Industry (Status: Final)
- Use of Serological Tests to Reduce the Risk of Transmission of Trypanosoma cruzi Infection in Blood and Blood Components: Guidance for Industry (Status: Final)
- Biological Product Deviation Reporting for Blood and Plasma Establishments: Guidance for Industry (Status: Final)
- Guidance for Human Somatic Cell Therapy and Gene Therapy: Guidance for Industry (Status: Final)
- Early Clinical Trials With Live Biotherapeutic Products: Chemistry, Manufacturing, and Control Information: Guidance for Industry (Status: Final)
- Quality Considerations for Topical Ophthalmic Drug Products (Status: Draft)
- Potency Assay Considerations for Monoclonal Antibodies and Other Therapeutic Proteins Targeting Viral Pathogens (Status: Draft)