Description
The potential pathogenicity of replication competent retrovirus (RCR) requires vigilant testing to exclude the presence of RCR in vector-based human gene therapy products (Ref. 1). We, the FDA, are providing you, sponsors of retroviral vector-based human gene therapy products,recommendations regarding the testing for RCR during the manufacture of retroviral vector based gene therapy products, and during follow-up monitoring of patients who have received retroviral vector-based gene therapy products. Recommendations include the identification and amount of material to be tested as well as general testing methods. In addition, recommendations are provided for monitoring patients for evidence of retroviral infection after administration of retroviral vector-based gene therapy products.
Scope & Applicability
Product Classes
3The potential pathogenicity of replication competent retrovirus (RCR) requires vigilant testing to exclude the presence of RCR in retroviral vector-based human gene therapy products.; Subject of the guidance regarding RCR testing; Subject of the guidance regarding RCR testing and patient follow-up.
determine the relative sensitivity of assay methods used for detection of RCR in retroviral vectors.
Material for Testing... 4. Ex Vivo Transduced Cells.
Stakeholders
1Assist sponsors in the nonclinical evaluation
Regulatory Context
Attributes
4Confidence level for supernatant testing
The number of replicates (r), can be determined using the formula, r = Vt / Vs.
The standard virus stock and its infectious titer can be used as a positive control.
Parameter (MOI) used in calculating test volumes for ex vivo modification.
Identified Hazards
Hazards
2The potential pathogenicity of replication competent retrovirus (RCR) requires vigilant testing.; Contaminant that may be below the level of detection; The primary safety concern (RCR) being monitored in gene therapy.; validation of assays used to detect the presence of RCR.
Historically, lentivirus RCR is referred to as replication competent lentivirus (RCL).
Related CFR Sections (3)
- 21CFR312.32§ 312.32 IND safety reporting.
(a) Definitions. The following definitions of terms apply to this section:Read full regulation →
- 21CFR312.33§ 312.33 Annual reports.
A sponsor shall within 60 days of the anniversary date that the IND went into effect, submit a brief report of the progress of the investigation that includes:Read full regulation →
- 21CFR601.2§ 601.2 Applications for biologics licenses; procedures for filing.
(a) General. To obtain a biologics license under section 351 of the Public Health Service Act for any biological product, the manufacturer shall submit an application to the Director, Center for Biologics Evaluation and Research or the Director, Center for Drug Evaluation and Research (see mailing aRead full regulation →
Related Warning Letters (1)
- 2024-06-18
Clinical Investigator (Sponsor)
Angela D. Ritter, M.D.
See Also (8)
- Expanded Access to Investigational Drugs for Treatment Use: Questions and Answers (Status: Final)
- Content and Format of Investigational New Drug Applications (INDs) for Phase 1 Studies of Drugs, Including Well-Characterized, Therapeutic, Biotechnology-derived Products: Guidance for Industry (Status: Final)
- PHS Guideline on Infectious Disease Issues in Xenotransplantation: PHS Guideline (Status: Final)
- Postmarketing Safety Reporting for Human Drug and Biological Products Including Vaccines: Draft Guidance for Industry (Status: Draft)
- Guidance for Industry: Providing Regulatory Submissions to CBER in Electronic Format -- Investigational New Drug Applications (INDs) (PDF) (Status: Final)
- Gingivitis: Development and Evaluation of Drugs for Treatment or Prevention (Status: Draft)
- How to Comply with the Pediatric Research Equity Act (Status: Draft)
- Establishment and Operation of Clinical Trial Data Monitoring Committees: Guidance for Clinical Trial Sponsors (Status: Final)