GMP Vector Production

The Vector Production Facility is a cleanroom facility that is fully compliant with FDA’s current Good Manufacturing Practices (cGMP) for the manufacturing of viral vectors in support of early phase clinical trials. The facility has been in operation since 2005.

The Aseptic Processing Laboratory Facility consists of approximately 1,600 square foot of controlled-access space that includes three (3) independent ISO Class 7 cleanroom suites equipped with biosafety cabinets for aseptic processing. Support areas include, a Gown and De-Gown room, a Materials Airlock, pre-and post-production corridors, and a support room for closed processing.

Services offered include pilot studies, development, optimization, scale-up and large-scale manufacturing of viral vector products. Products prepared in the past include cGMP-grade Master Cell Banks (MCB), gamma-Retroviral (gRV) vectors, Lentiviral Vectors (LV), Adeno-Associated Virus (AAV) vectors and Adenovirus (Ad). Custom services include certification testing, stability studies, purification, concentration and vialing as well as cryogenic storage of clinical products and validated shipping.

All critical facilities and equipment used in GMP manufacturing have been validated to meet Phase I/II drug product requirements and all instruments have been calibrated to NIST standards. Critical computer systems are compliant with 21 CFR Part 11 suitable for Phase I/II.  Aseptic processes have been validated to meet the requirements set forth in the Guidance for Industry, Sterile Drug Products Produced by Aseptic processing and are compliant with 21 CFR Parts 210 and 211.

A Type V Master File (MF-BB) is on file with FDA/CBER. A letter of cross reference to the DMF is available upon request. VPF staff have experience in providing investigators support in development of relevant CMC (Chemistry Manufacturing and Control) sections for vector production for both INDs and IMPDs.

Selected References

1. Hacein-Bey-Abina S, Pai SY, Gaspar HB, Armant M, Berry CC, Blanche S, Bleesing J, Blondeau J, de Boer H, Buckland KF, Caccavelli L, Cros G, De Oliveira S, Fernandez KS, Guo D, Harris CE, Hopkins G, Lehmann LE, Lim A, London WB, van der Loo JC, Malani N, Male F, Malik P, Marinovic MA, McNicol AM, Moshous D, Neven B, Oleastro M, Picard C, Ritz J, Rivat C, Schambach A, Shaw KL, Sherman EA, Silberstein LE, Six E, Touzot F, Tsytsykova A, Xu-Bayford J, Baum C, Bushman FD, Fischer A, Kohn DB, Filipovich AH, Notarangelo LD, Cavazzana M, Williams DA, and Thrasher AJ. A modified gamma-retrovirus vector for X-linked severe combined immunodeficiency. N Engl J Med 2014; 371(15):1407-17

2. van der Loo JC, Swaney WP, Grassman E, Terwilliger A, Higashimoto T, Schambach A et al. Scale-up and manufacturing of clinical-grade self-inactivating gamma-retroviral vectors by transient transfection. Gene Ther 2012; 19(3): 246-54

3. van der Loo JC, Swaney WP, Grassman E, Terwilliger A, Higashimoto T, Schambach A et al. Critical Variables Affecting Clinical-Grade Production of the Self-Inactivating Gamma-Retroviral Vector for the Treatment of X-linked Severe Combined Immunodeficiency. Gene Ther 2012; 19(8): 872-6

4. Schambach A, Swaney WP, van der Loo JCM. Design and production of retro- and lentiviral vectors for gene expression in hematopoietic cells. In: Baum C (ed) Methods in Molecular Biology, vol. 506. Humana Press: Totowa, NJ., 2009, pp 191-205

5. Nordling D, Kaiser A, Reeves L. Release testing of retroviral vectors and gene-modified cells. Methods Mol Biol 2009; 506: 265-79