Preparation of Reference Influenza Viruses in Mammalian Cells: FDA Perspective Prepared for the Vaccines and Related Biological Products Advisory Committee.

Slides:



Advertisements
Similar presentations
EPAA Annual conference November Regulatory acceptance of alternative approaches for pharmaceuticals Jean-Marc Vidal Safety & Efficacy of Human Medicines.
Advertisements

Use of MDCK Cells for Manufacture of Inactivated Influenza Vaccines: Introduction Philip R. Krause, M.D.
Biopharmaceutical Quality
18Feb2009VRBPAC Influenza Vaccine Manufacturing Industry Perspective for Vaccine Supply.
Influenza Vaccine Manufacturing
Use of Madin-Darby Canine Kidney (MDCK) Cells for Manufacture of Inactivated Influenza Vaccines: Introduction Philip R. Krause, M.D.
Vaccines and Related Biological Products Advisory Committee 18 February 2009 Topic 2: Considerations and Implications for adding two B Strains to the Seasonal.
Vaccines and Related Products FDA Advisory Committee Meeting
Vaccines and Related Biological Products
Control and response measures Dr. Christina Rundi Ministry of Health, Malaysia Foodborne Outbreak Investigation, Hanoi, 1-5 June 2009.
Overview of the Division of Viral Products
Overview of the Division of Viral Products VRBPAC Presentation of the Site Visit Report for the Laboratories of Retrovirus Research, Immunoregulation,
U.S. Food and Drug Administration Notice: Archived Document The content in this document is provided on the FDA’s website for reference purposes only.
CBER Regulatory Laboratory Planning & Preparedness for SARS-related Biologics Products Kathryn M. Carbone MD Associate Director for Research, Acting, Center.
Influenza Vaccine Manufacturing Industry perspective for influenza vaccine supply VRBPAC, 27 February 2013 The FDA CBER requested this annual.
Influenza Virus Vaccine Strain Selection Vaccines and Related Biological Products Advisory Committee (2/27/2013) Jerry P. Weir, Ph.D., Director.
QC/QA Mary Malarkey Director, Division of Case Management Office of Compliance and Biologics Quality Center for Biologics Evaluation and Research March.
Influenza Virus Vaccine Strain Selection Vaccines and Related Biological Products Advisory Committee (2/28/2014) Jerry P. Weir, Ph.D., Director.
Influenza Vaccine Manufacturing Industry perspective for influenza vaccine supply VRBPAC, 28 February 2012 The FDA CBER requested this annual.
Smallpox and Influenza "In early 1962 long queues attended any clinic in Birmingham offering vaccination, because three patients with smallpox were in.
Technical Report on Alternative Methods for Mycoplasma Testing Status update- Sept 2008 Kurt Brorson, Ph.D. CDER/FDA.
Influenza Virus Vaccine Strain Selection Vaccines and Related Biological Products Advisory Committee (2/25/2011) Jerry P. Weir, Ph.D., Director.
GLOBAL REGULATORY STRATEGY CONSIDERATIONS SCIENTIFIC SARAH POWELL EXECUTIVE DIRECTOR, REGULATORY STRATEGIES SEPTEMBER 14-17, 2008 BOSTON, MA.
Topic 1. Validation of Procedures to Prevent Contamination and Cross-Contamination with TSE Agents of Human Tissue Intended for Transplantation TSEAC June.
Critical Path Opportunities for Biologics Products Jesse L. Goodman, M.D. M.P.H. Director Kathryn M. Carbone, M.D. Associate Director for Research Center.
Ensuring Product Quality in Gene Transfer Clinical Trials
Nonclinical Studies Subcommittee Advisory Committee for Pharmaceutical Science CMC Issues for Screening INDs Eric B. Sheinin, Ph.D. Acting Deputy Director.
Influenza Vaccine Development
Pandemic (H1N1) 2009 Influenza Vaccine Manufacturing Considerations Vaccines and Related Biological Products Advisory Committee (7/23/2009) Jerry P. Weir,
Use of MDCK Cells for Manufacture of Inactivated Influenza Virus Vaccines VRBPAC – 16 Nov 05.
Influenza Vaccine Manufacturing Industry Perspective Tony Colegate Novartis Vaccines and Diagnostics Prepared by PhRMA Vaccine Technical Committee for.
VRBPAC 25 February 2011 Influenza Vaccine Manufacturing Industry Perspective for Vaccine Supply.
Secretary’s Advisory Committee on Human Subjects Protections (SACHRP) Summary of Responses on: Advanced Notice of Proposed Rulemaking (ANPRM) on Holding.
1 OIE Response to the HPAI Threat in the SADC Region 1 st SADC Meeting on Avian Influenza Pretoria, South Africa 7-9 March 2006 Sub Regional Representation.
“FluBlØk: A Recombinant Hemagglutinin Protein Vaccine for Influenza” Manon Cox VRBPAC February 27, 2007 A Vaccine Company for the 21st Century “Making.
Food and Drug Administration
1 Overview of the Division of Viral Products February 28, 2014 VRBPAC Discussion of the August 28, 2013 Site Visit for the Laboratory of Respiratory Viral.
FDA TSE Advisory Committee Meeting October 25, 2001 Topic 2 Amino Acid Production and the Associated Theoretical Risk of BSE Transmission from their Use.
Polio Eradication -- Global Progress and Development of Post-Eradication Strategies: Implications for U.S. Stockpile and Outbreak Response Preparations.
CHALLENGES FACED IN THE DEVELOPMENT OF BIOSIMILARS Dr.G.Hima Bindu MD; PG dip. diabetology Asst.Professor Dept. of Pharmacology Rajiv Gandhi Institute.
Options for Influenza Vaccine Composition Summary of Data Options with Pros and Cons.
STRATEGIES FOR THE DETECTION OF UNKNOWN BIOLOGICAL AGENTS Dr. Peter J. Stopa US Army Edgewood Chemical Biological Center Aberdeen Proving Ground, MD.
U.S. Food and Drug Administration Notice: Archived Document The content in this document is provided on the FDA’s website for reference purposes only.
COMPARABILITY PROTOCOLUPDATE ADVISORY COMMITTEE FOR PHARMACEUTICAL SCIENCE Manufacturing Subcommittee July 20-21, 2004 Stephen Moore, Ph.D. Chemistry Team.
Bioequivalence of Locally Acting Gastrointestinal Drugs: An Overview
Draft Guidance for Industry: CGMPs for Phase 1 INDs Joseph C. Famulare, Director Division of Manufacturing & Product Quality Office of Compliance, CDER,
Influenza A (H1N1) Vaccine Vaccines and Related Biological Products Advisory Committee Meeting, 23 July 2009 Raburn Mallory, M.D. Proprietary Vaccines.
Pandemic Vaccines Current and Future Issues 30 January 2007 Beijing Keiji Fukuda Global Influenza Programme.
1 Vaccines and Related Biological Products Advisory Committee (VRBPAC) Meeting Detection of Porcine circovirus (PCV) and PCV DNA Sequences in U.S. Licensed.
FDA’s Role in Facilitating the Availability of Influenza Vaccine Norman W. Baylor, Ph.D. Director, Office of Vaccines Research and Review CBER/FDA.
Minimizing the Risks of TSE Agents in Human Tissues Melissa A. Greenwald, M.D. Division of Human Tissues Office of Cellular, Tissue and Gene Therapies;
Office of Vaccines Research and Review
Research in the Office of Vaccines Research and Review: Vision and Overview Jesse Goodman, M.D., M.P.H. Director, Center for Biologics Evaluation and Research.
1 NVAC Washington, D.C. February 3, Agenda I.Overview of Influenza Vaccine Production and Development II.Vaccine Supply/Demand: Recent Trends.
Influenza Virus Vaccine Strain Selection Vaccines and Related Biological Products Advisory Committee (2/22/2010) Jerry P. Weir, Ph.D., Director.
1 IMMUNE CORRELATES OF PROTECTION AGAINST INFLUENZA A VIRUSES IN SUPPORT OF PANDEMIC VACCINE DEVELOPMENT FDA/NIH/WHO Public Workshop, December 10-11, 2007.
Options for Influenza Vaccine Composition Roland A. Levandowski, M.D. Division of Viral Products Prepared for Vaccines and Related Biological.
Carol Friedman, D.O. Associate Director for Adult Immunization Immunization Services Division National Center for Immunization and Respiratory Diseases.
NEW TECHNOLOGIES IN VACCINES. Vaccination – is the introduction into the body of a weakened, killed or piece of a disease-causing agent to prevent disease.
In the name of God. Common Technical Document On Biotech.
Pandemic Influenza Vaccine Manufacture Preparedness Lin Su Sinovac Biotech Co., Ltd.
Viral vaccines  .
DEPARTMENT OF HEALTH CENTER FOR BIOLOGICS AND HUMAN SERVICESEVALUATION and RESEARCH AND HUMAN SERVICES EVALUATION and RESEARCH Update on the Somatic Cell.
Influenza Virologic Surveillance and Vaccine Strain Selection Xiyan Xu MD Deputy Director WHO Collaborating Center for Surveillance, Epidemiology and Control.
BIODEEP-WP4 BIODEEP-WP5 Andrea Sass , Terry McGenity
The Lifecycle of Pharmaceutical products
Use of Madin-Darby Canine Kidney (MDCK) Cells for Manufacture of Inactivated Influenza Vaccines: Introduction Philip R. Krause, M.D.
Use of Madin-Darby Canine Kidney (MDCK) Cells for Manufacture of Inactivated Influenza Vaccines: Introduction Philip R. Krause, M.D.
The Role of NICs in Influenza Surveillance
ADVAC ALUMNI MEETING DURING SAGE
Presentation transcript:

Preparation of Reference Influenza Viruses in Mammalian Cells: FDA Perspective Prepared for the Vaccines and Related Biological Products Advisory Committee February 18-19, 2004 Zhiping Ye, M. D., Ph.D. Center For Biologics Evaluation and Research, Division of Viral Products

Objectives To review the issues associated with the source of reference influenza viruses To discuss possible strategies for using mammalian cell lines to prepare influenza reference viruses

Background Since the 1940s, inactivated influenza virus vaccines have been prepared in embryonated eggs, which provide reasonable virus yields The candidate vaccine viruses are originally isolated in surveillance labs using eggs as opposed to mammalian cells (a global consensus within WHO, national regulatory authorities and manufacturers) Over time, many surveillance labs have come to rely on cell cultures for virus isolation, for reasons of robustness and convenience, even though such isolates are not used as reference viruses

Background (cont.) Isolation of circulating viruses from clinical samples in National Influenza Centers (surveillance labs ) Cell culture (Not qualified) - MDCK cells (majority of surveillance labs) - Vero cells (some labs) - Chicken embryo kidney cells (few labs) Embryonated eggs (Few labs)

Isolation Rates of Influenza Viruses From Clinical Samples (Govorkova, et al., 1996, J. Virol., 70:5519)

Background (cont.) Yearly strain selection can be negatively affected by the requirement for an egg isolate as seed virus –Delayed recommendation for vaccine composition –Altered recommendation for vaccine strain component because of availability A delay in the availability of strain selection during a pandemic situation could have disastrous consequences.

Influenza Virus Vaccines (licensed in USA) Inactivated Influenza Virus Vaccines –Commercially available for more than 50 Years in USA –Produced in eggs –Parenteral injection Live Influenza Virus Vaccine –Recently licensed –Produced in SPF-eggs –Intranasal inoculation

Influenza Virus Vaccines (in development) Cell based- inactivated vaccines –MDCK –VERO Others: –Subunit DNA (Plasmid/bacteria) –Subunit Protein (Insect cells)

Reference and Seed Virus Development WHO global surveillance systems (National Influenza Centers) –Provide reference viruses isolated from clinical samples using eggs WHO collaborating centers (Atlanta, London, Melbourne and Tokyo) –Characterize and provide reference viruses (high growth reassortants for type A) to manufactures

Reference and Seed Virus Development (cont.) Manufacturers –Develop proprietary seed viruses from egg-isolates recommended by WHO and local authorities Regulatory agencies –Accept reference viruses and approve seed viruses for use in licensed vaccine preparation

Reference and Seed Virus Development (Summary) NIC (Egg-isolate) WHOCC (Vaccine candidate) RegulatoryManufactures Ref. Seed Ref. Seed Ref.

Use of Eggs for Isolation of Influenza Seed Strains A safety track record of more than 50 years Possible exclusion of some adventitious agents from clinical specimens Leads to high yields in vaccine manufacturing Validated for inactivation of common chicken viruses in vaccine process

Pros and Cons for the Consideration of Mammalian Cell Lines for Isolation of Seed Strains Pros –More robust than eggs for primary isolation of influenza A viruses from clinical specimens –Less selective pressure than in eggs for isolation of influenza virus with alternative receptor specificity –Ready availability in many WHO global surveillance centers (MDCK cell lines)

Pros and Cons for the Consideration of Mammalian Cell Lines for Isolation of Seed Strains Cons –Limited experience in influenza vaccine development and production (e.g. isolates may not necessarily grow well in eggs) –Issues related to the use of mammalian cells for isolation of seed strains (e.g. the possible contamination of adventitious agents)

Regulatory Requirements and Guidance Related to the Use of Mammalian Cell Lines 21 CFR (c) Cell lines used for manufacturing biological products (1) General requirements –Identified by history –Described with respect to cytogenic characteristics and tumorigenicity –Characterized with respect to in vitro growth characteristics and life potential –Tested for the presence of detectable microbial agents

Regulatory Requirements and Guidance Related to the Use of Mammalian Cell Lines (Cont.) Points to Consider in the Characterization of Cell Lines Used to Produce Biologicals –Published in 1993; currently under revision by Office of Vaccines Research and Review –Provides additional guidance on appropriate standards for characterization and qualification of cell substrates and viral seeds

Additional Regulatory Requirements and Guidance Related to the Use of Mammalian Cell Lines WHO Technical Report Series, #878 (Requirements for Biological Substances N o ) ICH Guidance, Q5A (Viral Safety Evaluation of Biotechnology Products) EMEA Guidance, CPMP/BWP/2490/00 (Cell Culture Inactivated influenza Vaccine-2000)

Strategies to Consider for the Use of Mammalian Cell-Isolates as Reference Viruses 1.Retain the clinical samples after initial isolation in NIC and forward the samples to select WHOCC for re-isolation in a qualified cell line –Similar to the current procedure except for the use of cell lines for re-isolation –An appropriate cell bank would need to be produced and qualified for distribution to select centers –Further purification or adaptation of cell-isolates for vaccine production in eggs could be considered if necessary

Strategies to Consider for the Use of Mammalian Cell-Isolates as Reference Viruses (Cont.) 2.Use reference viruses directly isolated on cell lines not characterized or qualified –Would require purification of reference viruses to be acceptable (e.g., plaque purification on SPF-CEK cells) –Resources and infrastructure for purification would be necessary

Strategies to Consider for the Use of Mammalian Cell-Isolates as Reference Viruses (Cont.) 3.Use reference viruses isolated on characterized and qualified cell lines –Would require production and qualification of an appropriate cell bank for distribution to NIC choice of cell lines (MDCK, Vero, others?) maintenance of quality control after distribution –Further purification or adaptation of cell-isolates for vaccine production in eggs could be considered if necessary

Strategies to Consider for the Use of Mammalian Cell-Isolates as Reference Viruses (Cont.) 4.Use reverse genetics methodology and a qualified cell line to generate new reference viruses –Would require production and qualification of an appropriate cell bank for reverse genetics –May eliminate concerns regarding contaminates regardless of the source of the sample –Acceptance of technology and intellectual property issues may not permit near-term implementation

Conclusions The use of influenza seeds obtained from non-egg sources may be acceptable if concerns regarding the presence of adventitious agents in the original isolate or in the cell lines used for isolation can be addressed An investment in resources and infrastructure will be necessary A global consensus (WHO, national regulatory authorities, manufacturers) regarding the issues to be addressed would facilitate implementation

Acknowledgments Jerry Weir Roland Levandowski Andrew Lewis Keith Peden Arifa Khan Philip Krause