Joint EMA/EDQM workshop on improved potency assays for inactivated influenza vaccines

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6 December 2011 EMA/902224/2011 Joint EMA/EDQM workshop on improved potency assays for inactivated influenza vaccines Draft workshop programme 12 December 2011, 8.30-17.00 (UK time) European Medicines Agency, London, United Kingdom See websites for contact details European Directorate for the Quality of Medicines & HealthCare www.edqm.eu Council of Europe www.coe.int European Medicines Agency www.ema.europa.eu 2011. Reproduction is authorised provided the source is acknowledged.

Programme overview Scope The lessons learnt exercise performed after the 2009 influenza pandemic recognised that the assays used for content of the hemagglutinin (HA) component in the influenza vaccine dose should be reviewed. During the pandemic and as part of the lessons learnt exercise, issues related to the interpretation due to variability/standardisation of the assays used for content determination were raised and particularly at the successive expert meetings held at the European Medicines Agency in July 2009, April 2010 and June 2010. Quantification of HA by the single radial immunodiffusion (SRID) assay has been for many years the recognised/accepted method to monitor potency (content) of trivalent seasonal influenza vaccines for HA antigen. The current SRID method however requires, for each of the three HA antigens, strainspecific virus reagents which may not be available when the early batches of a vaccine have to be filled and released for either clinical trial confirmatory tests or to speed up the early access to pandemic vaccine doses. During the expert meetings and lessons learnt exercise, it has been raised that alternative assays to measure the content of HA should be investigated and their relative performance validated against the current SRID, before being used on a routine basis. The timing of use of such assays will need to be discussed (e.g. at an early stage of development/qualification of the new strain vaccine until the SRID test reagents become available, and/or for a more general use as alternative assays to SRID). Also techniques for the characterisation of neuraminidase (NA) component and its assays could be considered. The guidelines on influenza vaccines are being reviewed as part of the lessons learnt exercise. In this context, it is proposed to hold a technical workshop to prepare the work and feedback the revision exercise of the guidelines. Furthermore it will be reviewed whether there are still gaps in the development and validation of alternative assays and how these gaps can be filled. The development of assays for HA content may impact the batch release and official control laboratory network (OMCL) testing and potential future revision of the European Pharmacopoeia monographs for influenza vaccines. Chairs and rapporteurs Jean Hugues Trouvin (workshop co-chair) Chairman of the CHMP s Biologicals Working Party / AFSSaPS Phil Minor (workshop co-chair) Ton van der Stappen (Rapporteur) Member of the CHMP s Biologicals Working Party / MEB Joep Bergers (Rapporteur) RIVM EMA/902224/2011 Page 2/5

Programme details Monday, 12 December 2011 Room 4A 8.00 Registration and coffee Please register with reception (ground floor) to receive your security badge. 8.30 Welcome and introduction Jean Hugues Trouvin (workshop co-chair) Chairman of the CHMP s Biologicals Working Party / AFSSaPS Phil Minor (workshop co-chair) 8.45 SRD (current) assay Reagents, origin, supply, timelines, calibration, antigen issues, antiserum issues Una Dunleavy (15 minutes) Usage of SRD/comments Francois Cano (15 minutes) AFSSaPS OMCL Tony Colegate (15 minutes) 9.30 Alternative assays (non-srd) used for IPCs and/or determination of Haemagglutinin content for drug substance and finished product: used in parallel with SRD or stand-alone pros/cons Characteristics for an improved potency assay & how the different methods compare in light of these characteristics Pascale Gonnet (20 minutes) EVM (Sanofi-Pasteur) HPLC (60 minutes) Dieter Pullirsch (10 minutes) AGES OMCL Francois Cano (10 minutes) AFSSaPS OMCL Hans Kapteyn (30 minutes) EVM (Abbott) Michel Girard (note: presentation to take place later in the morning) (10 minutes) Biologics and Genetic Therapies Directorate, Health Canada 10.50 11.10 Coffee break Coffee will be available outside the meeting room. EMA/902224/2011 Page 3/5

Other methods such as ELISA, SDS-PAGE, MS, SPR (50 minutes) ELISA Ethan Settembre Kendra Frederick Protein Sciences SDS-PAGE Jane King CBER experience on alternative assays Maryna Eichelberger (15 minutes) Center for Biologics Evaluation & Research, US Food and Drug Administration Comparison of alternative methods Othmar Engelhardt (15 minutes) 12.30 Potential assays for investigating the Neuraminidase content Elisabeth Neumeier (10 minutes) EVM (GlaxoSmithKline Biologicals) Towards qualitative and quantitative analyses of Neuraminidase in influenza vaccines - an update (10 minutes) Sean Li Biologics and Genetic Therapies Directorate, Health Canada Assessment of Neuraminidase in vaccines update from CBER (10 minutes) Maryna Eichelberger Center for Biologics Evaluation & Research, US Food and Drug Administration 13.00 14.00 Lunch 14.00 Moving forward - all participants - discussion Feedback from the Vaccine Working Party: clinical relevance of alternative assays (10 minutes) Michael Pfleiderer Chairman of the CHMP s Vaccine Working Party / PEI A) Haemagglutinin i. Value/limitation of currently published studies on alternatives ii. Validation of improved assays/clinical validation iii. Is a measure of HA protein content sufficient? If not, what else would be required (validation)? EMA/902224/2011 Page 4/5

iv. Combination approach: - company specific assay for IPC + internationally agreed immunogen assay, or - internationally agreed protein assay + internationally agreed immunogen assay? v. Stand-alone assay how to validate? vi. Develop Ph.Eur. mononographs? vii. Industry experience and comments viii. Consideration of SRD how to improve variability/timelines, can they be? ix. Future assays for novel vaccines x. Recommendations for future studies/collaborative studies B) Neuraminidase 16.00 16.30 Coffee break Coffee will be available outside the meeting room. 16.30 Wrap-up / Concluding remarks EMA/902224/2011 Page 5/5