National Institute for Biological Standards and Control

Assuring the quality of biological medicines

Seasonal vaccine approval

- EUROPEAN UNION -

Jim Robertson

National Institute for Biological

Standards and Control

Routes for approval

• National

• Mutual Recognition procedure� must have already received a marketing authorisation in

one Member State; compulsory for all medicinal products

to be marketed in a Member State other than that in

which they were first authorised

• Centralised (via EMA)

Regulations and guidance

European Commission

• Directive 2001/83 EC + amendments (mutual recognition)

• Regulation (EC) no 726/2004 (centralised procedure)

EMA website

• Pre-authorisation regulatory and procedural guidance

• Vaccine (general) specific guidance

• Influenza vaccine guidance

EU Seasonal vaccines

(not comprehensive)

National

• Abbott Influvac

Imuvac

• Baxter Preflucel

• Crucell Inflexal V

• CSL Enzira

• GSK Fluarix

Fluarix tetra (pend.)

• Novartis Agrippal

Fluad

• Omnivest Fluvalab

• PM-MSD Flu vaccine

Centralised

Medimmune Fluenz (LAIV)

Novartis Optaflu (cell)

SP IDflu/intanza

Annual updates

National/Mutual recognition

European Commission

NOTICE TO APPLICANTS

A GUIDELINE ON

FAST TRACK PROCEDURES FOR HUMAN

INFLUENZA VACCINES

MAY 1999

Being revised to take into account Variations Regulations

Annual updates

Centralised

Procedural advice on the submission of variations for

annual update of human influenza inactivated

vaccines applications in the centralised procedure 8 November 2010

EMA/CHMP/BWP/99698/2007 Rev. 1

Committee for Medicinal Products for Human Use (CHMP)

Annex I. variation application(s) content for live

attenuated influenza vaccines 21 July 2011

EMA/CHMP/BWP/577998/2010

Committee for Medicinal Products for Human Use (CHMP)

Being revised to take into account Variations Regulations

Variation regulations

COMMISSION REGULATION (EU) No 712/2012

of 3 August 2012

amending Regulation (EC) No 1234/2008 concerning the

examination of variations to the terms of marketing authorisations

for medicinal products for human use and veterinary medicinal

products

Article 12 refers to mutual recognition/decentralised proceduresArticle 13F refers to national proceduresArticle 18 refers to centralised procedures

Commission guideline on the details of the various categories of variations

(2010/C 17/01)

Variations Regulations

• The Regulations define a Type-II variation as a major

variation that may have a significant impact on the quality,

safety or efficacy of a medicinal product.

• The Regulations and the Classification guideline set out a

list of changes to be considered as Type-II variations.

22 September 2011

EMA/CHMP/VWP/734330/2011

Committee for Medicinal Products for Human Use (CHMP)

Concept paper on the revision of guidelines

for influenza vaccines

New guidance will replace:

• Pandemic guidelines

• Harmonisation guideline

• Cell culture guideline

• LAIV guideline, etc.

New influenza guidelines

Guideline on Influenza Vaccines –

Quality ModuleDRAFT

EMA/CHMP/BWP/310834/2012 (March 2013)

Vaccine Working Party and Biologics Working Party (VWP, BWP)

Scope: vaccines for which experience exists -

• Inactivated, seasonal, pre-pandemic, pandemic

• Live attenuated, seasonal

• Annual updates

Quality issues

Non-clinical and Clinical

• Under development

Seasonal updates

Note for Guidance on Harmonisation of Requirements for

Influenza Vaccines

(CPMP/BWP/214/96)

• Yearly choice of strain

• Labelling

• Potency

• Batch release

• Clinical trials

Small numbers of subjects (2 x 50)

Assess immunogenicity and tolerance

Novel vaccines

Guidance available

• Recombinant DNA products

• Adjuvants

• Pre-clinical assessment

• Clinical assessment

• DNA vaccines

• Viral vectored vaccines

Links for guidelines and Commission

documents highlighted

• List of EMA scientific guidelines for vaccines:

http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/general/general_co

ntent_000407.jsp&mid=WC0b01ac058002958b

• Regulation (EC) No. 726/2004 for the authorisation and supervision of medicinal

products: http://eur-

lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2004:136:0001:0033:EN:PDF

• Variations Regulation (EC) No. 712/2012: http://eur-

lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2012:209:0004:0014:EN:PDF

• amending Variations Regulation (EC) No. 1234/2008: http://eur-

lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2008:334:0007:0024:EN:PDF

• Commission guidance on categories of Variations:

http://ec.europa.eu/health/files/eudralex/vol-2/c17_1/c17_1_en.pdf

• European Commission guideline on fast track procedures for human influenza

vaccines: http://ec.europa.eu/health/files/eudralex/vol-

2/c/fast_trackfinal_may99_en.pdf

• Commission Directive 2001/83 EC on medicinal products for human use:

http://ec.europa.eu/health/files/eudralex/vol-

1/dir_2001_83_cons/dir2001_83_cons_20081230_en.pdf