Defi nition and Application of Terms for Vaccine ...

1 CIOMS WHO. This report from the Council for International Organizations of Medical Sciences (CIOMS) in collaboration with WHO covers Definition and Definition and Application of Terms for Vaccine Pharmacovigilance the activities and outputs of the CIOMS/WHO Working Group on Vaccine Pharmacovigilance (2005-2010). Application of This working group brought together experts from both industri- Terms for Vaccine alized and emerging countries representing regulatory agencies, Vaccine industry, national and international public health bodies including WHO and CIOMS, academia and clinical care, contrib- Pharmacovigilance uting from their different perspectives. The working group's report covers general Terms and definitions Report of CIOMS/WHO Working Group for Vaccine safety and discusses the Application of such harmo- nized tools in Vaccine safety surveillance and studies.

2 As well, on Vaccine Pharmacovigilance the report highlights case definitions for adverse events typically reported for vaccines. The report is addressed to those engaged in Vaccine safety data collection and evaluation, and will also make a useful reading for others who want to familiarise themselves with Vaccine safety terminology. ISBN 978-92-9036-083-4. Report working group on 1 19:06. Definition and Application of Terms for Vaccine Pharmacovigilance Report of CIOMS/WHO. Working Group on Vaccine Pharmacovigilance Report working group on 1 19:49. Council for International Organizations of Medical Sciences (CIOMS) 2012. All rights reserved. CIOMS publications may be obtained directly from CIOMS, c/o World Health Organization, 20 Avenue Appia, 1211 Geneva 27, Switzerland or by e-mail to CIOMS publications can also be obtained through the World Health Organization's e-com- merce web site ( ) or can be purchased from WHO Press, World Health Organization, 20 Avenue Appia, 1211 Geneva 27, Switzerland (tel.)

3 : +41 22 791 3264;. fax: +41 22 791 4857; e-mail: ISBN 978 92 9036 083 4. The authors alone are responsible for the views expressed in this publication and those views do not necessarily represent the decisions, policies or views of their respective institutions or companies. Report working group on 2 19:49. Acknowledgements T he Council for International Organizations of Medical Sciences (CIOMS). with the World Health Organization (WHO) gratefully acknowledges the contributions of the members of the CIOMS/WHO Working Group on Vaccine Pharmacovigilance as well as the drug and Vaccine regulatory authorities, Vaccine industry, and other organizations and institutions which by providing these experts and resources supported the work that resulted in this publica- tion. The work has required a number of meetings organized by the CIOMS.

4 Secretariat in collaboration with WHO. The consistent contribution of WHO. was represented particularly by its Department of Immunization, Vaccines and Biologicals and its Department of Essential Medicines and Pharmaceu- tical Policies. Dr Philippe Duclos of the WHO Department of Immunization, Vaccines and Biologicals was instrumental in the establishment of this joint CIOMS/WHO Working Group in 2004-2005, supported by Drs Mary Couper and Shanthi Pal of the Department of Essential Medicines and Pharmaceuti- cal Policies, as well as Professor Ulrich Heininger and Dr Elizabeth Loupi as representatives of the Brighton Collaboration. Moreover, contributions from regulatory agencies and Vaccine manufacturers that hosted the meetings (see Annex 1) are especially acknowledged. During this process helpful discussions were held with concerned par- ties such as the Brighton Collaboration, the US Centers for Disease Control and Prevention (CDC), the Public Health Agency of Canada and the Mainte- nance and Support Services Organization (MSSO) of the Medical Dictionary for Regulatory Activities (MedDRA).

5 A number of parties, including relevant regulators in the European Union via the Committee for Medicinal Products (CHMP) Pharmacovigilance Working Party (PhVWP) at the European Medi- cines Agency, the Global Advisory Committee on Vaccine Safety of WHO and selected individual Vaccine safety experts, were consulted on the general definitions for adverse events following immunization (AEFIs). Each Working 3. Report working group on 3 19:49. Group member participated actively in the discussions, drafting and redraft- ing of texts and their review, which enabled the Working Group to bring the entire project to a successful finalization. During the process new members were invited in capacity of their expertise. CIOMS thanks especially those members who chaired the meetings of the Working Group for their dedication and capable leadership.

6 Each of the meetings had a nominated rapporteur (or rapporteurs), and CIOMS ac- knowledges their professional contributions. The Editorial Group, comprising Drs Adwoa D Bentsi-Enchill, Priya Bahri, Michael D Blum, Ulrich Heininger, and Eliane Matos dos Santos, merits spe- cial mention and thanks. At WHO, Drs Duclos, Bentsi-Enchill and Patrick Zu- ber have supported the management of the Working Group. CIOMS wishes to express special appreciation to Dr Bentsi-Enchill who, as Chief Editor of the final report, assured the quality of the publication. CIOMS and the Working Group are grateful for important input received on several points of the report from many senior experts outside the Group who reviewed the entire manuscript and made valuable suggestions. At CIOMS, Dr Juhana E Id np n-Heikkil , former Secretary-General, Dr Gottfried Kreutz, former Secretary-General, Dr Gunilla Sj lin-Forsberg, Secretary-General and Ms Amanda Owden, Administrative Assistant man- aged the project.

7 Mr Sev Fluss contributed with editorial work and Ms Owden and Ms Louise Wakeford provided secretarial support throughout the project. Geneva, June 2011. Gunilla Sj lin-Forsberg, MD, PhD Juhana E Id np n-Heikkil , MD, PhD. Secretary-General, CIOMS Senior Adviser, CIOMS. 4. Report working group on 4 19:49. Table of contents Foreword .. 11. 1. 13. World Health Organization .. 15. Vaccine regulatory authorities .. 17. Vaccine industry .. 20. Public health agencies and academia .. 22. 2. Background and scope of the CIOMS/WHO. Working Group on Vaccine 25. Rationale for creation of the Working Group .. 27. Terms of reference .. 27. Membership .. 28. Mode of operation .. 28. 3. General definitions .. 29. Vaccine pharmacovigilance .. 32. Vaccination failure .. 34. Adverse events following immunization .. 39. Points to consider regarding differences between vaccines and drugs in signal detection.

8 54. 4. Brighton Collaboration case definitions and guidelines .. 61. AEFI-specific case definitions .. 64. General guidelines .. 115. 5. Methods to enhance the Application of Brighton Collaboration case 119. Translation of Brighton Collaboration case 122. Mapping of Terms : MedDRA and Brighton Collaboration case definitions .. 123. Reference to Brighton Collaboration case definitions in guidance documents .. 130. Industry survey on use of Brighton Collaboration case definitions .. 131. 5. Report working group on 5 19:49. 6. Conclusions and future directions .. 135. Practical use of the outputs of the Working 137. Gaps and future directions .. 139. Annex 1: Membership and meetings of the Working Group .. 143. Annex 2: Selected CIOMS publications .. 147. Annex 3: Data collection checklist for suspected vaccination failure.

9 149. Annex 4: Workflow for revision and endorsement of Brighton Collaboration case definitions by the CIOMS/WHO. Working Group on Vaccine Pharmacovigilance .. 155. Annex 5: Suggested generic introduction for use in translation of abridged Brighton Collaboration case definitions .. 157. Annex 6: Guidelines for collection, analysis and presentation of Vaccine safety data in pre- and post-licensure clinical studies .. 159. Annex 7: Guidelines for collection, analysis and presentation of Vaccine safety data in surveillance systems .. 177. 6. Report working group on 6 19:49. Abbreviations and glossary ADR adverse drug reaction AEFI adverse event following immunization AERS US Adverse Event Reporting System (for drugs other than vaccines see also VAERS below). ANVISA Ag ncia Nacional de Vigil ncia Sanit ria (Brazilian Health Surveillance Agency).

10 BCG Bacillus Calmette-Gu rin ( Vaccine ). CDC US Centers for Disease Control and Prevention CIOMS Council for International Organizations of Medical Sciences CNS central nervous system CSF cerebrospinal fluid CT computed tomography DCVMN Developing Countries Vaccine Manufacturers Network DTP diphtheria-tetanus-pertussis ( Vaccine ). EEG electroencephalography/electroencephalog ram EV eczema vaccinatum GBS Guillain-Barr syndrome GV generalized vaccinia HHE hypotonic-hyporesponsive episode HLT High Level Term (in MedDRA). ICH International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use IFPMA International Federation of Pharmaceutical Manufacturers and Associations LLT Lower Level Term (in MedDRA). MedDRA Medical Dictionary for Regulatory Activities MMR measles-mumps-rubella ( Vaccine ).