Presented at the 4th Global Animal Health Conference 2015 #GAHC2015 on Regulatory Convergence. Held in Dar Es Salaam, Tanzania, 24-25 June 2015. This was presented by GALVmed consultant Gilly Cowan and discussed GALVmed's progress in following up the recommendations from the 2010 Global Animal Health Conference when African regulators asked for a harmonised registration system, mutual recognition and training for their regulators in the registration of veterinary vaccines. GALVmed, the Global Alliance for Livestock Veterinary Medicines, works through its partners to protect livestock and improve human lives by making livestock vaccines, diagnostics & medicines accessible and affordable to the millions of those who rely on livestock. For more information on this conference, hosted by Health For Animals (formerly IFAH), visit here: http://healthforanimals.org/global-animal-health-conference-addresses-regulatory-barriers/ To read more highlights from the conference, click here: https://twitter.com/hashtag/GAHC2015?src=hash

1. A Case Study
Mutual Recognition in East Africa
Gillian Cowan
Regulatory Consultant
GALVmed

2. Background & Current Status
Introduction
• About GALVmed
• Background to GALVmed’s project
on Harmonised Registration for
Veterinary Immunologicals in Africa
• Technical Working Group (TWG)
• Mutual Recognition Procedures
• Adoption by East African Community (EAC)
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3. • Worked in Regulatory Affairs for several multinational
pharmaceutical companies
– Hoechst :1976 – 1996 in UK; 1996 – 2000 in Germany
– Intervet : 2000 in Boxmeer, NL
– Aquaculture Vaccine Ltd (AVL) : Aug 2000 – Aug 2002
– Schering Plough : 2002
– Pfizer Animal Health; Director of Regulatory Affairs, Biologicals:
Aug 2002 – retired April 2010
• Member of IFAH- Europe Biologicals WP
• Currently a consultant, mainly for GALVmed
Regulatory experience
3

4. • A not-for-profit Public-Private Partnership – registered charity
• Projects sponsored by the Bill & Melinda Gates Foundation and the UK
Government via UKAID.
• Pro-poor focus: working with key partners to make a sustainable
difference in access to animal health products for poor livestock keepers
GALVmed - GLOBAL ALLIANCE
LIVESTOCK VETERINARY MEDICINES
4

5. GALVmed’s Contribution
• Developing, registering and launching
vaccines, pharmaceutical and diagnostic
products for neglected livestock diseases
• Partnering with organisations in
developing countries to ensure
sustainable research, production and
delivery
• Educating stakeholders on the links
between livestock and poverty
• Facilitating dialogue and collaboration
in research efforts for new livestock
vaccines, medicines and diagnostic
systems
East Coast Fever vaccine
Newcastle Disease Virus vaccine
Porcine Cysticercosis vaccine
Protecting livestock, saving human lives by:
Slide 5
QC labs in Tanzania and Senegal
to check quality of trypanocides

6. COUNTRY Region COUNTRY Region
1 Algeria N 15 Burundi E
2 Egypt N 16 Comoros E
3 Morocco N 17 Djibouti E
4 Tunisia N 18 Kenya E
5 Cameroon C 19 Rwanda E
6 Congo - Brazzavile C 20 Seychelles E
7 Burkina Faso W 21 Sudan E
8 Cote D'Ivoire W 22 Tanzania E
9 Ghana W 23 Uganda E
10 Mali W 24 Angola S
11 Mauritania W 25 Botswana S
12 Nigeria W 26 Dem Rep Congo S
13 Senegal W 27 Lesotho S
14 Togo W 28 Madagascar S
29 Malawi S
30 Mozambique S
31 Namibia S
32 South Africa S
33 Swaziland S
34 Zambia S
35 Zimbabwe S
North: 4
Central: 2
West: 8
East: 9
Southern: 12
Two main activities were conducted
in 2010:
• Information on current status of
vaccine regulation through a
questionnaire sent to 49
countries.
• GALVmed-OIE-PANVAC
Workshop in South Africa on
future of harmonisation for
vaccine registration.
Baseline status of vaccine
registration in Africa
6

7. Many African countries asked for :
• Harmonised Registration system
• Mutual Recognition
• Training for their Regulators in
Registration of Veterinary Vaccines
Outcome of OIE/GALVmed
Conference in Johannesburg, 2010
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8. Capacity building:
Workshop in Nairobi, East Africa
East Africa (Nairobi – Nov 2011)
• Capacity building of regulatory authorities in charge of
vaccine registration in Africa
• First training for East Africa, in Nairobi, November 2011. 8 countries:
Djibouti, Burundi, Rwanda, Kenya, Ethiopia, Tanzania, Sudan and
Uganda.
• Activity conducted with AU-PANVAC, with contribution of OIE
• Gilly Cowan engaged to follow up activities as lead consultant.
8

9. 2011 Training Course in Nairobi
• Preceded by a Questionnaire about current status of
veterinary vaccine registration per country.
• Some represented countries already had a medicines
registration system. Some were developing the
legislation to establish a system. Others had nothing.
• Of the countries which already had a Regulatory
Authority it was recognised that their requirements for
veterinary vaccines were based on pharmaceutical
requirements.
9

10. Outcome of Nairobi Workshop 2011
• Participants identified tools required for establishing a
harmonised registration system.
• Participants volunteered to work on assignments:
- Uganda: Application Form (Elizabeth Okello)
- Kenya: Guidelines for SPC for IVMPs (Jafred
Kitaa)
- Tanzania: Collate all existing Guidelines from
participating countries (Charys Ugullum)
- Djibouti: Dossier Structure (Ibrahim Djama Ismael)
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11. Part 1
Summary
Part 2
Quality
Part 3
Safety
Part 4
Efficacy
Part 5
Particulars and
Documents
1.A: Application
form &
Annexes,
2.A: Composition,
Product
Development,
3.B1 - B3: GLP Lab
Safety, Single Dose,
Overdose, Repeated
Dose
4.B: Lab
Efficacy
(challenge)
Applicants
Summaries of Safety
and Efficacy studies
including objective
discussion of results
1.B:SPC &
Packaging
2.B: Manufacture 3.B.4-6: Other Safety
Studies
4.C: Field
Efficacy
Part 6
Bibliographical
references
1.C: Expert
Reports on
2.C: Control of SMs 3.B.7: User Safety;
residues; interactions.
C1 Quality 2.D: In-Process
Controls
3.C: Field Safety
C2 Safety 2.E: Controls on
Finished Product
3.D: Environmental
risk assessment
C3 Efficacy 2.F: Batch
consistency
3.E: GMOs
D. Benefit-Risk 2.G:Stability
Nairobi 2011
11

12. TWG formed in March 2012
Technical Working Group (TWG) formed to progress
harmonised registration of veterinary immunological products
(IVPs)
Regional representatives from 6 of the 9 countries requested
that regulators from the 3 countries with most regulatory
experience should draft the 4 Technical Documents:
• Kenya (PPB)
• Tanzania (TFDA)
• Uganda (NDA)
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13. Date Location Participants
9-12 July 2012 Dar es Salaam 6 regulators
Draft documents refined Topic leader
• Harmonised Application Form Elizabeth Okello
• Label, leaflet, SPC templates James Mbaria
• Dossier Structure Gilly Cowan
• Guideline Rosemary Aaron
Documents sent to Regulatory Authorities for comment
First Technical Working Group Meeting
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14. TWG’s Dossier Structure, Dar es
Salaam July 2012
Part 1
Administrative
Part 2
Quality
Part 3
Safety
Part 4
Efficacy
1.A
Application form
2.A: Composition 3.A.1 – A2:
Safety, Single Dose,
Overdose, Repeated Dose
4.A Lab Efficacy
1.B.1
SPC
2.B: Method of
Manufacture
3.A.3: Other Safety
Studies, e.g. Reversion to
Virulence.
4.B: Field Efficacy
1.B.2
Label and carton text
2.C: Control of SMs 3.B: Field Safety
1.B.3
Package Leaflet
2.D: In-Process
Controls
3.C: Safety to user and
environment; residues,
interactions.
Part 5
Bibliographical
references
2.E: Controls on
Finished Product
2.F: Batch consistency
2.G:Stability
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15. Held on 24-25 Oct. 2012 in Dar es Salaam
Participants: 6 regulators, Representative from DVS Kenya,
Representative from EAC
• Feedback and suggestions provided on Technical
Documents by NDA (Uganda) and TFDA (Tanzania).
• Suggestions considered and incorporated into the
Technical Documents
Second Technical Working Group
Meeting
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16. Second Technical Working Group Meeting
October 2012
• Dr. Timothy Wesonga (EAC Senior Livestock Officer)
indicated EAC would support the initiative.
• The East African Community Treaty already contains
provisions for adopting a common mechanism for ensuring
quality, safety and efficacy of veterinary vaccines.
• EAC Treaty Chapter 21, Article 108(e) on Plant and Animal
Diseases Control.
16

17. By end of meeting, TWG accomplishments were:
1. Harmonised Application Form for use in National and
Mutual Recognition Procedures (MRP)
2. Structure for a Registration Dossier for Immunological
Veterinary Products (IVPs)
3. Templates for Labels, Outer Packaging and Summary of
Product Characteristics (SPC)
4. Guideline on the requirements for each section of a
registration dossier for an IVP
Second Technical Working Group Meeting
October 2012
17

18. 2nd TWG meeting, Dar es Salaam,
October 2012
18

19. Meeting in Arusha in June 2013 with Heads of Regulatory
Authorities, DVSs, GALVmed, PANVAC, TWG and EAC:
1. The tools for harmonised registration of IVPs were
accepted and recommended for use.
2. A recommendation was made for initiating Mutual
Recognition Procedures (MRP).
• The recommendation document was signed by
representatives from all 5 Ministries of Agriculture,
Livestock, etc.
Next Step
19

20. Examples of establishing Registration
Systems
Normal sequence for development of Regulatory
Requirements
1.Human Medicines Regulations
2.Veterinary Pharmaceuticals
3.Veterinary Biologicals
20

21. Biologicals are not Pharmaceuticals!
• Question - What is the easiest option for
introducing a registration system for biologicals?
• Answer - copy/paste legislation and guidelines
directly from pharmaceutical documents.
• Consider mode of action:
- Pharmaceuticals – pharmacological
- Vaccines - immunological
21

22. Pharmaceuticals
Not necessarily
pharmaceuticals
22
What is the difference?

23. Biologicals are not Pharmaceuticals
• Molecule/Drug substance
• Pharmacology
• Pharmacokinetics
• Metabolism
• Toxicology in
Lab animals & TS
• Residues
• Withholding time
• Efficacy –
dose / kg bw
Biologicals
• Antigen (live or
inactivated)
• Not applicable
• Not applicable
• Not applicable
• Safety in Target
Species
• Not applicable*
• Zero days
• Efficacy –
Immunity/protection
Part 2 :
Active ingredient
Part 3:
Safety
Part 4
Efficacy
Dossier
*Exceptions, e.g. live zoonotic organisms
23
Pharmaceuticals

24. Meeting of Experts
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25. Progress in East Africa
• During meeting in Arusha in June 2013 Dr. David Adwok
of South Sudan adopted the TWG’s registration
procedure for immediate implementation.
• At the Regional Training meeting in Nairobi in June 2013,
Dr.Terzu Daya of Ethiopia adopted the TWG’s
registration procedure for immediate implementation.
• Later that year, the EAC requested a document
explaining how Mutual Recognition Procedures would
work.
• Provided to Sectoral Council of Ministers July 2014
25

26. Mutual Recognition Procedure for IVPs
MRP allows Marketing Authorisations to be issued without
long delays
• If no questions raised: <170 days to issue an
Authorisation
• If questions raised: <230 days to issue an Authorisation
Two types of MRP:
1. For new product applications
2. For expansion of existing Marketing Authorisations
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27. Mutual Recognition Procedure for IVPs
1. Applicant selects one EAC Member State to act as Reference Country
(RC). Coordination Group for Mutual Recognition (CGMR) is notified of
intention to request a MRP, indicating the Concerned Countries (CCs)
in which Marketing Authorisations will be sought.
2. One week before <CLOCK START> the Applicant sends dossier and
Application Form to RC and National Authorities of CCs
simultaneously.
Applicant
RC
CCs
MR Coordinator issues a calendar of critical dates for the MRP to CGMR
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28. Mutual Recognition Procedure for IVPs
CLOCK STARTS Duration
• Step 1: day 0 RC prepares Assessment Report (AR) 90 days
• Step 2: day 90 RC sends AR to CCs for review 30 days
• Step 3: day 120 If CC’s raise no objections, move to step 5
• Step 4: If CCs raise additional questions on AR, RC and Applicant
try to resolve them between days 120 - 180* 60 days
• Step 5: day 180 Applicant sends final (or revised) labels and
SPC to RC and CCs for approval 20 days
• Step 6: day 200 CLOCK STOPS
• RC and CCs issue National Marketing Authorisations 30 days
Total: if no questions – 170 days; if questions – 230 days
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29. Appeal during MRPs
Step 4: Day 180
“If CCs raise questions on AR, RC and Applicant try to resolve
them between days 120 - 180*”
Day 180* – 240 If no agreement has been reached by day
180, APPEAL is triggered.
4.1 Applicant has opportunity to generate more data and ask
for hearing by CGMR and appropriate technical experts.
4.2 CGMR take final decision by Day 240.
4.3 If decision is positive, Steps 5 and 6 are followed and
National MAs issued = 290 days to issue licence.
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30. Other Regulatory Meetings & Workshops
Location Event When
1. East Africa Nairobi Workshop 21-23 Nov 2011
2. UEMOA West Africa Workshop 8-9 Dec 2011
3. CEEAC Libreville Workshop 2-4 Oct 2012
4. EAC* Arusha Meeting 24-25 June 2013
5. EA region (9) Nairobi Workshop 27-28 June 2013
6. Inspectors Kampala Workshop 24 Sept 2013
7. ECOWAS Abuja Workshop 19-21 Dec 2013
8. Inspectors + Debre Zeit Workshop 1-3 July 2014
9. Manufacturers Lilongwe, Nairobi Dossier Training 2013 - 2014
10.Assessors Nairobi Training 4-7 May 2015
11.SADC Gaborone Meeting Planned
30

31. Recent updates:
1. The Sectoral Council of Agriculture and Food Security
adopted the Concept of Mutual Recognition Procedures
and the Terms of Reference for the Technical Working
Group (TWG) and the Coordination Group on Mutual
Recognition (CGMR) on the 5th September, 2014, in
Kigali, Rwanda.
• The decisions of the Sectoral Council of Agriculture and
Food Security were adopted by the EAC Council of
Ministers on the 28th of November, 2014 in Nairobi, Kenya
resulting in a Decision Number:
EAC/CM 30/Decision 34.
31

32. Recent updates:
2. Constitution of TWG and CGMR by the EAC
17 March 2015, in Arusha, Tanzania.
Representatives from: Burundi, Kenya, Rwanda,
Tanzania, Uganda, EAC,
PANVAC
6th TWG 18/19 March 2015
• Mock MRP rehearsed
• Publicity to Applicants and Stakeholders
needed. EAC to to seek funding for publicity to
stakeholders to give them access to Technical
Documents and MRPs.
32

33. Latest updates:
3. Joint Assessments: Workshop on Dossier
Assessment of Immunological Veterinary Products
• 4 – 7 May 2015, Nairobi
• 20 Participants from 8 East African countries
• Training provided by PANVAC and experienced
Regulators from TWG.
• After receiving training, participants invited to write
Assessment Reports on a mock dossier.
• Assessment Reports reviewed and feedback provided.
• Regulators from outside EAC requested MRP of
dossiers reviewed and approved by Regulators in EAC.
33

34. 4. Joint Inspections:
• Team of inspectors from NDA Uganda, PPB Kenya
and TFDA Tanzania planned to visited a veterinary
vaccine manufacturer to perform a joint inspection.
5. Publication of Technical Documents:
• The Guidelines and other Technical Documents are
being published by EAC Regulatory Authorities.
• Workshops proposed with Applicants and Regulators
• Applicants are expected to start requesting Mutual
Recognition Procedures in 2016.
Latest updates:
Slide 34

35. Conclusions
The value of MRP:
Accelerates availability of good quality, safe and efficacious
veterinary medicines.
Avoids duplication of assessment.
Improves predictability.
Builds trust between Regulators.
Allows rapid introduction of new
vaccines against new diseases.
The tools are now available.
Other African regions are interested in using the process.
“Thank you for your attention”
35

36. BACK UP SLIDES
Slide 36

37. VICH Guidelines relevant to Bios
GL17: Stability testing of biotechnological/biological veterinary
medicinal products (– well characterised proteins, recombinants)
GL25: Biologicals:Testing for residual formaldehyde
GL26: Biologicals:Testing for residual moisture
GL34: Testing for the detection of mycoplasma contamination
GL41: Target animal safety: Examination of live veterinary
vaccines in target animals for absence of reversion to virulence
GL44: Target animal safety for veterinary live and inactivated
vaccines (TAS)
GL50: Biologicals: harmonisation of criteria to waive target
animal batch safety testing for inactivated vaccines for
veterinary use (TABST)
Slide 37

38. MRP replaces lots of this….
Slide 38