Austrian Agency for Health and Food Safety www.ages.at

ASMF – Worksharing Procedure

AGES Gespräch 8 November 2016 Authorisation of Veterinary Medicinal Products (VMPs): an Update DI Susanne Stotter AGES MEA

frequent ASMF

updates (at NCA request)

high administrative

burden reduced

oversight of the ASMFs

duplicated scientific work

divergent decisions

increased workload (for all parties)

Active Substance Master File Assessment issues identified …

inconsistency in ASMF

assessment

2

one ASMF multiple procedures

multiple Member States

ASMF Assessment Worksharing Procedure pilot phase – key facts

A simple way for Competent Authorities to share assessment reports for the same version of the Active Substance Master File

Development of a procedure for Active Substance Master File Assessment Worksharing

Pilotphase

started 1st

December 2013

initially limited for

12 months

scope intentionally limited to

new ASMFs in DCP/CP

voluntary participati

on

3

reduction of workload

ASMF&MHholder

&CA

improvement oversight of

ASMFs

harmonisation of ASMF

assessment

within existing legislation and

regulatory procedures

no impact on procedure timings

ASMF Assessment Worksharing Procedure identified requirements …

… ability to identify conclusively where the same version of the ASMF is submitted in different procedures in Europe …

• the EU/ASMF numbering system for ASMFs (see Appendix 1)

• the Submission Details Form of CPMP/QWP/227/02 Rev 3/ EMEA/CVMP/134/02 Rev 3 Guideline on Active Substance Master File Procedure (http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2012/07/WC500129994.pdf)

• the ASMF-AR repository for NCAs

4

identified requirements …

EU Numbering System for ASMFs (1)

EU ASMF XXXXX YYYY

reference number ASMF

sequential number

independent from ASMF

holder

assigned by ASMF

repository

sequential Assessment

Report number/change

number assigned by ASMF holder

for new regulatory updates

0001 corresponds to the initial assessment of the ASMF

5

identified requirements …

EU Numbering System for ASMFs (2)

• EU/ASMF/XXXXX/0001 - initial ASMF (AP & RP) Applicant’s Part version: ABC/AP/01/2012-01-28 Restricted Part version: ABC/RP/01/2012-01-28 • EU/ASMF/XXXXX/0002 – updated AP Applicant’s Part version: ABC/AP/02/2012-04-10 Restricted Part version: (ABC/RP/01/2012-01-28) • EU/ASMF/ XXXXX /0003 – updated RP Applicant’s Part version: (ABC/AP/02/2012-04-10) Restricted Part version: ABC/RP/02/2012-10-16 • EU/ASMF/ XXXXX /0004 – updated AP & RP Applicant’s Part version: ABC/AP/03/2013-01-14 Restricted Part version: ABC/RP/03/2013-01-14

6

identified requirements …

Submission Letter and Administrative Details for documents relating to an ASMF (ASMF Submission Details Form) … standardisation of administrative information

(revision CHMP/CVMP Guideline on the Active Substance Master File procedure (CHMP/QWP/227/02 Rev 3; EMEA/CVMP/134/02 Rev 3)

o ASMF Submission Details Form (e.g. ASMF holder, manufacturing sites, list of procedures where the ASMF is used)

o The Annex 2 Letter of Access template was amended so that the ASMF holder acknowledges that the EEA National Competent Authorities, the EMA including all CHMP and CVMP Members and their experts, and the Certification of Substances Division of the European Directorate for the Quality of Medicines & Healthcare may share ASMF assessment reports amongst themselves.

o Lastly, at the request of Interested Parties/Industry, a Withdrawal of Access (to the ASMF) Letter was included as Annex 4, marking the end of the regulatory obligations of Applicants/MAHs concerning the ASMF.

7

identified requirements …

Assessment report templates

stand alone common Assessment Report template

easy upload/download from the EU/ASMF

repository

structured according CTD

templates

facilitates easy sharing among CAs

„add-on“ Assessment

Report

use appropriate national

assessmemnt report templates

ASMF in „old“ NtA structure

8

identified requirements …

EU/ASMF Repository for Worksharing Assessment Reports (1)

EU/ASMF repository for worksharing assessment reports https://asmf.cts-mrp.eu/

currently for ASMF

Assessment Reports

for associated administrative information ASMF

holder

manufacturing site

ASMF version

Procedures using ASMF

24 hours access

CHMP/CVMP and their experts NCAs

EDQM

9

identified requirements …

EU/ASMF Repository for Worksharing Assessment Reports (2)

10

identified requirements …

EU/ASMF Repository for Worksharing Assessment reports (3)

ASMF Assessment Worksharing Procedure

pilot phase - principles

12

13

pilot extended for further 12

months

designition of parent RMS

appears working well

reserving EU/ASMF number working

well

„Blockbuster

drugs“ would significantely

increase uptake

mandatory worksharing has been considered

ASMF Assessment Worksharing Procedure pilot phase – lessons learned February 2015

widening of scope has

been considered

cooperation with industry, NCAs, QWP to gain feedback

Lessons learned February 2015

uptake has

increased over the

year

CTS helpdesk provides support

• ASMF - WG agreed to publish a questionnaire to seek feedback on the pilot after two years

• Questionnaires circulated in February to March 2015

• Questionnaires were sent to

- ASMF holders taking part in WS pilot & Interested Parties (AESGP, EFPIA, EGA, EUCOPE, APIC/CEFIC, IFAH, EGGVP)

- National Competent Authorities & EMA

• Responses

- Interested Parties: 28

- Competent Authorities: 21

• ASMF-AR repository was audited

ASMF Assessment Worksharing Procedure pilot phase – results questionnaire May 2015

14

• The EU/ASMF reference number request form and process is working well - 75% numbers are issued within 9 days

- “10 days or longer”: difficult to say whether all were within target

• Majority of Interested Parties had a good/neutral experience in the First Assessment stage

- 15% had a poor experience and 20% experienced difficulties

• 90% of IP would use the worksharing procedure again

• 70% would recommend the procedure to others

• Good outcome, but room for improvement

ASMF Assessment Worksharing Procedure pilot phase – summary results questionnaire May 2015

Industry

15

• The EU/ASMF reference number request form and process is working well - 60% numbers are issued within 9 days

- Again “10 days or longer”: difficult to say whether all were within target

• Some issues with the repository

- New system and database, bugs were encountered

- Recently undergone a major update to fix most of the issues

- Guidance is being developed on how to use the repository and complete the records

- CTS Helpdesk continues to provide support and quickly resolve issues

ASMF Assessment Worksharing Procedure Pilot Phase – summary results questionnaire May 2015

Competent Authorities (1)

16

• Issues were raised over identification of the Parent Procedure and the QA step - Repository update should make identification of Parent Procedure easier

- Unforeseen issue with ASMF used in two Centralised Procedure with same timetable

- Worksharing procedure is being revised

• Standard file nomenclature was considered necessary but was not implemented in practice

• 80% of Competent Authorities did not experience any difficulties with the assessment as a result of the worksharing procedure

• 65% of Competent Authorities were aware of training material/guidance for CA and Industry

- Provided at the beginning of the pilot, but slow uptake prevented implementation

- Needs repeating

ASMF Assessment Worksharing Procedure Pilot Phase – summary results questionnaire May 2015

Competent Authorities (2)

17

update ASMF user guide

development of a guidance how

to use the repository

widening the scope of

the ASMF worksharing to

authorised ASMFs

start the discussion about

stand alone assessment of

ASMFs

Active Substance Master File Assessment way to proceed …

preparation of a second training

session refresher training

18

clarification of selection of parent procedure

next steps in/to the worksharing procedure

revision of procedural guidance

recommended to

adopt the pilot as a formal procedure by

CxMP, CMDx and HMA

improve flexibility

dealing with ASMF

updates