Dr. Pascale Poukens - Renwart - EDQM certification scheme

EDQM Certification 

Scheme 

P.Poukens-Renwart, PhD 

European Directorate for the Quality of Medicines & 

HealthCare (EDQM) 

Mumbai, 29 September 2012 

P.Poukens-Renwart, 29/09/2012 ©2012 EDQM, Council of Europe, All rights 

reserved

Summary 

•Regulatory background 

•Difference between CEP and ASMF 

•The Certification procedure role 

•The CEPs 

•Key figures 

•How to communicate with EDQM? 


reserved

Regulatory background 

For active substances in marketing authorization 

applications: 

Directives 2001/83/EC, 2001/82/EC, 2003/63/EC 

as amended, and the various quality guidelines 

give options on how to fulfil the same 

requirements 

P.Poukens-Renwart, 29/09/2012 ©2012 EDQM, Council of Europe, All rights reserved

Directive 2003/63/EC 

• In cases where a specification contained in a European 

Pharmacopeia monograph might be insufficient to 

ensure the quality of the substance (new impurities), 

the competent authorities may request more 

appropriate specifications from the marketing 

authorisation holder 

• The competent authorities shall inform the authorities 

responsible for the pharmacopoeia in question. The 

marketing authorisation holder shall provide the 

authorities of that pharmacopoeia with the details of the 

alleged insufficiency and the additional specifications 

applied 


Rationale for the use of CEPs 

• Directive 2003/63/EC: Where the active substance 

and/or raw and starting material or excipient(s) are 

the subject of a monograph of the EP, the applicant 

can apply for a certificate of suitability that, where 

granted by the EDQM, shall be presented in the 

relevant section of the Module. Those certificates of 

suitability …are deemed to replace the relevant data of 

the corresponding sections described in the Module… 

• “Summary of requirements for active substances in the 

quality part of the dossier” describes how to 

communicate the information on the active substance 

(AS) to European authorities 


NfG CHMP/QWP/297/97 rev. 1 corr 

« Summary of requirements for active 

substances in the quality part of the dossier » 

Gives three basic choices for providing 

information regarding the active substance: 

2.1. Certificate of suitability 

2.2. Active Substance Master File (ASMF) 

2.3. Full details of manufacture in Marketing 

Authorisation Application 

The information required is the same 

regardless of the procedure selected 


NfG CHMP/QWP/297/97 rev. 1 corr. 

« Summary of requirements for active 

substances in the quality part of the dossier » 

2.1 Certificate of suitability 

• requires Ph. Eur. Monograph (specific or TSE) 

• used for “existing” substances 

• “where applicable, option 2.1 has the advantage of 

generally avoiding any subsequent reassessment” 

2.2 Active substance Master File (ASMF) 

2.3 Full details of manufacture in marketing 

authorisation application 

• both procedures do not require Ph. Eur. Monograph 

• can be used for “new” and “existing” substances 


Differences between CEP & ASMF 

Scope: 

• CEP: pharmacopoeial substances only, 

-> active substances or excipients 

-> any substance with TSE risk 

• ASMF: active substances only, 

-> new or pharmacopoeial 


Comparison between CEP & ASMF procedures 

Dossier 

Additional 

data 

Link with a 

medicinal 

product 

Evaluation 

CEP procedure 

Full dossier sent directly by AS 

manufacturer to EDQM, it will be the 

holder of the CEP 

Independent from marketing 

authorization applications 

Single evaluation centralised at EDQM 

by assessors nominated by National 

Authorities / Certification Steering 

Committee 

ASMF system 

‐ Full dossier sent by AS manufacturer to 

National Authorities 

‐ Applicant’s part sent by AS manufacturer 

to MA applicant or holder of medicinal 

product 

‐ Letter of access (to be sent by AS 

manufacturer) 

In the context of a specific marketing 

authorization application or variation for 

medicinal products 

Assessment of ASMF by each national 

authority in the context of assessing a 

specific marketing authorization application 

or variation for medicinal products 

Deliverable 

Certificate including annexes 

(additional tests to be performed) 

granted to manufacturer who supplies 

a copy of it to customers (a MA holder 

using the AS) 

A Marketing Authorisation for the medicinal 

product using this particular AS 


The CEP procedure role 

• To demonstrate that the quality of a substance 

is controlled by the Ph. Eur. monograph + 

additional tests if needed (“Chemical CEP” or 

“Herbal CEP”) 

• To guarantee compliance with the Ph. Eur. 

general monograph on Products with TSE risk 

(« TSE CEP ») 


The CEP provides 

• Single centralised evaluation No duplication 

of work, avoids any potential divergences in 

assessments 

• Confidentiality of data : 

– Application submitted directly to EDQM by the 

applicant 

– Dossiers stored and assessed at the EDQM 

– Independent of any marketing authorisation 

application 


The CEP provides (cont) 

• Easier management of marketing authorisation 

applications and variations - replaces main part 

of 3.2.S 

• CEP accepted in all Ph. Eur. countries (36) + 

others (eg. Canada, Australia, New-Zealand etc.) 

Saving of time and costs for Industry and 

Licensing Authorities 


Governing document for the 

Certification procedure 

• Resolution AP-CSP (07) 1 adopted by the Public 

Health Committee of the Council of Europe 

• Describes the process for the procedure 

• Available on the EDQM website (www.edqm.eu) 


Scope of the CEP procedure 

• Substances described in monographs in the Ph. Eur. 

(Active substances, excipients, herbal drugs / herbal 

preparations) 

→ “Chemical” or “Herbal” CEP 

• Products with risk of TSE (SM, intermediates, 

reagents,..) 

→ “TSE” CEP 

• Substances described in monographs in PhEur and 

with TSE risk → “Double” CEP 

• Open to any manufacturer regardless of 

geographical origin 


Out of Scope of the Certification 

procedure 

• Substances not included in Ph. Eur (other than TSE 

substances) 

• Human tissues derivatives, blood derivatives, vaccines 

• Finished products 

• Products extracted from animal tissues: 

– List published by CMD(h)-2007 

http://www.hma.eu/uploads/media/070618.pdf 

– Ex. heparins, aprotinin,…. 

– No new application accepted (chemical evaluation) 

since end 2009 

– Still possible for a TSE CEP 


Certification: Organisation 

• Steering Committee 

• Technical Advisory Boards (TAB) 

Chemical 

TSE 

Herbals 

• Assessors 

• Certification Division 


Steering Committee 

• Representatives of main regulatory bodies (14 

members from EMA WP, EU Commission, Ph. Eur 

Commission, Non-EU licensing authorities,...) 

• Monitoring Certification procedure 

• Appointment of assessors 

• Appointment of Technical Advisory Boards (TABs) and 

their Chairperson 

• Policy adoption 

• Review and comment on issues raised by TABs 

• Co-ordination of issues between the represented 

parties 


Technical Advisory Boards (TABs) 

• Consist of experienced assessors involved in the 

CEP procedure for a substantial time 

Role: 

• To take decisions on technical matter 

• To assist assessors in case of doubt or 

disagreement 

• To prepare technical guidance 

• To identify technical/scientific problems and seek 

advice of SC 


Assessors 

– Are proposed by national authorities and 

approved by the Steering Committee. They 

come from the Licensing Authorities and are 

skilled in the relevant domain (chemical 

evaluation, TSE risk, herbal products, 

toxicologists) 

– Come regularly to EDQM premises for the 

evaluation of dossiers 

– They are also EDQM assessors who are 

appointed by the Steering Committee. 


Certification Division 

• EDQM scientific and administrative staff 

• Role : execution of the procedure and 

co-ordination 


How it works: 

Application 

To be updated : 

‐ at any change (notification, 

minor/major) 

‐ after 5 years (renewal) 

Request for inspection 

Validation at receipt 

Request for add info 

Revision of monograph 

Evaluation (2 assessors) 

+ TAB if necessary 

Refusal 

Transfer to the Ph. Eur. 

experts group 

CEP granted 

Possibility 

of hearing 

Info to 

licensing authorities 


reserved

How long does it take? 

• Applicant notified by EDQM on the assessment 

conclusion within 5 months of receipt of the 

new dossier 

• If additional information is requested, responses 

from applicant expected within 6 months 

• Responses assessed within 4 months 

• Strict procedure applied - only one request for 

additional information 

P.Poukens‐Renwart, 29/09/2012 ©2012 EDQM, Council of Europe, All rights reserved 

22

How long does it take? 

• Our performance figures are published in our 

monthly report on our website: 

• Also list other things which have changed in the 

month (suspensions etc.) 


23

How to apply for a CEP 

• Application form (for new application) 

www.edqm.eu 

– Contains tables to be filled in, statements and 

declarations to be signed 

!! Updated application form to be used for any 

application submitted from 1 September 2012 

(declaration related to sharing of reports with 

authorities, all sites + roles to be listed, re-test 

period, etc) 


24


• Dossier in English preferably (or French); 1 

copy; 

Content in compliance with: 

- Content of the Dossier for Chemical CEP : 

comparable to ASMF or 3.2.S of CTD 

- For TSE risk CEP: requirements from Ph Eur 

general text, 5.2.8 (=EU nfg) 

- Content of the dossier for herbal drugs/herbal 

drug preparations 



• Quality Overall Summary using the template 

available on the EDQM website 

• Fee: 3000 Euros 

• Electronic submissions encouraged 

(eCTD, NeeS, pdf) 


26

A CEP looks like: 


Declaration of Access 


All CEPs specify 

• Unique Reference number 

(e.g. R0-CEP 2009-001-Rev01) 

• Title: clear definition of the substance 

+ grade when necessary (e.g.. micronised, sterile,…) 

• Holder + manufacturing site(s) 

• Monograph(s) concerned 

• Starting validity date 

• Line numbering and annex details if appropriate 

• Packaging material (for recent CEPs) 

• Use or non-use of materials of animal or human origin 


And as necessary 

• Additional impurities/Solvents/Catalysts 

– With limits and methods 

• Characterisation of the grade 

– With limits and methods 

• Tests of the monograph which can be 

omitted 

• Re-test period 

– With storage conditions + packaging material 


And for a TSE certificate 

• Country(ies) of origin of animals 

• Animal and nature of tissue(s) used 

• Manufacturing process applied (when 

relevant, e.g. gelatins) 


The chemical certificate of 

suitability : 

• Certifies that the quality of a given substance 

can be suitably controlled by the Ph. Eur. 

monograph 

• - with additions if necessary (stated on the CEP) 

• It DOES NOT replace a certificate of analysis 

• It IS NOT a GMP certificate 


The TSE certificate of suitability: 

• Certifies that the substance complies with the 

EMEA NfG on minimising the TSE risk 

• It DOES NOT certify that the quality of the 

substance can be suitably controlled by the 

Ph.Eur monograph 

• It IS NOT a certificate of analysis 

• It IS NOT a GMP certificate 


When using a CEP, what should be 

addressed at the level of the MAA ? 

• In addition to supplying a copy of the full CEP 

including annexes, some items may need to be 

addressed in the marketing authorization application 

(MAA). 

• EDQM assessment is performed taking into account 

the general use of the substance. 

Specific requirements for a drug product 

should be addressed at the level of the MAA 


What should be addressed at the 

level of the MAA ? 

– Stability if no re-test period mentioned on the CEP 

(unless the MA applicant has committed to test 

the substance immediately prior to use) 

– All data relating to physico-chemical characteristics 

(e.g. particle size) if no grade claimed, or if there 

are particular requirements of the drug product 

– Viral safety if material of animal origin is used in the 

manufacture 


Revisions of a CEP 

Based on current EU Regulation on 

Variations to Marketing Applications 

Specific guidelines for revisions of CEPs: 

• Guideline on requirements for revision / renewal 

of CEPs 

• Procedures for management of revision / renewal 

of CEPs 

→ Available on the EDQM website (last version 

implemented on 1 March 2010) 


Key figures 

• > 5000 CEP applications received 

• > 3400 valid CEPs 

• 960 sites from 56 countries covered 

These numbers change frequently as new 

applications are received and existing CEPs are 

revised daily. 


Repartition of manufacturers (2011) 

1. India 214 sites 

2. China 202 sites 

3. Italy 90 sites 

4. USA 58 sites 

5. Germany 57 sites 


Communication with EDQM 

• EDQM Website (7 pages: procedure, 

guidelines, documents, news…): 

www.edqm.eu 


Communication with DCEP 

• A paper describing the ways to best 

communicate with EDQM is published 

on the EDQM web site: 


Is a CEP valid ? 

• www.edqm.eu 

Hints: 

To see all certificates, search for all 

certificate numbers containing CEP. 

In general you will get more hits with 

“contains” than “is exactly”. 

Spelling is important 


Is a CEP valid ? 

Holder name 

Full CEP number 

Issue date of the current CEP 

Status 



• General questions on CEPs: Look at the FAQs 

and if necessary use EDQM Helpdesk 



• For application specific queries: via the 

email address (included in our 

communication) 

• Technical Advice: to meet the EDQM staff 

and get advice about applications (fee) 


Thank you ! 


reserved

Dr. Pascale Poukens - Renwart - EDQM certification scheme

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