CEP Procedure - AGES

Österreichische Agentur für Gesundheit und Ernährungssicherheit GmbH www.ages.at

Dr. Wolfgang Herzog Abteilung Arzneimittelqualität

AGES Gespräch

Wien, 24.06.2014

CEP Procedure

www.ages.at 2 Wolfgang Herzog, 24.06.2014

Documentation of Drug Substance

•Active Substance Master File (ASMF)

• Certificate of Suitability (CoS/CEP)

• Full Documentation as part of the MA application


Council of Europe

• is a non-EU organisation of 47 states:

- 47 European states (> 800 million people)

- 1 applicant: Balearus (suspended)

- Observers: Holy See, U.S., Canada, Japan, Mexico, Israel

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Council of Europe


Council of Europe

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Certificate of Suitability (CoS/CEP)*

Purpose of the procedure

•Facilitating and simplifying exchanges between the partners to ensure that the quality of substances is guaranteed

•These substances comply with the European Pharmacopoeia

•Promote free movement of medicines



The CEP provides • Single centralised evaluation • Easier management of marketing authorisation – CEP replaces main

part of 3.2.S

• CEP accepted in all Ph. Eur. countries (36) + others (eg. Canada, Australia, etc.)

• Access to information on the need to revise monographs

• → Saving of time and costs for Industry and Licensing Authorities



Excluded from the Application:

•Direct gene products (proteins)

•Products obtained from human tissues, vaccines and blood products and preparations

• „other biological substances“ (see list of CMD(h))


Biological Substances!!!!!

• The characterisation and determination of biological active substances’ quality requires not only a combination of physico-chemical and biological testing, but also extensive knowledge of the production process and its control.

• The MAH/applicant for a biological medicinal product could therefore not comply with the requirement to ‘take responsibility for the medicinal product’ without having full and transparent access to these quality-related data. The use of an ASMF would prevent such access, and should therefore not be allowed for biological active substances.

Not in the Scope :



•98 Assessors (08/01/2014): Chemical evaluations (83), TSE (7), Toxicology (1), Herbal drugs (7)

Coming from 18 EU/EEA member states, plus Switzerland, Canada; Serbia and WHO

•29 Inspectors: from 13 EU/EEA member states and WHO

A large network of experienced people is driving the scheme!!!


Application types

- Simple certificate (chemical or TSE or herbal product)

- Certificate for chemical purity and sterility

- Double certificate (chemical and TSE)

- Double certificate (chemical and TSE) covering also sterility


Overview of the procedure

- Submission of the dossier

- Acknowledgement of receipt

- Designation of a rapporteur

- Assessment

- Notification of the decision

- Follow up the Certification of Suitability


Submission of the dossier

Manufacturer

- submits 2 copies of a dossier in English (preferably) or French

- declares that the manufacture of the substance in question takes place in accordance with

- a specified guideline on GMP

- the dossier presented

- declares its willingness to be inspected


Designition of a rapporteur

- Secriteriat designates a rapporteur and co-

rapporteur

- Confidentiality agreement and declaration of

interests are signed by them

- Examination of the dossier submitted and

preparation of a report in three parts


Assessment

- Preparation of a report in three parts:

- Report A or „Confidential report“

- Report B or „Request for revision of the monograph“

- Report C or „Comments for the inspectors“


Assessment

- Directives 2001/83/EC and

2001/82/EC as amended

- The monographs of the Ph. Eur. are mandatory

- Evidence that the quality of the material is suitably controlled by monograph

- Otherwise any additional impurity to be limited

- In case of doubt the relevant technical advisory board is consulted


Conclusion of the Assessment

- The certificate of suitability can be granted:

- - The monograph is able to control the quality of the substance and/or the substance meets the criteria of the monograph Products with risk of transmitting agents of animal spongiform encephalopathies

- - The monograph is not able fully to control the quality of the substance, but the information provided nevertheless guarantees that the quality of the substance is adequately controlled (note: not applicable for TSE risk assessment)


Conclusion of the Assessment

- The certificate of suitability can not be granted (yet*):

- - The information supplied is incomplete and does not allow a conclusion*

- - The monograph is not suitable to control the quality of the substance or an agreement on testing methods for (a) given impurity (ies) or an agreement on the TSE risk assessment has not been reached

o *two-round policy since September 2008


Follow up the CEP

- Any significant change must be reported and will be reassessed Update of the Certificate

- Revision of the monograph Update the dossier and revision of the CEP

The CEP will be renewed at least after a 5-year period on the basis of re-evaluation of an updated dossier!

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Knowledge Database

20 Wolfgang Herzog, 24.06.2014


Certificate of Suitability (CoS/CEP)

Documentation in the MA application:

- Copy of the CoS has to be enclosed

- Declaration of Access (not mandatory!)

- GMP Declaration from the Qualified Person of the Batch Releaser and Manufacturer


Certificate of Suitability (CoS/CEP)

Documentation in the MA application: - Specification of the FP-Manufacturer (with additional

Parameters e.g. physical-chemical characteristics such as particle size)

- Reference standards or materials relating to the product manufacturer

- Stability Data (if no re-test period is mentioned on the CEP)

Österreichische Agentur für Gesundheit und Ernährungssicherheit GmbH www.ages.at

Dr. Wolfgang Herzog Abteilung Arzneimittelqualität

AGES Gespräch

Wien, 24.06.2014

Thank You!

Documents

CEP Procedure - AGES