|
The revision of the Note for
Guidance on Chemistry of the New Active Substance (CPMP/QWP/130/96/Rev1)
can be read from two points of view: At first sight it is a news
regarding the dossier requirements for new active substances in accordance
with the Common Technical Document. From another point of view the
document gives a definition of an API starting material. That is no new
aspect and no topic of the revision – but in view of the fact that the
ICH Q7a 'GMP Guide for Active Pharmaceutical Ingredients' is published as
Annex 18 to the EC-GMP-Guide, this aspect should be given special emphasis
with regard to regulatory compliance in API manufacture.
In order to understand the meaning of the
above-mentioned revised NfG, please find some background information
regarding the granting of a marketing authorisation and the CTD (Common
Technical Document) below:
According to the Directive 65/65/EEC, no
medicinal product may be placed on the market of a Member State unless a
marketing authorisation has been issued by the competent authorities of
that Member State.
According to Directive 75/318/EEC the
particulars and documents accompanying an application for marketing
authorisation should be presented in four parts (Part 1: Summary of the
dossier, Part 2: Chemical, pharmaceutical and biological testing of
medicinal products, Part 3: Toxicological and pharmacological tests; Part
4: Clinical Documentation) in accordance with the requirements set out in
the Annex of Directive 75/318/EEC and taking account of the guidance
published by the Commission in The rules governing medicinal products
in the European Community.
Part 2, section C ('Controls of Starting
Materials') of the Annex to Directive 75/318/EEC is concerning the data
required for the 'starting materials', which means all the constituents of
the medicinal product and, if necessary, its container.
Further details regarding the data
required for active substances for marketing authorisation are laid down
in the Note for Guidance on Summary of Requirements for Active
Substances in Part II of the Dossier (CPMP/QWP/297/97). For new
chemical active substances, the requirements are set out in the
above-mentioned revised CPMP guideline Note for Guidance on Chemistry
of the New Active Substance (CPMP/QWP/130/96/Rev1), for
biotechnologically-derived new active substances, the requirements are
described in the guidelines in Volume III of The Rules Governing
Medicinal Products in the European Union and in the European
Pharmacopoeia.
In order to reduce time and resources
used to compile applications for the registration of human pharmaceuticals
and to simplify the exchange of regulatory information among regulatory
authorities, the Expert Working Group on Quality of the International
Conference on Harmonisation of Technical Requirements for Registration of
Pharmaceuticals for Human Use (ICH) has developed a guideline for a common
format for the technical documentation, a Common Technical Document (CTD).
The Common Technical Document was first proposed in July 1995, the first
concept paper was written in 1996, in November last year the CTD was
released at step 4 of the ICH procedure. The implementation of the CTD is
mandatory from July 2002.
Therefore, the Note for Guidance on
Chemistry of the New Active Substance (CPMP/QWP/130/96/Rev1) has been
prepared in accordance with the new format of the dossiers for marketing
authorisation, the Common Technical Document (CTD). In this document the
subheadings of the CTD have been included for the sake of clarity. The
deadline for comments is 30 June 2002.
Now another aspect mentioned in the NfG:
The revised Note for Guidance on
Chemistry of the New Active Substance (CPMP/QWP/130/96/Rev1) gives a
definition of an active substance starting material. That is no new aspect
and no topic of the revision – but in consideration of the fact that the
ICH Q7a 'GMP Guide for Active Pharmaceutical Ingredients' is published as
Annex 18 to the EC-GMP-Guide, this aspect should be given special emphasis
with regard to regulatory compliance in API manufacture.
According to Annex 18, GMP for APIs
applies to the steps after the introduction of the defined 'API Starting
Material' into the process. An 'API Starting Material' according to ICH
Q7a is (…) a raw material, intermediate, or an API that is used in
the production of an API and that is incorporated as a significant
structural fragment into the structure of the API. An API Starting
Material can be an article of commerce, a material purchased from one or
more suppliers under contract or commercial agreement, or produced
in-house. API Starting Materials normally have defined chemical properties
and structure (…)'.
According to this NfG the intermediate
and/or substance considered as active substance (AS) starting material
should be proposed and justified by the applicant. The AS starting
material should be fully characterised according to identity and purity.
In addition, the steps prior to the step where the starting material
appears should be provided in the form of a flow chart in order to make it
possible for the assessor to judge the adequacy of the choice and
specifications of the AS starting material. '(…) Generally the full
description of the process should cover all the synthetic steps critical
for the safety (impurities) and the efficacy (structural part responsible
for the activity) of the active substance (…)'.
With this, the Note for Guidance gives
some more detailed information on the API starting material than ICH Q7a
and can therefore help to define the 'API starting material' with regard
to the regulatory compliance of the process.
For more details, the complete Note
for Guidance on Chemistry of the New Active Substance
(CPMP/QWP/130/96/Rev1) can be downloaded from the EMEA homepage. Download
link
We recommend:
ICH
Q7a Training (with 3 former ICH Q7a Members)
Writer:
Dr Barbara Jentges, CONCEPT HEIDELBERG
|
