GMP News No. 424
27 May 2004
New FDA Draft Guidances
In Europe, new drug applications have to be submitted according to the CTD (Common Technical Document) format since 01 July, 2003. This is not mandatory in the US, where dossiers can be submitted in the CTD format. It should be emphasized that the CTD (1) only describes a harmonized format of the dossier; it does not give any advice or recommendation regarding the content of the dossier, as to which there are still different regional requirements.
In order to provide recommendations on the chemistry, manufacturing, and controls (CMC) information structured to facilitate the preparation of applications submitted in the CTD format, it was necessary to revise the Guideline for submitting supporting documentation in drug applications for the manufacture of drug substances and the Guideline for submitting supporting documentation in drug applications for the manufacture of drug products (2,3).
In January 2003 the 'Drug Product-Guideline (Guidance for Industry, Drug Product: Chemistry, Manufacturing, and Controls Information', Draft Guidance, January 2003 (4)) was revised, in January 2004 the draft of the Drug Substance Guidance' was published for comments (Guidance for Industry, Drug Substance: Chemistry, Manufacturing, and Controls Information', Draft Guidance, January 2004, (5)). Both guidances provide recommendations on the chemistry, manufacturing, and controls (CMC) information to be submitted for drug substances and drug products to ensure continued product quality. The guidances are related to Module 3, Quality, of the CTD (6). In Table 1 the chapters of CTD, Module 3 and the drafts Drug Substance- and the Drug Product-Guidance are being compared (see Table 1).
Especially the draft of the Drug Substance Guidance causes serious concerns when compared to the other drug-substance-relevant guideline, the ICH Q7a Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients. It seems that the new draft is not in line with ICH Q7a especially with regard to the definitions given there (e.g. the different wordings of the active moiety that is called 'Drug Substance' in the new draft of the Drug Substance Guidance, but is called 'active pharmaceutical ingredient' in ICH Q7a) nor with FDA's current risk-based philosophy. On the whole, it seems that the requirements defined in the draft of the Drug Substance Guidance are stricter than those defined before.
It will be interesting to see if and what kind of industry's comments
will be considered by the authorities.
|At this year's 7th APIC/CEFIC European Conference on Active Pharmaceutical Ingredients (held in Lisbon / Portugal from 20-22 October 2004) the revision of the Drug Substance Guidances will be one of the topics. Dr. Guirag Poochikian, FDA, will give a lecture about 'An update of FDA CMC Guidances Drug Substance and BACPAC II' (Friday, 22 October 2004, 08.00-09.00h). Please click here for further information about the conference.|