8/9 December 2020
GMP News No. 424
27 May 2004
New FDA Draft Guidanceson
In Europe, new drug applications have to be submitted according to the CTD(Common Technical Document) format since 01 July, 2003. This is notmandatory in the US, where dossiers can be submitted in the CTDformat. It should be emphasized that the CTD (1) only describes aharmonized format of the dossier; it does not give any advice orrecommendation regarding the content of the dossier, as to which there arestill different regional requirements.
In order to provide recommendations on the chemistry, manufacturing,and controls (CMC) information structured to facilitate the preparation ofapplications submitted in the CTD format, it was necessary to revise the Guidelinefor submitting supporting documentation in drug applications for themanufacture of drug substances and the Guideline for submittingsupporting documentation in drug applications for the manufacture of drugproducts (2,3).
In January 2003 the 'Drug Product-Guideline (‚Guidance forIndustry, Drug Product: Chemistry, Manufacturing, and Controls Information',Draft Guidance, January 2003 (4)) was revised, in January 2004 the draftof the ‚Drug Substance Guidance' was published for comments (‚Guidancefor Industry, Drug Substance: Chemistry, Manufacturing, and ControlsInformation', Draft Guidance, January 2004, (5)). Both guidancesprovide recommendations on the chemistry, manufacturing, and controls(CMC) information to be submitted for drug substances and drug products toensure 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 thedrafts Drug Substance- and the Drug Product-Guidance are being compared(see Table 1).
Especially the draft of the Drug Substance Guidance causes seriousconcerns when compared to the other drug-substance-relevant guideline, theICH Q7a Good Manufacturing Practice Guide for Active PharmaceuticalIngredients. It seems that the new draft is not in line with ICH Q7a– especially with regard to the definitions given there (e.g. thedifferent wordings of the active moiety that is called 'Drug Substance' inthe new draft of the Drug Substance Guidance, but is called 'activepharmaceutical ingredient' in ICH Q7a) – nor with FDA's currentrisk-based philosophy. On the whole, it seems that the requirementsdefined in the draft of the Drug Substance Guidance are stricter thanthose defined before.
It will be interesting to see if and what kind of industry's commentswill be considered by the authorities.