Already in January 2006, the FDA published the draft of a Guidance for Industryintended to describe in detail the special cGMP requirements on the manufactureof investigational medicinal products for phase 1 in connection with acorresponding adaptation of 21 CFR 210 and 211. This guidance was meant to giveassistance to the manufacturers in implementing the then planned legalrequirements
However, after the FDA had encountered considerable contradiction to the plannednew regulations, the planned changes to the CFR were withdrawn, and, for themoment, the draft guidance was abandoned.
Now the FDA is making a new attempt to implement the changes. According to theauthority, the proposals of that time have been taken into account and thedocuments, adapted correspondingly. The note in the Federal Register of 15 July2008 (Volume 73, No. 136) announces the adaptation of 21 CFR 210 and 211:Investigational medicinal products intended for use in phase 1 are to beexempted from complying with the "final rule". The text stresses that the cGMPrequirements of 21 CFR 211 are applicable to phase 2 and phase 3 drugs. Thechanges are scheduled to come into force on 15 September 2008:http://www.fda.gov/cber/rules/gmpind.pdf
At the same time the revised Guidance for Industry was published under a newtitle. The document now titled "Guidance for Industry: cGMP for Phase 1Investigational Drugs" describes FDA's proposals and expectations regarding themanufacture and control of phase 1 investigational medicinal products. Most ofthe changes are of editorial character and aim at harmonising and clarifying thewording as well as avoiding possible misunderstandings. Apart from that, thelevel of details has been raised. Instead of just listing the exemptions, thescope has now been defined exactly; it refers to, but is not limited to, thefollowing products:
- Investigational recombinant and non-recombinant therapeuticproducts
- Vaccine products
- Allergenic products
- In vivo diagnostics
- Plasma derivative products
- Blood and blood components
- Gene therapy products
- Somatic cellular therapy products (includingxenotransplantation products).
Products derived from human cells and tissue continue to beexempted.
Examples for increased or more detailed requirements comparedto the draft of 2006 are:
- Environmental monitoring
- Separation of quality control and production
- Deviations and appropriate investigations
- SOPs in the fields of packaging, labelling and shipment
The new FDA Guidance can be found here:
On behalf of the European Compliance Academy (ECA)