FDA: cGMP expectations in Pharmaceutical Development

In the EU, GMP-Guidance for investigational medicinal products (IMPs) is mainly defined in Annex 13 (Manufacture of Investigational Medicinal Products) of the EU Guidelines to GMP. This annex is considering special aspects of IMP manufacturing and the challenges with the complexity of this topic.

In their Code of Federal Regulations (CFR), the FDA has not defined special GMP-requirements for so called investigational drugs (INDs), except for NDA and INDA application procedure (21CFR Part 312 and 314).

Section 501(a)(2)(B) of the FD&C Act (21 U.S.C. 351 (a)(2)(B)) requires drugs, which include IND products, to comply with current good manufacturing practice (cGMP). Based on the statutory requirement for manufacturers to follow cGMP, the FDA issued cGMP regulations for drug and biological products (the 21 CFR parts 210 and 211). The FDA stated at the time of issuance that the regulations applied to all types of pharmaceutical production. Because certain requirements in part 211 were directed at the manufacture of products typically characterised by large, repetitive, commercial batch production (e.g., those regulations that address validation), they may not be appropriate to the manufacture of most investigational drugs. Therefore the preamble to the regulations indicated that FDA was considering proposing additional regulations governing drugs used in investigational clinical trials.

In July 2008, the FDA has then issued the Guidance for Industry: cGMP for Phase 1 Investigational Drugs, replacing the guidance issued in 1991 titled Preparation of Investigational New Drug Products. The intention of this document is to assist in applying cGMP in the manufacture of most investigational new drugs used in phase 1 clinical trials.

However there is still a big gap of cGMP requirements and expectations for Phase 1 investigational drugs and those of Phase 2 and 3. And in reality development of investigational drugs is more or less a continuous process. This might cause uncertainties in pharmaceutical industry while developing new drugs.

FDA-expectations from Phase 1 to Scale-up and Transfer are explained by Mark Tucker, a former FDA Investigator and Compliance Officer at the ECA Education Course GMP- and FDA-Compliance in Pharmaceutical Development and IMP Manufacturing in Prague, Czech Republic, from 24-25 September 2009 covering aspects like

  • Regulatory background: CFR and relevant guidelines
  • Particularities
  • IMP import and export
  • FDA Pre-Approval Inspection (PAI)

Compiled by
Wolfgang Schmitt
On behalf of the European Compliance Academy (ECA)

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