Human therapeutics include all products that transmit and unfold their effect through transcription or translation of transferred genetic material or through targeted modification of host/human gene sequences. Examples would be nucleic acids, genetically modified viruses, bacteria or fungi, artificially produced specific nucleases for processing the human genome or ex vivo genetically modified human cells. If these products are applicable for the prevention, treatment or cure of a disease or human condition, they are, by definition, "biological products" under 351(i) of the Public Health Service (PHS) Act (42 U.S.C. 262(i)).
For all submissions of new medicinal products (DPs), including gene therapy products, the description of the CMC information for the drug substance is required. In the event that the IND does not contain sufficient CMC information to assess the risks to subjects in the proposed studies, the FDA may put the IND on a clinical halt.
The CMC information submitted in an IND is mandatory. If there are changes in manufacturing during product development, these information changes must be submitted to complement CMC processes. If the effects of a change on product safety and quality are possibly not known, e.g. because the information submitted for Phase 1 was still limited in scope, the manufacturing change should be submitted prior to implementation.
Human gene therapy aims to modify the expression of a gene or to manipulate the biological properties of living cells for therapeutic purposes. With this document, the FDA seeks to make recommendations regarding the information to be provided on Chemistry, Manufacturing and Control (CMC) when submitting a Human Gene Therapeutic Investigational New Drug Application (IND). That way it can be ensured that and how sufficient CMC information necessary to warrant the investigational medicinal product's safety, identity, quality, purity and potency (including efficacy) can be provided according to 21 CFR 312.23(a)(7)(i).
This Directive applies to human gene therapy medicinal products and to combination products containing human gene therapy in combination with a medicinal product or device. The final guideline will replace the previous document "Guidance for FDA Reviewers and Sponsors: Content and Review of Chemistry, Manufacturing, and Control (CMC) Information for Human Gene Therapy Investigational New Drug Applications (INDs)," from April 2008. Due to the rapid and comprehensive development of the gene therapy sector since 20018, an update of the FDA recommendations was urgently needed. The guideline is now structured to follow the structure of the FDA's Common Technical Document (CTD) guidelines. Information on the CTD can be found in the "Guidance for Industry: M4Q: The CTD - Quality" from August 2001.