The technologies involved in cell and gene therapy products have been widely documented in the literature and are rapidly evolving.These products can be regulated as drugs,biologics,or devices,or not regulated at all,depending on how they are manufactured and used.The novel approaches permitted by these technologies may make it difficult to determine which FDAcenters will be involved in their regulation and the FDAhas advised manufacturers to seek clarification in the early stages of development.Regulation is the same as that for biotechnology-derived products.The general requirements are described primarily in the 21CFR.The federal government has issued many general guidelines as Points to Consideror Guidancedocuments (see www.fda.gov).ICHguidance documents for many of the quality-related areas are directly relevant to qualifying cell and gene therapy products (see www.ifpma.org/ich1.html)and some of these documents are reproduced in USP25as general informational chapters.National Institutes of Health (NIH)has published Guidelines for Research Involving Recombinant DNA Molecules(see http://www4.od.nih.gov/oba/guidelines.htmlfor text of the document and its amendments)that require NIHreview of research,including clinical research or trials,conducted or sponsored by institutions receiving NIHfunding.These guidelines apply to many gene therapy products.AATBhas developed guidelines for sourcing allogeneic tissue.Public Health Service (PHS),with input from the NIH,FDA,the Centers for Disease Control and Prevention (CDC),and Health Research Services Administration (HRSA),has developed guidelines for the use of xenogeneic-derived products (Draft Public Health Service(PHS)Guideline on Infectious Disease Issues in Xenotransplantation,August 1996).In addition,ASTMis also developing standards for tissue-engineered medical products.

Cost-effective commercialization of cell and gene therapy products requires the development and validation of new methodologies to assess product quality.USPwill adopt such new methodologies when they have been properly validated.Similarly,if reference standards or reference materials are needed and available,they could be included in the USPinventory to allow comparative analysis among various clinical trials or to serve as points of reference by manufacturers of these products for raw materials,process components,and process impurities.