REGULATIONS, STANDARDS, AND NEW METHODOLOGIES
Summary of Regulations and Standards
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 FDA centers will be involved in their regulation and the FDA has 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 21 CFR. The federal government has issued many general guidelines as Points to Consider or Guidance documents (see www.fda.gov). ICH guidance 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 USP 25 as general informational chapters. National Institutes of Health (NIH) has published Guidelines for Research Involving Recombinant DNA Molecules (see http://www4.od.nih.gov/oba/rac/guidelines/guidelines.html for text of the document and its amendments) that require NIH review of research, including clinical research or trials, conducted or sponsored by institutions receiving NIH funding. These guidelines apply to many gene therapy products. AATB has 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, ASTM is also developing standards for tissue-engineered medical products.
Need for New Methodologies
Cost-effective commercialization of cell and gene therapy products requires the development and validation of new methodologies to assess product quality. USP will 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 USP inventory 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.