The FDA hearing to obtain comments on the four draft guidance documents relating to the regulation of human cells, tissues, and cellular and tissue-based products (HCT/Ps) occurred on September 12-13, 2016. Dr. Phyllis Warkentin, FACT’s Chief Medical Officer, spoke on behalf of FACT and presented the following comments to the FDA:
- FDA should fulfill its responsibilities to protect patients in search of cellular therapies. FACT supports our parent society, ISCT, in its position on unproven therapies and agree on the importance of providing adequate education for patients. Development of professional standards and voluntary accreditation can play an important role in providing a bridge from basic research to clinical application.
- The tiered unified approach to HCT/P regulation fails to acknowledge the complexity of some tissues with multiple native functions and many cell types. It is difficult to strictly categorize complex tissues such as adipose tissue as only structural or cellular. Possible solutions to this problem include:
- Determination of “homologous use” could be not dependent on initial categorization of the whole tissue, but allow for cells and structural elements to be considered individually. The term “such HCT/P” could then be used to apply to either the cells or the structural elements, depending on intended use in the recipient.
- The term “homologous use” could be broadened to include any function or functions performed in the donor, not only the “basic function”.
- The Agency could recognize “standard of care” exceptions for certain procedures that have long been in place without such tissue regulation; those procedures in which data exist related to practitioners, procedures, and safety. Breast reconstruction is an example of this potential exception.
- There appear to be some inconsistencies in the definitions and examples of homologous use that would benefit from clarification.
- Although various phrases are used for the definition of homologous use, such as “perform the same basic function or functions” and “perform one or more of the same basic functions,” the examples seem to ignore the concept of more than one function of a tissue.
- The following example is also confusing to many: the guidance documents consider it to be non-homologous to put adipose tissue into breast tissue, since the basic function of the breast is lactation, ignoring the role of fat in support and shape. Yet it is considered to be homologous to put islets into liver, even though the primary function of liver is not glucose homeostasis.
- FACT suggests that the Agency expand upon its expectation for cord tissue, to include which regulations apply and when they apply, based upon the processes in place. For example, cord tissue is often collected, cryopreserved, and stored as whole tissue when the future use is undetermined at collection and storage, but it is likely intended for patient treatment. To ensure this tissue is considered to be a usable starting material in the future, the current regulatory pathway is unclear. In contrast, cord tissue may be significantly processed after collection, prior to cryopreservation and stored with the clear intent to use as MSCs or other product for an undetermined recipient.
- International harmonization is important to facilitate product development and world-wide availability of cell-based therapies for patients.
Dr. Warkentin’s full presentation is available online.