Draft Guidance, Current Good Tissue Practice (CGTP) and Additional Requirements for Manufacturers of Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps)

Re: Docket No. FDA-2008-D-0659. Current Good Tissue Practice (CGTP) and Additional Requirements for Manufacturers of Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps)

Dear Sir/Madam:

The Biotechnology Industry Organization (BIO) thanks the Food and Drug Administration (FDA) for the opportunity to submit comments on the draft guidance Current Good Tissue Practice (CGTP) and Additional Requirements for Manufacturers of Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps). BIO represents more than 1,200 biotechnology companies, academic institutions, state biotechnology centers and related organizations across the United States and in more than 30 other nations. BIO members are involved in the research and development of innovative healthcare, agricultural, industrial and environmental biotechnology products, thereby expanding the boundaries of science to benefit humanity by providing better healthcare, enhanced agriculture, and a cleaner and safer environment.

GENERAL COMMENTS In general, the draft guidance contains appropriately detailed and useful information for manufacturers of human cells, tissues, and cellular and tissue-based products (HCT/Ps). To enhance the current draft, we have the following recommendations:

a) Differentiation among product types

To ensure clear interpretation and rational nomenclature, we encourage FDA to ensure the recommendations in the Guidance are appropriate to the intended audience, i.e., establishments that must comply with Current Good Tissue Practice (CGTP) requirements under 21 CFR part 1271, subparts D and E. For example, at times the draft seems to use language that is more appropriate to the traditional hematopoetic cells or tissue based products that are infused to approximately 1-100 different recipients. However, novel cell-based products currently in development could reach thousands to millions of recipients (please see our comments regarding the phrase “final disposition” in section c) below). This is one of many differences among product types that should be reflected and addressed in this and future guidance documents.

b) Cross-referencing of other applicable guidance

We recommend that existing guidance/regulations be referenced in the appropriate sections and included in Section XXIV. For example, Section XIII provides information related to processing and testing to avoid pathogenic microbial organisms but lacks cross-reference to guidance(s) providing information regarding appropriate testing for adventitious agents, including viruses and mycoplasma, e.g. “Guidance for Human Somatic Cell Therapy and Gene Products,” March 1998. As another example, Section XXII pertains to adverse event reporting and should reference “Guidance for Industry, MedWatch Form FDA 3500A: Mandatory Reporting of Adverse Reactions Related to Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps)”.

c) Specificity regarding the establishment and maintenance of a quality program, training (Section V, G)

The draft guidance states that “personnel involved in activities related to core CGTP requirements have proper training, education and experience to perform those activities” (p. 15), but would benefit from more specificity. For example, the document states that it is the responsibility of the sponsor to investigate and investigations of adverse events where there is an allegation of the transfer of a communicable disease from donor to recipient, but does not indicate the training required to perform such investigations. For allogeneic products, there is a high price to be paid for inadequately performing these investigative functions, as thousands of patients may be exposed to a communicable disease from one donor. The responsibility for diagnosis or investigation of a communicable disease from donor to recipient should fall upon a qualified physician, and preferably upon a physician with specialty board certification in Family Practice or Internal Medicine or with sub-specialty board certification in Infectious Diseases and who has adequate knowledge of relevant federal regulations and guidance.

d) Tracking (Section XX)

This section places substantial responsibility on the manufacturer. We request further clarity regarding the scope of the manufacturer‟s responsibility in relation to other entities involved in the manufacturing process. Specifically, we recommend that the guideline clarify that each entity performing a step in the manufacturing process must create and verify its tracking system, and develop a compliant process. In addition, we note that the meaning of the phrase “final disposition”, as used in this section, is unclear. If this section is making a recommendation to track every treated patient, this would raise major concerns regarding protection of patient privacy. Furthermore, the number of patients that would need to be tracked for a mature product would be very high; for cell therapy products, the number of patients for whom prescription data would have to be managed over the life of the product could be on the order of millions of recipients. We request FDA to clarify that “final disposition” does not mean that every treated patient must be tracked by the manufacturer.

CONCLUSION BIO appreciates this opportunity to comment on the draft guidance Current Good Tissue Practice (CGTP) and Additional Requirements for Manufacturers of Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps). We would be pleased to provide further input or clarification of our comments, as needed.

Sincerely,

/s/

Sara Radcliffe Vice President, Science & Regulatory Affairs

Biotechnology Industry Organization