Industry representatives expressed both praise and concern over the FDA's proposed tiered approach to regulating cellular and tissue-based products.
In a meeting designed to solicit public comment, industry representatives praised the agency for taking a rational approach to regulating tissues while noting the current regulations may produce a confusing and potentially over-burdensome regulatory environment.
"Genzyme congratulates FDA on their proposed new approach and believes it is a thoughtful unified approach to regulating traditional and new products," said Lisa Raines, vice president of government relations for the Cambridge, Mass., company. However, Raines maintained that some of the requirements "are at odds with the agency's aim to provide only the oversight necessary to protect public health."
The agency's current regulatory framework results in a confusing patchwork of regulations for stem cells, leukocytes, bone and other tissue-derived products and fails to provide clear issues that companies must consider for product development or clear regulatory issues for the agency.
Standards Of Practice Needed
The FDA published a proposed set of guidelines in the Federal Register Feb. 28 that focuses the level of agency oversight with an eye to preventing transmission of infectious disease, preventing improper handling of tissue-derived products that might contaminate or damage tissues, and ensuring that clinical safety and effectiveness are demonstrated for highly processed tissues.
The agency has no infectious disease testing requirements for tissues that are removed and transplanted back into the same person during a single surgical procedure. For tissues intended to be used at a later time in the same individual, the agency is recommending but not requiring that the tissues be tested for diseases like HIV and hepatitis in order to protect health workers. The agency has the same standards for the reproductive tissues of sexually intimate partners.
Tissues meant for allogeneic transplantation (into another person) would be required to be tested for infectious disease.
Tissues that test positive for infectious disease could still be used in autologous transplants and for closely related family members as long as prior written consent has been obtained.
"The agency will not interfere between a patient and their family and their doctor," Deputy FDA Commissioner Mary Pendergast said.
The agency intends to establish Good Tissue Practices (GTP) requirements based on current industry standards to ensure that tissue is not contaminated during banking and handling. All tissues used for transplant and therapy will fall under GTP guidelines.
Companies would only have to seek FDA approval for tissue-derived products should the tissue undergo "more than minimal manipulation," be used for a non-homologous purpose, or be used for a metabolic rather than structural purpose.
However, the definitions used to determine the level of regulation create murky waters in which companies must navigate product development.
Thomas McKearn, CEO of Cytogen Corporation, of Princeton, N.J., pointed out that the agency's definition of metabolic use really means "systemic effect. It is confusing when you create terms that are not the standard usage," McKearn said.
In addition, McKearn said the definition of "more than minimal manipulation" includes not only cells that have been genetically manipulated but also cells that have been expanded. "These cells aren't undergoing anything more than the sorts of stimulation that they are likely to undergo under normal conditions," McKearn explained. "It just happens to occur ex vivo."
Allan Goldhammer, director of technical affairs for the Biotechnology Industry Organization (BIO), agreed that classifying expanded cells as highly manipulated tissues may be over-burdensome and recommended that the agency be willing to move those types of cells to the less regulated category as data on their safety accumulate.
Safety Testing Could Get Expensive
Genzyme's Raines pointed out that the agency's requirement that all tissue therapies adhere to general safety testing requirements may be particularly cumbersome to companies like Genzyme which manipulate a patient's own cells for transplant.
"General safety testing requires all lots be tested for toxicity in mice and guinea pigs seven days prior to use," Raines said. "Because autologous cell therapies are by definition custom made, each patient's cells are a new lot. We have the potential to need to perform thousands to tens of thousands of tests each year, and each test costs between $700 and $900 and requires the sacrifice of four animals."
Raines also noted the test takes seven days to perform and many cell therapies would have expired in that time.
Kathryn Zoon director of the Center for Biologics Evaluation and Research at the FDA, noted the agency had identified the general safety testing as a potential problem and was looking into ways to provide lot assurance without such a stringent test.
The agency will continue to receive public comment until April 17. *