Summing It All Up
In summary, CGTP requirements cover all aspects of production, including: cell/tissue recovery; donor screening and testing; donor-eligibility determinations; processing and process controls; supplies and reagents; equipment; facilities; environmental and labeling controls; storage conditions; product receipt, predistribution shipment and distribution; advertisement/deviation reporting; and tracking from donor to product consignee.
As indicated, each individual establishment must develop and maintain a quality program covering all these requirements.
The final rule affects several types of entities involved in HCT/P manufacture, including conventional tissue banks and those processing hematopoietic stem and progenitor cells, and eye banks.
Assisted-reproductive–technology establishments and semen banks are subject only to the inspection and enforcement procedures as they apply to donor-eligibility requirements and will be minimally affected by the rule. Information published with the rule demonstrates the size of this large and diverse industry.
For example, there are approximately 166 establishments for conventional tissue, 134 for eye tissue, 425 for hematopoietic stem/progenitor cells, and 510 for reproductive tissue. Each establishment is required to comply only with those requirements that apply to the specific activities in which it is engaged, and the Agency is working with industry and others to develop guidance specific to different types of HCT/Ps.
However, as noted by the diversity of HCT/Ps covered in the rule, requirements have been extended to products that were not considered earlier.
In general, public comments supported the rule, acknowledging that the development of the entire regulatory framework was an enormous undertaking of great importance.
Publication of the CGTP Rule completes the set of regulations, proposed in 1997 and issued in proposed or interim form since 2001, to implement FDA's framework for the regulation of HCT/Ps.
As will be readily recognized, there are many advantages to a unified comprehensive regulatory framework for these products. The risk-based approach is tiered, i.e., stratified, to provide the appropriate type and level of regulation based on a product's characteristics, with a platform of minimal requirements for all cells and tissues, and additional requirements where necessary for product safety and effectiveness.
Clear, enforceable requirements will protect the industry as well as the products and help assure the continued availability of products deemed medically necessary. Predictable regulatory requirements support innovation in technology and the industry and minimize elements of uncertainty in the product-development process.
Finally, reducing the risks of communicable-disease transmission through HCT/Ps will result in improved product safety, improved outcomes for patients, and reduction in health-care costs associated with treating complications from use of contaminated products, all helping to maintain the public confidence.
However, certain challenges still lie ahead, as articulated at the February 1 Dallas Conference by the staff of the Office of Cellular, Tissue, and Gene Therapies in FDA's Center for Biologics Evaluation and Research.
Among others, reliance on existing statutory authority limits the Agency's ability to address tissue quality and functionality, and efficient oversight of hospital-based treatments is a continuing problem. In addition, the Agency has not yet finalized its proposed rules regarding reproductive tissue.
Next steps and priorities in moving forward, as viewed by FDA, include, among others: measures to rapidly detect, analyze, and respond to adverse reactions relating to communicable-disease transmission; providing outreach, training, and guidance on implementation of the rule; defining licensure criteria for hematopoietic stem cells; and collaboration with the international community to enhance the safety of these products.
Future guidance documents can be anticipated to help the industry apply the HCT/P regulations to specific product classes or applications.