FDA issues guidance on license applications for placental/umbilical cord blood products

The Food and Drug Administration (FDA) has issued a draft guidance recommending a streamlined path to licensure for establishments that manufacture cord blood for certain medical conditions.

Placental/umbilical cord blood is a rich source of precursor cells capable of differentiating into mature blood cells. These precursor cells are known as hematopoietic stem/progenitor cells and can be used to replenish the bone marrow in patients with blood-based malignancies such as leukemia.

The draft guidance describes FDA's regulatory approach to the regulation of cord blood hematopoietic stem/progenitor cells that are:

• minimally manipulated (processing does not alter the original characteristics of the cells);
• used to replenish the bone marrow in patients with blood-related malignancies; and
• used in recipients unrelated to the donor of the stem cells.

"Cord blood hematopoietic stem/progenitor cells offer the potential for tremendous therapeutic benefit," said Jesse Goodman, MD, MPH, director of FDA's Center for Biologics Evaluation and Research (CBER). "In this draft guidance, FDA provides recommendations on a streamlined path to licensure for these promising products that also ensures their safety and effectiveness."

FDA first proposed a new regulatory framework for human cells, tissues and cellular and tissue-based products (HCT/P), including cord blood, in 1997. This tiered approach, fully implemented in May of 2005, requires that establishments register with FDA and list their products, ensure quality control by adhering to the agency's current good tissue practices and follow the agency's rules on donor eligibility. Under this framework, cord blood hematopoietic stem/progenitor cells from unrelated donors are regulated as both HCT/P and as biologic drugs subject to licensure.

In 1998, when cord blood transplants were still relatively uncommon, FDA sought input from scientists and industry to develop product standards, establishment controls, and processing controls that would clear the way for biologics license applications ensuring the safety and effectiveness of placental/umbilical cord blood from unrelated donors that is used to replenish a patient's bone marrow. To provide a scientific basis for the proposed standards, FDA requested the submission of clinical and non-clinical laboratory data to a public site created for this purpose.

In 2003, the agency convened its Biological Response Modifiers Advisory Committee to discuss the current clinical data, safety and effectiveness issues surrounding placental/umbilical cord blood transplantation, and possible quality measures. At that time, cord blood was being used in increasing numbers, and members of the interested public voiced their opinion that licensure of cord blood products would increase confidence in the safety and effectiveness of these products.

FDA has since determined that cord blood hematopoietic stem/progenitor cells are safe and effective for certain indications based on the data submitted to the public docket and the large body of published literature.

Therefore, the new draft guidance offers cord blood banks a less burdensome path to licensure. Rather than having to submit their own clinical data, they may cite existing data in the docket.

The draft guidance also provides manufacturers with recommendations on the content and format of information to be submitted with an application, discusses the manufacture of cord blood hematopoietic stem/progenitor cells and elaborates on how to comply with applicable regulatory requirements.

FDA is accepting public comment for 90 days from the date of publication in the Federal Register. Electronic comments may be sent to www.fda.gov/dockets/ecomments. Written comments may be sent to: Division of Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD, 20852. Comments must include the docket number (2006D-0514).

For a copy of the guidance, visit: http://www.fda.gov/cber/gdlns/cordbld.pdf