CCBB, DTRI submit BLA for cord blood, Duke's first
February 14, 2012
In September 2011, members from the Carolinas Cord Blood Bank (CCBB) and the Duke Translational Research Institute (DTRI) submitted a Biologics License Application (BLA), the first ever submitted by Duke. The working group on the BLA included Joanne Kurtzberg, MD, Medical Director of the CCBB, CCBB supervisors and staff, and the Quality Assurance group within the DTRI.
In October 2009, the FDA released a guidance document requiring cord blood banks to apply for a BLA in order to continue distributing cord blood products to transplant centers for treatment of certain diseases. These cord blood products are derived by isolating groups of cells from umbilical cord whole blood, and the cells can then be used to treat conditions such as metabolic diseases. Thus, the products are, from a regulatory standpoint, defined as drugs. Pursuant to the FDA’s requirement, DTMI’s Regulatory Affairs Group, including Bruce Burnett, PhD, Amanda Parish, PhD, Erin O’Reilly, PhD, Jelena Berglund, PhD, and Audrey Perry, began working with the Carolinas Cord Blood Bank (CCBB) and other groups on campus to prepare the BLA.
In March 2010, the FDA held a meeting geared to help cord blood manufacturers, mostly academic institutions, understand the process of preparing and submitting a BLA. DTMI Regulatory Affairs personnel assisted in organizing a meeting between Duke and the FDA in September 2010 to discuss submission of a BLA for the cord blood products manufactured by the CCBB. Following that pre-BLA meeting, all parties initiated work on the submission, which took about a year to complete.
Submission of a BLA typically includes information on pre-clinical testing, how a product is manufactured, and clinical data supporting the safety and efficacy of the drug. However, the process of submitting a BLA for cord blood use was quite different because of the history and nature of the therapy. For example, the first cord blood transplantations were done in humans, not in animals. The FDA had already reviewed a significant amount clinical data on the use of cord blood for a variety of conditions and had agreed in principle that they would approve the use of cord blood for specific set of diseases. Consequently, the amount of clinical data in the application was much less than what might normally be included. For Duke, therefore, the focus was on describing the manufacture of the product, which included donor consent, cord blood collection, shipping, cord blood processing, equipment, and CCBB standard operating procedures. The FDA wanted information about specific products that were previously processed and later transplanted into patients so that they could review the patients’ outcomes. The BLA team worked tirelessly to ensure that all information was covered and that the application would be applicable for future cord blood products.
The BLA was a paper submission shipped to FDA in September 2011 although the ultimate goal is to convert the BLA to an electronic submission, which will make ongoing maintenance much easier. One full set of Duke’s application was 21 volumes, and the regulatory team submitted 8 complete copies of the BLA to FDA, in addition copies of random individual volumes. The FDA is currently preparing for an inspection of the facility in February 2012 and reviewing the application to help ensure that good manufacturing practices are being followed. An initial action on the application is expected from FDA in July 2012. Between now and then, Duke expects to have numerous interactions with the review team at FDA in order to respond to questions and clarify any issues the Agency has with the application.
BLA submission team includes:
Bruce Burnett, PhD, RAC
Amanda Parrish, PhD, RAC
Erin O’Reilly, PhD, RAC
Jelena Berglund, PhD, RAC
Joanne Kurtzberg, MD
Ana Valverde Vidal, MBA