Members of the Blood Products Advisory Committee (the Committee) to the Food and Drug Administration (FDA) convened for their 115th meeting in Silver Spring, MD., on April 4-5, 2017. The Committee met in open session to discuss the safety of the Novo Nordisk product, N9-GP, a Recombinant Human Coagulation Factor IX, GlyPEGylated to treat Hemophilia B. In the afternoon, the Committee heard an update presentation on a summary of responses to Docket FDA-2016-N-1502: Blood Donor Deferral Policy for Reducing the Risk of Human Immunodeficiency Virus Transmission of Blood and Blood Products.
On April 5, in open session, the Committee heard overview presentations related to the research programs in the Laboratory of Emerging Pathogens in the Division of Emerging Transfusion-Transmitted Diseases, Office of Blood Research and Review (OBRR), Center for Biologics Evaluation and Research (CBER), FDA. This was followed by a closed session in which the Committee discussed the progress made by staff involved in the intramural research programs and made recommendations regarding their personnel actions and staffing decisions.
Novo Nordisk submitted the original Biologics License Application (BLA) seeking approval for the following indications for adults and children: a) for control and prevention of bleeding episodes; b) for perioperative management; and c) routine prophylaxis. The BLA included evidence to support licensure from three Phase 3 trials and a Phase 3 extension study in adults and children. The effectiveness of the product was not a primary issue for consideration by the Committee. However, the nonclinical studies found PEG accumulation in the choroid plexus following N9-GP dosing. Presentations noted the clinical trials did not find any safety signal that was clearly likely to be caused by PEG accumulation. However, it is unclear whether the clinical monitoring of neurologic function was adequate to detect all clinically important neurologic signs or symptoms.
FDA sought the opinion of the Committee as to the safety of the product. Of interest to the FDA was the Committee’s assessment regarding risks in the population, particularly in the pediatric and elderly populations, and particularly in the setting of chronic administration. FDA also requested the Committee consider whether monitoring, particularly of neurologic function, should be provided for the safety of patients or study subjects.
During the open public portion of the meeting, several patients and representatives of patient advocacy organizations addressed the benefits of N9-GP as an additional option for the treatment of Hemophilia B.
The Committee discussed questions related to the indications for use of N9-GP in adults and hemophilia B for:
There was no vote by the Committee on this topic.
FDA presented recommendations of the December 2015 Guidance, Revised Recommendations for Reducing the Risk of Human Immunodeficiency Virus Transmission by Blood and Blood Products, and reviewed the rational for the change to the deferral policy for men who have sex with men (MSM). The agency summarized comments to the public docket (as requested by FDA in July 2016) regarding HIV deferral policies, shared progress on the Transfusion-Transmissible Infections Monitoring System (TTIMS), and briefly discussed FDA’s future plans.
A total of 670 non-duplicative responses were received from a variety of stakeholders categorized as follows:
517 - Against further change in the deferral policy (252 appeared linked to a single write-in campaign)
86 - In support of further change in the deferral policy (included one petition with 300 signatures)
35 - Not responsive to the request for comments
32 - Responsive to the specific questions
A summary of public responses to 6 questions was presented, followed by a discussion of the TTIMS.
Potential next steps include: 1) The assessment of the impact of FDA’s current donor deferral recommendations, including the change to a 12-month deferral period for MSM; 2) Consideration of alternate donor history questionnaires; 3) The study of the feasibility of individual risk assessment strategies for assessing eligibility of all donors.
As FDA moves forward, the process will be based on gathering the necessary scientific evidence regarding policy change while ensuring the continued safety of the blood supply using epidemiology (infectious disease and behavioral risks, laboratory science (NAT and pathogen reduction technology), and social science (donor education and questionnaires). FDA will continue to work to maximize transparency of the process through stakeholder engagement and use of public meetings including scientific workshops and Advisory Committee meetings.
During the open public meeting, two patient advocacy organization representatives presented comments. A statement on behalf of the AABB was presented by Sharon Carayiannis, Director of Regulatory Affairs.
There was no Committee discussion or vote.
FDA presented an overview of the CBER and OBRR Research Programs including management processes, mission and research goals. This was followed by presentations on the Overview of the Division of Emerging Transfusion-Transmitted Diseases along with an Overview of the Laboratory of Emerging Pathogens.
There were no public comments for this session. The session ended with a closed Committee discussion followed by adjournment of the meeting.