The 120th meeting of the Food and Drug Administration’s (FDA) Blood Products Advisory Committee (the Committee) convened in Silver Spring, Md. on
Mar. 20-21, 2019. In open session on Day 1, the Committee met to discuss current strategies to reduce the risk of Zika virus (ZIKV) transmission by blood and blood components. The discussion focused on the decline of the ZIKV epidemic in the United States (U.S.) and worldwide, and whether universal testing of blood donations for ZIKV continues to be an appropriate strategy. In the afternoon, the Committee heard an overview of the programs of the Laboratory of Biochemistry and Vascular Biology, in the Division of Blood Components and Devices (DBCD), Office of Blood Research and Review (OBRR), Center for Biologics Evaluation and Research (CBER).
Day 2 began with an open session review of the current blood donation policies regarding men who have sex with men (MSM). The Committee heard an overview of international developments in MSM policy, the epidemiology of Human Immunodeficiency Virus (HIV) in the U.S., an update from the Transfusion-Transmitted Infections Monitoring Systems (TTIMS), and a proposed HIV risk questionnaire study. The day concluded with consideration and discussion of a proposed alternative procedure that would permit an exception to the 1-year deferral for MSM donors. The collections, restricted to apheresis platelet components, would then undergo further treatment for pathogen inactivation using the Intercept Blood System (Cerus).
Day 1 Mar. 20, 2019 In Open Session
Topic I: Evaluation of Strategies to Reduce the Risk of ZIKV Transmission by Blood and Blood Components
FDA is re-evaluating its July 2018 recommendations on testing blood donations for ZIKV using Minipool (MP) nucleic acid testing (NAT) or individual donor (ID) NAT given the available information about the decline of ZIKV in the U.S. and the Americas. Use of an FDA-approved pathogen reduction system for plasma or platelet components would remain an acceptable alternative to testing donations for ZIKV and was not further discussed.
- “Evaluation of Strategies to Reduce the Risk of ZIKV Transmission by Blood and Blood Components” by Caren Chancey, PhD, Product Review Branch (PRB), Division of Emerging and Transfusion Transmitted Diseases, OBRR, CBER, FDA
Dr. Chancey presented on the current testing strategies in place following the July 2018 recommendation for universal testing of U.S. blood donations by ID NAT or MP NAT with triggering to ID NAT when certain conditions are met indicating risk of ZIKV transmission. Dr. Chancey described how current available information indicates a decline in ZIKV transmission in the U.S. and the Americas and FDA’s considerations for re-evaluating its 2018 recommendations.
- “Update on the Current Status of ZIKV Epidemic” by Marc Fischer, MD, MPH, Arboviral Disease Branch, Division of Vector Borne Diseases, Centers for Disease Control and Prevention (CDC)
Dr. Fischer reported on the current epidemiology of ZIKV in the Americas and in the U.S. ZIKV disease and infection without disease became a notifiable condition in 2016 with surveillance via CDC’s ArboNET system using standardized case definitions, clinical, epidemiologic and laboratory criteria. Confirmed and probable ZIKV disease cases in U.S. states and territories peaked in 2016 at 41,680 and dropped to 220 in 2018. In 2018, 363 Zika viremic blood donors were reported to ArboNET with a drop to three cases by 2018. Very little evidence of circulating virus has been recently reported.
- “AABB ZIKV Biovigilance Network by Srijana Rajbhandary”, MPH, Department of Research, AABB
Ms. Rajbhandary reported data from the AABB Zika Virus Biovigilance Network. The network is a collaboration between AABB and U.S. blood collection establishments created in 2016 in response to FDA’s first ZIKV guidance. The platform was enhanced in 2018 to support updated FDA recommendations in the December 2018 Guidance. Highlights of the data reported to the Committee are as follows:
- There have been 880 initial reactive donations with 46 confirmed positives reported to the platform to date.
- The positive predictive value of the NAT tests is 2.36%.
- The last reactive donation reported to the platform on Feb. 4, 2019.
- The last confirmed positive was reported to the platform on Mar. 16, 2018.
- The last confirmed positive with exposure due to travel was associated with travel to Mexico in December 2017.
- The last confirmed positive reported in March 2018 was in Florida, with no exposure to travel or sexual contact identified.
- “Current Considerations for Reducing the Risk of Transfusion-Transmitted ZIKV” by David Leiby, PhD, Chief, PRB, OBRR
Dr. Leiby presented alternative strategies to universal testing based on a decline of ZIKV in the U.S. and the Americas. Dr. Leiby described that FDA is re-evaluating its July 2018 recommendations for universal testing of blood donations using MP or ID NAT. Dr. Leiby presented the three testing strategies under consideration. FDA did not propose pre-donation assessment for ZIKV risk factors such as exposure through travel or sexual contact. The options presented were:
|Option 1||No policy change; continue universal testing for ZIKV by MP or ID NAT.|
|Option 2||Regional testing for ZIKV with MP or ID NAT; with considerations for regional options.|
|Option 3||Eliminate all testing for ZIKV.|
Following the open session presentations and questions for speakers, FDA asked the Committee to provide an opinion on the three proposed testing options.
Questions for the Committee:
- At this time, do the available data support continuing universal testing for ZIKV using MP or ID NAT as recommended in the July 2018 Final Guidance (no policy change at this time (Option 1)?
The Committee voted 11 to 4 to continue universal testing for ZIKV using MP or ID NAT, as recommended in the July 2018 Final Guidance. There was no policy change at this time, with the Committee agreeing that more data was needed to make a change.
- Do the available data support a regional testing option strategy for ZIKV using MP or ID NAT in at-risk U.S. states and territories (Option 2)?
(Discussion of regional options)
With a 9 to 6 vote, there was not a majority opinion to support a regional testing option strategy for ZIKV using MP or ID NAT in at-risk U.S. states and territories. Several possible variations were offered. FDA agreed to identify the risk areas as part of the strategy.
- Florida, Texas and Puerto Rico, U.S. Virgin Islands where documented local, mosquito-borne ZIKV transmission has occurred.
- California and New York where the mosquito vectors are present, and the states previously accounted for a significant proportion of the ZIKV-reactive donations from travelers returning from ZIKV-affected countries.
- Hawaii, U.S. territories where mosquito vectors are present and documented transmissions of other
Aedes-borne arboviruses (DEN, CHIK) have occurred.
- Do the available data support the elimination of all testing for ZIKV without re-introduction of donor screening for risk factors (e.g. travel) in areas with no risk of ZIKV infection, pending another outbreak in the United States (option 3)?
In a 14 to 1 vote, the Committee dismissed the option to eliminate all testing for ZIKV without re-introduction of donor screening for risk factors (e.g., travel) in areas with no risk of ZIKV infection - pending another outbreak in the U.S.
In summary, the Committee felt that additional information and continued surveillance and reporting is needed. Based on a continued decline in ZIKV reactive reporting, the topic should be reconsidered in a year or two.
Topic II: Review of the Research Programs in the Laboratory of Biochemistry and Vascular Biology, Division of Blood Components and Devices, OBRR
In the afternoon session, overviews of the CBER, OBRR, DBCD and the Laboratory of Biochemistry and Vascular Biology were presented.
- “Overview of CBER Research Programs” by Carolyn Wilson, PhD, Associate Director for Research, OBRR
Dr. Wilson presented on the benefits of the CBER Research Program describing the integration of research and review to prepare for future innovative products and public health challenges.
- “Overview of OBRR Research Programs” by CD Atreya, PhD, Associate Director for Research, OBRR
Dr. Atreya described OBRR’s Mission and goals to ensure the safety, efficacy and availability of blood and blood products and related devices and technologies. The goals also promote the safety and effectiveness of transfusion-transmitted infectious disease agent screening and supplemental tests, and retroviral agents.
- “Overview of the Division of Blood Components and Devices Research Programs” by Orieji Illoh, MD, Director, DBCD, OBRR
Dr. Illoh reported on the research components of DBCD’s mission. Examples included the safety and effectiveness of oxygen carrying solutions, platelet derived products and related biologics. Dr. Illoh also highlighted pathogen reduction technology and its applicability to whole blood and blood components along with development of animal models to evaluate red blood cell quality.
- “Research Programs in the Laboratory of Biochemistry and Vascular Biology” by Abdu Alayash, PhD, Chief, Laboratory of Biochemistry and Vascular Biology, DBCD, OBRR
Dr. Alayash gave a presentation on the activities of the laboratory including transfusion products (hemoglobin and fluorocarbon-based products, dextrans and starches, albumin (human) and plasma protein fraction (human) products), red cell-derived hemin products, red cell preservation technologies and inter-office/center consultations.
Day 2 Mar. 21, 2019 In Open Session
Topic III: Blood Donation Policies Regarding Men Who Have Sex with Men (MSM)
Topic III A: Update on Donor Deferral Policies and Donor HIV Risk Questionnaire Study
FDA requested the Committee consider the blood donation and deferral policies regarding MSM, examine the current scientific data on HIV and MSM, and identify additional information that could support alternative procedures to FDA’s current MSM donor deferral policy that would maintain the safety of the blood supply. The Committee also discussed a proposed HIV risk questionnaire study and a proposal for the use of pathogen reduction technology as an alternative procedure to a time-based deferral for MSM.
- “Introduction to the Topic” by Anne Eder, MD, PhD, Acting Deputy Director, OBRR
Dr. Eder presented a brief history of the agency’s policy development, U.S. HIV epidemiology and continued commitment to evaluate their policies based on supporting evidence.
- “Review of Global Developments in MSM Deferral Policies” by Mindy Goldman, MD, Canadian Blood Services
Dr. Goldman shared the variety of time-based deferrals in use outside the U.S.
|England, Scotland, Wales|
|Denmark (summer 2019)|
|Canada, France, Sweden, Australia, Netherlands, Belgium, New Zealand, Finland and Germany|
An increase in HIV rates in donors or an increase in NAT only positive donors did not accompany the change to a 12-month deferral. Data from the United Kingdom 3-month deferral experience has not yet been published.
- “Epidemiology of HIV in the United States” by John Brooks, MD, Senior Medical Advisor, Division of HIV/AIDS Prevention, National Center for HIV/AIDS, Viral Hepatitis STD and TB Prevention, CDC
Dr. Brooks described that although new HIV diagnoses continue to decline, certain populations continue to be disproportionately and increasingly affected, and must be prioritized for prevention and treatment efforts. With the use of new antiretroviral treatments, there is the possibility that true HIV control is within reach.
- “Data from TTIMS” by Alan Williams PhD, Associate Director for Regulatory Affairs, Office of Biostatistics and Epidemiology (OBE), CBER
In an overview summary, Dr. Williams presented the following key information:
- Since its inception in September 2015, TTIMS has established a comprehensive and sophisticated monitoring capability for the safety of the U.S. blood supply.
- Major analyses are planned for 2019 to assess prevalence, incidence, and risk factors for HIV, Hepatitis C virus, and Hepatitis B virus infection among both first-time and repeat donors and assess time trends that may be associated with policy changes such as the 12-month MSM deferral.
- TTIMS has been responsive to contemporary needs for data related to pre-exposure prophylaxis and antiretroviral use among those who attempt to donate blood.
- Data for specific TTIMS studies described will be presented by the responsible investigators in the coming year.
- “Presentation of the HIV Risk Questionnaire Study” by Barbee Whitaker, PhD, Lead General Health Scientist, OBE, CBER
Dr. Whitaker described a pilot study of alternative MSM donor deferral strategies to help determine the feasibility and size of a larger study to assess whether reduction or elimination of the MSM donor deferral interval is possible. The pilot study sites will be selected from locations in states and cities with the highest new HIV diagnosis rates based on 2017 CDC HIV epidemiology reports. The larger study criteria would include a set of behavioral questions and responses that are associated with the absence of the detection of recent HIV infection.
Following questions for the speakers and an open public hearing, FDA requested the Committee discuss possible changes to the current deferral approach for MSM donors, including a move from a 1-year to a 3-month deferral for monogamous MSM. FDA asked the Committee to examine the current scientific data on HIV and MSM and to identify additional information that could support alternatives to the current MSM donor deferral policy that would maintain the safety of the blood supply. The Committee agreed that FDA should pursue data to support a shorter deferral period while ensuring the current level of safety, and improved assessment of risk for all individuals.
Topic III B: Pathogen Reduction of Platelet Donations as an Alternative Procedure to MSM Donor Deferral
- “Pathogen Reduction of Platelet Donations as an Alternative Procedure to MSM Donor Deferral” by Carlos Villa, MD, PhD, Medical Officer, DBCD, OBRR
Dr. Villa presented:
- The extent of HIV log reduction to prevent HIV transmission by transfusion
- The possible effect of the variance request on platelet supply
- Manufacturing process for pathogen reduced platelets
- Controls to prevent process failures
- Limitation of pathogen reduction to specific platelet platforms
- “Expanding the Rolls-Making Blood Donation by MSM a Reality” by James P. AuBuchon, MD, FCAP, FRCP (Edin), President and CEO, Bloodworks Northwest
Dr. AuBuchon’s presentation:
- Proposed an alternative procedure with an exception to the 1-year deferral for MSM donors.
- Proposed a restrictive donor profile for collection of apheresis platelets from MSM donors who would otherwise be deferred.
- Proposed collections from donors with the restricted profile would follow the standard donor screening and testing processes to ensure product safety as currently required by FDA.
- Proposed restricted collections would meet all other criteria, including negative test results for all transfusion-transmitted infections.
- Proposed the collected blood would undergo further treatment for pathogen inactivation using the Intercept Blood System (Cerus) to address concerns related to possible window-period donations (donations made during the short period of time after the donor is infected with HIV, but the virus is not yet detectable when tested).
- Proposed the blood establishment computer would override the current 1-year deferral for MSM contact to permit release of the Intercept platelets for transfusion only if all other product requirements are met.
- Proposed this alternative process would be used for Intercept platelets only collected from male and female donors with MSM contact.
Following questions for the speakers, FDA asked the Committee to discuss this proposed approach as an alternative to the current MSM deferral policy and to consider any associated risks and possible mitigations. Several members expressed the opinion that all of the questions currently asked of donors should continue to be used with the restricted donor profile. Members were concerned that, with removal of the MSM deferral, the same battery of infectious disease tests currently required by FDA would be used to ensure the blood safety. A number of members agreed that this tiered approach of measures would be adequate to ensure the safety of platelets collected from MSM donors.
The majority of the Committee expressed the opinion that such a proposal would be safe for patients, though great care would need to be taken to implement this approach. The Committee noted that there would be a number of logistical challenges to work out in order to implement this approach. Some members agreed that such blood products could potentially be even safer than currently available platelets that are not treated with pathogen reduction technology.
Discussion also focused on the need to prepare effective messaging for both the MSM donor and patient populations to communicate the safety of the platelets and the reasons for collecting and treating only platelets from MSM. Dr. AuBuchon stated that Bloodworks Northwest was already working internally on communications for various stakeholder groups.