Background Analysis: US FDA Blood Products Advisory Committee to Discuss Blood Donation and Screening Policies Pertaining to HIV and Zika Virus; Hear About Vascular Biology Research Programs at CBER – MAR 20-21, 2019 (BPAC)

Announcement

The US FDA has scheduled a Blood Products Advisory Committee (BPAC) meeting for Wednesday to Thursday, March 20-21, 2019.

On March 20, 2019, in the morning, the BPAC will discuss and make recommendations on strategies to reduce the risk of Zika virus (ZIKV) transmission by blood and blood components. In the afternoon, the committee will hear an overview of the research programs in the Laboratory of Biochemistry and Vascular Biology in the Division of Blood Components and Devices, Office of Blood Research and Review, Center for Biologics Evaluation and Research (CBER), FDA.

On March 21, 2019, the committee will discuss blood donation policies regarding men who have sex with men (MSM).

Screening of Blood Donations for Zika Virus

Agenda

The BPAC will discuss and make recommendations on strategies to reduce the risk of Zika virus (ZIKV) transmission by blood and blood components. The BPAC will be asked to weigh in regarding whether universal testing of blood donations for ZIKV is an appropriate strategy, considering the decline of the ZIKV epidemic in the US and worldwide.

Regulatory Background

In August 2016, the FDA issued a final guidance document recommending that all States and territories screen individual units of whole blood and blood components for ZIKV. Since no tests had yet been FDA-approved for this use, in order to follow the Agency’s recommendations, many blood collection establishments used  l tests in development under investigational new drug (IND) applications, or tests made available through an Emergency Use Authorization (EUA) that was previously issued by the Secretary of Health and Human Services (HHS) in February 2016.

By October 2017, the first test to detect ZIKV was approved by the FDA, namely the cobas Zika test, manufactured by Roche Molecular Systems, Inc.

In July 2018, the FDA revised their earlier guidance. The Agency noted that when ZIKV first emerged, the unknown course of the epidemic and the observed severe effects from the disease indicated that individual donor testing was needed to ensure the continued safety of the blood supply. However, they reported that a significant decrease in cases of Zika virus infection in the US and its territories prompted the FDA to move away from testing each individual donation, to testing of pooled donations.

A second test to detect ZIKV was FDA-approved in July 2018, the Procleix Zika Virus Assay, which is manufactured by Grifols Diagnostics Solutions, Inc.

Blood Donor Eligibility – HIV Risk Considerations

Agenda

The BPAC will discuss blood donation policies regarding men who have sex with men (MSM). To inform the discussion, the committee will hear presentations on the current epidemiology of HIV in the US, global developments in MSM blood donor deferral policies, and data on HIV incidence and prevalence among blood donors from the Transfusion-Transmitted Infection Monitoring System (TTIMS). TTIMS is a joint program involving CBER, the National Institutes of Health (NIH), and US blood collection establishments that monitors US blood safety. It provides information on more than 50% of the US donor base, monitoring HIV, Hepatitis B Virus (HBV), and Hepatitis C Virus (HCV) incidences. It also assesses behavioral risk factors. Its main function is to provide a framework for rapid data collection regarding new emerging infectious diseases and their effect on the US blood supply.

In addition, the BPAC will discuss 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.

Regulatory Background

The availability of HIV testing in 1985 eventually prompted calls to revise the FDA’s indefinite blood donor deferral policy for men who have had sex with another man (MSM). In the early 2010s, the Department of Health and Human Services (HHS) Advisory Committee on Blood Safety and Availability (now named the Advisory Committee on Blood and Tissue Safety and Availability) recommended a change in the policy, which was supported by data from:

- The Quarantine Release Error (QRE) Task Force assessment;

- The Donor History Questionnaire Study;

- The Retrovirus Epidemiology Donor Study-II (REDS-II);

- The RED-III Blood Donation Rules Opinion Study BloodDROPS); and

- The Australian experience over 5 years before and after a change to a 1-year deferral.

Subsequently, the FDA announced a revised blood donor deferral policy, along with Draft Guidance for Industry, in December 2015, to a 12-month deferral for men who have had sex with another man, rather than the indefinite deferral.

In July 2016, the FDA established a public docket requesting comments, supported by scientific evidence, about potential blood donor deferral policy options for HIV transmission.

At the April 4-5, 2017 meeting of the BPAC, the FDA reported that, during the comment period, they received 670 non-duplicative responses from individuals, advocacy groups, academic and research institutions, healthcare providers, local and state governments, blood product recipients, and the blood collection industry. Of the 670 comments, 517 were against further changes to the deferral policy (252 responses were thought to be linked to a single write-in campaign), and 86 responses were in support of further changes in the policy. The remaining responses were uncategorized. The FDA presented details on the responses to each of the six questions that they had posed and then summarized, as follows.

·      The policies suggested covered a broad spectrum, from recommending no further changes, to a return to an indefinite deferral, to no deferral for low-risk MSM and a 2-to-3 week deferral for MSM determined to be high-risk.

·      Multiple commenters noted the need for an improved donor questionnaire for all donors that more accurately assesses risk, while acknowledging the need for privacy and the potential benefit of electronic responses or specially-trained staff.

·      Several commenters called for continued improvement in donor testing technology to reduce the window period (where HIV is not detected by testing, but can still be present in the blood), or for the implementation of pathogen-reduction technology for blood components.

After considering the comments received, the FDA reported that they have already made a number of revisions and clarifications. Some of the key revisions included a clarification on the deferral for women who have sex with MSM, a change in the rationale for deferring individuals with hemophilia or related clotting disorders, the addition of a section that more completely explains the scientific rationale for the revised donor deferral policy for MSM, as well as a number of other minor technical corrections and clarifications. The upcoming meeting appears to be in keeping with their pledge to continue work on this topic and to review donor deferral policies to ensure they reflect the most up-to-date scientific knowledge.

Since the year 2000, the BPAC has met several times to discuss this topic, on the following dates: April 4-5, 2017; December 2, 2014; May 16, 2012; and January 14, 2000.

Laboratory of Emerging Pathogens

Agenda

The Committee will hear presentations on the research programs in CBER’s Laboratory of Biochemistry and Vascular Biology.

CBER Blood Research Projects

Several blood research projects are posted at the following website: https://www.fda.gov/BiologicsBloodVaccines/ScienceResearch/BiologicsResearchAreas/ucm124375.htm

The following projects are listed at this site under the topic of “biochemistry and vascular biology”:

·      Evaluating the Safety and Efficacy of Hemoglobin-based Blood Substitutes - Abdu I. Alayash, PhD;

·      Red Blood Cell Toxicokinetics and Proteomics- Paul W. Buehler, PhD; and

·      Vascular Responses and Biological Product Safety and Efficacy - Felice D'Agnillo, PhD.

Regulatory Background

CBER Site Review Process

CBER’s regulatory science program combines research and tool development to address a myriad of challenges associated with the wide range of complex products that CBER regulates. The Center operates under a model called the “Research/Reviewer Model.” About 20% of CBER’s research staff oversees laboratory programs and also devote up to 50% of their time on review activities, including submissions, inspections, and policy document development. Use of this model leads to the development of relevant guidance documents, publications, and interactions with sponsors. Research at CBER is evaluated annually through several levels, by the lab chief, division director, associate director for research, and office director. In addition, every four years, an external site visit process is conducted by a subcommittee of the BPAC. The process involves having external experts visit the research sites and draft a report that is distributed to the BPAC, which provides input, reviews any revised drafts, and ultimately votes on whether to accept the report. This report is used to evaluate FDA staff promotions, resource allocations, and any areas for improvement. It is unclear from the FDA’s meeting announcement if the upcoming overview of CBER biochemistry and vascular biology projects is associated with a site review report, however subsequent to hearing about CBER research programs, the BPAC will often proceed in closed session to review site reports and discuss resource allocation and staffing. This portion of the meeting is closed to the public in order to permit discussion where disclosure would constitute a clearly unwarranted invasion of personal privacy (5 U.S.C. 552b(c)(6)).

What’s Next?

Tarius will send a Briefing Summary after briefing materials are posted to FDA’s website (typically within 2 days of the meeting). This report will provide a summary of the FDA briefing materials.

Tarius will send a Results Wire soon after the meeting. This report will include the voting outcomes, if applicable, and key outcomes of the discussion.

METADATA: Sponsor: none Drug Name: none Drug Class: none Indication: none Other: Zika virus, HIV, blood donations

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DISCLAIMER: The information in this document is for informational purposes only. The SAC Tracker Background Analysis contains information from publicly available sources, including FDA, sponsor, scientific, and clinical websites. Tarius A/S assumes no liability for any inaccurate or incomplete information, or for any actions taken in reliance thereon. © Tarius A/S. All rights reserved.