REGULATORY UPDATE: FDA Expects IRA Final Guidance Before End of PHE

The Food and Drug Administration expects to issue a final guidance recommending the use of individual risk assessment (IRA) to determine blood donor eligibility before the end of the COVID-19 public health emergency, Peter Marks, MD, PhD, director of FDA’s Center for Biologics Evaluation and Research told the blood community during an AABB Hot Topic Discussion on Thursday, Feb 2.

FDA issued a draft guidance proposing recommendations for new protocols to determine a blood donor’s eligibility and an end the current time-based deferral for men who have sex with men (MSM) last Friday.. Marks joined the AABB event on Thursday to discuss the proposed changes and answer questions from the blood community.

Marks began with an overview of the proposed IRA process in the United States compared with the eligibility criteria of the United Kingdom and Canada. These countries adopted IRA to determine blood donor eligibility in 2020 and 2022, respectively.

Marks also touched on donor deferral rates, including some previously eligible donors who will be ineligible under the new criteria. Modeling data in Canada prior to implementation estimated a deferral rate of 0.74%. In the months following the September 2022 implementation, Canadian Blood Services (CBS) is seeing a a deferral rate of around 0.08%%, which is much lower than predicted in modeling, as described by Mindy Goldman, MD, FRCPC, of CBS during an AABB Jan. 26 Hot Topic Discussion. Marks shared that FDA models for the U.S. predict a donor deferral rate between .37% and 1.07%.

While many LGBT+ advocacy organizations welcomed the proposed move to IRA, some have criticized the other policy changes in the draft guidance, such as the deferral period for pre- and post-exposure prophylaxis (PrEP and PEP) medication used to prevent sexual transmission of HIV infection.

FDA provided an explanation for this deferral, which applies to all individuals taking PrEP, in the draft guidance and in a Jan. 27 news release, stating that the “available data demonstrate that the use of PrEP and PEP may delay detection of HIV by licensed screening tests for blood donations, potentially resulting in false negative results.” FDA first issued this clarification in a December 2019 Safety and Availability Bulletin, “Important Information for Potential Donors of Blood and Blood Products.”

“Public messaging, very rightly so, highly encourages PrEP as appropriate in men who are having sex with other men to prevent HIV transmission,” Marks said. “It’s highly effective. That being said, it’s not perfectly effective.”

In his presentation, Marks further clarified that the deferral is necessary, at least for the time being, because:

• "Non-compliant PrEP use can lead to HIV infection, but the continued use of PrEP may result in undetectable levels of HIV in the blood.”
• “Volume administered is relevant, as transfusion involves volumes 100 to 1000 times greater than previously associated with HIV transmission” [when compare to sexual contact].

“At least in our current state of knowledge of PrEP, we feel like [the policy] supports what is going on, as is the practice in the United Kingdom and Canada,” Marks said. In addition, FDA clarified in a Jan. 27 news release that the “ available data demonstrate that the use of PrEP and PEP may delay detection of HIV by licensed screening tests for blood donations, potentially resulting in false negative results.

Under the revised criteria, individuals using oral PrEP will continue to be deferred from donating blood for 3 months following their most recent dose of oral PrEP. Those using injectable PrEP will continue to be deferred for two years following their most recent injection of PrEP.

Before transitioning to audience questions, Marks encouraged attendees to submit comments on the draft guidance. The comment period closes March 31. AABB is preparing joint comments with other stakeholder organizations, such as America’s Blood Centers, the American Red Cross, and the American Hospital Association.

Throughout the Hot Topic Discussion, attendees had the opportunity to ask Marks questions. These touched on a variety of topics, including the following:

• The role of the Transfusion Transmissible Infections Monitoring System (TTIMS) in informing revised donor eligibility criteria. The TTIMS has become “a crucial help in policy change for us,” Marks said. TTIMS data demonstrated that there was no increase in HIV positivity in the blood supply following previous changes to donor eligibility in 2015 and 2020. FDA will continue to use TTIMS to monitor the blood supply after this change to maintain the safety of the blood supply.
• Anal sex. It is not necessary to ask a donor about anal sex unless a that individual has had multiple sexual partners or a new partner in the last three months, Marks said.
• Data concerning HIV transmission in females. Females with a history of anal sex, or more than one sexual partner and anal sex, have a higher risk of HIV than females with other sexual exposures, Marks said. This clarifies that the new IRA donor eligibility criteria apply to all individuals not just those in the LGBTQ community.
• Pathogen-reduction technology (PRT). Marks praised the benefits of PRT but said at this time, FDA does not believe that PRT can replace the DHQ. There are operational challenges for blood collectors to introduce this technology.
• Further reductions to PrEP deferrals. “Until we can feel comfortable and confident that there is a group of people who can donate while on PrEP, I think we have to say this is where we will stand on this,” Marks said. FDA will consider special circumstances and comments received during the comment period.
• Changes to donor eligibility for cellular and tissue donors: FDA is likely to reduce the current five-year deferral MSM that are cellular and tissue donors, but IRA may not be possible for tissue donors. (Eligibility requirements are the same for living and deceased tissue donors.)
• HIV lookback requirements: When asked about HIV lookback, Marks clarified several times that the new recommendation will be implemented prospectively. The new deferral criteria will not retrospectively trigger the HIV lookback process for prior collections that met all requirements at the time of collection. Marks shared examples using timelines to illustrate that new recommendations apply to collection on or after the date of implementation.

AABB members who were unable to attend Thursday’s Hot Topic Discussion may view a recording online.