US blood supply policy is notoriously stringent, placing significant limits on who can donate blood. However, with the ongoing COVID-19 pandemic, the FDA is allowing new individuals to donate blood.
Executive IQ Brief
- How Things Work Now: Blood is regulated as a biologic product under the Public Health Services Act. However, given the unique process of collecting blood and blood components, the FDA has additional standards for entities engaged in collecting blood products. These include eligibility standards for the kind of individuals who may donate blood.
- What’s New: With the US blood supply in shortage, the FDA issued new guidance to allow previously ineligible individuals to donate blood. The FDA will waive several donor eligibility requirements, such as measures of pulse, weight, and donation frequency. Additionally, it will shorten the window in which individuals identified to have been at risk of malaria and HIV are ineligible to donate.
- What’s Next: In general, the policies would be expected to slightly bolster the US blood supply. However, the new policies most significantly indicate both the increased risk the traditionally risk-averse FDA is willing to accept in light of COVID-19, as well as new science on the risk of HIV transmissions.
Under section 351 of the Public Health Services (PHS) Act, blood and plasma products are regulated by the FDA as biologic products. However, the collection, processing, manufacturing, and distribution of blood products often includes more facilities and establishments than are involved in traditional biologics manufacturing. These include licensed manufacturers, unlicensed blood establishments, transfusion services and contract organizations.
Licensed manufacturers of blood products are those that ship their product across state lines, the operation of which requires a license from the FDA. However, since blood is collected directly from donors, several blood establishments operate only within state lines (“intrastate”). These establishments are not required to receive a license from the FDA, but rather register with the agency annually under 21 CFR 607. Under that statute, any entity that manufacturers, prepares, propagates, compounds or reprocesses is required to register with the FDA annually.
Like other biologic products, the FDA sets standards for how blood products should be processed or manufactured to ensure safety, purity, and potency. For blood products, this includes some unique considerations. Under the Federal Food, Drug and Cosmetic (FD&C) Act, the FDA is directed to oversee various aspects of blood and blood components that are intended for transfusion (or other manufacturing) use (21 CFR 630). Under this authority, the FDA sets standards for the eligibility of blood donors, including “deferring” or prohibiting certain populations from donating blood.
The FDA is extremely risk-averse when it comes to regulating blood products, and takes what it callsa “conservative approach to ensure the safety of the Nation’s blood supply,” which the agency concedes “may result in the deferral of otherwise acceptable donors.”
Part of this approach involves screening donors, including physical assessments, questionnaires, and sample testing intended to identify potential risk factors.
Those risk factors are intended to minimize donations from persons testing positive for certain diseases, including HIV, Hepatitis B and C (HBV and HCV, respectively), human T-cell lymphotropic virus, syphilis, West Nile, Chagas, Creutzfeldt-Jakob disease and malaria. These conditions are collectively referred to as Relevant Transfusion-Transmitted Infections (RTTIs). Under 21 CFR 610.40(h), if a company finds that a sample tests positive for an RTTI, that blood product generally cannot use or ship the product. Donors with samples that are tested positive are typically deferred from eligibility to donate transfusable blood or blood components, although the time frame for deferral varies.
With the outbreak of COVID-19 continuing in the US, and cases expected to continue to increase, the US blood supply is currently in shortage as the number of critically ill patients increases while blood donations decrease as the result of social distancing measures.
Additionally, the FDA recently issued guidance allowing for the use of convalescent plasma, or antibody-rich plasma from an individual who has recovered from COVID-19, to treat individuals currently affected by COVID-19. That guidance outlined a series of strict eligibility criteria for individuals to donate convalescent plasma, including at least three confirmed COVID-19 diagnostic tests, a timeline for symptom resolution, and donor gender requirements.
The blood donor eligibility standards are intended to be exclusionary, although the amount of time an individual is deferred from eligibility depends on the specific RTTI of which they are at risk. For example, individuals who have travelled to a Malaria-endemic place are deferred from eligibility for three years, while certain individuals identified to be at risk of HIV are deferred for one year following a potential exposure. The FDA’s policies on donor deferral have been slowly relaxing in recent years, especially as screening methods continue to increase in efficacy and accuracy.
The deferral of men who have sex with men (MSM) from blood donation is possibly the best-known blood policy in the US. Between 1985 and 2015, all MSM were deferred from eligibility indefinitely, with no re-entry into eligibility possible. The MSM donation ban applied to all MSM, no matter the frequency of behavior, who had engaged in sexual activity after 1977 (when the virus was identified). In 2015, the FDA updated this policy, allowing MSM who had not engaged in any sexual contact in at least one year who were demonstrated not to have the virus to donate blood, if otherwise eligible. While the policy was generally welcomed by advocates, it was considered a first step. Notably, other countries including Canada and the United Kingdom have a three-month deferral system and have not identified any increased risk to their blood supplies.
Last week the FDA issued several guidance documents relaxing donor eligibility standards to help improve the supply of blood in the US, citing shortages. These include a policy change for general procedures for blood and blood components, as well as donor eligibility for individuals at risk of malaria and HIV.
Under the new recommendations, the FDA will allow certain donations to be used even if the donor or blood establishment has not met certain process measures. The guidance applies to both the donation of whole blood and source plasma intended for use to make plasma derivatives (i.e., convalescent plasma).
The agency is waiving requirements for certain donor-screening activities, such as a measurement of blood pressure, pulse, weight, and donation frequency before an individual makes a donation. “We are allowing release of blood components collected for certain ineligible donors” because of the “urgent need for blood components during the pandemic.” However, this doesn’t impact all other types of screenings, such as RTTI screening tests, other physical assessments, or other deferrals.
Currently, source plasma from paid donors is required to be held in quarantine for 60 calendar days before being released to a manufacturer to be turned into an injectable product. However, given the significant need, under the new guidance the FDA is shortening this time frame to 45 days. While this policy will no longer be in effect when the declared COVID-19 public health emergency expires, the FDA does state that the agency “intends at a later date to consider whether permanent changes” would be appropriate.
Additionally, the FDA will allow increased time to complete a donor’s eligibility responses. Currently, a blood facility has 24 hours after a donor has completed an eligibility assessment to follow up with that donor in the event of any inconsistencies or incomplete answers. If the donor’s information is not completed within a day, their blood donation is not eligible for use and must be discarded. However, the FDA will now allow blood facilities a 72 hours window in which to clarify answers from a donor’s information. This will not impact the physical assessment portion of donor eligibilities.
Any licensed blood establishment that intends to use these flexibilities is required to notify the FDA through a Changes Being Effected (CBE) Supplement. Unlicensed blood establishments are not required to report the change.
Under the new guidance, the FDA will allow a reduction in the amount of time in which a donor potentially exposed to malaria may be deferred. Individuals who have travelled to a malaria-endemic area, but have not resided there, would be deferred for three months. However, an individual who resided in a malaria-endemic country would be deferred for three years, as would an individual with a previous history of malaria.
The FDA will also allow individuals who have travelled to (but not resided in) malaria-endemic regions to donate platelets and/or plasma components without a deferral period, if the blood components are treated using an FDA-approved pathogen reduction device. However, this policy is not applicable for whole-blood, or individuals with a history of malaria or residence in a malaria-endemic country.
Any blood establishment or donation entity would be required to revise their donor educational materials and donor history questionnaires accordingly, and must notify the FDA through a Changes Being Effected (CBE) supplement. Unlicensed blood establishments are not required to report the change.
According to the guidance, this policy will remain in effect following the conclusion of the public health emergency.
In the most significant shift in policy, the FDA will reduce the time-based deferral for HIV-based eligibility from one year to three months. The policy will apply not only to MSM but also individuals with a history of intravenous drug use, as well as individuals who have engaged in commercial sex work or have a recent tattoo or piercing.
The FDA cites a significant amount of research, as well as past work, in the guidance indicating that the policy change would be unlikely to increase risk for the US blood supply. Additionally, the FDA cites donor deferral policies in the United Kingdom and Canada, which did not lead to an increase in blood-product related HIV transmission in the US.
Under this policy, MSM who have not had sex with a man for three months, individuals who have not engaged in sex work for three months, and persons who have no used drugs or gotten a tattoo or piercing within three months would all be eligible to donate blood (assuming they meet all other requirements).
Any blood establishment or donation entity would be required to revise their donor educational materials and donor history questionnaires accordingly (to be included in their annual report) and must notify the FDA through a Changes Being Effected (CBE) supplement. Unlicensed blood establishments are not required to report the change.
Overall, the agency states that it expects the relaxed deferral policies to help bolster the US blood supply during a time of increased need. However, given the ongoing social distancing guidance from the White House, individuals who are eligible to donate may remain unwilling to venture to a donation establishment, and it’s unclear to what extent the increased population of those eligible to donate are aware of their new eligibility to donate.
Although the policies have been issued in response to the public health emergency, it could indicate a significant shift in policy for the FDA. The blood regulations have long been considered the most risk averse framework from the agency. However, the current pandemic has fundamentally shifted the risk-benefit profiles on therapeutic and diagnostics that the agency is willing to accept. While the guidance on general procedures, such as taking an individual’s pulse and allowing three days for follow up, are unlikely to be implemented long-term, the policies on HIV and malarial deferments may remain in place.
The changes to the HIV deferral policies are likely to be the most controversial in the guidance. Although the agency has recently taken some actions to reverse indefinite deferrals, especially as nucleic acid testing (NAT) for all samples is standard procedure, the HIV/AIDS outbreak of the 1980s was the fomenting factor for the creation of the blood standards in place in the US. National fear surrounding infection via the blood supply, and Congressional concern about a lack of FDA oversight and regulation, lead to the creation of the exclusionary framework. If the policy in the guidance is implemented as intended and no risk is identified, the FDA may consider allowing a permanent relaxing in donor deferrals.
The guidance states that the agency is going to initiate a study on whether an alternative to time-based deferrals based on “lifestyle” factors could be more appropriate for reducing the risk of introducing HIV into the blood supply. The agency states that it is “committed to further investigating individual risk assessment” as an option.
However, other governmental entities have recently worked to identify an appropriate set of criteria for “risk assessment” for HIV infection or transmission—including the US Preventive Services Task Force (USPSTF), the non-partisan organization that identifies preventive services that are free to patients under the Affordable Care Act—and none have found an appropriate way to validate a risk tool. Because the risk of transmission of HIV is inherently complex, and cannot realistically be drawn down to certain sexual behaviors (including an individual’s knowledge of a partner’s sexual behaviors), as well as the time period after infection before the viral load is identifiable, such an “individual risk assessment’ does not exist. With the FDA initiating “a study of this approach” currently to identify its feasibility, the outcome of that study could impact not only blood donor eligibility, but also access to HIV prevention and treatments.