The
guidance, released by the Food and Drug Administration in December 2015, finalizes recommendations in the May 2015 draft guidance of the same title issued to blood establishments that collect blood or blood components, including Source Plasma. The recommendations reflect the improvements in the donation process, including testingand a greater understanding of options to protect the safety of the blood supply. The guidance provides new recommendations for donor eligibility, deferral, requalification, and inventory management for individuals with increased risk for transmitting human immunodeficiency virus (HIV) infection.
This guidance also includes other recommendations contained in the April 23, 1992 memorandum (the April 1992 memo) to blood establishments entitled, “Revised Recommendations for the Prevention of Human Immunodeficiency Virus (HIV) Transmission by Blood and Blood Products” and supersedes the April 1992 memo.
Background
The June 2010 meeting of the Advisory Committee on Blood and Tissue Safety and Availability (the Committee) focused on the issue of deferral of men who have had sexual contact with another man, even one time, since 1977. The Committee recommended “that the current MSM deferral policy, while suboptimal, be retained pending the completion of targeted research studies that might support a safe alternative policy.” Following the June 2010 meeting, the FDA evaluated research studies as they became available, advisory committee reports on risks associated with transfusion-transmitted HIV infection, and a range of policy options. The agency determined the best option is to implement a time-based approach to assess a potential donor’s risk for HIV. This approach permits the use of a shorter 12 month deferral where the risks permit and also preserves the level of safety that has been achieved with past measures.
The time-based approach makes it possible to replace a more conservative approach to screening blood donors, such as replacing the evaluation period “Since 1977…,” with a time period that more appropriately reflects the improved understanding of current risks and the ability to effectively assess and manage those risks. The donor will provide information on the donor history questionnarie (DHQ) that is bound to an appropriate period of time to capture any existing risks. Likewise, the time-based approach is applied to deferrals to effectively manage the risks. For example, a 12 month deferral replaces indefinite deferral for some risk behaviors with a corresponding 12 month deferral for the sexual contacts of those individuals.
Recommendations
The FDA recommends implementing the new approach by revising the DHQs (full-length and abbreviated), blood donor educational materials, and all accompanying materials, as well as standard operating procedures (SOPs) for donor requalification, product labeling, and product management to reflect the new recommendations.
Blood Donor Educational Material
The agency recommends that:
- Blood centers update the blood donor educational materials to be presented in a manner that will be understood, including oral, written, or multimedia formats, to enhance the effectiveness of the process, consistent with the new requirements in “Requirements for Blood and Blood Components Intended for Transfusion or for Further Manufacturing Use,” (the May 2015 final rule) which becomes effective May 23, 2016.
- Donors read the blood donor educational materials before each donation to ensure the donor fully understands the risks of transfusion-transmitted infections (TTIs), signs and symptoms of HIV infection, and the importance of the option to self-defer.
Donor History Questionnaire
The agency recommends that:
- Blood centers update both full-length and abbreviated DHQs, accompanying materials, and all related SOPs changing the questions using the time-based assessment of the risks.
- Male or female gender be self-identified and self-reported when completing the DHQ.
What recommendations, originally published in the 1992 memo, have changed? The new recommendations provide for:
- Asking male donors if they have had sexual contact with another man in the past 12 months rather than asking “From 1977 to the present, have you had sexual contact with another male, even once?”
- Updating the corresponding question asked of female donors to reflect this change.
- Removing the question asking have you ever “used clotting factor concentrates?”.
- Asking donors if they have ever received money, drugs, or other payment for sex, rather than asking “From 1977 to the present, have you received money, drugs, or other payment for sex?”.
NOTE: The update to these two “From 1977…” questions will effectively remove the “From 1977...” category of questions from the DHQ.
What recommendations, originally published in the 1992 memo, have NOT changed? Certain risks have not changed and the DHQ should still ask:
- If a donor has ever:
- Had a positive test for HIV,
- Injected non-prescription drugs.
- If a donor has, in the past 12 months,:
- Had sexual contact with a person who ever had a positive test for HIV, ever received money, drugs, or other payment for sex, or, ever injected non-prescription drugs,
- Received an allogeneic blood transfusion, been exposed to another person’s blood through percutaneous inoculation, such as a needle stick or contact with an open wound,
- Had a new tattoo, ear or body piercing,
- Had or was treated for syphilis or gonorrhea,
- (Female donors) Had sexual contact with a man who has had sexual contact with another man in the past 12 months. Note the time frame was reduced to 12 months for the male to male sexual contact to be consistent with the corresponding change described earlier in this section.
Donor Deferral
The agency recommends that deferral periods are consistent with time frames for the revised screening questions described above.
What deferral periods have changed? The recommendations no longer require:
- Indefinite deferral of males who have had sexual contact with another male. The new deferral period is 12 months from the date of the last sexual contact with another male.
- Deferral of a person who has had sexual contact with someone who has hemophilia or used clotting factors.
What has not changed? The agency continues to recommend the indefinite deferral of a person who:
- Has ever had a positive test for HIV,
- Has ever received money, drugs, or other payment for sex,
- Has ever injected non-prescription drugs,
AND, deferral of potential donors who have hemophilia or used clotting factors is now recommended for reasons of donor safety, rather than patient safety. FDA has not recommended a deferral for the receipt of other FDA-licensed plasma-derivatives because of risk of HIV or RTTIs, but the agency notes that a person with hemophilia or clotting disorders should be deferred to ensure that they are not harmed in the blood donation process.
Requalification of Deferred Donors
The agency recommends that blood centers make corresponding changes to requalifying donors based on the donor eligibility time frames.
What has changed?
- Donors who were indefinitely
deferred under the previous FDA policy for sexual contact with another male even once since 1977 are eligible to donate again if the donor has not had sexual contact with another male in the past 12 months. At each donation, the donor must meet all donor eligibility criteria prior to donation.
- Male donors who are
deferred for 12 months based on the new recommendations regarding sexual contact with another male are eligible to donate again if the donor has not had sexual contact with another male in the past 12 months. At each donation, the donor must meet all donor eligibility criteria prior to donation.
What has not changed? Previous FDA recommendations remain in place for all other donor eligibility assessments.
Inventory Management and Notification of Consignees
The agency recommends appropriate actions be taken for inventory control of unsuitable collections.
What has changed? The FDA does not make new recommendations in this section of the guidance.
What has not changed? The agency recommends for facilities to continue current practice. Blood centers should take actions following collections from a person who was not properly deferred based on the recommendations in the guidance:
- To quarantine or destroy unsuitable products collected from a donor following a failure to defer based on the recommendations.
- To notify consignees if the components have been distributed.
- Following notification, consignees should quarantine or destroy the affected components.
- Blood centers must follow the “Lookback” requirements of 21 CFR 610.46 for prior collections from a donor with evidence of HIV infection at a later donation.
- For plasma pooled for further manufacturing into products that are “manufactured under processes that include validated viral clearance steps shown to be robust in the clearance of lipid-enveloped viruses,” no further steps are needed for quarantine or destruction of the products.
Product Disposition and Labeling
The agency has recommendations for appropriate actions for proper handling and relabeling of unsuitable collections.
What has changed? The FDA does not make new recommendations in this section of the guidance.
What has not changed?
- Blood centers should destroy or relabel unsuitable blood or blood components that were collected from:
- A donor who was not properly deferred based on risk factors for HIV infection provided in the guidance.
- A donor who currently tests reactive for HIV or a donor deferred for reactive HIV testing.
- Blood centers relabeling unsuitable collections intended for research or for further manufacture into non injectable products or in vitro diagnostic reagents when no other suitable source is available, should use the following cautionary statements as applicable:
- “Caution: For Laboratory Research Only” or “Caution: For Further Manufacturing into In Vitro Diagnostic Reagents For Which There Are No Alternative Sources” or “Caution: For Use in Manufacturing Noninjectable Products Only”
- And, for recovered plasma, “Not for Use in Products Subject to License Under Section 351 of the Public Health Service Act”
- Blood centers must follow existing requirements at §610.40 regarding restrictions on shipment and use, and §606.121(f) regarding labeling requirements and cautionary statements for blood and blood components.
- The May 2015 final rule has minor revisions to certain regulations, referenced in this guidance, that do not change the intent or scope of the relegations.
Biological Product Deviation Reporting
What has changed? The FDA does not make new recommendations in this section of the guidance.
What has not changed? Blood centers must follow existing requirements in §606.171 for distributed products collected from a donor who was not properly deferred based on the recommendations in the guidance.
Testing Requirements and Considerations
What has changed? The FDA does not make new recommendations in this section of the guidance.
What has not changed? Blood centers must follow existing testing requirements in §§610.40 (a) and 610.40(b), deferral requirements in §610.41, donor notification requirements in §630.6 and
current blood guidance documents.
Implementation
Options for Implementation of Recommendations
Blood centers may implement these recommendations after the donor educational material, DHQs (full-length and abbreviated versions), and accompanying materials are revised, to reflect the new recommendations following one of several options. Depending on the approach for implementation, the changes will be considered either a major change or a minor change. Regulations in §601.12 require licensed blood establishments to report the revisions using one of these options:
- Report a Major Change using a prior approval supplement for approval by the FDA based on §601.12(b) if the blood center:
- Revises the donor educational materials, DHQ and accompanying materials.
- Revises a DHQ and accompanying materials previously recognized by FDA.
- Report a Minor Change in the annual report to FDA based on §601.12(d), with the date of implementation for a version of the blood donor educational materials, DHQ and accompanying materials prepared by the AABB Donor History Task Force or the Plasma Protein Therapeutics Association, and recognized found acceptable by FDA.
Planning
AABB’s assistance with planning for implementation of the recommendations includes:
- The AABB Donor History Task Force is finalizing revisions to version 1.3 of the DHQ, abbreviated DHQ, and all of the accompanying materials, to create version 2.0 that is consistent with the recommendations of this guidance, as well as the May 2015 final rule.
- AABB will submit the package of version 2.0 materials (Questionnaires, User Brochures, Blood Donor Educational Materials, Medication Deferral List, and flowcharts) to the FDA for review.
- At the time of submission to the FDA, AABB will make all of these
draft Version 2.0 materials available on the AABB website to assist with plans for implementation of the new recommendations in the guidance and the new regulations provided in the May 2015 final rule.
- The
draft version 2.0 documents from AABB must be considered a
draft until formally recognized as acceptable by FDA because:
- FDA can request additional revisions to version 2.0 documents during the review process.
- All changes to DHQs and accompanying materials used by a facility must be implemented under FDA regulations.
- Once recognized by FDA, facilities can utilize the accepted version 2.0 documents submitted by AABB, rather than undertaking extensive revisions to update existing documents, as described in “Options for Implementation under FDA Regulations” above.
Operational Considerations
In addition to plans for revising the DHQ and accompanying materials, blood centers should:
- Identify all SOPs that will require corresponding updates.
- Develop training plans and a timeline for completion to provide adequate instruction to all staff prior to implementation.
- Develop validation plans and a timeline for completion of corresponding updates to the blood center’s website, computer programs, forms, quality programs, program audits, etc. prior to implementation.
- Develop re-entry algorithms and SOPs for donors who were indefinitely deferred under FDA’s previous policy but are eligible to donate based on the new deferral criteria. This would include those who currently meet all criteria:
- And were previously deferred for sexual contact with someone who has hemophilia or used clotting factors,
- And males previously deferred for sexual contact with another male, even once, since 1977.
- Blood centers importing blood products should determine if the distributor’s implementation of the new recommendations is in alignment with their own policies, and evaluate any need for updated vendor qualification records to reflect the distributor’s new policies/SOPs implementing the new recommendations.
- For recovered plasma and products for further manufacture, consult the plasma fractionator or manufacturer regarding their requirements for:
- Compliance with international standards and regulations, which may vary by country of manufacture and country of distribution, related to the FDA’s recommended changes in donor eligibility, donor deferral and re-entry.
- Revisions to existing contracts and Short Supply Agreements to provide for shipment of collections under the new recommendations.
- Review of revised SOPs, documents and records, and future inspections to validate new systems and re-qualify as a vendor.
Facilities should note that several regulations referenced in this guidance were revised in the
May 2015 Final Rule, effective May 23, 2016. All revisions made to regulations in the May 2015 Final Rule will appear in the next version of the “Code of Federal Regulations” (CFR)
online on April 1, 2016, or in hardcopy afterwards when released by the Government Printing Office.
With respect to the CFR citations referenced in this analysis:
- The May 2015 Final Rule revisions update terms but do not change the intent or scope of the requirements in §610.40(h) which applies to shipment and use of unsuitable collections, §610.41 which applies to donor deferral, and §606.121 which applies to labeling of unsuitable products.
- The revisions update the regulations using terms such as eligibility, suitability, RTTI, and other terms for consistency.
- The May 2015 Final Rule, in addition to updating terms for 630.6 Donor Notification, relocated the requirements to new section 630.40 in subpart C.
Until the new versions of the CFR are available, review new §630.40 as shown in the
May 2015 Final Rule under List of Subjects, on page 29895, as published in the “Federal Register”. New §630.40, with Subparts A, B, and C, provides minimum criteria for determining the eligibility of a donor of blood and blood components, suitability of those components, and donor notification.
