I . Introduction
This guidance document provides you, blood establishments that collect blood and blood components, with our, FDA’s, recommendations for questioning and deferring donors of blood and blood components, allowing their reentry, and product management to reduce the risk of transfusion-transmitted malaria. The recommendations contained in this guidance apply to the collection of Whole Blood and all blood components with the exception of Source Plasma. Donors of Source Plasma are excluded from deferral due to malaria risk under Title 21 Code of Federal Regulations, 640.63(c)(9) (21 CFR 640.63(c)(9)).
This guidance finalizes the draft guidance entitled “Recommendations for Donor Questioning, Deferral, Reentry and Product Management to Reduce the Risk of Transfusion-Transmitted Malaria” dated June 2012, and supersedes the FDA memorandum to all registered blood establishments entitled “Recommendations for Deferral of Donors for Malaria Risk” dated July 26, 1994 (July 26, 1994 memorandum) (Ref. 1).
FDA’s guidance documents, including this guidance, do not establish legally enforceable responsibilities. Instead, guidances describe the Agency’s current thinking on a topic and should be viewed only as recommendations, unless specific regulatory or statutory requirements are cited. The use of the word should in Agency guidance means that something is suggested or recommended, but not required.
Transfusion-transmitted malaria occurs rarely, but is a serious concern in transfusion medicine (Refs. 2, 3). It has been shown to be caused by any of the following four Plasmodium species: P. falciparum; P. malariae; P. ovale; or P. vivax. In the absence of a licensed test for donor screening, the measure used to reduce transfusion-transmitted malaria in the United States (U.S.) has been the deferral of donors who have had a malaria infection or had a possible exposure risk to malaria. Accurate identification of donors with the potential to transmit malaria depends on the donor exposure history obtained during the donor interview, which may be facilitated through use of a donor questionnaire (Refs. 4-6).
The July 26, 1994 memorandum had the following recommendations:
Public comments on the July 26, 1994 memorandum and the June 2000 draft guidance on screening of donors for malaria risk raised several concerns about the need to standardize definitions used in the recommendations, and the scientific basis for the recommended deferral periods. These concerns prompted public discussions, including a meeting of the FDA Blood Products Advisory Committee (BPAC or Committee) on September 16, 1999. At that meeting, BPAC reviewed the current status of transfusion-transmitted malaria and its impact on blood safety in the U.S. BPAC also reviewed the usefulness of the available laboratory test methods to detect current malaria infection or to provide evidence of past exposure to malaria parasites.
On July 12, 2006, FDA convened a scientific workshop entitled “Testing for Malarial Infections in Blood Donors” to seek public discussion of scientific developments that might support donor testing for malaria infections as part of pre-donation testing, or as follow-up testing to permit a reduced deferral period for donors deferred for malaria risk (Ref. 7). There are no FDA-licensed tests to screen blood donors for malaria. Nucleic acid-based tests were deemed unsuitable for donor screening due to the limitation of the small sample size used in nucleic acid extraction; however, several speakers and panel members emphasized the value of antibody testing to reenter deferred malaria-risk donors who tested negative for malarial antibodies (Refs. 7, 8). The outcome of the workshop was summarized at the BPAC meeting held on July 13, 2006 (Ref. 9).
At the BPAC meeting on September 11, 2008, the Committee discussed donor testing for malarial antibodies as an indicator of possible exposure to malaria parasites (Ref. 10). At the meeting, FDA presented risk assessment data for three possible scenarios in which antibody testing could be of value: (1) testing all donors (universal testing); (2) reentry testing of all at-risk donors with a history of potential exposure to malaria anywhere in the world; and (3) reentry testing of only those donors who had traveled to malaria-endemic areas in Mexico. The risk assessment model assumed that donors would be deferred for four months after returning from endemic areas of Mexico or other parts of the world before antibody testing would be performed on the donor. At the meeting, two blood organizations (the American Red Cross and America’s Blood Centers) also presented data from surveys showing that approximately 41% of all blood donors deferred for risk of malaria exposure had been deferred because they had traveled to malaria-endemic areas in Mexico (Refs. 10, 11). The Committee considered all three risk assessment scenarios and the possible role that antibody testing could play in identifying or reentering malaria-risk donors, especially those donors who had traveled to endemic areas in Mexico. In the end, the Committee felt that additional risk analysis would be needed, and that the analysis should account for malaria risk globally and in Mexico, with and without antibody testing.
On November 16, 2009, FDA again sought advice from BPAC on an alternative strategy to minimize donor loss associated with deferrals for malaria risk. Specifically, FDA asked the Committee to consider a new risk assessment model which was focused on travel to malaria-endemic states in Mexico, and asked whether it was acceptable to allow blood collections without any deferral from individuals who have traveled to certain Mexican states that have a low malaria transmission rate. At that meeting, FDA presented data which showed that while travel to Mexico was a major contributor to donor deferrals due to malaria risk (about 41%), from 2006-2009, malaria transmission in Mexico was shown to be very low (average 2400 malaria cases annually) and limited only to certain Mexican states (Ref. 12). The malaria transmission rate was shown to be particularly low in Quintana Roo, a Mexican state that includes Cancun and Cozumel and is known to receive a high volume of U.S. travelers. Estimates also suggested that there was a great disparity in the contribution of different Mexican states to the number of donor deferrals among U.S. travelers. Data collected by the American Red Cross and Blood Systems Research Institute suggested that in 2006, among the 10 malaria-endemic states, Quintana Roo alone contributed approximately 70% of all malaria-risk-associated donor deferrals for travel to Mexico (Refs. 12, 13). While donors deferred because of travel to Quintana Roo were a significant percentage of deferrals, FDA’s risk assessment found that the calculated overall risk to the blood supply would be expected to increase by 1.1% (an absolute increase of 0.0166 infected blood unit per year, or one in 60 years) if prospective blood donors who visited Quintana Roo and another state, Jalisco, which includes the cities of Puerto Vallarta and Guadalajara, were allowed to donate blood without any deferral for malaria risk. However, the donor pool would increase by approximately 45,000 donors (79,000 blood units) each year (Ref. 13). FDA also found that the actual donor gain might be significantly higher if the agency took into account the total donor loss due to self-deferrals and the non-return of donors deferred under the current policy (Ref. 7). After these presentations and discussion, the Committee voted 17-1 in favor of allowing blood collection, without any deferral for malaria risk, from U.S. residents who have visited Quintana Roo. The Committee also discussed extending the proposed policy to other malaria-endemic states of Mexico that have a low malaria transmission rate.
Malaria - An infectious disease caused by a parasitic protozoan of the genus Plasmodium. Malaria diagnosis in a prospective donor is based on a positive laboratory test indicating Plasmodium infection, or a determination of a history of malariaade by the blood establishment’s Medical Director. For additional information regarding malaria and its associated symptoms, visit the Centers for Disease Control and Prevention (CDC) website at http://www.cdc.gov/malaria/.
Malaria-endemic area - Any areas with malaria where CDC recommends anti-malarial chemoprophylaxis in travelers in the most current version of the CDC Health Information for International Travel (commonly known as The Yellow Book) at the time the donor is screened. We recommend you access the “Malaria Information, by Country” table in the Malaria chapter of The Yellow Book for the most current recommendations on anti-malarial chemoprophylaxis. The Yellow Book is available on the CDC website at http://wwwnc.cdc.gov/travel/page/yellowbook-2012-home.htm.
Malaria-endemic country - Any country having an area or areas with malaria where CDC recommends anti-malarial chemoprophylaxis in travelers in The Yellow Book at the time the donor is screened. A country that has any malaria-endemic areas should be considered to be malaria-endemic in its entirety.
Residence in a malaria-endemic country - For purposes of this guidance, residence is defined as a continuous stay of longer than 5 years in a country or countries having any malaria-endemic area (see definition above). In determining residence, consideration is by malaria-endemic country and not by malaria-endemic area since the geographic distribution of malaria-endemic areas may change during the period of residence, or the resident may have traveled from a non-endemic area to an endemic area in the country during his or her stay.
Travel to a malaria-endemic area - Any travel to or through a malaria-endemic area or areas, as identified by CDC (see definition above). The duration of travel to a malaria-endemic area is defined as more than 24 hours to less than 5 years. Note that a passage greater than 24 hours through a malaria-endemic area while on route to a malaria-free area is considered a sufficient possible exposure to trigger donor deferral. Common examples of such possible exposure include passage through a malaria-endemic area to visit a tourist resort in a malaria-free area, or passage through a malaria-endemic area to board a cruise ship, or on-shore excursions into a malaria-endemic area when traveling on a ship. Travel to or through a malaria-free area within a malaria-endemic country does not constitute travel to a malaria-endemic area
FDA’s scientific rationale and further explanation for our recommendations are provided in the Appendix.
A. Donor History Questionnaire
B. Donor Deferral and Reentry
C. Product Retrieval and Quarantine, and Notification of Consignees of Blood and Blood Components
We recommend that you take the following actions if you determine that blood or blood components have been collected from a donor who should have been deferred according to the recommendations in section IV.B of this guidance.
D. Product Disposition and Labeling
You should not label these products with a U.S. license number unless FDA specifically approves you to do so. If appropriate, unlicensed products may be shipped solely to a manufacturer of a product subject to licensure, under a short supply agreement (21 CFR 601.22).
E. Reporting a Biological Product Deviation (BPD)
If you have distributed any cellular blood components for transfusion or for further manufacturing, collected from a donor at risk for malaria according to section IV.B. of this guidance, you should report a BPD as soon as possible, but you must report within 45 calendar days from the date you acquire the information reasonably suggesting that a reportable event has occurred (21 CFR 606.171).
You are not required to report a BPD if you have distributed an acellular blood component intended for transfusion or further manufacturing from a donor at risk for malaria.
Whole Blood and blood components intended for transfusion should not be collected from a possible malaria risk donor with the intent of converting or relabeling those products for further manufacturing use (e.g., relabeling of Fresh Frozen Plasma as recovered plasma).
We recommend that you implement the recommendations contained in this guidance within twelve months of publication of this guidance.
You may implement the recommendations once you have revised your donor history questionnaire (DHQ), including full length and abbreviated DHQs, and accompanying materials as necessary to reflect the new donor deferral recommendations. Licensed blood establishments must report the changes to FDA in the following manner:
If the current version of the DHQ and accompanying materials prepared by the AABB Donor History Task Force are revised to contain the recommendations in this guidance and are found acceptable by FDA, we would consider the implementation of the questionnaire and accompanying materials to be minor changes, if implemented without modification and in their entirety as a complete process for administering questions to donors. Report such a change to FDA in your annual report under 21 CFR 601.12(d), noting the date the process was implemented.
SCIENTIFIC RATIONALE AND FURTHER EXPLANATION FOR THE RECOMMENDATIONS
The scientific basis and further explanation for the recommendations in section IV of this guidance are as follows:
Based on the current epidemiological data and the definition of malaria-endemic area in this guidance, FDA does not currently recommend deferral of donors who have traveled to the Mexican states of Quintana Roo and Jalisco; thus, these donors, if otherwise eligible, may donate. Please note that the designation of malaria-endemic areas in Mexico or in any malaria endemic country and accordingly, a recommendation for donor deferral, are subject to change based on the most updated malaria transmission information with respect to that area, as listed in The Yellow Book. For example, if malaria transmission in these states changes and anti-malarial chemoprophylaxis is recommended by CDC, then the donor deferral recommendations would encompass donors who travel to these areas.
1 See Appendix for detailed scientific rationale for the recommendations contained in this guidance.
Additional copies of this guidance are available from the Office of Communication, Outreach and Development (OCOD) (HFM-40), 1401 Rockville Pike, Suite 200N, Rockville, MD 20852-1448, or by calling 1-800-835-4709 or 301-827-1800, or e-mail email@example.com, or from the Internet at http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/default.htm .
For questions on the content of this guidance, contact OCOD at the phone numbers or e-mail address listed above.
This guidance represents the Food and Drug Administration’s (FDA’s) current thinking on this topic. It does not create or confer any rights for or on any person and does not operate to bind FDA or the public. You can use an alternative approach if the approach satisfies the requirements of the applicable statutes and regulations. If you want to discuss an alternative approach, contact the appropriate FDA staff. If you cannot identify the appropriate FDA staff, call the appropriate number listed on the title page of this guidance.
Additional copies of this guidance are available from:
Office of Communication, Outreach and Development (OCOD), (HFM-40),
If you have questions regarding this guidance and FDA policies for implementing acceptable aDHQ documents, contact OCOD at the phone numbers or e-mail address listed above.
U.S. Department of Health and Human Services