Guidance for Industry: Recommendations for the Assessment of Blood Donor Suitability, Blood Product Safety, and Preservation of the Blood Supply

Name: Recommendations for the Assessment of Blood Donor Suitability, Blood Product Safety, and Preservation of the Blood Supply in Response to Pandemic (H1N1) 2009 Virus [Docket No. FDA-2009-D-0533]

Status of Guidance: Draft Guidance

Guidance Released: November 13, 2009

Due Date for Comments on Guidance: December 3, 2009. Although anyone may comment on any guidance at any time [see 21 CFR 10.115(g)(5)], to ensure that the agency considers comments on this draft guidance before beginning work on the final version of the guidance, written or electronic comments on the draft guidance were due by December 3, 2009.

Link to Draft Guidance: http://www.fda.gov/downloads/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/Blood/UCM190373.pdf
Link to Comments on Draft Guidance: http://www.pptaglobal.org/UserFiles/file/FDAA09015_FINAL.pdf

http://www.aabb.org/Content/News_and_Media/Comments/comments120309.htm

Target Audience: Blood establishments. Blood establishments are those facilities that manufacture whole blood and blood components intended for use in transfusion as well as whole blood and blood components that are intended for further handling, including the components of recovered plasma, source plasma, and source leukocytes.

Definition Terms Used in the Target Audience Section: Whole blood is a general description for a sample of blood drawn from a person’s vein or artery. Whole blood is composed of red blood cells, white blood cells, platelets (thrombocytes), and plasma. White blood cells are also called leukocytes of which there are several types, namely, granulocytes (neutrophils, eosinophils, and basophils), lymphocytes, and monocytes. Plasma is the pale yellow watery fluid of the blood that contains no cells, but in which the red cells, white cells, and platelets are suspended. Red cells, white cells, platelets, and plasma are blood components. Recovered plasma is plasma pooled from whole blood donations. Source plasma is plasma obtained directly from a donor by a process known as plasmapheresis in which the donor’s plasma is removed and his/her red cells, white cells, and platelets are returned to his/her circulation. Source leukocytes are white blood cells obtained directly from a donor by plasmapheresis in which the donor’s leukocytes are removed and his/her plasma, red cells, and platelets are returned to his/her circulation.

Laws and Regulations Referenced:

1. Section 319 of the Public Health Service Act, 42 U.S.C. § 247d grants the Secretary of Health and Human Services (HHS) broad authority to determine that a public health emergency exists.

2. 21 CFR 211.25 Personnel qualifications.

3. 21 CFR 601.12(c)(5) Biologics licensing; Changes to an approved application.

4. 21 CFR 606.20 Training of personnel.

5. 21 CFR 606.170(b) Reporting of blood donor and blood recipient fatalities.

6. 21 CFR 606.171 Reporting of product deviations by licensed manufacturers, unlicensed registered blood establishments, and transfusion services.

7. 21 CFR 640.3(a), (b)(1) and (4) Suitability of whole blood donors.

8. 21 CFR 640.63(a), (c)(1) and (7) Suitability of source plasma donors.

Summary:
This guidance provides US Food and Drug Administration (FDA) recommendations for assessing the suitability of blood donors, assessing blood product safety, and preserving the blood supply in reference to the 2009 pandemic (H1N1) influenza virus.

Rationale: Although the potential for transmission of the 2009 pandemic (H1N1) influenza virus by blood transfusion remains unknown, because of the known potential for this virus to spread rapidly, H1N1 infection has the potential to cause disruptions in the blood supply. Therefore, recommendations regarding how to assess the suitability of blood donors, how to assess the safety of blood products, and how to preserve the blood supply during this pandemic are necessary.

Resulting Recommendations: The first recommendation addresses the training of back-up personnel. Blood establishments are required by 21 CFR 211.25 and 21 CFR 606.20 to have an adequate number of employees to perform necessary tasks, and to ensure that all personnel possess the proper educational background, training and experience to assure competent performance of their assigned functions. The FDA recommends that blood establishments have adequate back-up personnel in the event of anticipatable personnel shortages as the result of disease caused by the2009 pandemic (H1N1) influenza virus.

The second set of recommendations addresses three issues: blood donor suitability, blood donor deferral, and blood product management. With regard to blood donor suitability, the FDA recommends that, because a blood donor’s responses to the donor questions presented before blood collection are occasionally found to be incomplete, blood establishments may obtain omitted responses to questions within 24 hours of the blood collection.

Regarding the deferral of blood donors, to ensure donors are in good health on the day of blood donation as required under 21 CFR 640.3(b) and 21 CFR 640.63(c), blood donors with a confirmed or probable case of pandemic (H1N1) 2009 virus infection should be deferred until at least 24 hours after they are free of fever without the use of fever reducing medications (a daily dose of pediatric aspirin [81 mg] is not considered fever-reducing medication) and they are otherwise asymptomatic. Additionally, data do not support deferring blood donors after vaccination with live attenuated influenza vaccines or inactivated influenza vaccines against pandemic (H1N1) 2009 virus or for prophylactic use of the antiviral medications oseltamivir (Tamiflu) and zanamivir (Relenza). However, to be consistent with the recommendation regarding blood donors who were infected with probable pandemic (H1N1) 2009 virus, blood donors taking antiviral medications for confirmed or probable pandemic (H1N1) 2009 virus infection should be deferred until at least 24 hours after they are free of fever without the use of fever reducing medications and they are otherwise asymptomatic.

The FDA’s recommendation on blood product management applies to donations of whole blood and blood components intended for transfusion. This recommendation does not apply to blood components intended for further manufacture such as recovered plasma, source plasma, and source leukocytes. The reason for this is that validation studies have shown that viruses with similar characteristics to 2009 pandemic (H1N1) influenza virus (a large lipid-enveloped virus) are effectively inactivated and/or removed during the manufacture of plasma derivatives. The FDA recommends that upon receipt of post donation information about a donor with confirmed or probable pandemic (H1N1) 2009 disease or influenza like illness within 48 hours after the donation, the Medical Director evaluate the safety of the donations from that donor consistent with existing Standard Operating Procedures.

The final recommendation addresses changes to approved applications from licensed blood establishments. The FDA recommends that the change of using a different outside testing laboratory may be submitted as a “Supplement-Changes Being Effected”. Also, the FDA recommends that the change of implementing self-administered donor history questionnaires may be submitted as a “Supplement-Changes Being Effected”.

In this guidance, the FDA also reminds blood establishments that if a complication of a blood transfusion results in the death of a blood recipient, then the blood establishment must report the fatality to the FDA as soon as possible. The last FDA reminder to blood establishments concerns convalescent plasma which is plasma obtained after recovery from an acute infection. In theory, the transfusion of convalescent plasma might be used as empirical treatment during an influenza pandemic. However, because of its experimental nature, collection and administration of convalescent plasma should be conducted only under an Investigational New Drug Application (IND). The FDA recommends that blood establishments that intend to manufacture convalescent plasma should contact the FDA to discuss their plans.

Impact: The goal of this recommendation is to ensure that the blood supply in the US is maintained at an adequate level and that the blood and blood products are kept free of the 2009 pandemic (H1N1) influenza virus so that this virus is not spread from person to person by the administration of blood and blood products. Patients who need blood transfusions most likely have serious health problems. The most severe outcomes of infection with 2009 pandemic (H1N1) influenza virus have been reported among individuals with underlying health problems that are associated with a high risk of complications from influenza. These severe outcomes can be avoided by maintaining a blood supply that is free of 2009 pandemic (H1N1) influenza virus.

Blogger’s 2¢: I found two sets of comments on this guidance. The first is dated December 3, 2009, and is from the American Association of Blood Banks (AABB). The AABB suggests three changes to this draft guidance. First the AABB comments that obtaining a donor’s omitted responses to questions within 24 hours of the collection should be made explicit not only for the 2009 pandemic (H1N1) influenza virus because it is applicable to assessments of blood donor suitability/eligibility in general. Second and third, the AABB suggests that two of the recommendations not be restricted to use in a pandemic. Namely, the fact that the change to a different outside test lab and the change of implementing a self-administered donor history questionnaire are now recommended to be submitted as a “Supplement-Changes Being Effected” should apply at all times, not just during a pandemic.

The second set of comments is also dated December 3, 2009, and is from the Plasma Protein Therapeutics Association (PPTA). The PPTA is the international trade association and standards-setting organization for the world’s major producers of plasma-derived and recombinant analog therapies. The PPTA also suggests three changes to this guidance. First, regarding the training of back-up personnel in blood establishments, the PPTA recommends that the following line be deleted, “more than one back-up personnel should be trained for each critical function” because the number of people trained for one function is not important as long as blood establishments take reasonable steps to assure continued operations during a pandemic. Second, regarding blood donor suitability, the PPTA would like the following statement deleted or further clarified to include interpretive criteria to prevent the needless destruction of life-saving blood components, “You may clarify a donor’s response to the donor history questionnaire or obtain omitted response to questions within 24 hours of the collection.” Third, with regard to the collection and use of convalescent plasma, the PPTA agrees that the administration of convalescent plasma should be conducted only under an IND; however, the PPTA disagrees that simply the collection of convalescent plasma must also be performed under an IND.

It will be interesting to see how the FDA includes the comments from the AABB and PPTA in the final guidance. If I become aware of the final guidance before the end of this semester, I will post a link to it on this blog.