Additional copies of this guidance are available from the Office of Communication, Training and Manufacturers Assistance (HFM-40), 1401 Rockville Pike, Suite 200N, Rockville, MD 20852-1448, or by calling 1-800-835-4709 or 301-827-1800, or from the Internet at http://www.fda.gov/cber/guidelines.htm.
For questions on the content of this guidance, contact the Division of Blood Applications, Office of Blood Research and Review (OBRR), Center for Biologics Evaluation and Research (CBER), at 301-827-3543.
U.S. Department of Health and Human Services
Food and Drug Administration
Center for Biologics Evaluation and Research
- REPORTING TO FDA THE IMPLEMENTATION OF ACCEPTABLE DONOR HISTORY QUESTIONNAIRE AND ACCOMPANYING MATERIALS BY LICENSED MANUFACTURERS
- Implementation of Acceptable DHQ Documents
- Implementing the Self-Administration of Acceptable DHQ Documents
- RECOGNITION OF V.DHQ-1.1
- RECOGNITION AND IMPLEMENTATION OF FUTURE ACCEPTABLE DHQ DOCUMENTS
- FOR MORE INFORMATION
Contains Nonbinding Recommendations
Guidance for Industry
Implementation of Acceptable Full-Length Donor History Questionnaire and Accompanying Materials for Use in Screening Donors of Blood and Blood Components
This guidance provides blood establishments that collect blood and blood components intended for transfusion or for further manufacture (referred to as "manufacturers" or "you") with advice on reporting to the Food and Drug Administration (FDA) a manufacturing change consisting of the implementation of a standardized full-length donor history questionnaire and accompanying materials (DHQ documents). The DHQ documents will provide you with a specific process for administering questions to donors of blood and blood components (referred to as "donors") to determine their eligibility1 to donate. Acceptable DHQ documents are DHQ documents that FDA has determined will provide licensed and unlicensed manufacturers with one means of complying with the donor screening requirements in §§ 640.3 and 640.63.
This guidance advises licensed manufacturers who choose to implement acceptable DHQ documents on how to report the manufacturing change to FDA under § 601.12 (21 CFR 601.12), and on the information they should submit. Since they are not required to report manufacturing changes under § 601.12, unlicensed registered manufacturers implementing the use of acceptable DHQ documents do not need to report this change to FDA.
In this guidance, we also recognize Donor History Questionnaire Version No. 1.1 dated June 2005 (v.DHQ-1.1), prepared by the AABB (formerly known as the American Association of Blood Banks) Donor History Task Force, as an acceptable mechanism that is consistent with FDA requirements and recommendations for collecting donor history information. In the future, we may recognize other DHQ documents as acceptable, and intend to make all of the acceptable DHQ documents available at http://www.fda.gov/cber/dhq/dhq.htm.
This guidance finalizes the draft guidance entitled "Guidance for Industry: Acceptable Full-Length Donor History Questionnaire and Accompanying Materials for Use in Screening Human Donors of Blood and Blood Components" dated April 2004 (May 12, 2004, 69 FR 26399).2
FDA's guidance documents, including this guidance, do not establish legally enforceable responsibilities. Instead, guidances describe FDA'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 FDA's guidances means that something is suggested or recommended, but not required.
A donor's eligibility to donate blood and blood components is determined in part by a physical assessment and medical history interview to determine whether the donor is free of any diseases transmissible by blood transfusion. Such determination must be made on the day of collection from the donor (§§ 640.3(a) and 640.63(a)). The first formal uniform donor screening questionnaire was developed in 1953 (Ref. 1). Since then, the number of questions and the amount of information captured during the questioning process has increased to capture information related to newly recognized risks of disease transmission, resulting in an increasingly complex and time-consuming process.
The primary purpose of questioning the donor is to ensure that the donor is in good health and the donation process is safe for the donor, and to identify risk factors for diseases transmissible by blood and blood components. The donor interview is especially important to identify risks for diseases and conditions for which there are no laboratory tests, for which tests are not sensitive enough to detect infectious disease agents, and for which tests are unable to identify early stage or window period infections.
Donor questionnaires play an important role in identifying most ineligible donors, but we are aware that the donor questionnaire processes currently in place at United States blood collection establishments do not prevent all ineligible donors from donating. This is evidenced by the numerous biological product deviation reports submitted to CBER each year related to errors in capturing information and identifying ineligible donors during the donor questioning process (Ref. 2).
In 2000, the AABB convened a multi-organizational task force3 to address several issues related to the donor questionnaire process (Ref. 3). The goals of the task force included reducing the complexity of the questionnaire and the educational materials to assure that donors will better comprehend the information and provide more accurate responses. The task force consisted of representatives from the blood and plasma industry and professional trade organizations to ensure, to the greatest extent possible, that all blood establishments would be represented, as well as support and use the donor history questionnaire and accompanying materials prepared by the task force. The task force also included an ethicist, statistician, experts in survey design and cognitive methods, and liaisons from the Centers for Disease Control and Prevention and FDA.
The task force revised and redesigned the pre-existing AABB Uniform Donor History Questionnaire and developed a new process for interviewing donors. The new process includes use of the following methods and materials to obtain information about a donor. The materials are intended to be used in their entirety.
- Full-Length Donor History Questionnaire - contains all initial donor screening questions.
- Donor History Questionnaire User Brochure - includes a glossary, flow charts and references; describes how questions should be administered; and contains follow-up questions to further evaluate a potential donor's response to capture questions. "Capture" questions ask a general question about a donor's history or behavior and are followed up by more specific questions if needed.
- Medication Deferral List - companion document to the questionnaire that contains a list of medications that may serve as a basis for donor deferral.
- Blood Donor Educational Materials - educates the donor about the donation process and risks and conditions that are the basis for deferrals.
The task force developed and evaluated new questions to determine if donors could comprehend them and provide correct information. Previously published focus group studies showed that questions should be simple and focus on one behavior rather than ask about several different behaviors, and that some terms required clarification in order to enhance donor comprehension (Ref. 4). Cognitive interview studies, conducted as part of the task force efforts, provided information on recall, suggested that questions should be reasonably specific, and indicated that individuals tended to answer the questions conservatively, even if they did not always interpret the questions uniformly. The results of the tests showed that there is a need to educate donors about why certain behaviors put them at risk to transmit diseases to recipients. Blood donor interviewers in several blood collection establishments also evaluated the final questioning process. The blood collection establishments stated that the new process for asking questions and for providing information to the donors was an effective, easy-to-use tool (Ref. 5).
We discussed the new donor questionnaire process during several Blood Product Advisory Committee (BPAC) meetings. Informational presentations were given during the BPAC meeting held on June 14, 2001. These presentations described the task force activities, the new questionnaire process developed by the task force, and the focus group study design (Ref. 6). The progress of the task force's activities and the results of the cognitive studies were presented during the BPAC meeting held on June 13, 2002 (Ref. 7). The BPAC unanimously supported the task force's efforts at each meeting.
We believe that the use of acceptable DHQ documents will provide one way to meet FDA requirements and recommendations related to donor eligibility interviews. Acceptable DHQ documents may also contain questions related to issues that FDA does not require or recommend for determining donor eligibility. By recognizing that the use of acceptable DHQ documents is one way to satisfy regulatory requirements, we are not requiring or recommending that donors be screened or deferred for these issues. Manufacturers are free to use an alternate questionnaire, which does not include questions related to these additional issues, or, if they choose to implement acceptable DHQ documents, to eliminate the additional questions from their procedures.
While we recognize that acceptable DHQ documents provide an effective tool for screening donors, we do not require that manufacturers implement acceptable DHQ documents. Licensed manufacturers may continue to use their previously approved full-length donor history questionnaire and accompanying materials, including any previously approved alternative procedures and wording, and may implement, consistently with § 601.12, other processes in the future.
- Implementation of Acceptable DHQ Documents
For licensed manufacturers that decide to implement acceptable DHQ documents, the implementation is a manufacturing change reportable to FDA under § 601.12.
- Report as a minor change if acceptable DHQ documents are implemented without modifications and in their entirety as a complete process for administering questions to donors. Report such a change to FDA in your annual report under § 601.12(d), noting the date the process was implemented. If donors will be allowed to self-administer acceptable DHQ documents, see section IV.B.
- Report as a minor change if acceptable DHQ documents are implemented in their entirety, but modified (a) by adding additional, more restrictive selection criteria that are specific to your blood establishment; or (b) by omitting questions that FDA has not required or recommended for determining donor eligibility. Report such changes to FDA in your annual report under § 601.12(d), noting the date the process was implemented and describing the additional criteria or questions that were omitted from your questionnaire.
- Report as a minor change if acceptable DHQ documents are implemented in their entirety but modified by displaying in another format that is compatible with your current standard operating procedures (SOPs) the information contained in the flow charts, provided that there is no change to the content of the flow charts related to an FDA required/recommended donor deferral criterion. Report such changes to FDA in your annual report under § 601.12(d), noting the date the process was implemented and describing how you modified the acceptable DHQ documents.
- Report as a minor change if acceptable DHQ documents are implemented in their entirety, but modified by reformatting any of the acceptable DHQ documents (other than the flow charts) to be consistent with your current SOPs, provided you do not change the wording and the order of content in the acceptable DHQ documents. Report such changes to FDA in your annual report under § 601.12(d), noting the date the process was implemented and describing how you modified acceptable DHQ documents.
- Because donor screening is so important to the safety of blood and blood components, and because screening procedures have a substantial potential to have an adverse effect on the quality, including safety and effectiveness, of blood and blood components, we cannot conclude at this time that the implementation of acceptable DHQ documents, which are modified other than as specifically described in sections IV.A.2, IV.A.3, and IV.A.4, will be a minor change.4 Therefore, if you wish to implement and modify acceptable DHQ documents other than as described in sections IV.A.2, IV.A.3, and IV.A.4, report such changes to FDA as a Prior Approval Supplement (PAS) under § 601.12(b). We recommend that you include the following in the submission:
- FDA Form 356h "Application to Market a New Drug, Biologic or an Antibiotic Drug for Human Use."
- A cover letter describing the request and the contents of the submission.
- A written SOP describing the donor questions and questionnaire process. Please highlight the modifications.
- The full-length donor history questionnaire and accompanying document(s).
For assistance in preparing the supplement, see FDA's "Guidance for Industry: For the Submission of Chemistry, Manufacturing and Controls and Establishment Description Information for Human Blood and Blood Components Intended for Transfusion or for Further Manufacture and for the Completion of the Form FDA 356h 'Application to Market a New Drug, Biologic or an Antibiotic Drug for Human Use'" dated May 1999 (Ref. 8).
- Implementing the Self-Administration of Acceptable DHQ Documents
The task force prepared the v.DHQ-1.1 to provide an option for the donor to self-administer the questionnaire. Future versions of the DHQ documents may also provide for donor self-administration. In July 2003, we issued a guidance document entitled "Guidance for Industry: Streamlining the Donor Interview Process: Recommendations for Self-Administered Questionnaires" (Streamlining Donor Interview guidance), advising licensed blood establishments to submit procedures for self-administering the donor history questionnaire to FDA as a Changes Being Effected in 30 days supplement (CBE30) under § 601.12(c) (Ref. 9). We determined in the Streamlining Donor Interview guidance that a CBE30 was an appropriate supplement to ensure that controls were in place to manage this process. However, when acceptable DHQ documents include instructions for controlling the self-administration process,5 as described below, this change may be reported in an annual report or, in some situations, as a CBE30. These provisions modify those stated in the Streamlining Donor Interview guidance. Licensed manufacturers planning to implement self-administration of a questionnaire other than acceptable DHQ documents should continue to consult the Streamlining Donor Interview guidance (Ref. 9).
Licensed manufacturers that want to offer donors the option of self-administering acceptable DHQ documents should report this change to us as follows:
- Report as a minor change if a manufacturer chooses to implement self-administration of acceptable DHQ documents using the written form or audio/visual presentation methods described in the acceptable DHQ documents. Report such a change to FDA in your annual report under § 601.12(d), noting the date the process was implemented.
- Report as a moderate change if a manufacturer chooses to implement acceptable DHQ documents using a computer-assisted interactive interview procedure. This change presents a potential to adversely affect the quality, including the safety and effectiveness, of blood and blood components because of concerns that the presentation of the questions and information may not be easily readable in all conditions and by all potential users. Additionally, implementation for the first time of a computer-assisted interactive interview procedure may raise new issues that should be evaluated, such as the management of electronic records. Report such change to FDA as a CBE30 under § 601.12(c).
For assistance in implementing and reporting of self-administered questionnaires other than as described above, and for preparing the supplement for the computer-assisted interactive interview procedure, see the Streamlining Donor Interview guidance (Ref. 9).
We recognize v.DHQ-1.1 as acceptable DHQ documents that provide an acceptable mechanism for implementing FDA requirements and recommendations related to donor eligibility interviews. The v.DHQ-1.1 contains questions related to the following donor medical history issues for which we currently do not have requirements or recommendations: cancer; organ, tissue, or bone marrow transplant; bone or skin graft; and pregnancy. As stated in section III, manufacturers implementing v.DHQ-1.1 that omit these questions would still be in compliance with FDA requirements.
In the future, we may issue regulations or guidance documents concerning donor deferrals when we identify new infectious diseases, medical conditions, or medications that have the potential to affect the donor's safety or the safety, purity, and potency of blood and blood components. Implementation of new safeguards would change your donor interview SOPs, and involve amending either acceptable DHQ documents(typically by adding a question at the end of the questionnaire in the area designated for additional questions or by implementing new or revised acceptable DHQ documents), or if you do not use acceptable DHQ documents, your own questionnaire. We anticipate that in the event we recommend a new donor deferral criterion, we will, in the same guidance, provide recommendations concerning implementing and reporting to FDA the manufacturing changes associated with this change in procedure. If revised DHQ documents are available and acceptable, we also intend to recognize those DHQ documents as acceptable and may do so in the document addressing the donor deferrals. We intend to make all acceptable DHQ documents available at http://www.fda.gov/cber/dhq/dhq.htm.
If you intend to use such future documents, we recommend that you have a mechanism in place for implementing the updated acceptable DHQ documents in all your facilities.
If you have questions regarding this guidance and FDA policies for implementing acceptable DHQ documents, call the Division of Blood Applications, OBRR, CBER, at 301-827-3543 or fax at 301-827-3534.
If you have questions regarding the v.DHQ-1.1 or other AABB DHQ documents, call AABB, at 301-907-6977 or fax at 301-907-6895 to the attention of the AABB Donor History Task Force.
DHQ documents that FDA has recognized as acceptable are available at http://www.fda.gov/cber/dhq/dhq.htm.
- American Association of Blood Banks, Technical Methods and Procedures of the American Association of Blood Banks, pp. 3-5, Minneapolis: Burgess Publishing Co., 1953.
- CBER Biological Product Deviation Reports, FY04 Summary, April 28, 2005. (http://www.fda.gov/cber/biodev/bpdrfy04.htm)
- FDA/AABB Workshop on "Streamlining the Blood Donor History Questionnaire" Transcripts - October 16, 2000. (http://www.fda.gov/cber/minutes/bldqstn101600.pdf)
- Orton, S., V. Virvos, and A. Williams, "Validation of Selected Donor-Screening Questions: Structure, Content and Comprehension," Transfusion, 40:1407-1413, 2000.
- AABB Task Force UDHQ Submission dated March 25, 2002.
- Blood Product Advisory Committee Transcripts - June 14, 2001.
- Blood Product Advisory Committee Transcripts - June 13, 2002.
- FDA "Guidance for Industry: For the Submission of Chemistry, Manufacturing and Controls and Establishment Description Information for Human Blood and Blood Components Intended for Transfusion or for Further Manufacture and for the Completion of the Form FDA 356h 'Application to Market a New Drug, Biologic or an Antibiotic Drug for Human Use,'" May 10, 1999. (http://www.fda.gov/cber/gdlns/cmcblood.htm)
- FDA "Guidance for Industry: Streamlining the Donor Interview Process: Recommendations for Self-Administered Questionnaires," July 3, 2003. (http://www.fda.gov/cber/gdlns/donorsaq.htm)
2 The April 2004 draft guidance referred to the DHQ documents version 1 (v.DHQ-1). Since the draft issued, the AABB task force revised the v.DHQ-1 slightly, creating Version No. 1.1. This guidance refers to that revised version as v.DHQ-1.1.
3 In the April 2004 draft guidance, we referred to this task force as the "Interorganizational Uniform Donor History Questionnaire Task Force." They have since changed their name to the "AABB Donor History Task Force" to reflect their broader initiative.
4 This would include any modification(s) to the acceptable DHQ documents for purposes of screening and determining the eligibility of Source Plasma donors consistent with FDA requirements and recommendations.