Vaccines, Blood & Biologics
Draft Guidance for Industry: Use of Donor Screening Tests to Test Donors of Human Cells, Tissues and Cellular and Tissue-Based Products (HCT/Ps) for Infection with Treponema pallidum (Syphilis)
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I . Introduction
We, FDA, are providing you, establishments that make donor eligibility determinations for donors of HCT/Ps (HCT/P Establishments), with updated recommendations concerning donor testing for evidence of Treponema pallidum (T. pallidum) infection, the etiologic agent of syphilis. As required under Title 21 of the Code of Federal Regulations (CFR), 1271.80(a) and (c) (21 CFR 1271.80(a) and (c)), you must test a donor specimen for evidence of the communicable disease agents specified in 21 CFR 1271.85, including T. pallidum, using appropriate FDA-licensed, approved, or cleared donor screening tests, in accordance with the manufacturer’s instructions, unless an exception to this requirement applies under 21 CFR 1271.90 (§ 1271.90). This guidance clarifies that we do not consider cleared or approved diagnostic tests or pre-amendment devices (which have not been licensed, approved, or cleared) to be adequate for use in donor testing for T. pallidum infection under the criteria specified in § 1271.80(c).
This guidance applies to HCT/P Establishments regulated under section 361 of the Public Health Service Act and 21 CFR Part 1271 (Part 1271). This guidance, when finalized, will supersede the earlier guidance on compliance with the testing requirements under § 1271.80(c), to the extent that the earlier guidance referred to the testing of HCT/P donors for T. pallidum infection. For your reference, these prior recommendations are contained in the FDA guidance entitled “Guidance for Industry: Eligibility Determination for Donors of Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps),” dated August 2007 (2007 Donor Eligibility guidance) (Ref. 1).
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.
This guidance updates previous recommendations contained in the 2007 Donor Eligibility guidance concerning donor testing for evidence of infection with T. pallidum and clarifies the type of tests FDA considers appropriate to adequately and appropriately reduce the risk of transmission of T. pallidum. We are providing this clarification to assist HCT/P Establishments in complying with the requirements under 21 CFR Part 1271, subpart C, for donor-eligibility determinations based on donor screening tests for T. pallidum.
Under § 1271.45(b), a donor-eligibility determination, based on donor screening and testing for relevant communicable disease agents and diseases, is required for all donors of cells or tissues used in HCT/Ps, except as provided under § 1271.90. To adequately and appropriately reduce the risk of transmission of relevant communicable diseases, and except as provided under § 1271.90, you must test a specimen from the donor of cells or tissue, whether viable or nonviable, for evidence of infection due to relevant communicable disease agents, including T. pallidum (see§ 1271.85(a)(5)). Under § 1271.80(c), you must test for evidence of infection using appropriate FDA-licensed, approved, or cleared donor screening tests in accordance with the manufacturer’s instructions to adequately and appropriately reduce the risk of transmission of the disease agent.
The 2007 Donor Eligibility guidance contains recommendations for complying with the requirements in 21 CFR Part 1271, subpart C, and applies to all HCT/Ps recovered on or after the effective date of these regulations, May 25, 2005. In footnote 6 of the 2007 Donor Eligibility guidance, we stated, “For purposes of this guidance, we consider FDA-cleared diagnostic serological tests to be adequate for use in donor screening for syphilis.”
The 2007 Donor Eligibility guidance did not address the use of pre-amendments devices to meet the requirements of § 1271.80(c), as applied to donor screening for syphilis. The term “pre-amendments device” refers to a device legally marketed in the United States before May 28, 1976, when the Medical Device Amendments of 1976 (Pub. Law No. 94-295, 90 Stat. 539 (1976)) became effective. A device can be a pre-amendments device if it has the same intended use as that marketed before May 28, 1976, has not been significantly changed or modified since then, and if a regulation requiring a premarket approval application for the device has not been issued by FDA. Pre-amendments devices meeting the above criteria are exempted from requirements for premarket submission and review requirements under the Medical Device Amendments of 1976.
When the 2007 Donor Eligibility guidance was issued, few screening tests for evidence of T. pallidum infection in donors were licensed, cleared, or approved. HCT/P Establishments expressed concern that the adoption of platform based donor screening tests would be overly burdensome during the early implementation of Part 1271. After considering these issues, and as an interim measure pending greater availability of and access to these tests, we advised in the 2007 Donor Eligibility guidance that we would consider all cleared serological diagnostic tests for evidence of T. pallidum infection to be adequate for donor screening purposes.
We are now updating the recommendation issued in the 2007 Donor Eligibility guidance regarding use of all cleared serological diagnostic tests to test for T. pallidum. In this guidance, we also are clarifying the status of pre-amendments devices used to test for T. pallidum. Since the 2007 Donor Eligibility guidance issued, several donor screening tests have been cleared. We believe that the technology for donor screening tests has evolved such that FDA-licensed, approved, or cleared test systems with an indication for use in donor screening to test for evidence of T. pallidum infection are now widely available, and that laboratories now are proficient in their ability to utilize such systems. The wide availability of this testing technology and widespread testing laboratory proficiency with these systems no longer support a policy for the use of diagnostic syphilis tests for use as a donor screening test. We also note that the 2007 Donor Eligibility guidance did not address the use of pre-amendment devices for this purpose. We now clarify that, as of the implementation date of the final guidance, we do not intend to exercise enforcement discretion related to the use of such tests as donor screening tests.
This guidance updates prior recommendations and clarifies that:
- We no longer intend to exercise enforcement discretion with respect to the use of diagnostic tests for evidence of infection with T. pallidum for use as HCT/P donor screening tests. Rather, we intend to enforce the requirements provided under § 1271.80(c) that establishments must use appropriate FDA-licensed, approved, or cleared donor screening tests in accordance with the manufacturer’s instructions to adequately and appropriately reduce the risk of transmission of disease agents such as T. pallidum.
- Pre-amendments devices are not acceptable for use as a donor screening test for evidence of infection with T. pallidum.
- This guidance, when finalized, will apply to all HCT/Ps recovered after the date of its implementation.
Once this guidance is finalized, you must, under § 1271.85(a), test all donors of HCT/Ps for evidence of infection due to relevant communicable diseases including syphilis, except as provided under § 1271.90(a). You must test using appropriate FDA-licensed, approved, or cleared donor screening tests, in accordance with the manufacturer’s instructions, to adequately and appropriately reduce the risk of transmission of the disease agent (§ 1271.80(c)). Current FDA-licensed, approved or cleared donor screening tests are listed on the FDA’s website at http://www.fda.gov/BiologicsBloodVaccines/SafetyAvailability/TissueSafety/ucm095440.htm.
- FDA Guidance for Industry: Eligibility Determination for Donors of Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps), August 2007. http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/Tissue/default.htm.
This draft guidance, when finalized, will represent 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.
Submit one set of either electronic or written comments on this draft guidance by the date provided in the Federal Register notice announcing the availability of the draft guidance. Submit electronic comments to http://www.regulations.gov. Submit written comments to the Division of Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852. You should identify all comments with the docket number listed in the notice of availability that publishes in the Federal Register.
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.
U.S. Department of Health and Human Services
Food and Drug Administration
- Center for Biologics Evaluation and Research
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