Why did FDA publish the final rule on donor screening and testing and related labeling for HCT/Ps?
FDA completed rulemaking that put in place requirements to help prevent the transmission and spread of communicable disease by human cells, tissues, and cellular and tissue-based products (HCT/Ps). The effective date for these requirements was May 25, 2005. After we, FDA, published final rules addressing donor screening/testing and good tissue practices, we heard from individuals who facilitate embryo donation and professional societies that represent reproductive tissue establishments. Their concerns were regarding the impact of the new regulations on embryo donation and the timing for testing of oocyte (egg) donors.
Since publishing the rules, we learned that specific provisions regarding timing for screening and testing of donors could have the unintended effect of discouraging oocyte and embryo donations. Screening and testing may be difficult to schedule in conjunction with conditioning regimens for oocyte donors and embryos originally formed for use by a sexually intimate couple. These HCT/Ps might not be donated until long after the tissues were collected and the prescribed time for screening and testing has passed. An interim final rule, published on May 25, 2005 for immediate implementation, addressed this situation ( 70 Federal Register 29949) . In addition, the interim final rule included a few technical corrections to the new regulations. FDA has now reviewed comments to the interim final rule and published without change this final rule that is effective immediately.
What are the changes in the final rule and how is the final rule different from the donor eligibility final rule?
Specific items, among others, that the final rule addresses are:
- A new exemption is added for cryopreserved embryos that, while originally exempt from the donor eligibility requirement because the donors were sexually intimate partners, are later intended for directed or anonymous donation. When possible, screening and testing of sexually intimate partners who later decide to donate embryos should take place before transfer of the embryo to the recipient.
- If appropriate screening and testing are performed at the time that the decision is made to donate the embryos, the HCT/P must be labeled with, "Advise recipient that screening and testing of the donors were not performed at the time of cryopreservation of the reproductive cells or tissue, but have been performed subsequently."
- If screening and testing of the semen and oocyte donors are not performed, this rule would not prohibit the transfer of the embryo into a recipient. In such an event, the labeling requirements in § 1271.90(b)(2) and (3) are applicable. The HCT/P must be labeled with "NOT EVALUATED FOR INFECTIOUS SUBSTANCES" and "WARNING: Advise recipient of communicable disease risks." This labeling would provide information to the treating physician to permit discussion with the recipient of the potential risks.
- Specimen collection for testing of donors of peripheral blood stem/progenitor cells, bone marrow covered by the HCT/P regulations, and oocytes, is permitted to occur in advance of conditioning regimens. We included a reference to peripheral blood stem/progenitor cells, bone marrow and oocytes in § 1271.80(b) to permit testing up to 30 days before recovery.
- HCT/P donations to first-degree or second-degree relatives may bear labeling containing information identifying the donor.
Section 1271.55(a)(1) requires you to affix a distinct identification code to the HCT/P container, e.g., an alphanumeric sequence that relates the HCT/P to the donor and to all records pertaining to the HCT/P. In the interest of confidentiality, the distinct identification code must not include an individual's name, social security number, or medical record number. We make an exception to this prohibition for autologous or directed reproductive donations because in such donations, the donor is already known to the recipient.
The final rule adds to this exception donations made by first-degree or second-degree blood relatives. Donors who are first-degree or second-degree blood relatives know and are known by the recipient, similar to directed reproductive donations. Adding this exception may increase the comfort of the recipient by helping to confirm that the HCT/P is from the designated donor.
- Where physically impossible to include warnings on container labels, the warning language must be placed on labeling that accompanies the HCT/P.
- We revised § 1271.370(b)(4) to state that if applying the applicable warnings to the container is physically impossible, the labeling must, instead, accompany the HCT/P. This change is necessary because the container for some HCT/Ps, such as those used for semen cryopreservation, is so small that it does not accommodate the warning language. In addition, the use of a tie-tag with warning language is not feasible because it is difficult to securely attach the tie-tag to a container stored in liquid nitrogen. In such cases, the warning language must accompany the HCT/P.
- We clarify labeling requirements that apply to HCT/Ps that are excepted from donor-eligibility determination requirements.
- We revised § 1271.90(b) to clarify when each required label is appropriate for the HCT/Ps described in § 1271.90(a), i.e., autologous cells and tissues, reproductive cells and tissues donated by a sexually intimate partner, and cryopreserved reproductive cells and tissues, including embryos, where the donor(s) was not screened and tested at the time of collection. We also clarified § 1271.90(b)(3), that cells and tissues for autologous use only do not require the label, "Advise patient of communicable disease risk" because the patient's own cells or tissues are being returned, and in this situation, there is minimal, if any, risk.
Does FDA require screening and testing of embryo donors?
According to § 1271.90(a)(2), a donor eligibility determination is not required for reproductive cells or tissue donated by a sexually intimate partner of the recipient for reproductive use. The donors would not have been required to be screened and tested for communicable disease agents at the time that oocytes and semen were recovered because the embryos were intended for use in a sexually intimate relationship. We added an exemption from screening and testing in § 1271.90(a)(4) for cryopreserved embryos that, while originally exempt from the donor eligibility requirement because the donors were sexually intimate partners, are later intended for directed or anonymous donation.
This change reflects the fact that sexually intimate partners may decide to donate their cryopreserved embryos long after their fertility treatments are completed; and, donated embryos may provide a very important treatment option to some individuals who may not be able to conceive a child. We believe this change will enhance the availability of embryos for donation while making clear through labeling any potential risk.
What is the timing of sample collection for donors of peripheral blood stem/progenitor cells; bone marrow when considered an HCT/P; and oocytes?
The final rule permits the collection of a donor specimen for testing up to 30 days before recovery of these HCT/Ps. In the donor eligibility final rule we state that we permit collection of the donor specimen up to 30 days before recovery for donors of peripheral blood stem/progenitor cells due to the myeloablative treatment regimen and the need to determine the eligibility of the donor before the recipient's treatment begins. Because this reasoning also applies to donors of bone marrow covered by the HCT/P regulations and donors of oocytes who must undergo conditioning regimens beginning more than 7 days before recovery of oocytes, we included a reference to bone marrow and oocytes in § 1271.80(b) to permit testing up to 30 days before recovery.
For a cadaveric donor, why did FDA delete the requirement in 1271.80(b) regarding specimen collection at the time of recovery?
Previous language: "(b) Timing of specimen collection. You must collect the donor specimen at the time of recovery of cells or tissue from the donor. However, if collection at the time of recovery is not feasible, then you may collect the donor specimen up to 7 days before or after recovery . . . " [Emphasis added].
Current language: "(b) Timing of specimen collection. You must collect the donor specimen for testing at the time of recovery of cells or tissue from the donor; or up to 7 days before or after recovery . . . "
We deleted the statement in § 1271.80(b) regarding specimen collection at the time of recovery, because we are aware that this has been interpreted to mean that a testing specimen collected from a donor on the day of donation is superior. We believe that, for a cadaveric donor, either a pre-mortem specimen collected within 7 days before death or a post-mortem specimen are appropriate specimens. However, the pre-mortem specimen, if available, may be preferable because it is likely to be less hemolyzed, and excessive hemolysis can interfere with the test results. In addition, a cadaveric donor may have received fluid infusions prior to death, resulting in plasma dilution sufficient to affect test results. For these reasons, a specimen collected on the day of donation from a cadaveric donor may not be superior to a specimen collected within 7 days before death.
* These Questions and Answers are intended to provide a quick reference to the provisions in the Final Rule and are not intended to be all inclusive. For complete information concerning the Final Rule, see that rulemaking at 72 Federal Register 33667, June 19, 2007.