| Comment Record|
Dr. Thomas Price ||
2002-07-08 18:37:36 |
Puget Sound Blood Center |
| Comments for FDA General |
1. General Comments
To Whom It May Concern:
Please accept these comments related to the Draft Guidance for Industry Use of Nucleic Acid Tests on Pooled and Individual Samples from Donors of Whole Blood and Blood Components for Transfusion to Adequately and Appropriately Reduce the Risk of Transmission of HIV-1 and HCV. The Puget Sound Blood Center was a study site for one of the clinical trials for blood donors and supports the introduction of this test to increase the safety of the blood supply. We submit the following comments on the draft guidance:
1. The FDA must address the real issues of donor management, counseling/notification, and lookback. The benefit of doing so in an alternate document is not apparent and compromises blood establishments' capacity to provide meaningful comment on the use of a licensed NAT test. Additional guidance, if provided, also increases the probability that further inconsistencies will develop. We are required by 21 CFR 610.40-47 to test, defer and notify all donors for HCV and HIV-1 and to perform HIV lookback and recipient tracing. Without attending to these requirements, this draft guidance is hollow and superfluous.
2. Does the guidance apply to ALL donors subject to 21 CFR 610.40, the Requirements for Testing Human Blood Donors for Evidence of Infection Due to Communicable Disease Agents (e.g., autologous and dedicated, too)? The samples tested under the INDs were comprised entirely of allogeneic donations. Thus, the clinical performance characteristics of the test were not determined using samples from autologous donors, for example. Autologous donations are known to have a higher reactive rate for HCV and HIV-1. Our concern is that the introduction of autologous samples might influence the performance characteristics of the test by increasing contamination rates. If it is not intended for auto donors, then it would seem that HIV p24 would need to be retained and all of the labeling, circulars, etc., would still need to allow for this test. Additionally, questions remain about its use for stem cell, BM, and other applications because it is licensed for screening whole blood donors. Is it the FDA's intent that these donations be likewise tested using NAT?
3. What is the intention of pg.3, Part IV.A. paragraph 3? What constitutes the approved components referenced? It seems as though the FDA is saying that if all aspects of the test system are not simultaneously cleared or approved, then the IND needs to be amended. With Roche, the DOMS system for computer control of test records will evidently not have its 510(k) clearance by the time the test is to be licensed--but it was not really part of the IND. So does that mean that the IND will still be in effect if DOMS isn't cleared? What about institutions who aren't using DOMS? This whole paragraph is confusing and seems to dance around obscure points.
4. Confirmatory testing is particularly problematic. What does one do with a positive NAT void of a RR antibody test and positive blot? The approved Chiron insert doesn't elaborate on donor management, counseling, or further testing strategies. Blood establishment approaches range from calling the donor back in for a repeat NAT to testing the FFP (if available) to using the alternate licensed test. Since contamination is a potential culprit and the NAT sample specifications are much more rigorous than for other screening tests, simply using another tube for verification isn't an option. At least under the IND the opportunity for follow-up provided some context to a positive result (we are not suggesting that this ought to be the way that the licensed NAT is managed!). It is bad enough with p24 to call the donor back in if non-neutralizable--imagine what to tell the donor (or potentially a prior recipient) with a positive NAT void of any way to confirm or independently verify. Also, this is a very expensive test--particularly if done individually. Participating centers have also seen situations where the NAT becomes negative or where the subject never seroconverts. Guidance in this arena is absolutely necessary.
5. What are the lookback and recipient tracing requirements? The Roche IND is very generic in its instruction that lookback/recipient tracing occur per established procedure. We have no doubt that institutions' established procedures differ. According to HIV lookback regulations and HCV guidance, there are very defined windows for action. Is it intended for an establishment to initiate recipient tracing without the required confirmatory testing? The donor may never come back for retesting or follow-up.
6. We saw the labeling statements being proposed by ABC/AABB. Could we not promote an even more generic statement; something to the effect of Negative by licensed tests for HIV-1 and HCV by serological and nucleic acid assays?
Thank you for the opportunity to comment on this draft guidance.
Thomas H. Price, MD
Medical Director, Executive Vice President
Puget Sound Blood Center
Linda S. Barnes, RAC
Quality Assurance/Regulatory Affairs
Puget Sound Blood Center