The federal government proposes to overhaul the guidelines for platelet donations to ensure donors are protected. Please see Guidance for Industry and FDA Review Staff: Collection of Platelets by Automated Methods: DRAFT GUIDANCE.

However, many donation center officials say the changes could have an unintended consequence, possibly causing as much as a 50 percent reduction in the supply of platelets, according to some individuals. Colleagues are encouraged to comment on the proposed new guidelines.

The following comments have been received.

ADDENDA Feb. 27, 2006

1. Dr. Louis Katz, past president of America's Blood Centers (attribution used with permission), is concerned about the impact of this draft guidance on the supply of apheresis platelets. In his opinion, the restriction on components donated annually might decrease the supply from 6 to more than 20% according to some estimates, and even more according to information provided by blood centers to the FDA during the "open comment period". Modeling at his center suggests a loss of 12.5% of components that would require expansion of their donor base by 33% to replace. The requirement for physician attendance within 15 minutes is more problematic. For example, his center (Mississippi Valley Regional Blood Center) would need to close three of four apheresis sites or cause the hiring of at lease two additional physicians. An extended deferral for aspirin use and requirement for a formal deferral for the use of non-aspirin nonsteroidal anti-inflammatory medications will complicate scheduling of donors to some degree and will certainly increase on site deferrals. He adds that the draft guidance has many features worthy of comment (addressing a broad range of process and quality control issues), but the aforementioned three items seem to have the most potential for impact on the US platelet supply. Dr. Katz is hopeful that the FDA is listening very closely to the comments of the blood community, and the upcoming discussion at the March 9-10 Blood Products Advisory Committee will deal with the implications of the draft guidance from both the FDA's perspective and concerns about donor safety and the collection organizations' long experience and concerns about both donor safety and an adequate supply.

ADDENDA Mar. 1, 2006

2. A colleague in Texas reports that their blood center is very concerned about the impact of the FDA's draft regulations on the platelet supply in their community. They have 20 remote apheresis draw sites over a 100 mile radius and 4 physicians to cover those sites. The Texas colleague reports that they have had an excellent experience with donor apheresis collections, with a 20+ year good safety record. Based on their experience, they do not share the same concern as the FDA that these procedures are dangerous and require a physician presence (or near presence). As a physician who, under the draft guidelines, would be present in what is essentially a non-health care facility (e.g. no cardiac monitors, no medications, no nurses) he would call 911 if there was a donor emergency. All of their staff are trained in basic CPR. Unfortunately, his center (like those under Dr. Katz; see posting above) would be forced to consolidate collections to one or two sites, thus losing the majority of their neighborhood donors (who would be unwilling to drive an hour or more to a donation site). He laments that "There is only so much we can expect of these donors in the way of time and commitment. The change will also foster ill will among our dedicated donors, not only for the change in location, but also the decrease in the number of products they can donate in one year." He adds that he is concerned that a limitation of apheresis donors to 24 products per year (versus 24 donations) will be devastating to collections, as they routinely do double and triple collections in donors with good platelet counts. This is an issue that Dr. Katz did not mention that will impact them greatly, as well as the addition of a deferral for non-steroidal anti-inflammatory drugs and increased deferral for aspirin that he did mention.

3. Pat Kopko, MD at BloodSource in Sacramento reports that her center's platelet production would drop by about 11%, if they could only collect 24 platelet components per year. Furthermore, they would experience an additional reduction in platelet production of up to 50%, if they had to close collection sites because of the new medical supervision requirement of the FDA draft guideline. Alternatively, they would need to hire many more doctors than they currently employ. They currently draw platelet apheresis donations at 8 of their centers, employ 3 full time physicians and three part time physicians. Since their collection centers are spread out geographically, they would need to hire at least one physician for every site. They would be looking to balance the cost and availability of adding those physicians to their staff, versus the economic impact to the cost of a platelet pheresis unit. Even if the economics worked out, Dr. Kopko reports that she does not know if she could find a sufficient number of physicians who are 'boarded' in transfusion medicine, since they currently require that their physicians have transfusion medicine boards.

ADDENDA Mar. 5, 2006

4. A California colleague reports that his center is concerned over the impact that the draft guideline might have on the availability of platelets for transfusion.
He points out that the FDA has posted a summary of comments at http://www.fda.gov/ohrms/dockets/dockets/05d0330/05d0330.htm but that there are many other comments posted on the "Dailies" section of the dockets management web site at http://www.fda.gov/ohrms/dockets/dailys/dailys06.htm. Those interested can click on each day listed to see the comments. The majority of the documents that pertain to this discussion were posted on 1/5, 1/6, 1/17, and 1/27. In summary, the responding colleague is hopeful that FDA will enter into a meaningful dialogue with industry prior to finalizing the guideline. It will be interesting to see what transpires during the March 9-10 BPAC meeting.

ADDENDA Mar. 8, 2006

5. Jim Perkins, M.D., Director, Evanston Northwestern Healthcare Blood Banks in Illinois (attribution used with permission) has submitted the following comments to the FDA regarding the draft guidance for "Collection of Platelets by Automated Methods". Comments are welcome.

1. "The draft guidance, and the current CFR, states that platelet donors should meet the "requirements described in 21 CFR 640.3 (suitability of donors of whole blood)." Those criteria include a hematocrit (hct) above 38 or hemoglobin (hgb) above 12.5. However, the lower limits of normal for women at our hospital (and most hospitals) are 12.0 for hgb and 36.0 for hct. If only a platelet or plasma component (or both) is to be collected, I believe that the criterion should be a hgb/hct equal to or above the lower limit of normal. Presumably the goal of this criterion is to prevent iron deficiency from developing in the donor. However, hgb/hct has been shown in multiple studies to be a very poor surrogate measurement for total body iron stores. Other criteria more directly prevent excess donor iron losses, specifically the limitation on the total number of procedures per year and the 8 week deferral after whole blood donation (16 weeks for a "double RBC"). Moreover, many centers, such as ours, continue to monitor yearly RBC loss and defer donors appropriately; such a practice is alluded to under 'Donor Monitoring" (pg 17 of 28) but is not specified. For some apheresis collection devices a lower hct correlates with a higher extracorporeal volume, but controls for this issue are also in place. Finally, for whole blood collection, the hgb/hct criterion is relevant to the content or "dose" of the RBC unit; this is obviously irrelevant to platelet collection."

2. "The draft guidance would limit the yearly number of collections to 24 products rather than 24 procedures. This does not seem rational to me, since there is no upper limit to the number of platelets that can be in a unit of Platelets, Apheresis (SDP). Thus, if I were to collect 6.2x10e11 platelets from a donor and not split the collections, but instead issue them as a single unit, I could do this 24 times a year. However, if I were to split each collection into two units, I would be limited to 12 collections per year. Yet the impact on the donor would be the same. As before, the question is, "What is the intent of this criterion." The potential impact of serum protein or RBC/iron loss is addressed by other criteria (as discussed above). If the intent is to address yearly loss of platelets or lymphocytes, these parameters should be addressed specifically rather than in surrogate fashion. Development of donor thrombocytopenia due to the cumulative effects of donation is specifically addressed by the deferral of donors with pre-collection counts of <150,000/microliter. Moreover, although concern has been expressed for the loss of lymphocytes over time by frequent donors, I am not aware that anyone has demonstrated a real adverse effect on donors."

3. "Regarding availability of medical coverage for donor adverse reactions within 15 minutes, the term "qualified" is vague. If the goal is to provide treatment for cardiac arrest, it might be more rational to specify that an individual trained in cardio-pulmonary resuscitation be immediately (within 4 minutes) available on premises. One would assume "qualified" in relation to physicians referred to CPR or advanced life support training, but this is not specified. Moreover, 15 minutes is too long if cardiac arrest is the concern. With respect to cardiac arrest, availability of emergency medial personnel (911) would be more relevant. Other donor adverse effects can largely be addressed by telephone interaction between an experienced blood bank physician and a trained/experienced phlebotomist, or by a similar interaction with a physician at a local emergency department (ED). And the guidance could specify that the latter interaction be defined in a contract between the collection site and the local ED."

4. "The draft guidance specifies target platelet yield settings for double and triple components. However, I believe that the various cell separators in use vary in the accuracy of their predictions, and there may be some variability between donors in this regard. The concern is that the final component has a platelet content of 3.0x10e11 is more specifically addressed by requiring measurement of this parameter in the finished product. Collection site SOPs can be depended upon to include a target value to achieve this release criterion based on local experience as well as, in some cases, experience with an individual donor. There is no need to impose an inflexible, 'one size fits all' rule."

5. "The draft guidance would limit testing for bacterial contamination to a "...bacterial detection system specifically labeled for testing of plateletpheresis components...." One such system is the BacT Alert™ system. The Bactec™ system works by the same principle, and is known to provide similar results in the routine microbiology setting. Many hospitals that owned the latter system successfully validated it for detection of bacteria in platelets collected on site when the AABB standard for such testing was adopted. Performance of blood cultures on patients is not essentially different from monitoring of platelets for contamination, and there is a vast literature on the sensitivity and response time of various systems. I believe that the guidance should allow other methods of bacterial detection if they have been adequately validated. The extent of validation required should depend on the degree to which the method differed from an approved method, and would take into account data in the literature."

6. "Finally, I concur with the concerns expressed by multiple colleagues regarding expanded deferral criteria for recent use of non-steroidal anti-inflammatory drugs in addition to aspirin. I need not re-iterate their concerns, but note that such drugs could, in fact, improve the efficacy of platelet transfusions if they were to decrease in-vitro activation of platelets during storage. I am not aware of data to support or refute this, but am concerned that the data is insufficient to support this expansion of the "aspirin deferral."

Dr. Perkins concludes: "I would like to commend the authors of this draft guidance on its readability."

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Ira A. Shulman, MD
CBBS e-Network Forum Editor & Moderator