A blood banker in North Carolina is concerned that the massive reporting requirements in the proposed rule "Safety Reporting Requirements for Human Drug and Biological Products" will have a negative impact on patient and donor safety. FDA is proposing changes to 21 CFR 606.170 to expand the definitions of what is a reportable "suspected adverse reaction" (SAR) to include all those events where there is "a reasonable possibility" that a causal relationship exists with the collection or transfusion of a blood product. "A reasonable possibility" is defined as "the relationship cannot be ruled out".

Classifying a case as "probably related, possibly related, remotely related, unlikely related" is equivalent to "the relationship cannot be ruled out". This expansion of definition would apply to fatalities, and events that are non-fatal, for both the donor and patient population. The North Carolina colleague believes that the sheer scope of this proposal is overwhelming, and that the current FDA requirements for Biological Product Deviation Reporting and Reports of Fatalities already capture the events where 'blood' is a contributing factor.

Adverse events where 'blood' is coincidental are captured and investigated by quality assessment programs already in place at the institution. She does not believe that these events need to be 'counted and stored' at at regulatory/enforcement agency. And then, there is the proposed reporting form (currently being used for medical device problems), FDA Form 3500A.... and the proposed required terminology contained in the Medical Dictionary for Regulatory Activies (MedDRA) that must be licensed for a fee ... etc. She laments that limited resources must be spent to provide meaningful advances to patient and donor safety.

The Proposed Rule on "Safety Reporting Requirements for Human Drug and Biological Products" can be viewed online at: http://www.accessdata.fda.gov/scripts/oc/ohrms/index.cfm. Search using the docket number 00N-1484. Section III.D.12 (pps 12435-437) contains key provisions affecting blood centers and transfusion services.

The North Carolina colleague suggests that a discussion on this forum is desirable as some of our FDA colleagues are viewers of the website. However, she adds that each opinion affects FDA agency thinking if it is also submitted as a comment to this proposed rule at: FDADockets@oc.fda.gov. Please reference the title, "Safety Reporting Requirements for Human Drug and Biological Products," including the Docket No. 00N-1484. Comments are due by Tuesday, October 14.

The following response was received.

ADDENDA Oct. 13, 2003

1. A colleague in Texas is in agreement with the North Carolina blood banker. The Texan believes (without providing references or other hard evidence) that most hospitals are already taking care of adverse events in ways that are beneficial for the patient, and that most transfusion facilities have oversight committees that look at all the adverse events and compile statistics on them. She has written to the FDA suggesting that they should receive a quarterly reports of the adverse events that are already being compiled by hospital oversight committees.

ADDENDA Oct. 14, 2003

2. A colleague in Colorado reports that she is at a facility in which over half the transfusion episodes involve oncology patients. In these situations, common practice is to premedicate these patients in an effort to ameliorate allergic or febrile reactions that are observed with their transfusions on a daily basis. When patients do have such reactions, they are reported and investigated appropriately under the auspices of the hospital blood utilization review team. The Colorado colleague suggests to the FDA that the agency will be overwhelmed with the number of these reports alone, potentially compromising its ability to recognize and address reports that are of greatest and most appropriate concern to them.

ADDENDA Oct. 16, 2003

3. Ron Domen, MD (Penn State) believes that the proposed rule is somewhat confusing. He states: "I think it is primarily aimed at pharmaceutical companies. However, I think the wording is vague enough to allow greater or lesser degrees of interpretation by the FDA and its field officers. The section specific to blood and blood components indicates that "all serious SADRs" [serious adverse drug reactions] are to be reported. What is considered serious is not really defined (that I could find) but two examples are given. One example is the adverse reactions reported a few years ago that were associated with Hemasure Leukonet [TM] filtration and that caused allergic-type reactions in recipients. The FDA feels that the "time to resolution" of the cause of these reactions "may have been shortened had these been required to be reported to FDA from all blood centers." The other example, was a blood center that seemed to have an increased number of vasovagal reactions because "the center had failed to establish a lower limit for blood pressure measurements for donors" and that an "immediate analysis" would have identified the problem sooner. If these are the sentinel examples held up by the FDA, then we will be reporting every transfusion reaction and every donor reaction to the FDA. The paperwork will be massive. Unfortunately, the comment period for this proposed rule is already passed and we will probably be stuck with whatever is finalized."

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