11 January 2013
Andrea Leonard-Segal, MD
Director, Division of Non-Prescription Clinical Evaluation
Office of Drug Evaluation IV, CDER, FDA
White Oak Campus
10903 New Hampshire Ave
Silver Spring, MD 20993
Dear Dr. Leonard-Segal,
We are writing to express concerns related to the recent class-wide labeling changes for specific classes of skin antiseptic products, including ChloraPrep® skin antiseptic solution, and to ask for assistance in resolving them. That said, we appreciate your rapid response to our inquiries on this issue during the holidays and your willingness to schedule deliberations as quickly as you have.
ChloraPrep, containing 2% chlorhexidine gluconate/70% isopropyl alcohol, is approved for use as a surgical preparation solution but is widely used by blood collecting establishments to disinfect the donor's arm prior to phlebotomy. It is our understanding that the recent label revision related to alcohol drying time for dry surgical sites from "approximately 30 seconds" to a "minimum of 3 minutes" was made to mitigate the well documented risks in surgical settings for patient injury associated with ignition sources such as electrocautery equipment and open lasers, and that the revision is not in response to a question of the effectiveness of disinfection with shorter drying times.
The process for collection of blood does not include the use of ignition sources near the phlebotomy site during the disinfection process. Heat sealers may be used to remove and to segment tubing of the collected unit of blood, but this occurs at the end of the donation process, after the unit of blood has been disconnected from the donor's arm and after much longer than the three minute drying time required in the new labeling. Therefore, the labeling revision does not address a risk present in the blood collection process or add to recipient safety by a more thorough disinfection of the phlebotomy site. As was discussed with Dr. Schiffenbauer, it does impose a considerable burden on the workflow for collecting blood donors. In addition, as phlebotomy at the time of blood donation is an FDA regulated activity, there is concern that the prolonged drying time will create compliance difficulties related to accurate timing and the need to revise SOPs and retrain staff. None of these concerns is balanced by improved safety since we do not use potential ignition sources at the bedside.
Blood establishment employees typically have responsibility for two to three donors during the collection process. The requirement to monitor an extended drying period for no anticipated safety benefit before proceeding with the next step in the collection process may detract from responsibilities that have a major impact on the safety of the donation process, for example monitoring donor well-being and intervening in vaso-vagal reactions. 16,000,000 whole blood donations are drawn annually in the US, so the additional 2.5 minutes delay translates to almost 700,000 additional hours for donors and staff in blood collection facilities. It will create a bottleneck between the donor screening processes and the actual phlebotomy that will be extremely disruptive for blood establishment operations. Donors are less likely to donate blood with any additional inconvenience; the single most common complaint by donors is the time required to complete the process.
We request CDER to
support a label change allowing use of the previous drying times for dry surgical sites (approx. 30 seconds) for certain uses, namely when an ignition source is not in use; and
provide a communication acknowledging the label change is to reduce risk of fire and was not made to address disinfection practice.
In support of the first request we are in contact with the manufacturer of ChloraPrep to discuss submission of a revision to the label. That will require time and does not address the immediate issue of compliance with the revised label instructions. Secondly, a communication to us and to CBER, responsible for inspecting and licensing blood and plasma establishments, that clarifies the intent of the label revision related to venues where ignition sources are present would be useful to support a potential decision by others at FDA to allow enforcement discretion if blood establishments use the previously approved drying time of approximately 30 seconds prior to completion of the requested label change.
Thank you in advance for your consideration of this issue. We understand a meeting has been scheduled for later this month to review the topic; we are available to provide additional information or clarification as needed.
Joel Schiffenbauer, MD
Deputy Director, Division of Non-Prescription Clinical Evaluation, ODEIV, CDER
Jay S. Epstein, MD
Director, Office of Blood Research and Review, CBER
Richard J. Davey, MD
Director, Division of Blood Applications, OBRR, CBER