February 2, 2015
Division of Dockets Management (HFA–305)
Food and Drug Administration
5630 Fishers Lane, Rm. 1061
Rockville, MD 20852
Re: Docket No. FDA-2011-D-0357 “Notification and Medical Device Reporting for Laboratory Developed tests (LDTs); Draft Guidance for Industry, Food and Drug Administration Staff, and Clinical Laboratories.”
Dear Dockets Manager:
We appreciate the opportunity to provide comments on the Agency’s recommendations contained in the “Notification and Medical Device Reporting for Laboratory Developed tests (LDTs); Draft Guidance for Industry, Food and Drug Administration Staff, and Clinical Laboratories.” We have comments on both subjects covered in the draft guidance.
It is especially helpful to have the initial option of notification in lieu of registration and listing. However, when the guidance publishes in final form we request that the agency provide more examples of what constitutes an LDT for notification and what constitutes a significant change to an LDT such than an additional notification is required.
For example, in transfusion medicine the search for compatible blood may result in a laboratory creating an antibody identification panel consisting of licensed reagents from more than one manufacturer. Is this an LDT? If so, how can the lab provide a timely notification? At the completion of the test, if the technologist decides to run the panel again using different incubation times, temperatures, or incubation or wash reagents, does this constitute a significant change to an LDT such that an additional notification is required? Again, how can the lab provide a timely notification?
The recommendation to report adverse events associated with a laboratory test or procedure through the MDR system is overly burdensome and without additional benefit to patients, donors, clinicians, or government agencies viewed in the context of already highly regulated blood establishments.We believe that the current level of adverse event reporting that blood establishments are required to comply with is sufficient and recommend that Medical Device Reporting not be added.
Laboratories involved in transfusion medicine, especially immunohematology reference laboratories use LDTs on samples from blood donors or potential blood recipients to resolve complex compatibility problems that that require reagents for which no licensed alternatives exist. These are often derived from rare donors and patients identified by the blood establishment for application to clinical problems too rare to support the development and approval of licensed materials. Many of the samples they work with are from chronically transfused, alloimmunized patients.
Blood establishments must comply with 21 CFR 606.170 and 21 CFR 606.171 for adverse event reporting. This includes reporting fatalities to FDA within 7 days, and reports of adverse events associated with blood or blood components within 45 days. 21 CFR 606.171 (f) includes the following statement: “All biological product deviations, whether or not they are required to be reported under this section, should be investigated in accordance with the applicable provisions of parts 211, 606 and 820 of this chapter.”
The draft guidance would require laboratories to submit Medical Device Reports (MDR) as a manufacturer. The MDR regulations (21 CFR 803.17) would require the laboratory to create written Standard Operating Procedures (SOP) specifically for Medical Device Reporting regardless of existing procedures for adverse event reporting under 21 CFR 606.170. The MDR regulations (21 CFR 803) require the manufacturer to submit an MDR within 30 days (not 45 days, as above) after becoming aware of an event that
might have been caused by a medical device. The determination whether the device was
actually the cause of the event is irrelevant to the timeline, and to the requirement to report, except that a subsequent, amended report would be required (21 CFR 803.56, supplemental reports). In addition, concurrent with the first MDR report for an LDT under 21 CFR 803.50, the IRL must file a “baseline” report [21 CFR 803.55 (a)] and annual reports [21 CFR 803.44 (b)] that include very detailed establishment and device information, including marketing authorization details.
An adverse event involving an LDT would investigate three potential causes in the following flow:
Did the patient respond in a manner predicted by the test result?
If no, did the technologist performing the test perform it incorrectly?
If no, was the test system at fault?
Due to the nature of these LDTs, and the complex blood compatibility issues they are attempting to resolve, it may not be possible to determine whether the test system was at fault. It is unclear what additional layer of safety MDRs add to the requirement for adverse event reporting contained in 21CFR 606, inconsistent timelines add confusion, and the requirement for additional SOPs to describe the MDR process is unnecessarily burdensome to laboratories.
AABB is an international, not-for-profit association representing individuals and institutions involved in the field of transfusion medicine and cellular therapies. The association is committed to improving health by developing and delivering standards, accreditation and educational programs that focus on optimizing patient and donor care and safety. AABB membership consists of nearly 2,000 institutions and 8,000 individuals, including physicians, nurses, scientists, researchers, administrators, medical technologists and other health care providers. AABB members are located in more than 80 countries.
Founded in 1962, America's Blood Centers is North America's largest network of community-based, independent blood programs. The network operates more than 600 blood donor centers providing over half of the U.S., and a quarter of the Canadian blood supply. These blood centers serve more than 150 million people and provide blood products and services to more than 3,500 hospitals and healthcare facilities across North America. America's Blood Centers' U.S. members are licensed and regulated by the U.S. Food and Drug Administration. Canadian members are regulated by Health Canada.
The American Red Cross shelters, feeds and provides emotional support to victims of disasters; supplies about 40 percent of the nation's blood; teaches skills that save lives; provides international humanitarian aid; and supports military members and their families. The Red Cross is a not-for-profit organization that depends on volunteers and the generosity of the American public to perform its mission. About 5.6 million units of whole blood are collected from roughly 3.3 million Red Cross volunteer donors, separated into 8 million transfusable blood products and supplied to approximately 2,700 hospitals and transfusion centers across the country for patients in need.
Thank you for the opportunity to offer these comments. We look forward to continuing to work with the FDA on patient and donor safety initiatives. Questions concerning these comments may be directed to
M. Allene Carr-Greer
Director, Regulatory Affairs