Ask Not for Whom the Bell Tolls, it Tolls for Your LDT (Part I)

On October 3 of this year, the Food and Drug Administration (FDA) published draft guidance documents that, when finalized, will mark a “game changer” for clinical laboratories. Specifically, these guidances call for the active regulation of a subset of in vitro diagnostic devices known as Laboratory Developed Tests (LDTs) and the firms that produce them. As a result, clinical laboratories that have developed and use their own clinical diagnostic tests in-house will find themselves regulated by FDA as medical device manufacturers and their LDTs as medical devices. This is the first of a multipart series of posts that will sketch out FDA’s plans for the regulation of LDTs and what they will require of clinical laboratories in the future.

The draft guidance documents may be found here: Draft Guidance for Industry, Food and Drug Administration Staff, and Clinical Laboratories: Framework for Oversight of Laboratory Developed Tests (LDTs); and here Draft Guidance for Industry, Food and Drug Administration Staff, and Clinical Laboratories: FDA Notification and Medical Device Reporting for Laboratory Developed Tests (LDTs).

Traditionally, most LDTs have not been actively regulated by FDA although FDA has repeatedly asserted its authority to do so. With the lack of such regulatory oversight, there has been the opportunity for much innovation in the field. However, in view of such innovation and the related growth in complexity of tests, the agency has come to believe that their active regulation and involvement in the field is now necessary to protect the public health.

The agency intends to apply varying levels of regulatory controls to LDTs based on the risk associated with the tests. In the guidances, the agency outlines various risk-based categories of LDTs and the regulatory controls it will apply to each group.

In the series of postings that are to follow, we will provide an overview of these various groups and the regulatory controls that the agency will impose upon them. In this posting, we begin by describing the notification and adverse event reporting requirements.

Notification and adverse event reporting will be required of all but a select few LDTs. Those that will not be required to comply with these, or any other planned LDT requirements are those laboratories that produce LDTs used exclusively for law enforcement purposes (forensic use) and those used in CLIA-certified, high-complexity histocompatibility laboratories for transplantation. FDA indicated that it intends not to impose any requirements on the limited number of LDTs that fall into these categories. Instead, the agency indicates that it will continue to exercise enforcement discretion for these tests. All remaining laboratories producing LDTs for clinical use that do not fall into either of these categories will be required, at a bare minimum, to comply with the notification and adverse event reporting requirements.


Laboratories that produce LDTs that are for clinical use will be required to notify FDA that they are producing LDTs and provide additional information regarding each of their tests to the agency. This option is being offered as an alternative to compliance with FDA’s Establishment Registration and Device Listing requirements found in 21 C.F.R. Part 807 that otherwise apply to medical device manufacturers. Notification will be required prior to the introduction of a new LDT for clinical use by the laboratory and when the laboratory significantly modifies one of its existing LDTs. Once the final version of the guidance document has been published, these labs must, within six months, provide information on its existing LDTs to FDA and continue to comply with these requirements for new and significantly modified existing LDTs on an ongoing basis. Laboratories have the option to opt out of the notification requirement. However, those that do will be required to comply with the Establishment Registration and Device Listing requirements applicable to other device manufacturers. Among other things, this process requires payment of a registration fee which, for the Fiscal Year 2015, will be $3,646.


In addition, FDA will require these laboratories to comply with its Medical Device Reporting (MDR) regulation (21 C.F.R. Part 803) beginning six months after the date the final guidance is published by FDA. The MDR regulation requires manufacturers (laboratories in this case) to submit reports to FDA whenever they become aware of information that reasonably suggests that a device they market (use) may have caused or contributed to a death or serious injury or has malfunctioned in a way that would be likely to cause or contribute to a death or serious injury should the malfunction recur in the future. What the guidances do not reveal are the underlying requirements that are necessary to establish a compliant MDR reporting system nor does the guidance shed any light on the historical fact that that many established medical device companies have had difficulties in establishing and maintaining compliant MDR reporting systems leading to enforcement actions being directed against them by FDA.

Among other things, establishing a compliant MDR reporting system requires manufacturers to develop, maintain, and implement written procedures that provide for the timely and effective identification, communication, and evaluation of events that may be MDR reportable. These procedures must also provide for a standardized review procedure for determining when an event meets the criteria for reporting as an MDR and, in the case that it does, the procedures must also ensure the “timely” transmission of any MDR report to the agency. Moreover, such procedures also include documentation and recordkeeping requirements for information that was evaluated to determine if an event was reportable as well as the reports themselves and other information submitted to FDA. One should note that the regulation requires that such records be available for inspection by FDA upon request. See 21 C.F.R. § 803.17.

There are even requirements for the information that must appear in and be maintained in a firm’s MDR event files. Among other things, these files are required to contain all information in your possession (or references thereto) related to the adverse event, including all documentation of the company’s decision making processes used to determine if an event was or was not reportable as an MDR. In addition, there are FDA requirements that affect where these files must be maintained and how long they must be retained and kept accessible by FDA. See 21 C.F.R. § 803.18.


Unquestionably, these minimum requirements that will apply to virtually all LDTs intended for clinical use will create significant regulatory challenges that will be novel to the laboratories that produce them. Fortunately for the affected laboratories, there are a few organizations that possess the regulatory expertise to assist them in meeting these challenges if one knows where to look.

In the second part of these series of postings, we will give an overview of the additional levels of regulatory oversight in the works, on whom they will be imposed, and when FDA plans to do so.

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