FDA’s Backup LDT Enforcement Method: Specimen Collection Kits

We have written at length about the U.S. Food and Drug Administration’s (FDA’s) actions to promulgate regulations specifying the agency’s authority to regulate laboratory developed tests (LDTs) as medical devices and to phase out the agency’s historical approach of enforcement discretion towards such tests (see here, here, here, and here). However, one infrequently considered regulatory compliance issue for LDTs is their reliance on separate specimen collection devices or convenience kits. All LDTs require the use of some form of biological specimen, such as blood or saliva, which may be collected by health care professionals in a clinical setting or by consumers in their homes before being submitted to a laboratory for testing. 

As we detail below, specimen collection devices and kits are independently regulated as medical devices by FDA, and any clinical laboratory developing or performing LDTs must have a sound strategy for either manufacturing and distributing them in compliance with device regulations or sourcing them from FDA-compliant third-party suppliers. Although the LDT final rule is currently under attack in the courts and may not survive those challenges, stakeholders should keep in mind that FDA has an alternative method to bring enforcement actions against clinical laboratories: targeting noncompliant specimen collection devices and kits being distributed in interstate commerce.

How Are Specimen Collection Devices and Kits Regulated?

Under long-standing FDA regulations, any product that is “intended for use in the collection, preparation, and examination of specimens taken from the human body” for the ultimate purpose of diagnosing diseases or other conditions is an “in vitro diagnostic product” (see 21 C.F.R. 809.3(a)). This means that any device that collects patients’ biological specimens for use in clinical assays is an in vitro diagnostic (IVD) product. Furthermore, all IVD products are regulated as medical devices under the federal Food, Drug, and Cosmetic Act (FD&C Act) because they are “intended for use in the diagnosis of disease or other conditions, or in the cure, mitigation, treatment, or prevention of disease” (see 21 U.S.C. 321(h)).

In addition, FDA considers individual devices packaged together in a branded and marketed kit (i.e., not just co-packaged in the same shipping container) to be a “convenience kit” because they are assembled and sold together as a unit for the convenience of the end user. The agency has clearly stated that “[c]onvenience kits are…medical devices in their own right, apart from their constituent devices” (see the Unique Device Identification (UDI) System Rule at 78 FR 58792) and are subject to the device general controls, such as establishment registration, product listing, labeling (including UDI requirements), and quality system requirements. Therefore, specimen collection kits, which typically include multiple devices whose purpose is to aid in the collection of a biological sample for subsequent diagnostic testing, qualify as convenience kits and must comply with FDA device regulations separate and apart from the individual device components contained within the kit.FDA’s “interim” guidance on convenience kits (published almost 30 years ago, in May 1997) includes a list of convenience kit types that are subject to enforcement discretion with respect to pre-market notification (510(k)) requirements only, which by definition means that all other device general controls apply to such kits.

If a specimen collection device or convenient kit must be cleared by FDA through the 510(k) pathway prior to marketing, the 510(k) submission must include an intended use describing the environment in which the device may be used, such as point-of-care by a medical professional or at home by a consumer. In particular, 510(k) submissions for specimen collection devices and kits that are intended for at-home use by laypersons without the assistance or supervision of a health care professional must specify the user’s home as the intended use environment and must include substantial evidence, such as data from human factors studies, demonstrating that the design and labeling are sufficient to allow a consumer to use the device or kit safely and effectively with minimal risk (see FDA’s guidance for industry on Design Considerations for Devices Intended for Home Use).

Enforcement Hooks for Specimen Collection Devices and Kits Used for LDTs

A clinical laboratory must have some method to distribute (either itself or through a third-party vendor) specimen collection devices or kits to health care professionals or consumers so that the laboratory can receive the necessary biological specimens to test with its LDT. There are many specimen collection devices that are already authorized and marketed in the United States (e.g., blood vials, urine containers, safety lancets, saliva collection systems), so in many cases, laboratories do not need to design and develop a brand-new collection device or engage a contract manufacturer to do so for their specific LDTs. Specimen collection kits are also common in the marketplace, but as described above, each custom kit with specific components is subject to general controls and the manufacturer of such devices, also called a kit assembler, must be registered as a medical device establishment and must list the kit with FDA. 

Despite FDA’s requirements relating to specimen collection devices and kits, some laboratories and even kit assemblers developing and providing such products are not aware that convenience kits are separately regulated devices and may not be complying with applicable general controls.  There also are specimen collection devices or kits being marketed for intended uses that are not consistent with their FDA-authorized uses (e.g., dried blood spot cards to collect blood specimens for testing other than newborn screening), as well as kits containing class II devices being distributed directly to consumers even though they are not specifically cleared for at-home use. All of these situations lead to the manufacture and distribution of noncompliant commercial device products and could lead to FDA enforcement action.

It is also important to remember that the specimen collection device or kit is not a “component” of an LDT being offered by a licensed clinical laboratory – it is a separate medical device that is independently subject to FDA regulations when placed in interstate commerce. This means that even if FDA exercises enforcement discretion with respect to a given LDT, the specimen collection device or kit used in conjunction with that LDT is not necessarily under enforcement discretion as well. In contrast, IVD manufacturers may submit information relating to a specimen collection device or kit with a pre-market submission for an IVD assay because FDA will review all information about the assay and collection method (including validation testing data showing that the collection method reliably and safely collects biological specimens that lead to accurate results) together. The option to couple the assay and collection method into one submission is not available to a clinical laboratory, unless its entire LDT assay is submitted for pre-market review.

If a clinical laboratory decides to use a class II or III specimen collection device or kit in conjunction with an LDT, it can create a Catch 22 for some clinical laboratories because FDA will require adequate data demonstrating that the specimen collection device or kit (especially those intended for at-home use) is safe and effective for use with the LDT in order to clear or approve the kit for that specific intended use. But obtaining such data can be difficult without conducting a formal clinical trial—the laboratory cannot collect real world data because the specimen collection device or kit cannot be distributed to consumers prior to obtaining marketing authorization. Moreover, submitting a novel specimen collection device or kit for pre-market review means providing assay-specific information to FDA, which could result in the agency scrutinizing and commenting on the LDT assay itself. Distributing and promoting a class II or III specimen collection device or kit for an unauthorized intended use is at high risk of enforcement action, especially in the context of LDTs that FDA considers inherently to pose greater risks for patients, such as tests for serious communicable diseases or cancer.

Although FDA has not frequently targeted specimen collection devices and kits in enforcement actions in the past (especially in the context of LDTs), there has been a recent uptick in agency warnings and safety notices relating to collection kits, indicating that the agency is monitoring compliance in this area. State agencies with authority over clinical laboratories and LDTs, such as the New York State Department of Health Clinical Laboratory Evaluation Program (CLEP), have also stated to clinical laboratories that any device or kit intended to collect biological specimens for an LDT must comply with FDA’s device regulations.

Impact of the LDT Final Rule

The LDT final rule is currently in effect and year one of the enforcement discretion phase-out process is almost complete. In May 2025, clinical laboratories are expected to be complying with medical device reporting, correction and removal reporting, and compliant handling requirements. As the phase-out process continues (if it is not invalidated by a court or otherwise rescinded) and FDA begins to review LDTs for device marketing authorization, it is possible that enforcement of specimen collection devices and kits will increase because the agency will have better information about the intended uses and distribution of such products to obtain patient specimens for those LDTs.

However, even if the final rule is invalidated or rescinded, FDA may resort to increasing compliance monitoring and enforcement for specimen collection devices and kits as a method of maintaining an oversight foothold in clinical laboratories that design, offer, and perform LDTs. As described above, certain intended uses of specimen collection devices and kits may require pre-market clearance or approval, irrespective of what happens to the LDT final rule, such that FDA could demand detailed data demonstrating safety and effectiveness, which could even include clinical trials that involve the LDT itself.

Conclusion

Throughout the LDT design, development, and validation process, clinical laboratories and those who assist laboratories with bringing an LDT to market should remember that the design or selection of the device or kit that will be used by health care professionals or consumers to collect the biological specimens needed for the assay is a critical decision with many regulatory implications. FDA has been clear that specimen collection devices and kits are medical devices separate and apart from the assay used to test the specimen, even if the assay is an LDT, and the agency is beginning to step up enforcement against noncompliant devices and kits. Moreover, in the preamble to the final rule, FDA highlighted the desire to use its existing device authority to ensure the safety and effectiveness of LDTs, and full implementation of the final rule’s framework will likely lead to increased oversight of and enforcement actions against clinical laboratories. However, even if the final rule is invalidated or rescinded, it is possible that FDA will still increase oversight and enforcement activities against clinical laboratories by focusing on the specimen collection devices and kits they choose to pair with their LDTs.

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