Diagnostics & Imaging Week

The FDA has issued draft regulatory guidance for the medical device industry on commercially distributed active ingredients of medical tests, or analyte specific reagents (ASRs).

ASRs are chemicals used in tests intended for use in the diagnosis of diseases and conditions and to help guide medical decision-making. The FDA said that companies that commercially distribute ASRs must follow FDA requirements for marketing an in vitro diagnostic device.

"ASRs are the building blocks of medical tests," said Daniel Schultz, MD, director, of the FDA's Centers for Devices and Radiological Health. "This guidance is intended to clarify how FDA defines ASRs and what the role and responsibilities of ASR manufacturers are so that the tests that are developed using these ingredients are as safe and effective as possible."

The agency in 1997 issued a rule on ASRs in order to define and classify the substances, imposed restructions on their sale, distribution and use, and established their labeling requirements.

"The ASR rule was designed to accomplish several policy objectives," the agency said in the most recent Q&A guidance. "These include ensuring the quality of materials used as components of in-house laboratory tests, and providing appropriate labeling so that healthcare users would understand how these tests were being validated."

In its introduction to the current draft guidance, the FDA said it is providing it "to eliminate confusion regarding particular marketing practices among ASR manufacturers."

The agency specifically mentions two practices as being "inconsistent" with certain established rules, for example, combining or promoting the use of a single ASR with another product such as another ASR, general purpose reagents, controls, laboratory equipment, software, etc.

FDA also specifies as inconsistent the promotion of an ASR "with specific analytical or clinical performance claims, instructions for use in a particular test, or instructions for validation of a specific test using the ASR."

"Some manufacturers have believed that when they combine a Class I ASR, which is exempt from premarket notification requirements . . . with other products, or with instructions for use in a specific test, the product remains exempt because of the presence of an ASR," the draft guidance states.

However, the FDA views this type of arrangement as a "test system."

While the current ASR rule classifies most ASRs as Class I devices, in the new guidance, FDA suggests that while that is still the case, "there are some ASRs that are Class II and Class III and that must be cleared or approved by FDA before they can be marketed in the U.S."

To meet the FDA's definition of an ASR, it should have the following characteristics: a single moiety; a single endpoint; no instructions or performance claims and; not promoted for use on specific instruments or in specific tests or test systems."

Microarrays, which are increasingly being developed to detect disease, for example, would not fall into this category. Any example where antibodies, probes or primers are "bundled together in a pre-configured or optimized manner so that they are intended to identify and quantify more than one chemical substance or ligand," also would not be considered an ASR and would fall under FDA purview.

Also falling in the "inconsistent" with FDA thinking on ASRs category would be software for interpretation of assay results.

Regarding marketing, the FDA draft guidance suggests that manufacturers who want to market ASRs as something other than as test systems, avoid listing ASRs, general purpose reagents (GPRs) and controls in catalogues, web sites and other promotional materials.

And the agency suggests that while instructions on how to use an ASR included in packaging is acceptable, the manufacturer cannot make any claims that would indicate that "when used as directed, the ASR will perform to detect a particular chemical substance or ligand."

The FDA suggests in its draft guidance, however, that ASRs can be used for research applications, saying the requirement for the laboratory report disclaimer applies only to clinical diagnostic use of such products.