During the past few weeks, I’ve been reporting on a letter that Bradley M. Thompson, JD, and James A. Boiani, JD, attorneys at Epstein Becker Green (Washington, DC), recently sent to FDA Commissioner Margaret Hamburg. The attorneys sent this letter on behalf of the Combination Products Coalition, an association of drug, biologic, medical device, and IVD manufacturers dedicated to working with FDA to improve the regulation of combination products. In the letter, they discussed the regulation of laboratory-developed tests (LDT) and made the argument for creating a single regulatory framework for IVDs and LDTs. This week’s blog presents further information from this letter.

According to the letter, although FDA has considerable discretion in how it administers the Food, Drug, and Cosmetic Act (FDCA), its discretion is not unlimited. Under the Administrative Procedure Act (APA), the agency must treat similarly situated parties and products in the same way. The current dual system of regulation for IVDs and LDTs violates this legal requirement. Non-lab companies that manufacture IVDs and labs that manufacture LDTs are both manufacturers for purposes of the APA. Both labs and non-labs offer products with similar technologies and similar uses that can help or harm patients. All IVDs, including LDTs, are run in CLIA-regulated clinical laboratories. However, laboratories and their LDTs go unregulated by FDA, while IVD manufacturers are required to comply with extensive and costly FDA standards.

Read: Breaking Down the Regulation of LDTs: FDA Jurisdiction

“In similar situations, courts have found such disparate treatment unacceptable,” said the letter. “For example, consider Bracco Diagnostics v. Shalala, a case where different manufacturers that made similar products were regulated by different FDA centers (Center for Drug Evaluation and Research, and Center for Devices and Radiological Health) that applied different standards to product approvals. The Bracco court held that ‘the disparate treatment of functionally indistinguishable products is the essence of the meaning of arbitrary and capricious,’ violating the APA. LDTs and IVDs are functionally indistinguishable, yet are regulated in two completely different ways based solely on FDA’s decision to favor laboratories. As in Bracco, there is no legitimate reason for continuing disparate regulation.”

Requested Actions
The letter stated that in order to move toward equal regulation, FDA should share its thinking on what it believes LDT regulation under FDCA should look like in practice, or how it plans to deregulate IVDs, by releasing its draft guidance on regulating LDTs. The agency has drafted three guidance documents describing how it would propose to regulate LDTs, so releasing them is the best way to move the discussion forward. In addition, a separate guidance document on the co-development of companion diagnostics with therapeutics has been held up based on potential issues associated with LDT regulation.

Read: Breaking Down the Regulation of LDTs: FDA Authority

“This has been very unfortunate for patients who need advances in personalized medicine, and we request that this guidance be released as well,” said the letter. “To the extent that other agencies within the Obama administration are holding up release of these guidances, they should stand aside. To be clear, we do not ask for these guidances because we believe they will answer every question regarding LDT regulation. They won’t. However, releasing the guidance and moving them through FDA’s good guidance practices is the best way to move the dialogue on equal regulation forward.”

[Last month, five democratic U.S. Senators sent a letter to the Office of Management and Budget (OMB) regarding the regulation of LDTs. In this letter, the senators called on the Obama administration to release the draft guidance that FDA submitted several years ago to ensure appropriate oversight of LDTs. In addition, more than twenty laboratory directors at prominent academic medical centers also sent a letter to OMB urging it not to release FDA’s guidance for LDTs. This letter stated that FDA regulation would add another cumbersome layer to the already heavily regulated approval process for LDTs.]

Read: Breaking Down the Regulation of LDTs: Public Health, First Amendment, and Innovation

The letter also stated that as stakeholders and FDA work to create an equal system of regulation for IVDs and LDTs, the agency should modify its current LDT enforcement discretion to extend the application of certain general controls to LDTs. The American Clinical Laboratory Association (ACLA) effectively supported this recommendation while Congress considered the Modernizing Laboratory Test Standards for Patients Act (MLTSPA) (H.R. 3207). In a 2011 letter to U.S. Congressman Michael C. Burgess (R-TX), ACLA stated that the legislation was “in lock-step with the need for existing regulation to keep pace with the advancements in science that will move our healthcare delivery system to one focused on what is best for the patient, public health, and the economy.” Among other things, the bill proposed new requirements to the current CLIA licensing requirements, including those for an LDT registry (similar to FDA’s listing database), complaint investigation, and adverse event reporting.

“In light of ACLA’s support for MLTSPA, the benefits that ACLA acknowledged the controls would bring to ‘enhancing public transparency for patients, providers and regulatory agencies’ and ‘strengthening reporting for adverse events,’ and the fact that there are FDA general controls that would function like the MLTSPA provisions, we ask FDA to modify its LDT enforcement to extend these general controls to LDTs,” said the letter. “Under this system, CLIA licenses would serve the function of registration, and LDT listings would reference those licenses. Adverse events reports for death and serious injuries and complaint handling would be handled in accordance with FDA requirements that align with MLTSPA. We also believe a reasonable transition period, consistent with the six-month period provided in MLTSPA for adding existing LDTs to the bill’s proposed registry, would be appropriate.”

Read: Breaking Down the Regulation of LDTs: Access to Innovative IVDs

The letter concluded that the dual regulatory framework for LDTs and IVDs does a disservice to the public health. FDA and the rest of the Obama administration can, should, and must fix this problem by creating a single regulatory system that treats IVD manufacturers and their products equally. To move the process forward, the administration should immediately release for comment the draft guidances that FDA has developed to address LDT regulation. Also, in the interim, the agency should take the modest steps of extending general controls for registration, listing, complaint investigations, and medical device reporting for serious injuries and deaths for as long as LDT enforcement discretion continues.