On Dec. 13, President Obama signed into law the 21st Century Cures Act (Cures). The goal was to “accelerate the discovery, development and delivery” of innovative products, including by adding and modifying various programs administered by the Food and Drug Administration (FDA) under the Federal Food, Drug, and Cosmetic Act (FDCA). Although the new legislation broadly affects research and development, it is also significant for issues it does not address:
1. The law codifies several mechanisms intended to facilitate product development but does not change the evidentiary standards for clearance and approval.
The new mechanisms include specialized FDA review procedures for rare disease drugs, regenerative therapies, antibacterial and antifungal drugs and breakthrough devices. They also include processes for qualifying drug development tools, using novel clinical trial designs and incorporating patient experience and “real world” data into product approval decisions. Many of these are already in place or being developed by the FDA, and nearly all were codified with language explicitly disclaiming any effect to lower existing standards for product clearances and approvals. Thus, there must still be “substantial evidence” of efficacy for new drug approvals and “valid scientific evidence” of efficacy for device clearance and approvals. This means that it will still take considerable time, effort and money to develop sufficient evidence to support product clearances and approvals.
2. The law includes provisions about clinical decision support software but leaves key digital health questions unanswered and raises new ones.
In the digital health space, the FDA has already made clear that it does not intend to regulate low-risk clinical decision support software (CDSS) and other certain other low-risk software, and it has issued guidance regarding health apps that run on general purpose mobile platforms. Critical questions remain regarding the application of good manufacturing practice requirements to software development and the regulatory status of platforms intended for both general purpose and health-related functions, such as wearables. Resolution of the former requires a modernization of the quality system regulation, also known as QSR, and the latter requires answers that are not provided in the FDA’s existing guidance.
The digital health provision in Cures partially codifies the existing policy by describing specific categories of CDSS products that the FDA shall not, as a default rule, regulate as devices. It states that the statutory definition of “device” shall not include software intended to (1) provide administrative support of a healthcare facility, (2) maintain or encourage a healthy lifestyle, (3) serve as electronic patient records, (4) facilitate transmission and display of clinical laboratory test data and other device data or (5) support or provide recommendations to healthcare professionals about prevention, diagnosis or treatment of a disease or condition. The legislation further provides, however, that the FDA may effectively override the default exclusion for a software function that falls within one of the last three categories by finding that use of the function would be reasonably likely to have serious adverse health consequences.
This introduces new interpretive and policy questions because it does not explicitly address the scope of the FDA’s authority when a software function falls within one of the last three categories but not within the statutory definition of “device” — e.g., because it is not intended for use in the diagnosis of disease or other conditions or in the cure, mitigation, treatment or prevention of disease. The plain text of Cures suggests that the FDA could regulate such a product solely based on concern about potential adverse health consequences, but that would be contrary to the extant device definition, the overall structure of the FDCA and the general intent of the new provision.
3. The law made some clarifying changes related to communication of healthcare economic information (HCEI), but questions remain.
Section 114 of the FDA Modernization Act of 1997 (FDAMA) established a framework for promotional communication of HCEI. Industry has not used FDAMA 114 as widely as Congress intended due to lingering interpretive questions and the lack of FDA implementation in regulations or guidance. Section 3037 of Cures addressed some of those questions by removing “directly” from the “directly relates” limitation, clarifying the scope of permissible audiences for HCEI and explicitly providing that the clinical data and assumptions that make up HCEI may be based on competent and reliable scientific evidence rather than substantial evidence.
There is still no explicit safe harbor in FDAMA 114 that provides manufacturers with protection from a Section 502(f)(1) “adequate directions” misbranding charge — the principal charge used in off-label promotion cases. Whether HCEI that involves an unlabeled clinical endpoint creates a new intended use within the meaning of Section 502(f)(1) is a hard question to answer given the dearth of the FDA guidance and expansive interpretations in government investigations. As a result, even after the FDAMA 114 “fix” in Cures, manufacturers must proceed at risk if they would like to provide payors and managed care organizations with economic analyses that are based on clinical endpoints not included in FDA-approved labeling.
The industry has sought clarifications to FDAMA 114 for years, and Section 3037 is for that reason a welcome development. But it does not provide a complete solution to the problem of manufacturer communication. The FDA has announced that it is extending the comment period following the Nov. 9-10 public hearing on these issues and has still not fulfilled the promises made by the agency in June 2014 in granting two industry petitions requesting clarifications to existing FDA safe harbors. Nor has FDA completed the “comprehensive review” of its regulations and policies promised several years ago to address First and Fifth Amendment limitations.
Section 3037 of Cures is also limited to products that qualify as “drugs,” meaning medical device manufacturers that would like to provide comparative economic analyses about their products lack any statutory safe harbor covering such communications. In addition, in what may be a drafting oversight, the revised statutory language now refers inconsistently to biological products and biosimilars and, in one instance, appears to exclude the latter.
4. Some of the law’s more obscure provisions regarding clinical trials and combination products are likely to provide the most practical near-term benefit to drug and device firms.
The legislative changes discussed here have garnered significant attention but are likely to be less useful to the industry in the near term than some more nuanced provisions of Cures. These include provisions that will make clinical trials easier to conduct by allowing waiver of informed consent for trials that pose no more than minimal risk and by allowing a sponsor of a device trial to use a central institutional review board. They also include provisions that will likely help developers of combination drug-device products. As examples, Cures explicitly limits the FDA’s discretion when determining whether a combination product is to be regulated primarily by the Center for Drug Evaluation and Research (CDER) or the Center for Devices and Radiological Health (CDRH), and establishes a procedure for resolving disputes over such a jurisdictional determination.