FDA recently signaled that it plans to be more involved in facilitating expanded access to investigational new drugs. This follows the agency’s announcement of its efforts to improve and clarify the expanded access program (EAP), as well as state and federal legislation intended to simplify the process to use investigational drugs for treatment purposes.
One item that stakeholders may have missed, given the almost daily FDA developments, was the agency’s announcement that it will continue to improve and clarify its expanded access program (EAP). Specifically, FDA
- updated its EAP webpage to streamline content and make the page more user friendly;
- established an agency-wide Patient Affairs Staff and Health Care Provider Affairs Program to increase FDA engagement with stakeholder groups;
- established an agency-wide Expanded Access Coordinating Committee to facilitate cross-center communications and discussion of cross-cutting issues; and
- established a work group for the implementation of the Federal Right to Try law.
These follow a May 2018 independent assessment commissioned by the agency, which found that while stakeholders reported positive overall perceptions of the EAP and FDA’s role, there continue to be “pain points.” For instance, there continues to be confusion regarding program navigation, difficulties with multi-stakeholder coordination, and administrative burden.
In the wake of several high-profile incidents regarding data privacy and the misuse of genetic and personal information, including the case of a Chinese scientist who attracted worldwide criticism after reportedly creating the world’s first human babies whose DNA is genetically modified, the Chinese government has recently issued several top-level policy directives reaffirming its commitment to strengthening cybersecurity and the protection of personal data and human genetic information and material. Though driven by recent events, these policy directives are intended to build upon and further strengthen already existing protections enshrined in the country’s constitution and Tort Liability Law, a process that had already begun with the passage of the country’s Cybersecurity Law (CSL) and General Principles of Civil Law in recent years. Specifically, the recent policy directives place strict prohibitions on the unauthorized use of human genetic material for research purposes and create administrative penalties for the unlawful cross-border transfer of genetic information, while simultaneously streamlining the regulatory approval process for such transfers in an effort to mitigate the impact of increased regulation on international cooperation within the life sciences industry.
The proposed Over-the-Counter Monograph Safety, Innovation, and Reform Act of 2018 could become law in the near future as the Congressional Budget Office reported that the legislation would not increase the budget deficit. The proposed bill would change the oversight of the commercial marketing of OTC drugs by the FDA and authorize the collection and spending of user fees to cover the cost of expediting FDA’s administrative procedures related to OTC products. Both the Senate and the House have proposed versions of the bill that are largely similar with variances mostly in the length of exclusivity. Therefore, manufacturers can reasonably rely on the major provisions of the bill that are not likely to change. Manufacturers can start preparing for the proposed revisions by organizing their current OTC product portfolios according to the ingredients’ current monograph status and identifying any ingredients that may be at risk for more immediate FDA action that could impact their regulatory marketing status.
FDA recently released the framework for its Real World Evidence (RWE) program, educating stakeholders about the agency’s approach to RWE when making efficacy decisions. The document is notable more for its discussion of the limitations rather than the potential for RWE. Although FDA plans to issue a number of RWE guidance documents and conduct RWE stakeholder events, the path to routine use of RWE looks to be a long and winding one.
Crucial to understanding FDA’s RWE approach is understanding the distinction between Real World Data (RWD) (e.g., data on patient health status and/or delivery of routine healthcare from a variety of sources) and RWE (e.g., clinical evidence on the use and potential benefits/risks of medical products derived from RWD). FDA intends to limit RWE use to supplemental indications and label changes for approved drugs/biologics (e.g., adding/modifying indications, changing dose/dosing regimens and routes of administration, adding new patient populations, adding comparative effectiveness/safety information). Moreover, while the life sciences industry tends to see the opportunities from RWD (e.g., electronic health record, medical claims/patient billing, patient/disease registry, and mobile device data), FDA primarily sees this information as an RWE source. This is not to say, however, that RWD is without use, as FDA plans to allow its use to improve study efficiency.
FDA recently announced a proposal to add an exception to the agency’s informed consent requirements. Under the proposed rule, FDA will allow Institutional Review Boards (IRBs) to waive or alter informed consent for clinical trials that present only minimal risk to the subjects. This proposal is similar to the policy set forth in FDA’s guidance document on the same topic, which we have written on previously.
Although federal efforts on drug pricing remain at the proposal stage, recently enacted legislation in six states on drug price transparency requires pharmaceutical manufacturers to review and update their approaches to prescription drug pricing and price increases on an ongoing basis to ensure compliance with state laws. Beginning in 2019, some states will impose penalties for noncompliance with reporting obligations. The state statutes raise various concerns, including that they vary from state to state, are often unclear as to what products are covered, and use different calculation methods and evidence to support price increases.
President Donald Trump announced that, as of September 24, 2018, additional tariffs of 10% were imposed on hundreds of chemical ingredients, many of which are used in the manufacturing of dietary supplements, cosmetics, and over-the-counter (OTC) drug products. Manufacturers have had to develop contingency plans and strategies for dealing with the imposition of these tariffs. Such contingency plans may include renegotiating supplier contracts; re-sourcing the ingredients; and notifying distributors and customers of disruptions, delays, or price changes. A rise in the tariff rate to 25% for these products, scheduled for January 1, 2019, has been delayed pending current negotiations with China, and during this period no exclusion requests on particular products are being accepted by the Office of the US Trade Representative.
Law360 published an article on August 18, 2018, by Morgan Lewis life sciences lawyers that discusses the FDA’s plans to advance biosimilar products. In an effort to reduce the cost of prescription drugs, the Biosimilars Action Plan (BAP) focuses on four key strategies: (1) improving the efficiency of the biosimilar and interchangeable product development and approval process; (2) maximizing scientific and regulatory clarity for the biosimilar product development community; (3) developing effective communications to improve understanding of biosimilars among patients, providers, and payors; and (4) supporting market competition by reducing gaming of FDA requirements or other attempts to unfairly delay market competition to follow-on products. As discussed in the article, the BAP outlines several priority deliverables to achieve each strategy. Time will tell, however, if the BAP is able to achieve its goal of facilitating biosimilar development and promoting biosimilar use.
In an attempt to minimize perceived obstacles to generic drug market entry, the FDA issued two draft guidance documents on May 31, 2018, related to shared system risk evaluation and mitigation strategies (REMS), providing the industry with insight into a previously underdefined area of FDA regulation. A shared REMS is one that encompasses multiple prescription drug products and is implemented jointly by two or more applicants. One of the new draft guidance documents sets forth the circumstances when a shared REMS program is required. The other draft guidance explains how to request a waiver from a shared REMS, signaling FDA’s willingness to grant such waivers.
Unfortunately, FDA did not provide any concrete steps to assist drug manufacturers with the challenging task of working cooperatively with market competitors on these drug safety programs. Nevertheless, the two guidance documents are a must-read for both brand and generic drug applicants.