YOUR GO-TO SOURCE FOR ANALYSIS OF ISSUES AFFECTING THE PHARMA & BIOTECH SECTORS

Over the last few months, FDA has continued its efforts to encourage and facilitate the use of the agency’s Expanded Access Program (EAP). This follows other FDA EAP actions, including its announcement of program improvements. Overall, these steps appear to signal that FDA is trying to position the EAP as a desirable option for patients, healthcare providers, and industry following the passage of the Federal Right to Try statute, in which, as noted in FDA’s recent Right to Try Frequently Asked Questions (FAQs), the agency plays a very limited role.

The US Supreme Court held on May 20 that a judge, not a jury, must decide the question of whether federal law prohibited drug manufacturers from adding warnings to the drug label that would satisfy state law. To succeed on a pre-emption defense on failure-to-warn claims, the drug manufacturer must present “clear evidence” that it fully informed the US Food and Drug Administration (FDA) of the justifications for the warning, and that the FDA, in turn, informed the drug manufacturer that the FDA would not approve the addition of the warning to the drug’s label. The Court remanded to the US Court of Appeals for the Third Circuit to decide the pre-emption question. Two concurring opinions provide the Third Circuit with roadmaps to opposite conclusions.

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The US Food and Drug Administration (FDA) issued an updated draft guidance on March 7 on the nonproprietary naming of biologics, titled Nonproprietary Naming of Biological Products: Update. This update is FDA’s second attempt at guidance concerning nonproprietary name suffixes for biologic products. It also highlights the perceived tension between FDA’s pharmacovigilance role and goal of increasing the availability of biosimilars. At least for this round, FDA’s interest in tracking pharmacovigilance data seems to have received priority.

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The US Food and Drug Administration (FDA or Agency) on January 30 signaled what could be an about-face with regard to its role administering the List of Approved Drug Products with Therapeutic Equivalence Evaluation (referred to as the Orange Book). Historically, FDA’s Orange Book role has been solely ministerial. However, over the next year, FDA may begin taking a more active approach to the Orange Book.

Human cell and gene therapy research has advanced dramatically in recent years and opened the door to potential treatments for diseases once considered incurable. On January 15, FDA Commissioner Scott Gottlieb, M.D., and Peter Marks, M.D., Ph.D., director of the Center for Biologics Evaluation and Research (CBER), issued a joint statement announcing plans to keep pace with the rapidly growing and evolving field through new policy guidance and other assistance. According to the statement, FDA is turning its attention and additional resources toward these therapies in 2019 due to a “large upswing” in the number of cell and gene therapy investigational new drug (IND) applications. Based on an assessment of the more than 800 cell-based and gene therapy INDs current on file with the agency, FDA projects that it will receive more than 200 cell and gene therapy INDs per year by 2020, and will approve 10 to 20 such products per year by 2025.

To accommodate the uptick and to ensure regulation of firms that may be operating outside of regulatory compliance, the statement sets forth FDA’s planned actions to support cell and gene therapy product development in 2019:

After several delays, the revised US Federal Policy for the Protection of Human Subjects (also known as the Common Rule) went into effect on January 21. The Common Rule is generally applicable to research conducted or supported by one of the federal departments or agencies that has integrated the rule into its own regulations (e.g., US Department of Health and Human Services (including the National Institutes of Health), US Department of Agriculture, US Department of Defense). Some clinical trial sites may also apply the Common Rule across all clinical research projects, regardless of funding source, through a US Office for Human Research Protections Federal Wide Assurance.

Despite the mandate under the 21st Century Cures Act to harmonize FDA regulations with the Common Rule to the extent practicable and allowable under existing legislative provisions, FDA has yet to propose aligning regulations. Rather, FDA issued guidance titled Impact of Certain Provisions of the Revised Common Rule on FDA-Regulated Clinical Investigations. As of right now, while FDA is aware of new inconsistencies between its human subject regulations and the revised Common Rule, the agency has advised that when a given study is subject to both sets of regulations, the rule that offers greater human subject protection should be applied. The guidance sets forth FDA’s position on the following areas of potential discrepancies between the Common Rule and FDA regulations:

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.

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. 

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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.