Modernizing FDA’s New Drugs Regulatory Program – Reviewing the Guidance Ecosystem and Implications for Life Sciences Companies

In 2016, Congress passed the 21st Century Cures Act (Cures Act), which contained provisions to help accelerate medical product innovation while reducing regulatory burden, as well as to increase efforts for critical research and increase the involvement of patients and their perspectives in research and the product development process. The Cures Act specifically provided the US Food and Drug Administration (FDA) authority to modernize product development and review, and create greater efficiencies and predictability in product development and review. In June 2018, in response to this congressional mandate and corresponding new authorities, as well as reauthorizations of FDA’s user fee agreements, FDA made a series of announcements for a proposal to modernize new drug development.

Highlights of FDA’s initial proposal included:

• Focusing on recruiting talent across disciplines;
• Building multidisciplinary teams for more efficient collaboration;
• Prioritizing operational excellence through a single and consistent review process;
• Improving knowledge management through enhancements to information technology and honed expertise within review divisions;
• Emphasizing safety and risk-benefit analysis before and after approval; and
• Incorporating the patient voice into product development.

As articulated by former FDA Commissioner Scott Gottlieb, “[a] principal aim of these proposed changes is to elevate the role of . . . scientists and medical officers to take on even more thought leadership in their fields.”  The agency contemplates implementing organizational and structural changes that make drug review divisions more therapeutically-focused to promote efficient review and transparency in – as well as patient and stakeholder access to – the review process. According to the agency, these and other changes that are part of the Cures Act will result in a 20 percent improvement in efficiency.

Modernizing the Medical Research Ecosystem

Another major agency priority is modernizing clinical trials in order to encourage collaboration and data sharing and the adoption of disruptive technologies that make clinical research more effective, both in time and cost.  FDA has partnered with other stakeholders, such as regulated industry, to evaluate the role of decentralized trials and mobile technologies and to explore innovative trial designs (including validating novel endpoints).

The Complex Innovative Designs Pilot Meeting Program is a key initiative aimed at advancing innovation in the development of drugs, particularly for hard to treat medical conditions.. The program creates additional avenues for drug developers to meet with FDA staff to discuss the use of novel complex innovative trial designs (CID), such as seamless trial designs, modeling and simulations to assess trial operating characteristics, use of biomarker-enriched populations, complex adaptive designs, Bayesian models and other benefit‑risk determinations, and other novel designs for their clinical development programs.

Real World Data and Real World Evidence

Another major component of FDA’s effort to accelerate product innovation includes the expansion of the real world data (RWD) and real world evidence (RWE) program. In December 2018, FDA issued a framework for its RWE Program, followed by long-awaited draft guidance for drugs and biologics – Submitting Documents Using Real-World Data and Real-World Evidence to FDA for Drugs and Biologics – in May 2019 See an in-depth discussion on the potential impact RWD and RWE may have on accelerating the approval of new drugs and biologics or new or modified indications for approved drugs and biologics here.

Significance of the Changes

FDA’s recently announced initiative, Modernizing FDA’s New Drugs Regulatory Program, has six major strategic objectives, which expound upon the original June 2018 proposal and will continue throughout 2020:

1. Scientific Leadership to grow its scientific expertise and clarify pathways to regulatory approval;
2. Integrated Assessment to assess whether information in new drug applications meet legal and regulatory requirements using a consistent, critical, and collaborative approach;
3. Benefit-Risk Monitoring to systematically monitor the benefits of drugs, both pre- and post-approval to protect the public health;
4. Managing Talent to attract, develop, and retain the next generation of leaders;
5. Operational Excellence to standardize workflows, business processes, roles, and responsibilities to improve efficiencies and enable scientific staff to focus on substantive matters; and
6. Knowledge Management to facilitate and encourage the identification, documentation, distribution, and effective use of information.

More significantly, FDA detailed the six programs and projects currently underway, which demonstrate FDA’s commitment to implementing the initiative:

1. A new integrated review process for drug marketing applications, including a tracking tool from investigational new drug (IND) to post-approval, redefined roles to streamline review, and purposeful interdisciplinary working meetings;
2. IND review management to streamline the scientific review and management processes during IND development;
3. Post-market safety management to create a standardized and consistent approach to managing drug safety after approval;
4. Assessing talent, particularly by exercising Cures Act pay authorities to hire exceptional talent;
5. Optimizing administrative operations; and
6. Transition management and reorganization of the New Drugs Regulatory Program to create offices that align interrelated disease areas, and divisions with clearer and more focused areas of expertise.

The FDA Center for Drug Evaluation and Research and Center for Biologics Evaluation and Research have also published a number of guidance and draft guidance documents that align with FDA’s initiative to support accelerated medical product innovation while reducing regulatory burdens, including the ANDA Submissions — Content and Format of Abbreviated New Drug Applications (June 2019), Determining Whether to Submit an ANDA or a 505(b)(2) Application (May 2019) and Citizen Petitions and Petitions for Stay of Action Subject to Section 505(q) of the Federal Food, Drug, and Cosmetic Act (Oct. 2018).

Following the publication of these guidance documents, sponsors and applicants can expect faster approvals, largely in part due to FDA’s efforts to align expert staff with their respective therapeutic areas and to retain and increase talent via the Cures Act pay authority. Sponsors and applicants can also anticipate more certainty and greater transparency in product application reviews and should anticipate the need for increased communication with FDA throughout the approval process. Another potential outcome of FDA’s initiative, and in particular, its stated goal of shifting to benefit-risk monitoring of drugs from pre- through post-approval, is that while the approval process becomes shorter and less burdensome, FDA may focus its attention on closer monitoring of adverse event trends.  Sponsors and applicants should consider the potential for more rigorous data submission requirements post-approval.