Introduction

he world watched as global regulators and sponsors worked together with a sense of urgency to bring diagnostics, treatments, and vaccines to market within a year of identifying coronavirus disease (COVID-19). This incredible accomplishment offers a unique opportunity to apply similar efforts to other diseases of significant public health burden. Cardiovascular and neurological diseases are both associated with even greater morbidity and mortality compared to COVID-19. We cannot ignore the lasting social and economic impact of other highly prevalent, serious illnesses.

As patients with other highly prevalent, serious illnesses watched the intense focus on combatting COVID-19, they asked, “What about me?” The world observed regulators and sponsors working together with a sense of urgency to bring diagnostics, treatments, and vaccines to market within a year of identifying the virus. This incredible accomplishment offers a unique opportunity to apply similar efforts to other diseases of significant public health burden. As of May 20, 2022, the World Health Organization reports over 6 million confirmed COVID-19 deaths. In comparison, cardiovascular and neurological diseases are associated with even greater morbidity and mortality. One cannot ignore the lasting societal and economic impact of other highly prevalent, serious illnesses.

Patients with HIV/AIDS dramatically influenced regulator views 30 years ago with their willingness to accept greater uncertainty in exchange for earlier treatment access. Continued evolution of our regulatory tools and flexibilities has occurred since then, largely driven by patients, and has led to a greater consideration of emerging regulatory science tools. Regulatory policies issued during the COVID-19 pandemic reflect a similar mindset. The pandemic represents an opportunity to drive sustained change in our regulatory systems for other highly prevalent, serious illnesses.

Regulatory authorities have provided significant flexibilities during the COVID-19 pandemic, particularly for vaccines, without sacrificing quality, safety, and effectiveness standards. That agile approach will need to continue in the fight against COVID-19, including application of even greater flexibility in assessing emerging therapeutic options, which have not been viewed with the same sense of urgency despite being so desperately needed in regions where vaccination rates are low, access to therapies is strained, and breakthrough cases are high. Beyond the pandemic, regulators should apply similarly enhanced, risk-based regulatory approaches to other highly prevalent, serious illnesses where development speed matters to patients with unmet needs. This approach is supported by use of benefit-risk assessment frameworks developed globally by various regulators. Each framework is grounded in the context of the disease state and the available treatment armamentarium as benefit and risk attributes are considered and weighed for regulatory decision making.

The significant public health impact of many of these diseases warrants this approach. The time for this intentional and permanent shift—to apply a selective, enhanced benefit-risk framework that systematically leverages tools across all development stages—is now. We offer an approach for identifying illnesses that would benefit from this sense of urgency and a unified effort grounded in risk-based principles, to support this approach.

Therapeutic Context Should Inform Application of Risk-Based Regulatory Framework

Pre-Clinical Assessment

Fortunately, regulators and industry have extensive experience in successfully navigating this paradigm to benefit oncology patients. Globally recognized principles in ICH S9 Nonclinical Evaluation for Anticancer Pharmaceuticals are primarily responsible for this success and offer a blueprint to treat even more patients in great need. Because the burden for many diseases is comparable to that of advanced cancer, a similar risk-based approach should be considered to treat them. In those cases, post-approval studies should be used to address residual uncertainties.

Clinical Assessment

Manufacturing Approaches

Drug manufacturing is a continuous process where modifications to the product can occur throughout the drug’s lifecycle. In this space, a risk-based framework refers to deferring collection and reporting of certain chemistry, manufacturing, and controls data to later stages of development (or even post-approval) as appropriate based on risk, while ensuring the availability of quality products. Areas that would benefit from enhanced regulatory flexibility and deferral of information collection include process validation (especially during scale-up and employing prospective comparability protocols), longer-term stability data, reliance on platform technologies, and recognition of foreign inspections. Further, allowing more post-approval changes to occur within a company’s quality system (versus submitting for regulatory approval) would increase the ability to react to global supply challenges, consistent with ICH Q12 Guideline Technical and Regulatory Considerations for Pharmaceutical Product Lifecyle Development. When warranted, these approaches can enable earlier market entry and robust supply chains for therapies targeted to treat highly prevalent, serious illnesses.

Now That We Know We Can Do Better for Patients, We Must

To start, public and private stakeholders must align globally on a transparent set of criteria and regulatory guidance for identifying and developing treatments for diseases with the most significant impacts on public health that could benefit from the application of an enhanced risk-based approach. The process that we are proposing could be based on methods used by the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) to identify, vet, and prioritize potential topics for focus, an excellent example of public and private stakeholders coming together to address common challenges. However, we propose that these efforts initially focus on the attributes of the disease to establish an objective set of criteria for identifying diseases for which the use of a more directed risk-based regulatory framework is appropriate. Applicable therapies should leverage increased regulatory flexibilities and improved communication between regulators and sponsors, and benefit from greater global regulator consistency. Governments and other public and private stakeholders must align around a shared sense of urgency for patients with diseases that meet these criteria.

Once these criteria are established, and to enhance the chance for real progress, efforts to launch this initiative should include clear communications of the rationale for the disease state(s) selected and the magnitude of impact the disease(s) will continue to have on public health without targeted intervention. These may be based on World Health Organization (WHO) communications about emerging public health threats which serve to align and catalyze focus on a particular disease. Transparency from public health authorities will promote trust and understanding about the investment into disease areas with high unmet need and show why the consistent use of an enhanced risk-based regulatory framework across drug development is imperative.

Finally, international collaboration and sharing of best practices in the application of an enhanced risk-based regulatory framework are needed to achieve success. These best practices need to be internationally harmonized and effectively communicated to the regulated industry. An international, multistakeholder forum should be identified to drive accountability across health authorities and sponsors. If this approach proves successful, policy makers should consider how to expand to other seriously debilitating conditions.

The Future is Bright!

The views expressed in this paper are the independent views of the authors and should not be understood or quoted as being made on behalf of or reflecting of the position of their respective companies.