In the last decade alone, the cost of developing a pharmaceutical asset has nearly doubled. In such a competitive market, it is key to capitalize on cost-effective strategies to secure approvals and bring a product to consumers. Whilst rates of approvals by government bodies fluctuate around the world, the US and its associated Food and Drug Administration (FDA) far outpace its counterparts globally, with over 100 new drug approvals every year. The US, still to this day, consistently represents the greatest market development opportunity for those that can navigate the FDAs comprehensive approval framework.
For companies looking to embark on a smooth process on the path to approval it’s key to develop a clear strategy and identify what is required for biotechs globally, especially given that in the case of the FDA, frameworks and guidance may fluctuate from time to time.
Clinical pathways with the FDA
Depending on the product, its intended use, and the stage of development, the FDA process generally follows the following steps:
- Preclinical testing - extensive preclinical testing in the laboratory and animal models.
- Investigational New Drug (IND) application - before human testing begins sponsors must file an IND application.
- Clinical trials - Phase 1, 2 and 3 trials are conducted.
- New drug application (NDA) or biologics license application (BLA) - if clinical trials are positive the sponsor can submit an NDA or BLA to the organization.
- FDA review
- Approval or rejection - rejected products may be required to provide additional data or testing.
- Post-market surveillance - continuous monitoring of the safety and effectiveness of approved products.
These steps have traditionally been the clinical pathway for approval at the FDA, but in the past decade there has been several significant changes affecting how products are assessed.
- The 21st Century Cures Act, initiated in 2016, aims to accelerate the development and approval of new drugs.
- Expedited approval designations where there is an immediate unmet need for consumers.
- Expanded access - the FDA is making it easier for patients with serious or life-threatening conditions to access investigational drugs and therapies.
- Digital health - the FDA has been working to develop regulatory framework for digital health companies to streamline the approval process.
- Biosimilars - an approval pathway for biologics that are unique but nearly clinically identical to an already approved biologic.
- Real world evidence - the use of real-world evidence is being investigated by the FDA to support decision-making.
- The FDA sees Decentralized Clinical Trials (DCT) as a way to potentially reduce patient and sponsor burden and increase accrual and retention of a more diverse trial population.
These regulatory developments for the FDA have led to creation of special regulatory designations that can alter the approval pathway for products and are intended to encourage the development of medical assets for rare or serious diseases. Some examples of special regulatory designations include; Fast Track Designation and Breakthrough Therapy Designation expedite the development and review process and offer benefits like more frequent interactions with the FDA, Orphan Drug Designation provides tax credits, waived FDA fees, and market exclusivity for seven years, and Priority Review Designation shortens the application timeline for products that offer substantial treatment improvement.
Designing a trial for success
The FDA has always placed high priority on ensuring clinical trials are conducted with rigorous trial design using sound scientific methods and appropriate study endpoints. The concept of ‘rigorous trial design’ however, has evolved over time due to keeping pace with scientific advancements and regulatory requirements. Increased emphasis on patient-centered outcomes, novel trial designs (for example adaptive and platform trials), technological advancements like wearable devices and electronic health records and regulatory changes have all contributed to or influenced the FDA's definition of rigorous trial design as it is today.
And, with the changing framework over time, it’s key to understand how this may affect pathway approvals in future. The FDA itself has several initiatives that are currently being implemented and could potentially lead to changes in the agency’s approval framework. The agency, for example, is taking into account more real-world evidence in its decision making process and making allowances for emergency use authorisations (EUAs) brought on by the Covid-19 pandemic.
Impediments and how to avoid them
Obtaining FDA approval for a new drug or therapeutic product can be complex, and biotech and pharmaceutical companies may face several consistent roadblocks. These include designing and executing successful clinical trials, regulatory compliance, safety concerns, demonstrating efficacy, manufacturing challenges, competition, cost, and time. Addressing these potential roadblocks early in the development process is crucial for avoiding some of the most common pitfalls and ensuring success for the product.
How CROs can support biotechs on the path to approval
Clinical research organizations (CROs) play a vital role in helping sponsors design and analyze clinical trials, ensuring that biotechs are maximizing their resources efficiently and increasing regulatory success. These practices include, but are not limited to, hiring experienced personnel, effective cro project management, risk-based monitoring, use of technology, quality management systems, regulatory expertise, and continuous improvement. By implementing these practices, CROs can increase trial efficiency and the likelihood of regulatory success. Identifying a trusted and reputable global CRO partner is key in delivering a strong and compliant submission to the FDA, and a successful approval from the organization.