As Pfizer, Moderna, and other pharma
companies prepare to seek emergency authorization for their SARS-CoV-2
vaccines, the FDA has laid out a roadmap designed to ensure appropriate
scientific rigor and help engender public trust. That plan was the subject of a
special meeting of the Vaccines and Related Biological Products Advisory
Committee (VRBPAC) on October 22, 2020, where experts discussed 2 critical FDA
guidance documents that provide a blueprint for development and approval of
SARS-CoV-2 vaccines. That blueprint is at the center of a massive government
effort to quickly and safely speed vaccines to the American public and bring
the pandemic to an end.
Members of the VRBPAC, with expertise in
infectious disease, epidemiology, and vaccine development, focused on issues
around the FDA standards for safety and effectiveness that will support
Emergency Use Authorization (EUA) of vaccine candidates. They discussed the
need to continue the phase 3, randomized, placebo-controlled trials to
completion after an EUA is granted. They considered how the vaccines will be
rolled out to the American public, and they raised concerns about whether the
public will embrace the vaccines and roll up their sleeves.
One of the fundamental responsibilities of the US Food and Drug Administration (FDA) is to approve effective medicines for people who need them, while upholding high standards for safety. That mission also demands that the FDA work efficiently and not delay approval of life-saving medical advances. Today, the FDA is reviewing applications for approval of new medicines faster than ever, and that’s a welcome change from the status quo 25 years ago. In the era from 1962 (immediately following the thalidomide recall) to the early 1990s, FDA review times for a New Drug Application (NDA) or Biologic License Agreement (BLA) were often measured in years rather than months. In 1993, the standard review time (from NDA or BLA submission to decision) for a new molecular or biologic entity (parlance for a drug not previously approved for any other use) was about 28 months,1 and in some cases, approvals were delayed for many years.
The US Food and Drug Administration (FDA) review of drugs, although guided by broad standards, remains individualized. Each drug or drug class faces unique challenges during the FDA review phase – thus no two reviews are exactly the same. Each review division within the FDA has its own approach, and evaluations often differ among the centers. To help understand the review process, the team at ProEd Regulatory sought to learn from the past to inform our future. We reviewed applications submitted to the Center for Drug Evaluation and Research (CDER) data over the last 70 years to see what patterns might emerge. Although the largest proportion of products (drugs and biologics) fails between discovery and Phase 3, an evaluation of applications submitted to the FDA over the last 70 years shows that the vast majority of products that reach the submission stage are ultimately approved (Figure 1).1
It wasn’t until the Kefauver-Harris Drug Amendments of 1962 that the FDA required sponsors to demonstrate both efficacy and safety of their drugs prior to market access. In the wake of this significant legislation’s impact on drug development, we still see a consistent flow of approved applications and a corresponding subset of new molecular entities (NMEs) (Figure 2).1