Poorly Structured Survey Misrepresents FDA Approval Process 
[Posted on: Thursday, May 12, 2016]

Over the last few years, FDA has implemented several new pathways to expedite patient access to new drugs, biologics and medical devices. These programs, such as breakthrough designation, Fast Track review, Expedited Access Pathway and Priority Review, have significantly reduced the development and review time for new products. Faster approval adds more pressure on FDA to conduct its review in shorter time and approve products based on partial information. A drug designated as a breakthrough product for example, could reach market in about one-third of the average time-to-market for conventional new drugs based on one or few clinical trials. Add to that the very public campaign by FDA to address data integrity issues during manufacturing and increasingly common findings of non-compliance of GMP for investigational and marketed products. This has led to increasing public perception that riskier, expensive drugs may be coming to market sooner than they should. In a survey led by researchers at Harvard University, it was observed the majority of people have reservations about fast FDA approval of new medical treatments. From the survey it also appears that public is not in favor of direct-to-consumer advertisements, or that FDA approve products approved in other countries. There seems to be significant support for price control as well. However, the survey has many issues. Like all surveys of this nature, the framing of questions asked could influence the kind of answers obtained. For example, the survey questions asked if changing government safety and effectiveness standards to allow for faster approvals of new prescription drugs is acceptable without clarifying what “changes” meant. The tone of the question indicates as if the standards are being reduced. On the contrary, the regulatory changes have taken a risk-based approach where instead of “reducing” standards, FDA reviews have shifted to “focus” on major issues and using common sense and logic to only ask for most relevant studies. This approach is new and this change is positive. Similarly, FDA is not allowed under the law to make product approval decisions based on the potential market price of the drug. So, the question about price control does not explain that it would require major shift in US regulations. The strongest argument against expedited approval is if the clinical trials that led to the approval decision were conducted with good quality investigational drug product. FDA allows significant relaxation of the GMP requirements for first-in-man and Phase 1 clinical trials. So, what happens if the first-in-man study supports market approval of the drug, which can be expected for a drug designated as breakthrough therapy? This is particularly true if the drug in early phase of development is used for an emergency application (such as for treatment of Ebola infection), or on a compassionate basis to provide options where none exist. It is important to note that the guidance on GMP for Phase 1 or first-in-man trials takes a risk-based approach to tailor standards to the risk to quality. So, in effect, it does not “reduce” standards but optimize them to the stage of development. The discussion of expedited approval of FDA-regulated products is multi-dimensional and could be fairly conducted only by providing complete contextual information. Otherwise it will give answers manipulated by the bias of the questioners.