Advisory Committees, Drug Reviews, and CRL’s. Oh My!
To many of us, advisory committee meetings are emblematic of an FDA that listens, is open to diverse viewpoints, and is willing to change direction when other views prove compelling.
FDA never yields the authority to decide. Yet, agency decisions about high-profile new drugs often feel more complete when they incorporate an advisory committee's review of the data.
The reality of advisory committees may often fall short of their promise. Still, the symbolism never loses its power to remind us that the FDA is committed to serving the American people fairly, dispassionately, and in accordance with science.
My positive view of advisory committees may not be shared by Commissioner Makary. By actions-- more than words—he has given the impression that he does not value the advisory committee system.
Advisory Committee Responsibilities Delegated to the Individual Centers
Decisions about advisory committees have traditionally been delegated to the Centers, which make their own decisions about whether and when to hold advisory committee meetings. Particularly for new drug reviews, it makes sense for the CDER and CBER staff to decide whether an advisory committee meeting would add value to their own evaluation.
However, the Commissioner has the right to order center directors to follow any FDA policy he establishes regarding advisory committees.
Thus, if he chooses to do so, it is within the Commissioner’s authority (with a couple of statutory exceptions[1]) to decide when, whether, and how many advisory committees will be held. Likewise, if FDA opts to have advisory committees, the Commissioner can direct the Centers to choose specific speakers, topics, panel members, and the agenda.
Commissioner Makary’s Approach to Decision-Making
Commissioner Makary has his own ideas about how decisions should be made and how input should be gathered.
Some we already know about, notably ad hoc panels instead of formal ones; fewer opportunities for public comment; and no vetting process to assure a balanced set of views on an advisory panel. He also seems to share the Administration’s disregard for the Federal Advisory Committee Act (FACA).[2] Other insights into Commissioner Makary’s approach to decision-making are being learned week by week, action by action.
No matter how any of us might feel about Commissioner Makary’s approach to decision-making or about any specific decision he makes, it’s his prerogative (along with the Center directors if he so chooses) to run the agency as he thinks is best. The only caveat is that his actions need to conform to statute.
Advisory Committees, New Drugs, and CRL’s
As a case in point, this past week, Arthur Allen of KFF Health News reported (here) that FDA wants to abandon advisory committee review of new drugs.[3] Since there was later a denial that this had been said, I am treating it as a signal of intent and direction, rather than a literal statement that new drugs would never be the subject of an advisory committee review.
The given rationale for the policy change was that advisory committee review of new drugs is no longer necessary because companies and other stakeholders could become educated about FDA’s thinking by reading Complete Response Letters (CRL).[4] This follows a prior FDA decision that, henceforth, CRL’s will be released routinely and in real time.
I agree with those quoted in the KFF Health News article that this doesn’t quite add up.
An advisory committee review of a new drug is about FDA making the right decision on the product after consulting experts and receiving input from the public (who can avail themselves of the open comment period). Not only does the advisory committee’s discussion contribute to the agency’s yes/no decision, but it may also influence labeling, post-approval studies, and whether a REMS (Risk Evaluation and Mitigation Strategy) program is needed (more about REMS).
Sponsor and public education about FDA’s views and process for new drugs may occur as a byproduct of an advisory committee meeting, but it is never the main point.
Why Eliminate Advisory Committee Review of New Drug Applications?
The rationale (public release of CRL’s) doesn’t explain why FDA would want to limit (or eliminate) advisory committee meetings on new drug applications.
I can think of two possible explanations behind a change of policy in this area. They are purely speculative on my part.
First, FDA may not want to expose its pending product decisions to a process that it can’t control. We all have a natural inclination to want to stage-manage events, and advisory committees often don’t follow the planned script.
Second, FDA may feel that it has sufficient expertise to make product decisions using FDA staff, and supplementing that with advice from the other public health agencies, the agency’s paid consultants, and the extensive professional networks of Commissioner Makary and Drs. Prasad and Tidmarsh.
Of course, I am speculating on those two possibilities. Over time, we will have a better idea if these alternative explanations have merit.
Ultimately, it’s the Commissioner’s Prerogative
Regardless of “why,” it is the Commissioner’s prerogative to limit or exclude advisory committees from the agency's process for making decisions on new drugs and biologics.
Many of us may prefer that he keep the advisory committee system involved in some drug reviews. But, in the end, it is his decision.
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[1] The FDCA requires FDA to hold an advisory committee for new molecular entities (NMEs) or original biologics. Alternatively, the agency may explain why not. I was not able to ascertain how this has worked in practice, but my impression is that it is treated as a formality rather than a necessity.
[2] The Federal Advisory Committee Act (FACA) governs the establishment, operation, and termination of advisory committees within the executive branch of the Federal Government. FACA defines what constitutes a Federal advisory committee and provides general procedures for the executive branch to follow for the operation of these committees.
[3] At the same time, it was suggested that Commissioner Makary would be open to more advisory committee meetings that address policies and priorities. If true, that would be good for the agency and particularly valuable for the food and tobacco centers.
[4] CRLs are letters from the FDA to a sponsor saying that their drug or biologic application is not approvable in its current form. It is not necessarily a final rejection and usually leads to dialogue between the company and FDA.
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