Enforcing The “Least Burdensome” Requirement for Premarket Review of Devices

June 22, 2015

By Jeffrey K. Shapiro

Last week, Senators Richard Burr and Al Franken introduced legislation aimed at easing the burdens of the Food and Drug Administration’s (FDA) review of devices.  The bill is called “The FDA Device Accountability Act” (FDAA).   A copy of the press release announcing the bill is available here, and a one-page summary of the bill is available here.

The FDAA: (i) extends application of the “least burdensome” requirement to premarket application (PMA) reviews and to all significant decisions, and adds training, review and auditing of FDA’s application of the requirement; (ii) explicitly permits non‑local or centralized IRBs for device clinical trials; and (iii) requires FDA to update its existing regulatory guidance to clarify the criteria for waiving CLIA requirements, specifically certain considerations for in vitro diagnostics.

These reforms are all worthy; however, as discussed below, the first reform relating to the “least burdensome” requirements is unlikely to achieve the hoped‑for results. 

What are the “least burdensome” requirements?  In 1997, the Food and Drug Administration Modernization Act (FDAMA) added two provisions to the Federal Food, Drug, and Cosmetic Act (FDCA).  One provision, relating to 510(k) reviews, was section 513(i)(1)(D).  It states:

Whenever [FDA] requests information to demonstrate that devices with differing technological characteristics are substantially equivalent, [FDA] shall only request information that is necessary to making substantial equivalence determinations.  In making such a request, [FDA] shall consider the least burdensome means of demonstrating substantial equivalence and request information accordingly.

The other related to clinical data.  In connection with “determination meetings” to obtain a written statement of the clinical data required to obtain PMA approval, section 513(a)(3)(D)(ii) states:

Any clinical data, including one or more well-controlled investigations, specified in writing by [FDA] for demonstrating a reasonable assurance of device effectiveness shall be specified as a result of a determination by [FDA] that such data are necessary to establish device effectiveness. [FDA] shall consider, in consultation with the applicant, the least burdensome appropriate means of evaluating device effectiveness that would have a reasonable likelihood of resulting in approval.

After FDAMA was enacted, it turned out that “determination meetings” were rarely held, which means the occasions for FDA to follow the foregoing mandate have also been rare.

FDA’s guidance on “least burdensome” summarizes the agency’s view of these provisions:

A central purpose of the Food and Drug Administration Modernization Act of 1997 (FDAMA) is ‘to ensure the timely availability of safe and effective new products that will benefit the public and to ensure that our Nation continues to lead the world in new product innovation and development.’  [Citation omitted.]  As can be seen in this statement, Congress’ goal was to streamline the regulatory process (i.e., reduce burden) to improve patient access to breakthrough technologies.

But FDA notes a caveat:  

While Congress wanted to reduce unnecessary burdens associated with the premarket clearance and approval processes, Congress did not lower the statutory criteria for demonstrating substantial equivalence or reasonable assurance of safety and effectiveness assurance of safety and effectiveness.

The FDAA bill summary asserts that implementation of the “least burdensome” over the years as been unsatisfactory:  “Unfortunately, these principles have not been consistently applied.”  Section 2 of the FDAA bill would reform the “least burdensome” requirement with the following directions to FDA.

  • FDA must train all premarket review staff and supervisors in the “meaning and implementation” of the requirement. 
  • FDA’s device ombudsman must conduct an audit of FDA’s implementation of the requirement within six months of the bill’s enactment and the report must be provided to Congress and posted on FDA’s web site.
  • FDA must periodically assess the implementation of the requirement, including training.

In addition, the FDAA bill would explicitly extend the “least burdensome” requirement to requests for information during review of a PMA.  It also would require FDA’s summary of a “significant decision” during a premarket review to state how FDA applied the “least burdensome” requirement in reaching the decision.  (The “significant decision” documentation requirement was imposed on FDA in 2012 under the Food and Drug Administration Safety and Innovation Act (FDASIA), § 602.)

We do not disagree with Senators Burr and Franken that the “least burdensome” requirement since 1997 has been applied inconsistently.  Actually, we would go further and say that it has proven toothless.  FDA’s correspondence concerning data requirements typically has boilerplate language stating that the “least burdensome” requirement was “carefully” considered.  Yet, the burdens of device review still seem excessive in many cases, and there is no transparency as to how FDA actually applies the principle in any individual case.

But is the problem really one of “consistency” and “transparency”?  The FDAA bill proposes reforms on that premise.  In our view, these issues do not get to the root cause, which is that the “least burdensome” requirement is inherently subjective.  The fact is, FDA must make safety and effectiveness determinations according to statutory requirements.  The “least burdensome” requirement does not lower the safety and effectiveness requirements.  When FDA requires specific data, it is almost always because premarket review officials within the Office of Device Evaluation (ODE) have concluded that doing so is necessary for the product sponsor to meet the statutory requirements.

The true problem is not a misunderstanding on their part as to how to consistently apply a “least burdensome” requirement.  Rather, in most cases, the dispute is a disagreement between ODE officials and the applicant about how safety or effectiveness should be demonstrated.  So as long as there is no independent check on the judgment of ODE officials, they will generally decide these disputes in their own favor.  And that is what has generally happened since the “least burdensome” requirement was imposed in 1997.

At present, the applicant’s only slim hope is to seek supervisory review within FDA (21 C.F.R. § 10.75) and perhaps convince a supervisor that a less burdensome data requirement is adequate.  Unfortunately, it is only to practical to file such appeals a small percentage of the time, and the odds of success are low.  There is also an inherent conflict of interest in having the supervisor review the employee’s decision, as discussed here.  

Hence, the FDAA bill is correct in recognizing that the “least burdensome” requirement has not achieved its original intent.  However, it is questionable whether this package of reforms will have a meaningful impact.  On the plus side, the FDAA bill does seem likely to provide greater transparency about the rationale for FDA’s decisions when applying the “least burdensome” requirement.  The increased documentation will facilitate the additional requirement for FDA to periodically conduct internal assessments as to how it is doing in implementing the “least burdensome” requirement.  The training requirement will also help teach and remind reviewers about the requirement.  Thus, the FDAA bill should be successful as a consciousness‑raising exercise for the agency.

Nonetheless, at the end of the day, under this bill, FDA will continue to be the judge of its own “least burdensome” decisions.  It would be preferable for an independent entity to adjudicate these disputes, if an entity could be established with the expertise and resources to allow it master the details of each regulatory dispute, similar to what judges are expected to do in court cases.  The entity would also need to have the authority to overturn or reshape ODE’s data requirement determinations.  Otherwise, it seems unlikely that the general tenor of ODE’s decisions will change.

If it is not realistic to establish an independent entity such as this one outside of FDA, perhaps in the judicial or legislative branch, a next‑best alternative would to create a specific office within Device Center with the bureaucratic mission of handling appeals from ODE in an impartial manner.  For example, we put forward an idea long these lines a few years ago, which was basically to create a specialized Office of Appeals for Premarket Submissions (OAPS) (see our previous post here).  This independent entity could handle, among other things, disputes over the application of the “least burdensome” requirement.

The Burr and Franken bill is a worthy reform effort.  It might prove even more effective if it were broadened to attack the root cause of the disappointing results achieved so far with the “least burdensome” requirement.

Categories: Medical Devices