Regulatory Focus™ > News Articles > Industry Weighs in on Expedited Products Guidance, Calling for Definitional Clarity

Industry Weighs in on Expedited Products Guidance, Calling for Definitional Clarity

Posted 28 August 2013 | By Alexander Gaffney, RAC

In June 2013, the US Food and Drug Administration (FDA) released a long-awaited and much-anticipated guidance document on its new breakthrough product designation, and in the process of doing so overhauled much of its existing guidance on so-called "expedited programs" as well. Now one of the pharmaceutical industry's most prominent groups is weighing in on the topic, saying that while the guidance is "critical," extensive changes to definitions are warranted.


At FDA, fast track development is meant to focus agency resources on an application for a promising drug or biological product intended for a serious or life-threatening condition for which there is no adequate treatment or cure.

There are currently four main programs used by FDA to expedite the process of approving a drug intended to treat a serious or life-threatening condition:

  • Fast track designation - A designation given to a drug application for which there is evidence that it has the potential to address an unmet medical need or one that has been designated as a qualified infectious disease product. Allows for a rolling review of an application by FDA and the ability to expedite certain aspects of development and review.
  • Priority review designation - A designation given to applications (either new or supplemental applications) for which there is evidence that a treatment would provide a significant improvement in the standard of care for a patient. The designation shortens FDA's timeline for reviewing the application from 10 months to six.
  • Accelerated approval - An approval pathway through which a drug that provides a "meaningful advantage over available therapies" can obtain approval based on data in support of a surrogate endpoint. No change in the review timeline.
  • Breakthrough product designation - An approval pathway first introduced into law under the 2012 FDA Safety and Innovation Act (FDASIA), breakthrough product designation is intended for first-in-class products that treat a serious condition based on preliminary clinical evidence that indicates the drug may demonstrate substantial improvement on clinically significant endpoints over available therapies.

Unlike the other designations or pathways, breakthrough product designation isn't meant to expedite development based on shortened timelines or surrogate markers, but rather to grant access to enhanced review tools such as all of the features of the fast track designation, as well as "intensive guidance" from FDA regarding the development of the product.

Much of FDA's guidance on the breakthrough product designation is focused on the definitional details of evidence needed to support the indication, with FDA saying companies need to have data supporting preliminary evidence of an effect, as well as a rationalization that the effect would be a substantial improvement over the current standard of care. Clinical data is preferable, while certain pre-clinical data might also be used to support application of the designation.

As with the other two types of designations, FDA may withdraw breakthrough status if the product no longer meets the qualifying criteria for the designation.

Pharmaceutical Industry Weighs In

Now the Pharmaceutical Research and Manufacturers of American (PhRMA), a prominent DC-based pharmaceutical industry group, is weighing in on the guidance, calling it critically important but in need of changes.

Much of PhRMA's comments, sent to FDA on 26 August 2013 and provided in advance to Regulatory Focus, highlight definitional areas where industry feels FDA either missed the mark or neglected to include relevant information.

"Serious" Problems

For example, one comment notes that a portion of a preamble included in a 2006 guidance on fast track drug development programs was omitted from the new breakthrough guidance. This section had contained a statement that FDA would interpret the term "serious condition" consistent with how it had in the past, PhRMA explained, adding that FDA should reinsert the section so as to reaffirm the intent of the original guidance.

PhRMA also said FDA had changed the criteria for priority review designations, which now require diseases to meet "a 'serious' standard"-a "significant change in Center for Drug Evaluation and Research Policy," PhRMA added. This change did was not accompanied by any rationale or explanation, it continued.

Indeed, PhRMA spends a considerable amount of attention on the definition of the term "serious condition," arguing that FDA "should consider broadening the definition of a drug intended to treat a serious disease or condition" to make the guidance more consistent with the Federal Food, Drug and Cosmetic Act (FD&C Act).

For example, PhRMA says the guidance doesn't include any text to say that a drug intended to mitigate a serious disease or condition-or its side effects-would get breakthrough designation consideration. Neither is the guidance explicit on products intended to prevent a disease from progressing to additional stages or those that would "constitute a significant contribution to human health and fill an important unmet medical need." The comments propose text to remedy all three points.

Other Changes

But other parts of the comments also call attention to other issues, such as the definition of "Available therapy"-a term intended to assist regulators in determining if there is an unmet medical need for a given condition. While PhRMA wrote that it recognized that this definition "may be subject to clinical and regulatory interpretation and judgment … it would be helpful if FDA specifically noted in this section that these circumstances do not prohibit the Agency's consideration of other conditions that constitute a new treatment addressing an unmet medical need."

Examples of unmet medical needs would also be helpful, FDA added, as would definitional clarity to the terms "superiority", "failure to respond" and "similar" in Lines 166, 171 and 174/176 of the guidance.

Elsewhere in its comments, PhRMA also recommends FDA "consider expanding the criteria for determining whether a drug effect on a given endpoint is reasonably likely to predict clinical benefit," arguing that uncertainty must, in addition to the severity of a disease, be weighed against its rarity and the prevalence of a condition.

The comment, once published, will be available on the website under docket number FDA-2013-D-0575.

Guidance for Industry: Expedited Programs for Serious Conditions--Drugs and Biologics

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