Hamburg Touts Regulatory Flexibility of Agency, Notes Upcoming Breakthrough Guidance

Posted 18 March 2013 | By Alexander Gaffney, RAC 

In a speech before the biotechnology industry of Massachusetts, US Food and Drug Administration (FDA) Commissioner Margaret Hamburg explained that her agency is doing all that it can to meet the myriad of challenges facing the industry, including enacting new measures meant to provide regulatory flexibility to ensure products make their way to patients more quickly. Also discussed by Hamburg were submission trends for biosimilar products, the agency's desire for the creation of a limited-use pathway, and an upcoming guidance meant to clarify the breakthrough products designation process.

Focus on Regulatory Measures

In her speech, Hamburg noted that the biopharmaceutical sector is facing a number of "daunting" regulatory challenges-everything from foreign competition and complex reimbursement to the patent cliff and cuts to FDA and the National Institutes of Health (NIH). To face those challenges will take not a single panacea-like approach, but rather a multifaceted "integrated strategy," said Hamburg.

And key to that strategy will be regulatory policy and regulatory reform, she added.

Some of those policies and reforms are already in the works thanks in part to frequent feedback from industry that Hamburg said she was well aware of. "We have heard loud and clear that you want increased clarity, certainty, and predictability about FDA's standards and expectations," she said.

"Thanks in part to these conversations, we are well aware of the challenges you face in bringing promising large and small molecule products to market, and we are trying to respond by achieving smarter regulation, greater flexibility, and creative approaches to drug development and evaluation."

More Flexibility for Innovative Products

One of the challenges associated with making those changes, however, is simply communicating that they have occurred. Hamburg explained not everyone has understood her agency's adaptive approaches toward regulating new products, which now includes fast-track, priority review and accelerated approval pathways meant to get critical drugs to patients more quickly.

These expedited approval measures have had the practical effect of getting many new products to market in the US more quickly and earlier than in any other country, Hamburg noted. Those products are also increasingly targeted toward rare disease populations, and made up one in every three products approved in the last five years.

One such product, Juxtapid (lomitapide), is used to treat a rare disease known as homozygous familial hypercholesterolemia, a condition marked by high levels of low-density (LDL) cholesterol. The condition is thought to affect just one in every million people, giving it an estimated patient population of 313 in the US.

FDA approved the product based on just one clinical trial involving 29 patients-far, far fewer than the patient requirements for non-rare diseases reviewed by the agency. As a result, the product's main obligations will be in post-marketing settings, where it will be evaluated in three trials meant to gauge its safety and efficacy more closely.

Hamburg highlighted the product, noting it "fits the mold" of the agency's new, more patient-friendly approach toward product approvals.

Breakthrough Products Guidance on the Way

That approach will also be seen in a new regulatory pathway known as breakthrough designation, intended for when "preliminary clinical data suggest that a new drug holds real promise to offer substantial improvements over available therapies to treat a serious condition."

In a recent speech, Janet Woodcock, director of FDA's Center for Drug Evaluation Research (CDER), said the breakthrough products designation could be used to approve some of those products using just one phase I clinical trial.

"We'll continue to use our existing tools and the new 'breakthrough' authority to make our expedited drug development process even more effective, with the ultimate goal of benefiting patients with unmet medical needs," she explained. Hamburg concurred in her speech, adding that the agency is in the midst of developing a guidance document on the topic.

Hamburg also noted that the agency has received 31 breakthrough designation requests. Nine have been granted, 10 denied, and one withdrawn. The rest are awaiting agency decisions.

The numbers indicate a considerable amount of interest in the pathway, as the first submission for the pathway-new indications for Kalydeco, an already-approved drug for cystic fibrosis-only came in early December 2012.

But no matter how good an application, Hamburg explained that without an acceptable inspection of a company's manufacturing facility and scaled-up production, accelerated approval will be for naught.

"Sadly, too many start-up companies fail to recognize this fundamental fact, and so approval is delayed," she added.

Biosimialrs and Limited Use Pathways

The speech also touched on two other topics of frequent interest to the regulatory community: biosimilars and limited-use pathways.

Hamburg explained that "FDA has yet to receive an application for a biosimilar or interchangeable product despite 51 meeting requests regarding 12 different products. It has received 15 investigational new drug applications to start clinical testing, though none have yet resulted in a 351(k) biologics licensing application.

Hamburg also explained she is looking at the feasibility of a "special limited use" pathway for drug products, which could be useful in cases where a drug has dramatically different risk paradigms in various populations. The pathway could be used to limit off-label prescribing for certain drugs.

"Under current requirements FDA cannot be assured that use of a product will be limited, so drug development plans must often evaluate the risks in a broader populations resulting in larger, lengthier trials," she noted.

Hamburg noted that FDA would need to work with Congress to create the pathway, as it does not yet have statutory approval to do so.

An initial meeting to discuss the pathway's feasibility was held in February 2013.

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