From The Editor | March 29, 2016

Is FDA Biosimilar Regulatory Process Defeating Purpose Of BPCIA?

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By Anna Rose Welch, Editorial & Community Director, Advancing RNA

Is FDA Biosimilar Regulatory Process Defeating Purpose Of BPCIA?

In 1984, the Hatch-Waxman Act was launched, ushering in the regulatory pathway for generic medicines. However, the generics industry faced legal, educational, and regulatory challenges that extended years beyond the establishment of the approval pathway. Today, biosimilar makers are finally beginning to navigate the 351 (k) approval pathway, which was established in 2010 following the launch of the Biologics Price Competition and Innovation Act (BPCIA). The biosimilar pathway was intended to be an abbreviated pathway, helping drugmakers get their biosimilars more quickly to market. The approval pathway was formed not only to decrease healthcare costs, but also to improve patient access. According to Dr. Bert Liang, CEO of the biosimilar company Pfenex, the establishment of the BPCIA, at least conceptually, has been more efficient than Hatch-Waxman. However, when it comes to developing the policies that will shape the biosimilar market and ultimately impact its success, Liang says, “There’s a lot of reinventing the wheel.”

Why The 351 (k) Pathway Is Currently Not “Abbreviated”

In recent months, the FDA has faced enquiries from Congress and drugmakers about the agency’s progress developing biosimilar policies and industry guidance. The lack of guidance on labeling and interchangeability, among other key topics, has become a roadblock to an efficient biosimilar development process. As Liang describes, companies in the midst of the early to middle stages of development “are regularly going back to the agency and scheduling type-2 and other meetings because they need clarification every step of the way.”

Drugmakers’ reliance on the FDA, however, introduces challenges for both drugmakers and the FDA. As biosimilar makers continue to schedule additional meetings, the FDA becomes backlogged. Without guidances to fall back on, the FDA review teams are left to address issues on a case-by-case basis. Therefore, reviewers are faced with increased workloads, and timelines get pushed back. “By increasing the amount of time it takes to develop these programs and having multiple meetings with the agency, we’re increasing the cost of these programs — both for the agency and drug developers,” Liang explains. “This defeats the purpose of BPCIA.”

According to a report released by the Eastern Research Group (ERG), there are 57 biosimilar products in development and six products currently awaiting market approval. However, by the FDA’s own admission, the agency is troubled by a lack of resources — especially a lack of personnel — to address this workload.

The agency’s inability to hire a large enough team could, perhaps, be blamed on a lack of financial resources. The FDA has spent a considerable amount on biosimilar-related activities over the past few years. According to the ERG report, the FDA spent $81.7 million on biosimilar-related work from 2013 to September 2015. In 2015 alone, the agency spent $32.3 million. However, as the FDA’s Janet Woodcock told the Committee on Energy and Commerce’s Subcommittee on Health in a recent hearing, drug makers paid $23 million in biosimilar user fees in 2015. Based off these figures, BsUFA payments were not enough to cover the total amount spent on the agency’s biosimilar work in 2015.

However, the lack of transparency over how companies’ user fees are being spent remains a key question among industry members. After all, drug companies are paying their user fees upfront. “We pay our fees and expect a certain level of performance and transparency,” Liang states. Just as a CEO would not expect investors to provide financial support without insights into how their money will be used, drugmakers expect a certain amount of transparency as well from the FDA.

What Progress Has Been Made?

Though there are frustrations with the FDA’s progress in releasing guidance, the industry cannot overlook the approval of the U.S.’s first biosimilar — and the agency’s progress toward a second approval. In February, the Arthritis Advisory Committee voted in favor of approving Celltrion’s biosimilar of Remicade (infliximab; CT-P13) for all indications on Remicade’s label. This approval would open up the biosimilar to also treat gastroenterology indications, even though the biosimilar had not been tested in trials for these patient populations. While the FDA still has yet to grant the final nod, Liang argues that this advisory committee (AdCom) meeting signifies the ongoing evolution within the agency.

“Reading the CT-P13 briefing documents and listening to the meeting both suggest that the AdCom was starting to feel comfortable with the pathway,” Liang offers. After the meeting, the agency released a written statement arguing that performing clinical trials for all indications goes against the intent of the biosimilar pathway. “That, to me, was a very good sign they are feeling more comfortable,” Liang says. This decision goes a long way to differentiating the 351 (k) pathway from the standard biotech pathway. Should extrapolation become an accepted practice, biosimilar makers will be privy to an accelerated pathway, which is greater incentive for filing through the 351 (k) pathway.

How Can Biosimilar Makers Shape The Pathway?

Since their launch, generic medicines have grown in popularity. According to the Generic Pharmaceutical Association (GPhA) 2015 Generic Drug Savings Report, 3.8 billion of the total 4.3 billion U.S. prescriptions in 2014 were for generic drugs, saving the health care system $254 billion. Over the past 10 years, generic drugs have cut $1.68 trillion from the nation’s healthcare bill. As recent hearings have shown, Congress is concerned with ensuring that the biosimilar pathway will do as was intended: increase access to patients and save money. “We have to continue to remind Congress that establishing the biosimilar pathway is the way to see increased healthcare savings,” Liang says.

Biosimilar makers should also continue to speak with the FDA and work with the agency on furthering knowledge about biosimilars. Education will be key for establishing the biosimilar market. As Liang discusses, the FDA is currently focused on educating providers, which is how the agency approached education for small molecule generics. The FDA then expanded its efforts to a broader population. Liang expects that following in the educational footsteps of the generics market is a sound way for the FDA to go. However, as chair of the GPhA’s Biosimilar Council, Liang also emphasizes the importance of educating all biosimilar stakeholders, including state legislators, congressional offices, payers, and patients, about what biosimilars are and the purpose they can serve.

As the industry continues to battle over the appropriate way to name or label biosimilars, for instance, Liang highlights the importance of approaching the 351 (k) approval pathway differently than that of traditional biopharmaceuticals. “Biosimilar makers are trying to increase access for patients. If we’re going to try to increase access to patients, that is the key objective by which we should derive all of our policies,” says Liang.