Posted 20 March 2015
By Alexander Gaffney, RAC
New legislation introduced in the US House of Representatives this week would require the US Food and Drug Administration (FDA) to expedite the review and approval of pharmaceutical products already approved in Europe.
The bill, the Speeding Access to Already Approved Pharmaceutical Act, is sponsored by Reps. Tim Ryan (D-OH) and Steve Stivers (R-OH), who introduced the same bill in June 2014.
As with the original, the bill targets something known in the pharmaceutical industry as "drug lag"—the difference between when one product is approved and marketed in one country and when it is finally approved and marketed in subsequent countries.
While the issue was once a major concern in the US, the passage of the 1992 Prescription Drug User Fee Act (PDUFA) largely erased the drug lag problem by providing FDA with additional resources to conduct drug reviews. PDUFA has been reauthorized four times, most recently in 2012 under the auspices of the Food and Drug Administration Safety and Innovation Act (FDASIA).
In the 1980s, less than 10% of all New Active Substances (NAS)—drugs never before approved—were launched in the US before anywhere else in the world. As of 2013, FDA said that 74% percent of NMEs approved in 2013 were approved in the US before anywhere else in the world—a record high according to data compiled by FDA. In 2014, FDA approved 66% of drugs before any other country.
Part of FDA's advantage over other regulators—which has been shown in several previous studies—is the speed with which is approves new therapies. A recent study by the Centre for Innovation in Regulatory Science (CIRS) shows that FDA approves new drug products more quickly than any other regulator, and has consistently done so for the past 10 years.
Other Calls for Harmonized Approvals
But while FDA approves between 66% and 74% of drugs before anywhere else in the world, a handful of drugs are approved elsewhere—including Europe—first.
That discrepancy has drawn the attention of the US' former top medical researcher, Elias Zerhouni, the former head of the National Institutes of Health (NIH) and now the head of research and development at the biopharmaceutical giant Sanofi.
In remarks made at the European Medicines Agency (EMA) on 18 March 2015, Zerhouni said a lack of regulatory consistency between regulatory bodies, including FDA and EMA, was baffling. "In my short experience of five years, I have not seen a single regulatory decision that was fully consistent across regulatory agencies," he said, according to Reuters.
The gap is all the more perplexing due to a convergence of regulatory standards between bodies like FDA and EMA, which have harmonized pharmaceutical regulatory standards through international groups like the International Conference on Harmonisation (ICH).
What hasn't been harmonized, Zerhouni noted, is standards of risk and benefit—the ultimate arbiter of whether a drug can and should be approved by a regulatory body.
Bill: If it's Been Approved in the EU, Expedite its Review in the US
But if Stivers and Ryan have their way, FDA could rely more heavily on EMA when regulating products.
“Unfortunately, the United States FDA’s red tape causes delays of up to several years in approval for life-saving and life-changing medical treatments,” Stivers said in a statement. “These delays could result in the unnecessary death and suffering of American patients."
The Speeding Access to Already Approved Pharmaceutical Actwould accelerate the review process by requiring FDA to review any drug approved for use in the EU in just 90 days—far more quickly than FDA's current fastest assessment, which takes six months (priority review designation).
The accelerated review would need to be made at the request of a drug's sponsor, the bill states.
The bill applies to any "pharmaceutical" regulated under Sections 505 (pharmaceuticals) or 351 (biologics) of the Federal Food, Drug and Cosmetic Act, and also to medical devices, which the European Union regulates much differently than does FDA.
Potential Problems With the Legislation
The bill does have a few gray areas in need of clarification. While the bill notes that any drug "approved for marketing in the European Union" is eligible for review, it does not clarify if this means a drug approved under the EU's centralized procedure (i.e. approved for use in every country in the EU) or the decentralized procedure, in which individual EU countries may approve a drug for use only in that country.
It's also not clear what effect the bill would have in practice. Many companies file their drugs for review simultaneously in the EU and US, making differences in approval time negligible. In other cases, companies only file their drug in one country, leaving the other regulator without sufficient data or information to support a positive approval decision. One example of this is Novartis' Bexsero—a meningitis B vaccine, touted by some as a case study for improving regulatory reciprocity. Despite being approved in Europe since January 2013, Novartis only filed for approval in the US in June 2014. It was approved by FDA in January 2015.
FDA and EMA also require different data to approve different pharmaceutical products. An acceptable clinical trial design in one country may be insufficient for approval in the US. In addition, while FDA is asked to review a drug in just 90 days, that may simply result in the agency issuing faster complete response letters (CRLs)—rejection letters—to companies, as FDA has done in the past when Congress has mandated faster review times.
Other hurdles to approving a drug quickly stem from FDA needing to inspect a drug manufacturing facility prior to a drug's approval. A facility may have been approved by EMA, but not yet inspected by FDA.
Ryan and Stivers also use FDA's regulation of sunscreen ingredients as a point to support passage of the bill. "Currently it can take more than a decade for a product to get approved by the FDA," they write. "For example since 2002, eight companies have submitted new and innovative ingredients for sunscreen, but all are still languishing in the FDA’s approval process."
Unfortunately, the EU regulates sunscreen ingredients as cosmetic products, meaning they would not qualify as a "new pharmaceutical," and would thus not be eligible for expedited review under their bill. Congress recently passed legislation to expedite the review of sunscreen ingredients using similar expedited-review measures as are found in Ryan and Stivers' bill. As Regulatory Focus has previously reported, Congress' attempt to force FDA to approve those ingredients has not been successful.
Speeding Access to Already Approved Pharmaceutical Act