Biosimilars regulations unlikely to unfold soon
As soon as members of Congress took their seats last month, the new Republican majority announced it would make good on its pledge to repeal the Patient Protection and Affordable Care Act. The effort largely is symbolic and unlikely to succeed, so at least one portion of the healthcare-reform law will likely remain in effect, namely the abbreviated approval pathway for follow-on biologics, also known as the Biologics Price Competition and Innovation Act.
In November, the Food and Drug Administration sponsored a public meeting to collect input from interested parties about what form regulations for follow-on biologics will take. The meeting was attended by the Pharmaceutical Research and Manufacturers of America, the Biotechnology Industry Organization and the Generic Pharmaceutical Association. In all likelihood, it will be a while before draft regulations come out; GPhA VP regulatory affairs Gordon Johnston and IMS Health VP industry relations Doug Long said guidance for draft regulations could appear this year.
“Historically, regulations have been slow to come,” Johnston told Drug Store News, noting that regulations for generic pharmaceutical drugs didn’t appear until four years after the 1984 passage of the Hatch-Waxman Act. “But certainly there’s a lot of interest in moving the process along, so I expect in 2011 we’ll see some sort of significant guidance or perhaps even draft regulations from the agency.”
Long thinks the process could take longer. “In discussions with others, there is a belief that it will be three years from the time of final guidance to see biosimilars on the market,” he told Drug Store News, saying that guidance could be issued in the latter half of 2011, but this was “very optimistic.”
Whatever the timeline, manufacturers aren’t sitting idly by. Teva Pharmaceutical Industries, the world’s largest generic drug maker and a major supplier of biosimilars in Europe, has sought to win approval for biosimilars in the United States using the existing unabbreviated pathway for biologics. So far, the Israeli company has had mixed results. It recently began marketing its generic version of Sanofi-Aventis’ anticoagulant Lovenox (enoxaparin), which the FDA approved as a pharmaceutical, though many experts said its chemical complexity places it more in the league of biologics. In September, Teva received a complete response letter from the FDA to its application for Neutroval (filgrastim), a biosimilar of Amgen’s Neupogen. Last month, Spectrum Pharmaceuticals and Viropro announced plans to develop a biosimilar of Genentech’s cancer drug Rituxan (rituximab), while Merck announced a deal with drug industry services firm Parexel International to develop biosimilars.
When a formal regulatory process takes shape, it is likely to look quite different from the one for generic drugs. For one, follow-on biologics will cost a lot more to develop. According to a 2006 study led by Duke University economist Henry Grabowski and published in the journal Health Affairs, simply building cell culture facilities can take three to five years and cost anywhere from $250 million to $450 million, which will keep the pool of manufacturers small.
On top of that, manufacturers must conduct clinical trials to prove their follow-on biologics are comparable to the originals, something that BIO and PhRMA strongly support, but that will incur additional costs for any prospective manufacturer.
Three issues that will define 2011
Years 2009 and 2010 were up and down for the generic drug industry and its main trade group, the Generic Pharmaceutical Association. On one hand, there were the departures of president and CEO Kathleen Jaeger and member company Teva Pharmaceutical Industries. On the other, a regulatory approval pathway for follow-on biologics was created — though it granted longer market exclusivity periods to biotech drugs than the GPhA desired — and there were increases in the use of generics, which accounted for 77% of dispensed prescriptions in the first half of 2010, according to IMS Health.
But 2009 and 2010 are behind the industry, literally and figuratively. In interviews with Drug Store News, GPhA VP regulatory science Gordon Johnston and IMS Health VP industry relations Doug Long spoke about three issues that will be important for the industry in 2011 — probably in a good way.
1. Drug safety : Drug approval in the United States is no easy task because of the strength of the Food and Drug Administration’s regulatory system. But the system still has weak points — particularly the inspection of foreign manufacturing plants. According to a September 2010 Government Accountability Office report, while the FDA inspected more than 1,000 domestic manufacturing plants in fiscal 2009, it inspected 424 in other countries, around 11% of the total.
That could change soon. “Whether supply chain safety comes in the form of legislation or FDA regulations, we … expect to see something coming down the pike in 2011,” Johnston said. Long, however, told Drug Store News he didn’t expect to see “anything major” this year.
2. Generic user fees : A perennial problem facing the generic drug industry is the backlog of applications at the FDA’s Office of Generic Drugs — and it keeps getting bigger. According to the GPhA, the number of applications submitted to the office increased from 361 in 2002, to 830 in 2008, creating a backlog of almost 2,000 applications in 2010, according to a presentation by office director Gary Buehler at the GPhA’s 2010 annual meeting. While federal regulations allow six months’ review time for an application, in practice it often takes 21 months.
Johnston said he expected a user fee program to be implemented by 2013. “I expect that a user fee program will be designed and recommended this year, with [the] industry and FDA working together,” he said.
Long agreed. “There is a very good possibility that user fees will be passed by Congress in 2011,” he said.
3. Patent settlements : When a generics company wants to market its version of a drug ahead of the branded version’s patent expiration, it will file an application with a paragraph-IV certification, asserting the patent is invalid, unenforceable or won’t be infringed, thus usually prompting a lawsuit from the branded drug’s manufacturer. In most cases, the two companies will settle, allowing the generics company to market its drug ahead of patent expiration in exchange for not immediately launching. Delaying launch after a patent has expired would be illegal.
The Federal Trade Commission has assailed the settlements as “pay-for-delay” deals and has sought to ban them, asserting they cost taxpayers $3.5 billion per year. The FTC may find its efforts frustrated with the Republican majority in the House, but it could use other means as well. Johnston said the outcome in Congress was difficult to determine. “Regardless of what happens on the legislative front, this issue may go to the Supreme Court to decide,” Long said.
ReportersNotebook — Chain Pharmacy, 2/7/11
SUPPLIER NEWS — The Food and Drug Administration has approved a generic drug made by Watson Pharmaceuticals for cancer-related breakthrough pain, Watson said. The drug is a generic version of Cephalon’s Fentora, which had sales of around $179 million during the 12-month period ended in November 2010, according to IMS Health.
The FDA has approved a generic version of Duramed’s contraceptive Seasonale (levonorgestrel and ethinyl estradiol) made by Sandoz, the generics arm of Swiss drug maker Novartis. Branded and generic versions of Seasonale had sales of around $91 million during the 12 months ended in November 2010, according to IMS Health.
Spectrum Pharmaceuticals and Viropro plan to develop a biosimilar of Genentech’s Rituxan (rituximab), used to treat cancer and autoimmune disorders. The companies plan to develop the biosimilar in anticipation of expirations on Rituxan’s patent protection over the next few years. Rituxan had sales of $5.6 billion in 2009, according to Spectrum.
Merck plans to develop biosimilars under a partnership with drug industry services organization Parexel International that will give Merck access to its clinical and regulatory services. Financial terms of the deal were not disclosed.
Mylan subsidiary Dey Pharma has launched MyEpiPenn, a smart phone application for patients at risk of severe allergic reactions, which is tied to its EpiPen product.