Journal of the National Cancer Institute Advance Access originally published online on August 28, 2007
JNCI Journal of the National Cancer Institute 2007 99(17):1286-1287; doi:10.1093/jnci/djm147
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
© Oxford University Press 2007.
NEWS |
Generic Biologics May Be Coming to the Marketplace If Legislation Passes In Congress
Legislation currently moving through the Senate would allow the U.S. Food and Drug Administration to regulate generic biologic agents, an industry potentially worth billions of dollars a year. But it would also establish protections that favor the original developers, giving them 12 years without direct competition.
Although a relatively young field, there are already a handful of blockbuster biologic agents, especially in oncology, where these treatments promise a more targeted approach to the disease. Everything from blood and blood products to cellular and gene therapies falls under the FDA's definition of protein products, or biologics, which the agency regulates under different authority from that of standard drugs because of their unique complexity. Both the structure and manufacture of biologics, also called large-molecule products, are far more difficult to replicate than conventional pharmaceuticals.
The agency has determined that rules on comparability, therapeutic equivalence, and interchangeability—used to justify abbreviated approval for generic drugs—can not be readily translated to biologics. The rules have been used in only a limited number of cases.
"Because of the variability and complexity of protein molecules, current limitations of analytical methods, and the difficulties in manufacturing a consistent product, it is unlikely that, for most proteins, a manufacturer of a [generic] protein product could demonstrate that its product is identical to an already-approved product," FDA Deputy Director Janet Woodcock, M.D., recently told a House committee.
However, there has been a push from both the generics industry, which would like to get a piece of what has rapidly become a billion-dollar business, and consumer advocacy groups concerned about the high cost of brand-name biologics, to allow more competition into the marketplace.
The Senate bill is an attempt to balance everybody's interests, said Stephen Albainy-Jenei, J.D., a patent attorney specializing in biotechnology at Frost Brown Todd LLC in Cincinnati, Ohio.
"Innovators want protection to last as long as possible. If they could get it forever, they would definitely want that. And the generic companies would like it to be as close to zero as possible," he said. "Currently, there are no [biologic] generics, because there is no path to get one approved. That's great if you’re a brand company because effectively your exclusivity is running forever and that's an awfully nice position to be in. But if you’re the paying public, you don’t like that situation, because when generics enter the market, prices plummet."
Congress has a tricky job finding a middle ground between those conflicting interests. On the one hand, they need to ensure that there is enough incentive to stimulate innovation. On the other, they are under pressure to bring health care costs down, including the price of drugs and other medical therapies, he explained.
The Senate compromise would allow companies to solely manufacture their biologics for 12 years before a generic can be approved by the FDA.
"Drugs inherently get both patent protection and a layer of protection from the need for regulatory approval. No one enters the market without that. Giving [biologic makers] this extra 12 years is not extending the patent protection, but it might as well be," Albainy-Jenei said.
There is nothing magic about 12 years, but it is a number that both the House and Senate seem to agree on. It's included in the Senate bill that has passed through the committee process and is now awaiting a floor vote. It is also in a House measure introduced by Rep. Jay Inslee (D-Wash.) and forwarded to the House Energy and Commerce committee's Health subcommittee.
Naturally, the biotech industry has complained that 12 years is too short, while patient groups, such as AARP, say it is too long. This difference could turn into a bitter debate given that even one extra year of data exclusivity can mean a billion dollars in profit for a blockbuster agent.
"It's crucial that Congress get this right because biologics are the future of medicine," said Sen. Orrin Hatch (R-Utah), a sponsor of the bill as well as the Hatch–Waxman Act, the legislation that established a pathway for approval of generic pharmaceuticals.
|
"It's taken a lot of effort, but we’ve achieved a good balance in this bill. Just as we did with Hatch–Waxman in 1984, we’re giving incentives for both pioneer and generic drug firms," he said in a group statement from the bill's lead sponsors, Sens. Edward Kennedy, Hillary Clinton, and Michael Enzi.
If passed into law, the bill would allow the FDA to approve similar biologics if the applicant can show that there are no meaningful differences in safety, purity, and potency between their agent and the original. The generics companies could use analytical data, animal testing, and one or more clinical trials. The legislation leaves it to the discretion of the agency to determine which of these criteria are required in each case.
"Biotechnology innovators share the goal of ensuring all patients have access to life-enhancing and life-saving biologics. We support the development of a pathway for the approval of follow-on biologics," said Jim Greenwood, a former chairman of the House Energy and Commerce Committee and currently president and CEO of the Biotechnology Industry Organization.
However, Greenwood said that the bill gives the FDA too much latitude in deciding whether generic biologics need to be tested in humans before they are approved and places no restrictions on whether patients can be switched to a generic biologic without their physicians’ consent.
While the Senate legislation does stipulate that the FDA can allow generics applicants to forgo clinical trials, it appears more likely that agency officials would take a more conservative approach up front, said Henry Grabowski, Ph.D., a professor of economics and director of Duke University's program in pharmaceuticals and health economics. They might be more likely to use such an exception once the process is more established. The House bill doesn’t give the FDA any margin, mandating that clinical studies be conducted on similar biologics.
Conducting clinical trials is just one of many things that makes the market for biologic agents look much less attractive than that for traditional pharmaceuticals. Trials could cost companies between $10 million and $40 million, just one of the more costly aspects of getting approval compared with the relatively straightforward approval process for generic pharmaceuticals, Grabowski said. Also, the development times for generic biologics are expected to take 5–8 years, and manufacturing biologics is a much more complex and costly process than manufacturing standard drugs.
While a big-selling drug may attract 10–20 competing generics, the economics of biologics would support only a few generic versions, Grabowski told a House committee in March. "Even very large selling biological products are likely to have only a few entrants. Accordingly, price discounts are expected to be moderate. For markets with only one to three entrants, we project that price discounts will be in the range of 10%–25%," he testified.
What the final legislation might look like is unclear, and once it passes, the FDA will still have to work out much of the science. Ultimately, however, Congress will move forward to make generic biologics a reality, Albainy-Jenei said.
"You have to remember, the number-one consumer of health care, the number-one payer is the federal government. ... If there is anyone who would like to see some generic price breaks, it's the government," he said.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  J. M. Hoffman, N. D. Shah, L. C. Vermeulen, F. Doloresco, P. K. Martin, S. Blake, L. Matusiak, R. J. Hunkler, and G. T. Schumock Projecting future drug expenditures--2009 Am. J. Health Syst. Pharm., February 1, 2009; 66(3): 237 - 257. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Hoffman, N. D. Shah, L. C. Vermeulen, F. Doloresco, P. Grim, R. J. Hunkler, K. M. Hontz, and G. T. Schumock Projecting future drug expenditures--2008 Am. J. Health Syst. Pharm., February 1, 2008; 65(3): 234 - 253. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||