New Rules On Generic Biological Medicines Under US Congressional Debate

By Liza Porteus Viana for Intellectual Property Watch
When Biotechnology Industry Organization CEO Jim Greenwood meets with members of the United States Congress to talk to them about follow-on biologics, he brings a graphic model of an aspirin and a DVD showing the complex molecules of a biologic drug. He uses these visuals to help explain the differences between traditional chemical drugs and newer, cutting-edge biological ones being used in many breakthrough therapies for cancer, multiple sclerosis, HIV/AIDS, and other diseases.

The differences between traditional chemical drugs and biological ones is the crux of the debate going on in the United States as Congress and the Food and Drug Administration (FDA) try to create a regulatory pathway that gives consumers greater access to cheaper, generic biological drugs, but still spurs innovation and protects innovator patent claims.

“When the legislation was introduced at the beginning of this Congress, most pundits expected that we’d oppose it,” said Greenwood, a former House representative from Pennsylvania, told Intellectual Property Watch. “But that was a mistake the pharmaceutical industry made in the ’80s – trying to resist the notion you could safely make generics. Our view at BIO is that we need to follow the science, and science says you can make follow-on biologics that can be safe and can save the consumer money and therefore we support it.”

The Debate

At question is just how easy it should be for the generic drug industry to market and sell copycat biological products (called “follow-on biologics,” or FOBs, but also referred to as “biosimilars” or “biogenerics”) of the brand-name companies, the latter of which pour billions of dollars into research and development, and clinical trials, to get the products approved.

Biologics are complex, more expensive medicines manufactured with living organisms. Whereas traditional, small molecule chemical drugs always have the same material makeup – making them easy to copy and usually fast to be approved – biologics are extremely difficult, if not impossible, to replicate.

Congress is working to pass a measure to create a regulatory pathway for the FDA to approve FOBs. The European Union established such a path in 2004, although market access and pricing differs by country. There has been criticism that the US lags behind its European counterparts in this area, and that if a proper pathway is not created in the US, it could drive investment overseas. Canada also has begun creating a regulatory framework.

A major concern of brand companies is that their intellectual property – their drugs and processes – is protected and that the patents covering those products are adequate enough to protect against infringers before they can recoup the costs of developing their biologics.

“Development of biologics is scientifically complex, time-consuming, and requires significant investment,” said Ken Johnson, vice president of the Pharmaceutical Research and Manufacturers of America (PhRMA), which represents many of the country’s leading pharmaceutical research and biotechnology companies. “Strong intellectual property protections are essential to such innovation and, therefore, are critical for patients to continue to enjoy access to a wide array of new medicines.”

The other large obstacle is the issue of data exclusivity – the period of time that must pass after approval of a brand drug before a generic company can copy it.

Under current US law, innovator patents can protect a product for up to 14 years after FDA approval, plus, manufacturers are provided with five years of data exclusivity. The Europe Union provides up to 11 years of market exclusivity.

Generics cannot enter the market until a brand drug’s patent has expired. Even if a patent life is about 20 years, the drug may only be on the shelf for seven to 12 of those years. Whereas a single patent can easily protect a conventional drug of which the structure and process to make it is always the same, several patents may cover a biologic, for the molecule and the various processes used for creating the different versions of it.

Patent owners say longer periods of data exclusivity are needed for biologics than traditional drugs because of the larger amounts of time, money and resources needed to make them. Brand companies say this longer window spurs innovation and provides incentives to pour money into manufacturing the products.

Large pharmaceutical companies and their lobbying groups favour a 14-year window and want to be sure legislation does not allow FOB companies to “design around” the patent protecting the brand product.

“The most critical thing for us is the question of data exclusivity,” said Greenwood. “It’s critical Congress does this in a way that preserves the incentive to make the investment in innovative products.”

But groups such as the Coalition for a Competitive Pharmaceutical Market, which includes consumer groups, the Generic Pharmaceutical Associations, Kaiser Permanente and Blue Cross Blue Shield Association, see no need for a longer exclusivity period and argue that only brand-supported studies call for such an extension. They also say there is no proof that patent protection may be less meaningful for biologic drugs.

“Patent protection, patent restoration, and other laws such as the Orphan Drug Act offer abundant incentives,” the generics coalition recently told Congress. “Adding market exclusivity to current patent incentives presupposes that they are necessary for investment.”

Generics groups also note that although the EU has a longer exclusivity period, “nonetheless, the US pharmaceutical industry has maintained a high level of competitiveness and profitability.”

Congressional Action

There are bills in both the Senate and the House of Representatives. The Senate Health Committee last summer passed a bill (S 1695) sponsors say will provide for an approval pathway for safe FOBs and interchangeable biological products (relying, in part, on the previous approval of a brand product), that includes 12 years of data exclusivity for the brand product and one year for the first interchangeable biological product. It also includes a process to identify and resolve patents that the generic biologic may infringe. The Congressional Budget Office recently estimated the bill, if enacted, would save Americans $25 billion on prescription drug costs over the next 10 years.

“This budget score confirms that our biosimilar therapeutics bill will save Americans billions of dollars in prescription drug costs,” said Sen. Mike Enzi, R-Wyoming, one of the sponsors of the bill. “If the leadership of the House is serious about controlling the long-term health costs, they will take steps to pass this legislation soon, not wait until the next Congress.”

A Senate Health Committee aide told Intellectual Property Watch that the lead senators are waiting to bring the bill to the full Senate floor for a vote until the House agrees on its bill. If the House version is slightly different but still agreeable to Senate sponsors, they may just adopt that language in an effort to move the bill through the chambers faster.

“We are waiting to see what the House’s intention is, trying to keep our demands on floor time minimal because there’s clearly not much floor time left before the fall,” the aide said.

The House Energy and Commerce Subcommittee on Health has received input from various groups and companies, including Consumers Union, AARP, Federal Trade Commission, pharmaceutical industry groups and companies, as well as venture capitalists, to meld together aspects of several FOB bills into one comprehensive one. The responses are under review.

“Our hope is that these responses will better inform the committee’s efforts to craft legislation that can achieve consensus among the members,” a spokeswoman for the House Energy and Commerce Committee told Intellectual Property Watch. “There is no set timeline for moving forward, but committee leaders are committed to ensuring that FDA has the authority to approve safe, affordable biosimilar products in an appropriate and timely fashion.”

The data exclusivity period is really the main sticking point in House negotiations, according to several sources.

“It will affect our ability to license patents, depending on how it’s done,” said John Vaughn, executive vice president of the Association for American Universities (AAU), which favours a 12-year exclusivity period and argues that an insufficient exclusivity timeframe could be a disincentive for brand companies to invest in making products, which would, in turn, reduce universities’ ability to license their discoveries to those firms.

Many groups, including Consumers Union, also want to be sure legislation does not encourage protracted litigation but does include strict penalties for, and easy legal pathways to prosecute, infringement. The AARP, which cites a biotech-supported study estimating that generic versions of the top 12 categories of biologics with patent protections that have expires or are about to expire could save Americans $67 billion to $108 billion over the next 10 years, wants to be sure patent disputes can be solved quickly to bring generics to market faster.

The AAU also wants to ensure the final bill allows patent-holding universities to be notified when a generic company files for a patent for a biosimilar drug. Some bills only specify that innovator companies be notified. Vaughn said he has spoken with many in the biotech industry and they have no problem with this provision so long as it does not create any unintended liability for them.

Many observers think that because of the limited time remaining in this Congress and the plethora of other, larger issues, on the agenda, the bill may get pushed off to the next Congress. But they say it is not a question of if, but rather when, especially when other countries are ahead of the US in the effort.

“My sense is this is one where they’re probably trying to build as much support in this session so it gets a head start next session,” Vaughn said.

Added Greenwood: “It would be one thing if our industry was saying ‘Hell no, we don’t want a biologics bill,’ but we’re saying, ‘Yes, create competition for us.'”

Liza Porteus Viana may be reached info@ip-watch.ch.