US FDA’s Tough Road Ahead In Creating Pathway For Life-Saving Biologics

The US Food and Drug Administration heard from myriad pharmaceutical companies, patient groups, and other stakeholders last week as the agency considers how to create an abbreviated pathway to bring more biologic drugs to market.

The Biologics Price Competition and Innovation Act of 2009 (BPCI Act) was passed by the US Congress earlier this year as part of the broader health care reform bill. The BPCI Act establishes an abbreviated approval pathway for biological drugs proven to be “highly similar” (biosimilar) to, or “interchangeable” with, an FDA-licensed biological product. These drugs, which attempt to replicate their brand-name counterparts as closely as possible (though it is impossible to 100 percent replicate a biologic drug) are also called “follow-on biologics” or “biosimilars.”

Brand-name firms have fought for as much protection as possible while they research, develop and market their drugs, so that they may have sufficient time to recoup their investments. Allowing generic firms to use their data to try to manufacture cheaper, similar drugs would serve as a disincentive to innovation, they argue. Generic advocates, however, argue that giving brand firms too many years’ exclusivity on the market, plus patent protection, is to the detriment of patients, their wallets, and the government.

Many patient groups, academics and some innovator drug companies warned the FDA that it must ensure that clinical trials and studies are done on the biosimilars to ensure they work in a similar enough way as their brand counterparts as to not harm the patient or cause any unanticipated effects.

“We want maximum choice for our members … we are not against biosimilars or saving money in healthcare,” explained Seth Ginsberg, president of the Global Healthy Living Foundation, which accepts donations from large pharmaceutical companies, government, private foundations and individuals. But, he added, safety standards should not be lowered just to make it easier for these “miracle” drugs to come to market.

Jay Siegel, chief biotechnology officer for Johnson & Johnson, added: “Unnecessary differences create unnecessary risks and should not be permitted.”

Academics, pharmacy representatives, generic firms and others in favour of speeding up the delivery of such drugs said it often is unnecessary for redundant, duplicative testing if biosimilar manufacturers have already proven themselves in Europe or other countries. They argue that brand name companies already have the benefit of a 12-year data exclusivity period in the BCPI Act, which prohibits generic firms from relying on innovator companies’ data to market their version of the drug during that time.

That, plus patent protections, leave brand companies with “very rich monopoly protection,” said Jonah Houts, chairman of the Alliance for Affordable Medicine. Requiring unnecessary, lengthy additional studies would stifle innovation and leave many patients without cost-effective medicines, these groups add.

“Virtually all existing biotherapeutics can be manufactured to the highest clinical standards at substantially reduced costs,” particularly with iBioLaunch whole green plant technology, said Terence Ryan, senior vice president of iBio, Inc. – a biotech company that commercialises its technology to help produce biologics. “Public health is best served by products that are both safe and effective, and also readily accessible.”

James Love, director of Knowledge Ecology International, stressed that the FDA should not utilise any biosimilars approval process that results in unethical clinical trials being conducted on humans and animals just for the sake of testing a drug that already has been proven safe. He urged the US to follow the guidelines set out by the Declaration of Helsinki on Ethical Principles for Medical Research Involving Human Subjects and voiced support for a bill introduced in October by Senator Bernard Sanders, a Vermont Independent. That legislation would ensure that rules for the approval of pharmaceutical and biological products do not require violations of medical ethics in the testing of products in humans and animals.

European Example

Generic drug groups and those advocating a faster pathway encouraged the FDA to allow biosimilars makers whose products have already been approved in highly regulated overseas markets to use clinical trials results and other studies proving their effectiveness and interchangeability to the US. They cautioned against a blanket clinical trial mandate, which could lead to duplicate animal and human studies that could be both unethical and uneconomical.

”Forcing the industry to fit into a one-size-fits-all kind of approach I think would seriously keep the development of these biogeneric compounds back,” said Rasmus Rojkjaer, vice president and head of global biologics research and development for generic and brand drug maker Mylan who also represented the Generic Pharmaceutical Association (GPhA) at the FDA hearing.

The European Union in 2004 adopted legislation to establish a regulatory pathway to bring biosimilars to market. The European Medicine Agency (EMEA) further developed guidance documents in this area after public input; at least 10 biosimilars have been approved in Europe so far. Generics makers say the technology does exist to design many biosmilars in ways that make them virtually indistinguishable from the brand version.

Rojkjaer said approving biosimilars in the US that have already established their efficacy and safety in highly regulated biosimilars markets in Europe, Canada, Japan and other countries is a “scientifically sound way of thinking.” It increases the availability of drugs while minimising “questionable” studies,” he added.

Joerg Windisch, vice chair of the European Generic Medicines Association (EGA), stressed there’s “no reason to reinvent the wheel,” and a close collaboration with the FDA and EMEA can allow biosimilars to come to market quicker. According to the EGA, generics save Europeans more than $30 billion euros and new biosimilars contribute 1.4 billion euros per year to European health care systems.

“We don’t think it [the biosimilar] should be required to duplicate preclinical studies for each country or region,” Windisch added.

Richard Kingham, a partner at law firm Covington & Burling who has worked in Europe and Canada on the issue of biosimilars, said the US is “somewhat behind other parts of the world” in biologics; Europe, for example, started working on legislation approving an abbreviated pathway in 2001. The World Health Organization developed guidance to assist countries on how to better bring biosimilars to market; countries such as South Africa, Singapore, Japan and Saudi Arabia are among those that have developed guidance – many of which have relied heavily on Europe’s framework, Kingham added.

Industry groups representing brand-name titans in the industry such as the Pharmaceutical Research and Manufacturers of America (PhRMA) agreed that the FDA should consider the EMA processes for biologics. Yet they still urged the FDA to preserve the legislation’s exclusivity language in its approval decisions, and require trials to ensure the biosimilars’ safety and efficacy.

“In the interest of patient safety, FDA should require that companies seeking to demonstrate biosimilarity to an existing licensed biologic should use a stepwise process requiring high quality, well-designed comparative studies beginning with molecular evaluation and ending in safety and efficacy trials in patient,” said Maria Vodicka, PhRMA’s associate vice president of scientific and regulatory affairs.

The WHO has been finalising guidelines for Similar Biotherapeutic Products, according to sources. The WHO reportedly expects these guidelines, prepared by the Expert Committee on Biological Standardization, to be circulated to interested parties this year or next. Key concepts to be included in the document are expected to be similar to those included in regimes in the EU, Australia, Switzerland, Japan, Canada, Republic of Korea, Malaysia and Singapore. Similar discussions are ongoing in countries such as Brazil, South Africa and Mexico.