Earlier this week, the US Food and Drug Administration suspended the approval of a generic version of Pfizer's high blood pressure drug Norvasc (amlodipine besylate) developed by India's Dr Reddy's Laboratories. The case could have significant implications for companies developing generic versions of biologic drugs.
In the US, the approval of generic versions of marketed drugs that are not exactly identical to the original product are allowed via a regulatory route known as a 505(b)(2) filing. This allows a sponsor to reference the safety data from an existing New Drug Application (NDA). Dr Reddy's had filed for a different salt of the hypertension drug, AmVaz (amlodipine maleate) via this route.
Earlier this week, the FDA informed Dr Reddy that it will suspend the tentative approval granted to AmVaz on the basis that Pfizer claims the application illegally references proprietary safety data. The product had been approved in October 2003.
Pfizer maintains that the application submitted by Dr Reddy's contained insufficient data to establish the safety of its product and that, instead, it improperly relied on data proprietary to Pfizer.
"Put very simply, the Dr Reddy's application relies more on Pfizer's research than on scientific research conducted by Dr Reddy's," said Jeffrey Kindler, senior vice president and general counsel of Pfizer. Any delay in the launch of AmVaz is worth millions to Pfizer - Norvasc achieved sales of $1.9 billion last year and is patent protected in the US until 2007.
Analysts at SG Cowen believe that if Pfizer prevails, the implications for early generic biologicals (human growth hormone and insulin), which are expected to be evaluated under a 505(b)(2) filing in the US, could be considerable.
They suggest that companies with established, lucrative franchises in biological drugs such as hGH and insulin could use the precedent set by the Pfizer case to delay generics by forcing their sponsors to generate proprietary safety. In turn, this would hike the investment needs and delay approval.
Those who pay the healthcare bills of patients - whether governments, insurance companies or individuals - are interested to see generic versions of biological drugs coming to market, as these medicines tend to be very pricey.
However, the FDA is hamstrung by the fact that they are handled under the Public Health Service Act in the US, while conventional medicines are covered by the country's Food, Drug and Cosmetic Act.
This means that biologics are approved on the basis of purity, potency and identity, rather than safety and efficacy as is the case with conventional drugs. In the eyes of the biotechnology industry, this distinction is crucial, as it means that a biologic must always be produced using an identical manufacturing process.
This is near-impossible for biogenerics companies to achieve, forcing them down the route of carrying out a full, expensive clinical development programme for their biogeneric.
The 505(b)(2) route is seen as a viable alternative to this route, allowing companies to bring a 'bioequivalent' biologic to market based on physicochemical results and citation of the originator's safety data. There is still a lot of detail to be worked through before even this process could be used, but should Pfizer prevail in its appeal, the 505(b)(2) door, currently ajar, could be slammed shut.