One aim of the 1984 legislation was to maintain a balance between encouraging generic-product development and maintaining incentives for innovation. This goal has been tested over the years by efforts on both sides to game the system. Generic-drug makers have aggressively challenged drug patents before scheduled expiration,
and brand-name manufacturers have delayed the market entry of generic drugs through 30-month stays, citizen petitions, and deals to "authorize" generic products that are less threatening to the brand.Ensuring quality
Such intense market competition has generated disputes about the quality and safety of generic products. Officials at the US Food and Drug Administration maintain that the agency's test procedures and standards ensure that an approved generic drug will yield the same clinical results and safety profile as the reference product. Such assurance, though, requires clear documentation that generic drugs are made according to good manufacturing practices (GMPs) and in compliance with regulatory requirements.
Holding a majority of the market, generic-drug makers have to assume more responsibility for informing doctors and patients about how to use drugs safely, commented FDA's Deputy Commissioner Joshua Sharfstein at the annual meeting of the Generic Pharmaceutical Association (GPhA) in September 2009. He noted that overdoses of acetaminophen, for example, can cause liver damage and urged greater industry collaboration on important public-health issues.
The emphasis on safety should help the generic-drug industry deal with questions about product quality and general skepticism about the equivalence of generic drugs. Gary Buehler, director of OPS's Office of Generic Drugs (OGD), pointed to publications and television programs featuring individual patients who claimed extreme adverse reactions to generic therapies. Recent FDA approval of generic versions of new epilepsy treatments has generated complaints from neurologists about poor patient response and serious adverse events related to these new products.
In addition, a wave of product recalls and FDA warnings about lax generic-drug manufacturing practices have tarnished the industry's image and aggravated public concerns. FDA compliance officials are looking hard at drug companies in the US and abroad, Winkle noted, including generic-drug makers who fail to respond quickly and completely to Warning Letters or to plant-inspection citations.
Last year, FDA banned the importation of Ranbaxy (Gurgaon, India) products from two plants in India and subsequently halted the review of new applications until the company addressed charges of data-falsification at its Paonta Sahib, India, facility. FDA hit KV Pharmaceuticals (St. Louis) with a consent decree in March 2009 after years of inadequate responses to inspection reports and letters citing GMP violations.
Another consent decree requires Caraco Pharmaceutical Laboratories (Detroit) to submit a remedial plan and conduct audits of its Michigan facility following a high-profile product seizure. FDA also recalled some 50 drug products produced at Actavis's (Haf-narfjordur, Iceland) New Jersey plant and blocked the importation of drugs made by Apotex (Toronto) when the firm failed to address batch failures and GMP deficiencies at its Ontario plant.
Manufacturers have a responsibility to be vigilant in monitoring manufacturing processes and supply chains, particularly those for active ingredients and excipients, Winkle emphasized.
At the GPhA meeting, CDER compliance officer David Jaworski highlighted the importance of securing contractors and suppliers with a high commitment to quality. Contractor agreements, he noted, should allow for periodic audits, describe clear procedures for handling changes, and provide full information on deviations, changes, out-of-specification results, investigations, and adverse events.
As the demand for affordable generic drugs grows, it's important for the public to have confidence in these treatments, Buehler noted. "Many Americans are waiting for our products," he said, "but we want them to be the products they are waiting for."