Since the enactment of the Hatch-Waxman Act 25 years ago, the generic-drug industry in the US has grown exponentially. The
landmark Drug Price Competition and Patent Term Restoration Act of 1984 generated more than 1000 applications for new generic
drugs in its first year, boosting generic-drug use initially to 22% and to nearly 30% by 1989. Sales have tripled in the past
decade, from $15 billion in 1999 to nearly $50 billion today. Generic drugs now account for 70% of prescriptions in the US,
as health plans, payers, and pharmacy-benefit managers (PBMs) promote these inexpensive medications as a bioequivalent way
to reduce healthcare costs and facilitate patient access to important treatments. Industry analysts anticipate further growth
as brand-name products with about $60 billion in sales lose patent protection over the next two years.
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.
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.
At GPhA's fall technical conference in October 2009, Helen Winkle, director of the Office of Pharmaceutical Science (OPS)
in FDA's Center for Drug Evaluation and Research (CDER), described efforts to ensure safety throughout the drug product life
cycle that involve more collaboration between CDER offices that approve new drugs and those that regulate generic drugs. She
anticipates that more information about how generic drugs will be involved in CDER's Safety First initiative will be included
in an upcoming guidance.
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
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
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."