By John Gever, Senior Editor; Kristina Fiore, Staff Writer; Todd Neale, Staff Writer
Published: August 26, 2009
Recent high-profile actions taken against generic drug firms have, in many people's eyes, undermined confidence in the safety of these products.
Consider the following:
April 2008 -- Some double-thickness tablets of generic digoxin produced by Actavis Totowa are discovered, prompting a nationwide all-lot recall.
May 2008 -- ETHEX Corp. begins a series of recalls of potentially oversized tablets, eventually affecting more than 200 products.
September 2008 -- The FDA blocks imports of 30 major-market generic drugs produced by Ranbaxy Laboratories, charging that the firm falsified data on its manufacturing practices.
June 2009 -- The FDA sends federal marshals to seize 33 different generic drug products at two Caraco Pharmaceutical Laboratories plants in Michigan.
August 2009 -- Barr Laboratories begins national recall of amphetamine-dextroamphetamine tablets because some tablets may have contained excess active ingredients.
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Then there were revelations in July concerning Mylan Laboratories' main U.S. manufacturing plant. According to an internal company report obtained by the Pittsburgh Post-Gazette, workers had deactivated quality-control alarms on at least several occasions to keep the production line moving.
An FDA investigation found that the company handled the situation properly, and no products were recalled.
All of these problems with generics were widely publicized.
The only product-quality problem affecting a major branded drug firm to attract much attention during this period was the contamination of Baxter's heparin with melamine in early 2008 -- eventually traced to the company's bulk suppliers in China.
That generic producers are more prone to manufacturing problems "is a plausible impression to have," said Jeffrey Lieberman, MD, a psychiatrist at Columbia University. "There's a higher degree of variability of companies [and] quality control likely is variable."
This third installment in our generic versus brand series explores that issue.
A question of what 'generic' means
A superficial look at recent FDA warning letters issued to drugmakers for deviations from current good manufacturing practices, or cGMP, suggests that Lieberman is correct.
Since January 2008, the agency has sent 35 warning letters for cGMP violations related to nonbiologic drugs.
Of those, just three went to big-name branded drug companies: Procter & Gamble for potentially contaminated Sinex nasal spray; Legacy Pharmaceuticals for the Efudex brand of topical fluorouracil cream; and Noven Pharmaceuticals for its Daytrana transdermal methylphenidate patch.
But Gordon Johnston, vice president of regulatory sciences at the Generic Pharmaceutical Association (GPhA), and a former FDA official, pointed out that not all unbranded products are generic drugs per se.
He said only those covered by approved Abbreviated New Drug Applications and included in FDA's "Orange Book" are properly considered generics.
Such products as individually compounded drugs (for example, positron emission tomography tracers) and repackaged drugs are not, he said.
Nor are drugs manufactured under so-called OTC monographs -- a separate type of regulation under which over-the-counter drugs such as ibuprofen may be marketed without formal bioequivalence testing, as long as they're made with approved recipes.
Still others are raw ingredients sold to other manufacturers, rather than finished drug products.
Of the 32 warning letters sent to makers of unbranded medications, 21 appeared to be for products the GPhA does not consider to be generics, although the FDA sometimes obscures specifics in redacting the letters for public inspection.
And for three of the remaining 11, it was unclear whether the product was covered by an ANDA or not, owing to the redactions.
Even the apparent eight-to-three disparity is not what it seems, said GPhA spokesman Charles Mayr.
He pointed out that there are about 10,000 approved generic products compared with just 2,500 innovator drugs. Nearly 70% of all prescriptions in the U.S. are filled with generic medications.
"You would have to normalize for the number of units dispensed," Mayr said.
Consumer groups known for taking tough stances against defective goods also defend the generic drug industry's record.
"Overall, generic drugs appear no more likely than brand name drugs to pose risks, according to our review of available data and interviews with experts," Consumer Reports said in March.
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