As the horror builds with the increasing number of meningitis casualties from contaminated steroid medication provided by a Massachusetts compounding pharmacy, a disturbing report was published last week in the New York Times that details how such problems aren’t limited to that niche of the drug-manufacturing sector.
Weevils in vials of heparin; morphine containing as much as twice the labeled dose; manufacturing plants with rusty tools and mold. All were found at big drug companies that are supposed to be regulated much more rigorously by the federal government than compounding pharmacies, which are regulated by individual states.
In the last three years, The Times says, six major manufacturers of sterile injectable drugs have been warned by the FDA about serious violations of manufacturing rules. Four closed factories or slowed production to fix the problems. Nearly one-third of pharmaceutical manufacturing has been shuttered because of quality issues.
Although it’s essential that dangerous plants be closed, less production has contributed to a shortage of critical drugs, as we’ve previously noted. Shortages have encouraged compounding pharmacies to breach the gap. Supplies of the injectable steroid that was contaminated in the meningitis outbreak, The Times reports, were in short supply because two manufacturers had stopped making it.
Although worrisome, the situation doesn’t describe all drugs. Most sterile injectable drugs sold in the U.S. are safe. But both industry observers and former plant employees say that manufacturers are slow to address problems because it’s too expensive—drug profits are driven by volume. Some inexpensive drugs are made in huge volume on production lines that operate around the clock.
Big Pharma, of course, rejects the idea that plants are deteriorating and that their owners don’t care. In The Times, an executive of the Generic Pharmaceutical Association compared some facilities to vintage cars. Some are old and decrepit, but some, he said, are “maintained [like] muscle cars.”
Manufacturing scrutiny has increased since 2009, when the FDA cited Teva for violations at an injectable drug plant, charging that it had failed to catch bacterial contamination of propofol, the anesthesia drug. And Hospira, the leading manufacturer of injectable drugs, has been the subject of several major product recalls because of poor quality control at several of its plants. The faulty products included infusion pumps (see our story) and morphine vials.
Apparently Hospira didn’t care if its muscle cars stalled—as The Times reports, its manufacturing problems became public after the company initiated a plan designed to save more than $100 million a year by, for example, shrinking the work force. Some shareholders filed a lawsuit against Hospira claiming that the initiative led to deep cuts in quality control and the failure to maintain equipment. An Hospira executive, The Times said, acknowledged the company had gotten “a little lazy” and was “skating behind the puck.”
There must be a lot of errant pharmaceutical industry pucks. Last year, Ben Venue closed a plant after FDA inspectors found rusty tools, mold and a barrel of an “unknown liquid” later determined to be urine. A.P.P. Pharmaceuticals received a warning letters when FDA inspectors said it failed to investigate problems including human hair and fungal growth in vials. There were also reports of vials infested with weevils and spiders.
A former plant supervisor told The Times that managers were reluctant to stop the production lines. “It’s like trying to fix your car when you’re driving down the Thruway,” he said. (What is it with Big Pharma and car metaphors?)
The FDA message seems to be getting results. Several manufacturers, including Ben Venue, Teva and Hospira, are spending significant amounts to upgrade factories and open new ones, even if full production has not yet resumed. Dr. Sandra Kweder of the FDA’s Office of New Drugs told The Times, “I would say we are encouraged. But we also know it takes three to five years to get one of these plants up and running.”