It’s hard to read a newspaper or check a website without seeing news of more drug shortages, recalls and compliance problems. Pharmaceutical counterfeiting is a booming shadow economy that shows few signs of slowing down.
In parallel we see the growing threat of economically motivated adulteration, as happened with heparin.
Avoiding adulteration is the cornerstone of GMPs and one of the reasons that FDA was established in the first place. The word seems old-fashioned, even quaint, today, suggesting a time when thuggish criminals, rather than educated chemists, knowingly added poisons to drugs.
It can happen by accident, as occurred in the sulfonilamide elixir tragedy of the 1930’s, when safety tests were not required on what seemed like the perfect sweet-tasting solvent for a children’s liquid formula for an antimicrobial.
It can happen through carelessness, when GMPs are not followed.
Increasingly, though, it is happening by intent, and desire for economic gain, whatever the human cost.
The future seems grim. As USP experts have asked in the past, how can you anticipate a moving target? FDA is taking steps to address these problems, and working with USP to modernize compendial tests and methods to help make pharma’s products more tamper-proof.
In an October report, requested by Representatives Henry Waxman (D-CA), Frank Pallone (D-NJ), and John Dingell, the Government Accountability Office (GAO) suggested that FDA do much more to fight economic adulteration of pharmaceuticals and food.
The report called for FDA to establish a working definition of economically motivated adulteration and to provide offices more guidance on how to work together and address it. The Agency recently established a working group on economically motivated adulteration, with Commissioner-level involvement, to coordinate these efforts.
Its Center for Drug Evaluation and Research is also involved in a pilot program which has developed a model to rank pharmaceutical APIs now in current use, based on their susceptivility to economic adulteration, based on various factors such as volume of use, cost per unit and quality testing methods.
So, FDA can say that it is doing its part.
Drug manufacturers say they are implementing or improving their quality systems. But together, will these actions be enough? Experts agree that situations like heparin, the industry’s recall of recalls, are likely to recur until or unless decisive actions are taken, within individual companies and by the industry.
Although it focused on FDA and the Agency’s need to better coordinate its offices activities in this area, the GAO report depicted industry’s response to FDA’s efforts as less than cooperative. Similar to their initial response to drug counterfeiting, companies have been reluctant to share data that could be considered trade secrets, especially on precommercial products, or to open themselves up to the threat of future lawsuits from business partners.
One comment suggested that FDA needs additional authority to force drug manufacturers to provide it with info required to secure the supply chain. Without this authority, FDA has said that it cannot be sure that the industry can account for control of its complex supply chains.
Two laws now being considered in Congress (S.1584, Drug Safety and Accountability Act of 2011” and HR3026, Safeguarding American’s Pharmaceutical Act of 2011) would provide this authority, and make companies with inadequate quality systems legally liable for any economically motivated adulteration that takes place.
Other options being discussed include establishing industry data clearinghouses, which could be managed by a third party, but would track leads (such as spot price changes for raw materials and intermediates) and information that could be used to study economic adulteration cases as they start.
Concerns about trade secrets aside, the industry needs to share data relevant to economic adulteration, just as it has learned to do on counterfeiting, aided by groups such as Rx360.
Do to so will not just be good ethics, but critical for survival.
Today, after any tampering incident, the actual adulterators will disappear into the woodwork, leaving authorities to pursue those whose actions or inaction allowed the adulteration to take place. That means “responsible corporate officers,” the executives and managers of the companies that sold the tampered drugs.
In fact, it is exactly what happened over 70 years ago, in the first major case to come up after the U.S. Food Drug and Cosmetic Act was amended. Buffalo Pharmacal Co, a distributor of drugs who repackaged drugs from manufacturers and sold them under its own label, was charged with shipping adulterated drugs.
Charges against the company were dropped but its CEO, Joseph Dotterweich, was held responsible. The landmark decision, handed down by Supreme Court justice Felix Frankfurter, stated that the court had to stand up and protect the public, even if it meant penalizing managers who weren’t aware of wrongdoing.
Also offering a precedent is the often discussed Park case, which FDA officials have explicitly mentioned.
No action was taken against corporate officials after the tainted heparin was recalled three years ago. But, whether such action is logical or irrational, it’s more likely to happen in the future.
How well do you know your supply chains? The benchmarking 2011 Pew Report,
published earlier this year, suggests that some of you still might know more.
Where protecting the public’s health is concerned, perhaps it’s wisest to expect the irrational, and be prepared.