By Ralph Tarantino, PhD
Pharmaceutical Consultant and Principal, SteriTech Solutions, LLCMiddletown, NJ
It wasn’t all that long ago that generic drugs were the exception rather than the rule. On expiration of the innovator’s patent, there would be a somewhat gradual decline in sales due to generic competition, but a loyal following of prescribers and patients would keep the product afloat for a few years. Their faith in the brand name would be buoyed by the know-how behind the product, the innovator’s history of success, and the knowledge that there was a best-in-the-field staff of scientists and technologists who made the product possible. It was good decision making. Drug product choice is a very important decision.
It also wasn’t that long ago that counterfeit drugs weren’t an issue, much less the topic of a dire presentation by an FDA commissioner. However, in a speech at the Partnership for Safe Medicines Interchange 2010, Commissioner Hamburg reported that in some parts of the world 30% to 50% of the drugs to treat serious diseases are counterfeit. She also pointed out that “nearly 40% of the drugs Americans take are imported and nearly 80% of the active ingredients in the drugs on the American market come from overseas sources.” This unhealthy extension of the supply chain coupled with the increased complexity of newer medicines should be worrisome in and of itself to those who prescribe and dispense medication. Superimpose on this situation the temptation of a business capable of generating billons of dollars per year and drug counterfeiting becomes a true health care problem—a problem that has resulted in patient deaths.
The uncertainty of the actual source of drug product being dispensed to a patient and the overall effect of forcing prescribers to use only generic drugs has now left patients open to risk greater than in the 50 years since the Kefauver-Harris Amendment was passed. The prescriber and dispenser have more liability and less freedom in practicing their professions than they ever had with respect to pharmacotherapeutics. How a drug is made is important; quality must be built into a product, not just tested.
Low-dose oral medications are among the most challenging to develop and manufacture reproducibly. Many of drugs most often prescribed by ObGyn specialists are low-dose (< 1 mg) medications. Lower drug concentration in a formulation generally results in more issues with content uniformity. Supportive of this issue is the fact that a good portion of FDA warning letters and inspection observations center on content uniformity problems. A drug innovator has years of experience and usually the optimal technology to ensure content uniformity. This can’t always be said about generic manufacturers and certainly not about counterfeiters.
Consistent bioavailability is another issue with low-dose medications. Certain excipients and methods of preparation can be used to ameliorate this effect. However, there is no requirement by a generic manufacturer to directly reproduce a formulation or method of manufacture—only to demonstrate bioequivalence. For low-dose medications, does bioequivalence remain consistent form batch to batch? From manufacturer to manufacturer? This type of assurance can’t be tested, and I have personally heard from physicians about cases in which a change of generic manufacturer has caused different therapeutic results.
I don’t consider this topic to be random whistleblowing. Health care costs are an issue, and where they should be cut is always a matter for debate. Do we want pharmacotherapeutics to be that place? Over the thirty years I have spent as a pharmacist and pharmaceutical research scientist, I have seen the professional choices of physicians diminish significantly in the area of pharmacotherapeutics. This isn’t progress and it isn’t beneficial to the patient. Medicines are the still the way most patients are treated most of the time. They are still our greatest tools in treating disease. Their quality must never be in doubt.