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Clinicians should openly discuss concerns over generics with patients
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The idea that generic drugs are equivalent to brand-name medications is based on a lack of understanding of U.S. Food and Drug Administration guidelines and regulations. Generic medications have a place in our clinic, but as knowledgeable physicians we must clearly understand why generics are not the same as innovator products and realize that there are underlying differences, with both legal and clinical implications.
The FDA’s website states: “A generic drug is identical – or bioequivalent – to a brand-name drug in dosage form, safety, strength, route of administration, quality, performance characteristics and intended use.” However, despite the long history of ophthalmic generics failing to perform, we still falsely believe ophthalmic generics are the same as innovator products.
Differences in packaging, inactive ingredients
It is clear that insurance companies and pharmacies have taken charge of most treatment courses for our patients, often by dictating what medications to use and by favoring generics, believing that they save money and are the same as brand-name products.
However, there are clearly many differences worth noting.
The composition, packaging and manufacturing of the innovator or brand product is strictly controlled in the production process. This is not the case for the generic counterparts, as manufacturers are allowed differential packaging, with formulations typically varying from the innovator product by as much as 5% (Peterson).
Agustin L.
Gonzalez
It is also common for manufacturers to use their own formulations and differing inactive ingredients. This small but crucial detail often makes generics less consistent in therapeutic benefit, safety and effectiveness. In ophthalmic medications it is worth noting that the less regulated inactive ingredients often comprise 99.99% of the formulation, and changes in the formulation often accompany changes in efficacy and safety and may be associated with the drop’s physical characteristics such as size and quantity of medication delivered.
Many studies have noted a higher incidence of adverse events in ophthalmic generics. With patients not recognizing adverse events and doctors not asking about them, clearly, medication errors and adverse events are speculated to be underreported. In fact, the Institute of Medicine reports that medication errors affect approximately 1.5 million Americans a year.
Problems with overseas manufacturing
More than 40% of generics are manufactured overseas, and 80% of the active ingredients in those drugs come from foreign plants. Most doctors, pharmacists and patients may believe that the U.S. has much control over the generics it imports, but that is not the case. Oversight of these manufacturing facilities is so lax that according to a 2010 report to Congress from the Government Accountability Office, in 2009 the FDA inspected less than 10% of the more than 3,700 foreign facilities where drugs and active ingredients are manufactured for the U.S. market.
In overseas manufacturing, problems relating to product purity and equivalence have been well noted. Just this year the U.S. imposed restrictions and banned imports from Ranbaxy, a generic drug manufacturer in India. Concerns over quality and safety including falsified testing and fake ingredients were partly to blame for the ban. The same company had pleaded guilty to federal drug safety violations in 2013 and paid $500 million in fines and penalties for exporting generic Lipitor (atorvastatin calcium, Parke-Davis) in 2012. The same year the company stopped production of this drug after tiny pieces of glass were found in the tablets.
Melvin
Friedman
With unrestricted online access to foreign manufacturers, pharmacies and suppliers, counterfeit medications obtained directly by the public or introduced into the supply chain have long been a public safety issue. We have had warnings about counterfeit ophthalmic medications as far back as 2012 when the FDA warned surgeons about counterfeit Avastin (bevacizumab, Genentech). Some pharmaceutical trade groups believe we can expect counterfeit medications to be a bigger problem in the future.
No liability for generic manufacturers
One of the most worrisome facts from a professional liability point of view is that in 2013 the U.S. Supreme Court ruled that makers of generic medications could not be sued for any adverse reactions caused by their products. Keep in mind that generic manufacturing companies are not consistently tested for efficacy and impurities. On the other hand, manufacturers of brand medications can be liable for inadequacies in performance and safety warnings. This loophole for generic pharmaceutical manufacturers clearly places the burden of efficacy in the prescriber’s hands.
Recently the FDA has become more aware and concerned about generic medication manufacturing, safety and efficacy in the U.S. to the extent that it has begun a $20 million quality, efficacy and adverse event testing program. This project involves a dozen major academic medical centers in the U.S., and the generic drug testing program will run through 2017. It will initially look at cardiac, attention deficit and hyperactivity disorder, immunosuppressant, antiseizure and antidepressant medication categories.
For many reasons, it is difficult for physicians to not be skeptical of certain generic medications and frustrated with other physicians and pharmacists who defend generic medications’ quality and efficacy. With the history of topical ophthalmic medications failing to perform, higher variability in ingredients, manufacturing concerns and legal implications, it is important that as clinicians and prescribers we are both knowledgeable and transparent with our patients in discussing these issues.
We are held accountable for the therapeutic outcome based on our diagnostic and management capabilities. With all these concerns and lack of noninferiority studies to substantiate equivalence, it is difficult to comfortably ascertain the safety and efficacy of generic drugs and make the statement that they provide “the same” therapeutic results.