The paper by scientists from Brigham and Women's Hospital and Harvard Medical School, Massachusetts looked at people taking generic beta-blockers, angiotensin-converting enzyme inhibitors/angiotensin II-receptor blockers, or statins in the months after a heart attack.
The odds of abandoning treatment rose by 66% after a change in tablet shape and 34% after a change in colour in a study of 11,513 patients taking cardiac drugs after a heart attack.
The results of the cardiac study fit with those in a previous paper by the same lead author which showed changes in pill colour among otherwise equivalent anti-epileptic drugs were associated with a nearly 30% increased chance of non-persistence (doi: 10.1001/2013.jamainternmed.997).
Regulators worldwide require generic drugs to be therapeutically interchangeable following bioequivalence studies, but generic tablets are not obliged to look like the original branded product or each other.
Intellectual property experts have suggested this is in part due to the influence of historical patent laws. Past US court decisions have held that the appearance of a medication was protected against copying on the grounds that these features constituted “trade dress” (that is, they help identify the product’s manufacturer).
While the FDA says it does not regulate “aesthetic factors” of pharmaceutical products, the Supreme Court has judged this does not include functional attributes. Competitors “might be free to copy the colour of a medical pill where that colour serves to identify the kind of medication (e.g., a type of blood medicine) in addition to its source,” said one ruling.
The Massachusetts authors argued their demonstration of a link between tablet appearance and non-persistence makes shape and colour “clinically relevant” and therefore under FDA purview:
“In principle, the FDA could require new generic applicants to conform the shape and colour of their pills to the brand-name reference listed drug. Formal rulemaking or legislative changes to the Federal Food, Drug, and Cosmetic Act should not be necessary,” they said, since existing law allows the FDA to reject generic drug applications on the grounds of unsafe excipients.
Generics in Europe
When in-Pharmatechnologist.com approached the European Generics Association (EGA) with the paper’s findings, the organisation responded that while the US-based research might not be representative abroad, it is also the case for the EU’s 28 different national systems that “there is no existing legal or regulatory requirement in terms of shape, size or colour for generic medicines.
“Each EU Member State has its own intellectual property regimen in terms of design patent with which generic medicines producers have to comply,” said spokeswoman Julie Marechal-Jamil. “In the case of a valid design patent, generic medicines manufacturers would simply not be allowed to use a similar shape, size or colour.”
Instead, the organization called for “a careful evaluation of individual potential causes” of non-adherence to treatment, and “a more systemic overview of causes and their relationships.”
Source: Annals of Medicine
Burden of Changes in Pill Appearance for Patients Receiving Generic Cardiovascular Medications After Myocardial Infarction, Vol. 151, No. 2, July 15, 2014. doi:10.7326/M13-2381.