Substituting brand-name drugs with low-cost generic alternatives has substantially lowered the overall healthcare costs. Brand name and generic drugs have the same active ingredients but may differ in color, inert binder, and manufacturing process. For a generic product to be approved by the FDA, sponsors must submit results of bioequivalence clinical trials.
Bioavailability and bioequivalence (BABE) studies are crucial determinants of a successful drug product campaign. In bioequivalence analysis, researchers must demonstrate pharmacokinetic data based on the absorption rate As the amount of scientific rigor for generic drug products is relatively low compared to a novel brand name drug, necessary steps are required to maintain adequate drug integrity. These required steps bring us to the topic of our current article, transparency in bioequivalence testing. So let us dive deep into the importance of transparency in bioequivalence clinical trials.
Why transparency becomes crucial for bioequivalence testing of generic drug products?
Generic drug products have alleviated economic challenges for several patients, and therefore their conduct should be highly transparent. To understand the economic advantages of generic products, in the US alone generic drugs helped save more than $734 billion between 1999 and 2008. Hence, as a large patient population uses generic drug products, the registrations of trials and adequate data reporting and publication are crucial for transparency in bioequivalence testing. This transparency will help understand the methodology of bioequivalence clinical trials and decode whether trials are adequately documented and reported.
Bioequivalence testing has a predetermined format with objectives and methodology. Bioequivalence clinical trials are generally randomized crossover studies consisting of a small sample of healthy individuals. The primary goal of bioequivalence testing is to demonstrate that the given two drug molecules are biochemically equivalent based on their pharmacokinetic properties. Pharmacokinetic parameters include the study of absorption rate based on peak plasma concentration and area under the curve.
Despite understanding the importance of a transparent bioequivalence clinical trial, the ground reality is entirely different. Research suggests that bioequivalence analysis has several loopholes in transparency. A literature review evaluating bioequivalence studies between 2005 and 2008 reported that only one article gave the registration number of the trial in an international database. Notably, the FDA approved 1661 new generic drug products between 2005 and 2008. Moreover, none of these generic drugs had clinical trial reports on the EMA or FDA websites.
Furthermore, most of the studies were missing important information such as the country, funding source, and methodology details. Knowing the population type and the study methodology is vital to critique study results. Additionally, around one-third of single-dose trials for bioequivalence did not meet the required criteria of 90% CIs for all three FDA criteria. Furthermore, most studies did not cite the name of the reference drug, creating additional confusion of whether the reference drug was a branded drug or just another generic drug.
Conclusion
As discussed earlier, generic drug products are increasingly becoming mainstream in prescribed drugs, and therefore transparency in bioequivalence clinical trials has paramount importance. Additionally, emphasis should be given to the documentation and reporting of bioequivalence trials, complemented with trial registration and trial protocols.