Chasing Precision in Bioequivalence

The buzz around bioequivalent studies has been increasing in industry circles, pointing up the demand for a higher caliber of off-branded drugs. As these studies become more and more precise, generics manufacturers will gain a better foothold in the world of semi-innovative drugs, which could then put added price pressure on payers.

It is safe to say that the generics drug market is not going anywhere in coming years; if anything, it is only going to grow. Accepting that reality means that organizations have to find a way to fit mandatory bioequivalence studies into their processes as they attempt to push generic drugs to market.

These companies have a number of factors to consider as they seek to integrate the need for bioequivalence studies into their business approaches.



To help set the parameters of discussions of quality and development, it is vital to establish that bioequivalence studies can only be conducted on brand-name drugs in certain scenarios, including for formulation changes.

The Canadian Agency for Drugs and Technology in Health (“What are Bioavailability and Bioequivalence?”) pointed out that bioequivalence studies are normally performed on health volunteers “in order to reduce the variability not related to differences between products.” As a result, it is incumbent upon the company developing the generic drug to demonstrate 80 to 125 percent bioequivalency.

As patent and exclusivity protection expires and pay-to-delay deals are debated, companies move in quickly to manufacture, gain approval for and market these drugs in generic form.

Generics are expected to be bioequivalent innovator drugs in a comprehensive range of areas ranging from active ingredient to dosage form to strength, among others. Should there be any questions about this bioequivalence, the FDA is poised to measure, according to the agency’s director of the Division of Product Quality Research, Mansoor Khan, R. Ph., Ph.D.

“If we have reason to believe a generic drug does not perform the same as a brand-name product, we have the ability to perform experiments in the FDA laboratories and take a comprehensive, scientific look at the differences between the products,” Khan told James Limbach of Consumer Affairs (“Generic Drugs: Same Medicine for a Lower Price”).



From a costs perspective, generics manufacturers save overhead by avoiding the expenditures associated with preclinical and clinical trials and other normal drug development requirements. In addition, these companies are spared the exorbitant postmarketing and promotional costs.

These savings can be passed down to pharmacies and individual patients as well. According to Congressional Budget Office estimates, consumers at retail pharmacies saved $8 to $10 billion a year between 1984 and 1994. A 2012 report from the IMS Institute for Health Care Informatics found that generics saved more than $1 trillion in the previous decade—including $193 billion in savings in 2011 alone, according to Limbach’s article.

In an article from Dieter Hauschke, Volker, Steinijans and Iris Pigeot (“Bioequivalence Studies in Drug Development: Methods and Applications”), the authors pointed out that “savings in time and cost are substantial when using bioequivalence as an established surrogate marker of therapeutic equivalence.”



The demand for generic equivalents has escalated as a means of addressing concerns about medication costs. Bioequivalence has been commonplace for more than two decades, but even though generics are increasingly available, the practice of establishing bioavailability and bioequivalence is no less complex despite a host of advancements and a trend toward standardized approaches. However, even better harmony from a regulatory standpoint would ensure that quality and interchangeability remain constant in all parts of the world.“BA and BE have become the cornerstones of the approval of brand-name and generic drugs globally and have been utilized for brand-name drugs to reduce cost of development,” wrote Kamal K. Midha and Gordon McKay (“Bioequivalence; Its History, Practice and Future”).According to Midha and McKay, significant strides have been made in the areas of study design and protocol, bioanalytical methods and validation, metrics, data transformation, and statistical approaches and analysis, among others.

The challenges posed by quality, speed, costs and complexity cannot be ignored. And as soaring demand mandates a better quality of off-branded drugs, bioequivalence studies will be expected to attain higher levels of precision.

Indeed, in early April, FDA demonstrated further proof of the rising importance and ongoing pursuit of regulatory management of BE studies by announcing the publication of revised recommendations for product-specific bioequivalence. These recommendations are intended to lend guidance to the design of BE studies to support abbreviated new drug applications.

Keeping these developments and industry realities in mind, it has become apparent that the companies that push to the head of the pack will be the ones who find better ways to mesh drug development process with BE studies—incorporating the four factors detailed above along the way.



Scott can be reached by e-mail at scott.vogelsberg@datatrial.com or on Twitter (@Datatrial).

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