Driving Your Bioequivalence Research And Development During Covid-19 Era

Generic drugs have a substantial share in the prescribed drug market. They must provide similar clinical benefits as reference listed drugs (RLDs) and comply with FDA standards. Generic drugs must show “bioequivalence” to an RLD in pharmaceutical, therapeutic and biological, terms. The active ingredients, dosage forms, administration routes, strengths, and related properties must be the same (pharmaceutical). The drug must offer a similar safety and efficacy profile in a clinical setting (therapeutic). Moreover, the active pharmaceutical ingredients (APIs) must be similarly available and active at the site of action (biological).

An integrated approach to bioequivalence

An integrated bioassay-based approach (IBA) can support biowaiver applications, enabling in vitro data to be used instead of clinical data. The biochemical, structural, and physical characteristics of a drug’s dosage form directly influence the in vivo parameters of a formulation, such as the rate and extent to which the drug gets delivered to the target site. A generic drug may have a similar formulation to an RLD but perform differently in vivo, primarily depending on the frequency of inter-subject variability within a reference population.

To meet regulatory requirements, drug developers require evidence on a formulation’s characteristics and in vivo behavior to confirm the therapeutic equivalence to an RLD. For this, an integrated approach in which bioassays are used alongside existing tests has proven to be effective at characterizing not just formulation property but also the overall behavior of a formulation in a particular biological setting. This approach helps drug developers to select the most relevant system or assay for assessing CGDP performance and also to evaluate the combined impact of discrete physicochemical characteristics in a multifaceted way. In vitro bioassays can reveal whether changes in the microstructure of a complex formulation will impact critical performance parameters in vivo, explicitly connecting API and formulation to biological effect.

High-quality in-vitro data to accelerate bioequivalence research and development

Establishing the rate and extent of drug absorption is an essential determinant of a compound’s safety during drug development. Adverse effects may be observed if a drug is released in the systemic circulation too quickly, while slow or inadequate may not be sufficient to produce the desired outcome. Clinical studies are challenging, time-consuming, expensive, and can be burdensome for subjects.

Any opportunities to bypass the clinical studies in humans represent massive time and cost-savings. It is estimated that the replacement of in vivo bioavailability and bioequivalence studies saves $50–150 million per drug product. In the case of orally administered drugs, there are several opportunities to expedite the development of some compound classes. As high-quality data is collected from specialized in vitro experiments, it has become possible to obtain a “biowaiver” as a surrogate for human BABE studies.

The Biopharmaceutics Classification System

The Biopharmaceutics Classification System (BCS) was developed to enable the identification of compounds that meet the criteria for a BCS-based biowaiver. BCS classifies drugs into four classes based on two determinants, aqueous solubility, and intestinal permeability. The classes are:

Class 1: High Solubility, High Permeability

Class 2: Low Solubility, High Permeability

Class 3: High Solubility, Low Permeability

Class 4: Low Solubility, Low Permeability

Compounds categorized as Class I or III are eligible for BCS biowaivers.


Under the challenging circumstances of the current COVID-19 pandemic, innovative approaches are needed to maximize the opportunities for advancing drug development. The pharma industry is seeking some accurate, reproducible, and efficient ways to assess CGDP bioequivalence.

Augmented and integrated testing using advanced bioassays can avoid the roadblocks to CGDP development. Through the BCS classification system, it is possible to gain exemption from human BABE studies for certain drug classes. BCS has allowed drug development companies to move forward and reduce the need for human studies. Due to this, patients can gain access to drugs that might not have been able to progress otherwise.