The utility of BCS-based biowaivers

The pharmaceutical industry is feeling the acute effects of disruption caused by the COVID-19 pandemic. With most human trials on hold, drug developers and generics companies will be looking for new ways to progress product portfolios. This series of blog posts aims to highlight BCS and BCS-based biowaiver applications as such an opportunity.

This blog will cover how BCS classification can be used to waive the need for certain in vivo studies in regulatory approval applications. To find out more about BCS, read the first blog here.

A biowaiver allows in vitro data to be used as a reliable surrogate for in vivo bioavailability/ bioequivalence studies during regulatory approval of new generic and novel drug products. As described by the FDA:

“When the in vivo dissolution of an IR solid oral dosage form is rapid or very rapid in relation to gastric emptying and the drug has high solubility, the rate and extent of drug absorption is unlikely to be dependent on drug dissolution and/or gastrointestinal (GI) transit time. Under such circumstances, demonstration of in vivo BA or BE may not be necessary” –  2017 FDA Guidance for Industry¹

Biowaivers are particularly relevant in the current climate. The impact of the Coronavirus pandemic on clinical research in the US cannot be understated, with a near complete shut-down in human studies not directly related to tackling the virus². Biowaivers enable companies to progress products towards approval by providing the necessary in vitro data for a biowaiver application, reducing the burden of need for human studies.

What drugs are eligible for biowaivers?

Drugs can be assessed based on their solubility and permeability under the Biopharmaceutics Classification System, or BCS ¹. First defined in 1995, BCS is the basis on which the major regulatory bodies decide on biowaiver approval (see Table 1). BCS consists of the following four classes (1-4) based on the aqueous solubility and intestinal permeability.

• Class 1: High Solubility – High Permeability
• Class 2: Low Solubility – High Permeability
• Class 3: High Solubility – Low Permeability
• Class 4: Low Solubility – Low Permeability

Table 1: Criteria from different regulatory bodies for defining BCS parameters

Encouragingly, there has been a concerted and fruitful effort to harmonize how biowaivers are assessed between organizations. The FDA’s initial guidelines for biowaivers only supported Class I drugs. However, in 2017, updated guidance allowed Class III (high solubility, low permeability) drugs to be eligible for biowaivers, bringing the US in line with the EMA². This has significantly opened up the market, as Class I and III drugs combined account for over 60% of all marketed drugs in the US³. Later this year, the ICH M9 guideline, which aims to harmonize much of the various BCS guidance criteria, will take effect in many of the major geographical jurisdictions, including the United States, EU, Japan, China, and Brazil.

In addition, although biowaivers are typically used for ANDA applications of generic products, they have much wider applicability, including in INDs (Investigational New Drug) and NDAs (New Drug Application). Thus understanding when and how a biowaiver is applicable can be extremely beneficial when preparing a product for the market.

Here to help

Absorption Systems offers a streamlined approach to providing the experimental data and expert advice for biowaiver applications. Products are initially assessed in an eligibility screen that provides customers with a clear ‘go/no-go’ decision for committing to the full experimental data recommended by FDA. Our 20-year expertise in working with BCS means we have experience in overcoming hurdles in BCS classification, such as pH-dependant stability or inaccurate internal standards for permeability.

References:

1. Food and Drug Administration, 2017. Waiver of In Vivo Bioavailability and Bioequivalence Studies for Immediate-Release Solid Oral Dosage Forms Based on a Biopharmaceutics Classification System, Guidance for Industry. https://www.fda.gov/media/70963/download
2. A. Hofsäss, J.B. Dressman. The Discriminatory Power of the BCS-Based Biowaiver: A Retrospective With Focus on Essential Medicines. J Pharm Sci. (2019)
3. L.Z. Benet., The role of BCS (biopharmaceutics classification system) and BDDCS (biopharmaceutics drug disposition classification system) in drug development., J Pharm Sci. (2013). DOI: 10.1002/jps.23359