How do drugs get BCS classified?

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 what BCS classification studies entail, and how Absorption Systems can help you obtain all the right documentation to submit data on your drug to the regulatory agencies. To find out more about BCS, read the first blog here. To find out more about biowaivers, click here.

There are three main factors involved in the rate and extent of drug absorption in the body: the dissolution, aqueous solubility, and the permeability of the compound. The Biopharmaceutics Classification System (BCS) is a scientific framework that classifies drug substances based on their aqueous solubility and intestinal permeability.

Based on the permeability and solubility, compounds are classified into four classes:

Figure 1: Illustration of BSC classification classes based on solubility and permeability

The FDA and the EMA grant biowaivers for both Class I and III compounds. Clinical bioavailability or bioequivalence studies may not be necessary for regulatory submission of drugs within these classes. Use of this pathway can save significant time and money in drug development of both generics and new drugs and is endorsed by the World Health Organization to make generic drugs more readily available to the global population.

BCS classification studies

At Absorption systems, we have over 20 years of experience working with BCS and have conducted hundreds of definitive BCS classification studies, resulting in numerous successful biowaivers. We can determine the biowaiver eligibility of your compound in 1-2 weeks using non-GMP material.

1. Eligibility screen

A go/no go decision point – this step offers a prequalification and determination of the eligibility of the test compound for a BCS biowaiver.

The main determinants in these experiments include:

• Is permeability greater than minoxidil?
• Is the efflux ratio < 2?

After determining eligibility, we produce a report and expert statement. This includes a consultative support letter to regulatory authorities providing support to request the biowaiver approach.

1. Protocol optimization

This step includes the conduct of FDA-required experiments to establish the most cost-effective protocol for pivotal studies.

Quality permeability data will be obtained, including:

• Concentration range
• Impact of internal reference compounds
• Mass balance

1. GLP BCS classification of permeability and/or solubility

All experimental tests required will be performed under GLP.

The classification includes experiments providing data on:

• Multiple concentrations
• GLP analytical validation
• Additional replicates

With our extensive experience and innovative solutions, we can classify a broad range of drugs using in vitro methods alone.

The entire study process, including all three steps, could take approximately as little as six weeks to complete. Submission of the data from a BCS biowaiver to the FDA, as well as the ANDA review and approval process, is similar to those with data obtained by regular in vivo experiments.

Absorption Systems’ in vitro test systems

At Absorption Systems, we have employed a patented in vitro test system based on the Caco-2 cell monolayer model. This model can assess passive permeability, a current prerequisite for nonclinical classification. The Caco-2 cell line model is highly representative of the human intestine, as the cells share the morphology of intestinal enterocytes and express physiologically relevant efflux and uptake transporters, as well as intestinal enzymes and carriers.

This model is an intrinsically conservative test system that has never produced any false positives. The system is uniquely validated for both transporter interaction assessment and BCS classification.

Here to help

Data obtained with our validated system can guide clinical strategies, assist in formulation development, enable predictions of metabolism and food effects, and may waive clinical studies. In our next blog, we will detail the in vitro model systems we have available and how we are equipped for preclinical testing of complex compounds, including locally-acting topical dermal and ophthalmic drugs.