Why Use the Developability Classification System (DCS)?
Approximately 40-75% of drugs in current development pipelines can be considered to have either poor bioavailability, nonlinear pharmacokinetics, or a significant food effect on drug bioavailability due to low solubility.
A suboptimal formulation can have significant negative effects on both project timelines and patient exposure; for example, a too-low dose can impact therapeutic effect. If a formulation strategy is not performed properly, delays and surprises can add up to two years to your development.
Our pharmaceutical scientists are expertly trained in the developability classification system (DCS), which uses a visual ranking to predict the factors that are critical to in vivo performance, such as drug solubility.
To select the most appropriate formulation strategy, the DCS classifies potential drug molecules into five categories: Class I, Class IIa, Class IIb, Class III, and Class IV.
Applying DCS as a Formulation Strategy During Hit-to-Lead
In traditional preformulation approaches during the hit-to-lead phase, the kinetic solubility and Caco-2 cell permeability of several potential drug series are determined. These evaluations are critical for conducting early ADME and biology studies, but potential challenges to oral drug delivery are rarely considered at this stage.
The hit-to-lead stage is seen as an early opportunity to understand potential development risks associated with a chemical series. Using in-house assays, the solubility in fasted state simulated intestinal fluid (FaSSIF) and permeability in Caco-2 cells are determined.
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This data is then evaluated using an in-house DCS tool to determine a classification and risk factor for a series. This information guides formulation strategy scientists to an appropriate series to take forward and to determine a suitable development pathway during lead optimization.
DCS during Lead Optimization for Maximum Drug Bioavailability
The DCS class is determined as part of the comprehensive early pharmaceutics assessment at the end of lead optimization. The thermodynamic FaSSIF solubility and Caco-2 permeability data are assessed to determine the classification. The API is assessed further to determine the rDCS classification, leveraging proprietary dissolution, and precipitation assays.
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When incorporating DCS into a formulation strategy, clients have a full understanding of potential barriers to drug bioavailability and elucidates strategies to overcome them. Determination of this classification empowers both the formulator and the chemist, ensuring more predictable drug bioavailability and a formulation strategy that can be taken forward.
How We Can Advance Your Formulation Strategy?
Following determination of a compound’s DCS class, here’s what you can do next:
- Using data derived from ADME and solid-state studies, a suitable drug candidate can be nominated.
- Further dissolution studies can be performed to refine the classification further. These studies account for biorelevant conditions, inhibition of crystallization, a compound’s ionization properties, and potential food effects.
- Initiate appropriate formulation strategy in order to maximize exposure of the drug for PK studies or safety studies when delivered orally.
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Our comprehensive set of pharmaceutical sciences and approaches can bring your formulation strategy to the next level. We work with clients to seamlessly develop and execute the most cost-effective strategy based on the outcomes of the DCS.
Frequently Asked Questions (FAQs) about Formulation Strategy
What is the Developability Classification System (DCS) and what is it used for?
The Developability Classification System (DCS) is a methodology used by chemists, pharmaceutical scientists, and preformulation scientists to rank compounds for solubility and permeability. The DCS is incorporated into a formulation strategy and, if used properly by trained scientists, can shave two years off the drug development process.
What is the difference between DCS and BCS?
As opposed to the Biopharmaceutics Classification System (BCS, which is regulatory focused), the DCS is development friendly, removing the requirement for in vivo permeability data and relaxing the dose. The Class II category is split into two new categories (Class IIa and Class IIb) to ensure the barriers to oral absorption are fully understood. Drug bioavailability of Class IIa drugs is limited by the rate of dissolution; consequently, control of the particle size distribution can typically overcome this barrier. Class IIb drugs are limited by the solubility of the compound and as such, require complex preformulation techniques (i.e., amorphous solid dispersions) to ensure suitable drug bioavailability. The DCS has subsequently been updated to the Refined DCS (rDCS) which takes into other physicochemical properties, namely pKa and dissolution rate, to aid a more in comprehensive understanding of the potential drug’s in vivo behavior.
Does Charles River offer preformulation studies and/or services that include the Developability Classification System (DCS)?
Yes, Charles River offers preformulation and formulation services such as the DCS in collaboration with the medicinal chemistry, biology, and drug metabolism and pharmacokinetics (DMPK) groups to offer clients with a developability assessment to support candidate nomination and allow for seamless transition into preclinical development.