Which enzymes and transporters are covered in CYP induction studies?

Standard panels include CYP1A2, CYP2B6, and CYP3A4, with extended assessments possible for CYP2C enzymes, UGTs, and transporters such as P-gp depending on program needs.

Are the studies aligned with FDA/EMA guidance?

Yes. Study design, analysis, and reporting align with current FDA and EMA guidance for in vitro DDI assessment, supporting IND/BLA submissions.

Can Pharmaron help interpret RIS for clinical strategy?

Pharmaron supports data interpretation and IVIVE, helping translate in vitro findings into actionable clinical DDI risk assessments and next-step recommendations.

CYP Induction & RIS Services | Pharmaron Drug Development

Q: What is the Relative Induction Score (RIS)?

RIS is a quantitative approach that relates in vitro mRNA induction responses to expected clinical exposure changes to help predict DDI risk and inform regulatory decisions.

Capabilities

Regulatory in vitro ADMET Studies

Relative Induction Score: Predictive Power for DDI Risk

CYP Induction Assay: Predicting CYP3A4 Induction

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Helping you make confident decisions in drug development

Cytochrome P450 (CYP) enzymes determine much of how the body handles drugs. When those enzymes are induced their activity can shift enough to change drug exposure, efficacy, or safety. This change in activity can make a medicine less effective, or in some cases lead to therapeutic failure or unexpected toxicity. Pharmaron’s CYP Induction and RIS services are built to identify and manage those risks early, before they complicate a development program.

Why CYP Induction Studies Matter

Regulatory bodies such as the FDA and EMA recommend assessing CYP induction potential early so clinical studies can be designed with drug-drug interaction (DDI) risk in mind. Pharmaron combines validated laboratory platforms with experienced scientists to produce reproducible, regulatory-ready data to help de-risk programs and keep development timelines on track.

Our Capabilities

Primary human hepatocyte assays for CYP1A2, CYP2B6 and CYP3A4
Optional screening for CYP2C8, CYP2C9 and CYP2C19 isoforms
mRNA and enzyme-activity readouts to capture both transcriptional changes and functional induction
RIS methodology to translate in vitro findings into predicted clinical insights
Qualified positive controls spanning a range of non-inducers to strong inducers
Expedited study options with four-week turnaround options Custom study designs to support projects from early discovery through NDA submission

Pharmaron’s RIS Methodology

Our RIS platform uses cryopreserved human hepatocytes with seven-point concentration curves and validate against a broad panel of clinical inducers. The platform provides robust, regulator-accepted predictions that correlate strongly with observed clinical AUC changes (R² > 0.9), giving teams a reliable basis for assessing DDI risk.

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Q&A: Understanding P450 Induction and RIS Assays

What is P450 induction and why is it important in drug development?

Answer:

There are two main ways in which P450 induction can occur. The most common is by nuclear receptor-mediated induction; the increased expression of cytochrome P450 enzymes through induction of transcriptional gene activation resulting in changes in the expression of phase I and II enzymes and transporters. Less common, but just as important, is induction by enzyme or mRNA stabilization. These mechanisms typically occur in response to a drug or compound, and can affect the metabolism of other drugs, leading to reduced efficacy or increased toxicity. In order to properly assess potential drug-drug interactions (DDIs) and meet regulatory requirements, it critical to assess induction potential.

What is the Relative Induction Score (RIS)?

How does RIS improve traditional induction assays?

Answer:

More traditional P450 induction assays often rely on fold-change thresholds, which can be variable, hard to interpret and can result in conservative DDI-risk estimates. By comparison, the RIS method provides a more standardized and predictive approach by characterizing specific batches of hepatocytes and integrating multiple data points and parameters, resulting in an improved accuracy of risk assessment.

Which enzymes can be assessed using RIS?

How can Pharmaron support RIS testing?

Learn more about how Pharmaron’s CYP Induction and RIS services can support your drug development strategy.

Find out more about our research and development in CYP induction models:

For more information, contact us at [email protected] or complete our Contact Us form to speak with one of our experts.