In Vitro Pharmacology

Challenge

A number of in vitro assays are recommended or required for evaluating the safety as well as the efficacy of active substances, predominant metabolites and some impurities submitted in either Investigational New Drug (IND) and New Drug Application (NDA). Screening of metabolic enzymes and transporters for small molecules is essential for predicting and/or avoiding drug-drug, food-drug interactions, or variability in response due to polymorphism in an enzyme or transporter within a given population. Many substances are also screened against many receptors and enzymes that may or may not be related to the intended therapeutic effect or may induce serious safety concerns (secondary pharmacology). This allows determination of the therapeutic target specificity and safety profile as well as the assessment of potential liabilities during the forthcoming clinical trials. Inclusion of secondary pharmacology studies’ results is recommended as per International Council of Harmonisation (ICH) Guidance S7A to support the safety of new drugs (US Food and Drug Administration, 2001).

Before now, there has not been a consistent data standard for in vitro pharmacology (IVP) data. IVP data must be shared with regulatory bodies throughout the drug development process. If target panels, file structure, and nomenclature are not consistent across the dossier submitted, this can delay regulatory review and approvals.

Solution

The aim of the In Vitro Pharmacology- (IVP) Working Group is to develop data standards and tools for in vitro bioassays by working with stakeholders within the FDA, other regulatory agencies, biopharmaceutical industry and interested vendors for structuring this data in regulatory submissions.

Consistent with this aim, the IVP working group comprises regulators, reviewers, scientists, and pharmacologists collaborating to establish a unified and standardized data framework. This framework utilizes pre-existing ontologies to describe the data generated by laboratories for regulatory submissions. Additionally, a repository of assays will be developed to host standardized descriptions of methodologies used in safety and secondary pharmacology, which will be linked to the result submission documents.

Output will be computer readable standard data, increasing capacity for provenance and attribute connection for insight and analysis.

Importance of the IVP working group

Numerous benefits will be retrieved with the setting up of a common and standardized data structure and utilizing existing ontologies. The benefits can be summarized as follows:

For Biopharmaceutical companies

• Submissions can be reviewed faster by regulatory bodies.
• Limited pre and post marketing requirements.
• Defined ontologies will enable better data reuse, interpretation and understanding.

For Regulatory bodies:

• The ability to review across different applications.
• Organization of in vitro data from INDs allows more efficient in vitro pharmacology testing.

For CROs:

• Standardized format to share data with biopharma and regulators will improve efficiency.
• Data can be structured in Electronic Lab Notebooks (eLNs) enabling more efficient search & analysis.
• Defined ontologies will enable better data reuse, interpretation and understanding.

The resulting deliverables will include:

• Establishment of a platform allowing submission of in vitro pharmacology result data set using a standardized template during IND registration.
• Establishment of a platform allowing registration of in vitro assays used in safety and secondary pharmacology.
• Incorporate the full scope of bioassays into the ontology and submission template.
• Widening the scope of the template for other safety pharmacology.