Reports of chemical similarity for scheduled drugs and the chemical space

The FDA and EMA require CNS penetrant drug candidates to be assessed for abuse potential. As part of this assessment, the chemical similarity to known drugs of abuse is analyzed.

Scitegrity Limited utilizes its expertise, extensive database of controlled substances, and industry-leading tools to quantitatively evaluate whether the candidate exhibits chemical similarity to known drugs of abuse. This evaluation is based on data rather than subjective opinions.

By combining this assessment with in vitro and early in vivo pre-clinical studies, there is the potential to eliminate the need for extensive, costly, and time-consuming full pre-clinical abuse liability packages.

Key features

Scitegrity Limited offers a comprehensive report that assesses the chemical similarity (or dissimilarity) of the candidate to known scheduled drugs and the chemical space associated with human abuse liability.

• Detailed methods, rationale, and results, encompassing all assessed substances of abuse
• Rapid and customized assessments and reports
• Non-subjective – quantitative and reproducible reports
• Reports tailored to specific regulators or countries such as FDA, EMA, UK, Japan, and others
• Check metabolites as well as parent compounds
• Highly curated and up-to-date data

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Abuse potential

Guidance from regulators

Both the EMA and FDA have issued guidance documents that include sections on Drug Abuse Potential, particularly for drugs with CNS penetrant or CNS activity. In the EMA’s guidance document, on page 22, under section 15 - Non-Clinical Abuse Liability, it is stated that:

“For drugs that produce central nervous system activity, regardless of therapeutic indication, it should be considered whether or not an evaluation of abuse liability is warranted.”

It goes on to state: “These early indicators would typically be available before first human dose and include the PK/PD profile to identify the duration of action, similarity of chemical structure to known drugs of abuse, receptor binding profile, and behavioral/clinical signs from in vivo nonclinical studies. When no abuse potential is apparent from these early studies, extensive testing in nonclinical abuse liability models might not be warranted.”

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A comprehensive pre-clinical abuse liability package typically requires 1.5 to 2 years and entails a cost of two million dollars. However, successfully demonstrating the absence of apparent abuse potential can result in substantial savings in both time and expenses.

What are FDA guidelines?

The drug abuse potential section of a New Drug Application (NDA) usually encompasses or refers to detailed study protocols and all primary data related to abuse from the following sources:

1. Chemistry studies
2. Studies on the binding of receptors and ligands, as well as functional (second messenger) studies
3. Studies on the pharmacokinetics in animals and humans
4. Studies on animal behavior related to abuse:
   1. General observations on behavior from safety pharmacology studies
   2. Studies on drug discrimination
   3. Studies on self-administration
   4. Studies on physical dependence
5. Studies on abuse potential in humans:
   1. Human abuse potential (HAP) study
   2. Study on physical dependence
6. Abuse-related AEs from clinical studies
7. Information pertaining to overdose, both intentional and accidental, during clinical studies
8. Assessment of the incidence of abuse during clinical studies (source: Assessment of Abuse Potential of Drugs Guidance for Industry, page 8)

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Scitegrity Limited’s assessments 

As part of the FDA’s “Chemical Studies,” Scitegrity can efficiently and cost-effectively generate a Drug Abuse Potential and Chemical Similarity assessment for controlled drugs listed in Schedules 1 to 5 within the United States of America.

For the EMA, Scitegrity also provides a separate assessment of similarity to known drugs of abuse, following the laws of various EU nations. It is important to note that narcotic, psychoactive, and drug abuse legislation in the EU is primarily governed at the national level, which significantly varies from regulations in the USA.  

This assessment encompasses controlled drugs as defined by the laws of Austria, Belgium, Denmark, France, Finland, Germany, Ireland, Italy, Netherlands, Poland, Spain, and Sweden.

Scitegrity offers similar assessments for several other countries, including the United Kingdom, Switzerland, Brazil, and Canada.

By leveraging its expertise and comprehensive datasets in controlled substances and chemical space, Scitegrity eliminates the subjective aspect of determining chemical “similarity” to the known controlled substances. These assessments rely on data rather than opinion.

Alternatively, through its partnership with Develrx, Scitegrity provides an extensive regulatory submission service that integrates its proficiency and data on drugs of abuse with Develrx’s expertise in CNS (central nervous system) drug discovery, development, and regulatory submissions.