Developing CNS-penetrant drugs is a challenging task. The properties that make brain-penetrant small molecules effective drug candidates also raise concerns about abuse potential.
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Pharmaceutical companies must assess this risk at the early stages, long before drug products with blood-brain barrier (BBB) penetrative qualities make it to clinical trials.
The drug development process is long and expensive, and evaluating abuse potential adds to the cost and time. There is no avoiding this process, but there is a way to streamline it.
What is drug abuse potential?
Regulatory agencies like the EMA and FDA provide guidelines on drug abuse potential, including its definition, causes and preclinical assessment
Differentiating between dependence syndrome (when a patient relies on a medically prescribed drug) and drug abuse is crucial. Drug abuse, which occurs when medications are taken for non-medical purposes or in excessive doses, can occur independently from dependence syndrome.
There are many central nervous system (CNS) agents that are both safe and effective for various conditions, with 126 agents currently being studied for the treatment of Alzheimer's disease.
However, before these promising therapies can be approved, they must undergo drug abuse potential assesments during the development and regulatory stages. All drugs that impact or target the central nervous system (CNS) must be evaluated for abuse potential.
Any drugs that produce CNS activity have the potential to be abused, and it must be decided if a full evaluation of abuse liability is needed before the development can continue.
Drug products with chemical similarities to those with known abuse potential must also undergo testing.
Testing for drug abuse potential
Regulatory bodies such as the EMA and FDA have guidelines on assessing drug abuse potential indicators.
Early indicators of abuse potential, available before the first human dose, include PK/PD profile, chemical structure similarity to known abusive drugs, receptor binding profile, and behavioral/clinical signs from non-clinical studies.
It critical that these early indicators are comprehensively assessed, as crucially if regulators can be shown convincing evidence of no apparent abuse potential from these early studies, extensive testing in non-clinical abuse liability models and Human abuse liability studies can be avoided.
Extensive pre-clinical testing can cost $2 million and take up to 2 years, so a strong set of early indicators of low abuse potential can save both time and money.
Due to changing regulations for substances with abuse potential, it is important to work with a partner that is knowledgeable in the relevant rules and testing methods.
Scitegrity conducts comprehensive assessments to determine a product's abuse potential and regulatory compliance in the target market.
Streamlined testing with Scitegrity
Pre-clinical drug abuse liability assessments can be costly and complex. Scitegrity aims to streamline the process by quickly and effectively demonstrating low abuse potential, reducing time and costs.
Scitegrity can create a drug abuse potential and chemical similarity evaluation acceptable for submission to the FDA and EMA.
Scitegrity accomplishes this by utilizing vast data sets and algorithms of controlled substances and abuse-prone chemical space.
Scitegrity and its network partners can offer complete packages, including in vitro and in vivo testing and report submission, for CNS drug discovery and regulatory submissions.
References and further reading
- https://alz-journals.onlinelibrary.wiley.com/doi/10.1002/trc2.12179
- https://www.ema.europa.eu/en/documents/scientific-guideline/ich-guideline-m3r2-non-clinical-safety-studies-conduct-human-clinical-trials-marketing-authorisation_en.pdf
- https://www.fda.gov/regulatory-information/search-fda-guidance-documents/assessment-abuse-potential-drugs
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