Abuse liability assessment for biologic drugs - All molecules are not created equal

Area of Science:

• Pharmacology
• Drug Development
• Biotherapeutics

Background:

• Global increase in prescription drug misuse necessitates robust safety evaluations.
• Health authority guidances exist for assessing therapeutic abuse liability.
• Current guidances do not differentiate between small molecules and biologics regarding abuse potential.

Purpose of the Study:

• To analyze the abuse liability of biologic therapeutics.
• To identify key differences between biologics and small molecules relevant to abuse potential.
• To determine the necessity of nonclinical abuse liability studies for biologics.

Main Methods:

• Analysis of biologic properties influencing abuse potential:
• Central nervous system distribution
• Pharmacokinetic properties (half-life, metabolism)
• Off-target binding potential
• Physicochemical characteristics of biologic drug products

Main Results:

• Biologics exhibit limited potential for drug abuse.
• Marketed biologics (e.g., antibodies, recombinant proteins) are associated with adverse effects like headache and dizziness, not psychoactive effects.
• Biologics do not typically cause rapid-onset psychoactive effects characteristic of drugs of abuse.

Conclusions:

• The inherent properties of biologics suggest a low risk for abuse.
• Factors considered indicate that nonclinical abuse liability studies may not be required for biologics.
• Aggregate assessment supports the conclusion that biologics pose a limited abuse risk.