Biowaiver monographs for immediate release solid oral dosage forms: pyrazinamide.

Area of Science:

• Pharmaceutical Sciences
• Drug Development
• Regulatory Science

Background:

• Pyrazinamide is an Active Pharmaceutical Ingredient (API) in immediate-release (IR) solid oral dosage forms.
• It exhibits BCS Class III characteristics with linear absorption, suggesting low risk of bioinequivalence.
• Pyrazinamide may be considered a narrow therapeutic index (NTI) drug, which typically requires in vivo bioequivalence (BE) testing.

Purpose of the Study:

• To review literature data supporting a waiver of in vivo bioequivalence (BE) testing for pyrazinamide IR solid oral dosage forms.
• To establish criteria for granting biowaivers for pyrazinamide-containing products.
• To assess the feasibility of biowaivers considering pyrazinamide's properties and regulatory guidelines.

Main Methods:

• Literature review of scientific data concerning pyrazinamide's pharmaceutical properties and therapeutic index.
• Analysis of regulatory guidelines and criteria for granting biowaivers for immediate-release solid oral dosage forms.
• Evaluation of drug product characteristics, including excipient composition, dissolution profiles, and Summary of Product Characteristics (SmPCs).

Main Results:

• Pyrazinamide demonstrates linear absorption and a low risk of bioinequivalence.
• A biowaiver for pyrazinamide IR solid oral dosage forms is deemed feasible under specific conditions.
• The drug's classification as NTI is acceptable if liver function monitoring is mandated in the SmPC.

Conclusions:

• A biowaiver for pyrazinamide IR solid oral dosage forms can be recommended.
• Conditions for biowaiver include approved excipients, normal excipient amounts, very rapid dissolution, and mandatory liver function monitoring in the SmPC.
• These criteria aim to ensure product quality and therapeutic equivalence without in vivo BE studies.