Risk Assessment for Different Formulations in a Highly Potent Drug Facility: Oral Solid Dose & Liquid Dosage Formulations
RICH ARNETT
Pharmascience Inc., Candiac, Canada
Abstract
Handling of highly potent active pharmaceutical ingredients (HPAPIs) within a shared multi-product GMP facility requires proactive risk assessment for both quality and occupational reasons: preventing cross-contamination means safer medicines for patients, while preventing unacceptable exposure means a safer environment for workers. Thorough risk assessment requires careful consideration of numerous factors including health-based exposure limits, the formulation and associated physical properties, the manufacturing process, batch size, and the available facility and product handling engineering controls. Personal protective equipment must always be a last resort. In this article, some important considerations are presented when assessing risks for different formulations in a highly potent drug facility for oral solid dose and liquid dosage formulations, including contrasting cross-contamination risk assessment vs occupational risk assessment.
IDENTIFYING THE BIGGEST RISKS – DURING MATERIAL TRANSFERS/PROCESS STEPS
Several factors must be carefully assessed to ensure safe handling, especially for production processes involving numerous material transfers and multiple processing steps, from handling of the pure active pharmaceutical ingredient (API) to the finished dosage form.
KEY MATERIAL & PROCESS CONSIDERATIONS
Material Health Based Exposure Limits (HBELs): The risk controls to be used when handling HPAPIs should be commensurate with the HBELs used (1).
Material Physical Properties: key considerations during handling of the API, drug product, and any associated intermediates include:
- Physical state: powders become more easily airborne than liquids, thus leading for potential exposure scenarios when not properly controlled.
- Particle size: smaller particles become very easily airborne and can remain as such for several hours (2).
Quantity & Concentration of API: Larger batch sizes often require more complex and expensive controls; handling of pure API requi ...
