Containment Control Strategy
A robust containment control strategy is essentials as a growing number of pharmaceutical products contain highly potent active pharmaceutical ingredients (HPAPIs) that are capable of targeting disease selectively and more precisely than other compounds. HPAPIs are more effective medicines that require lower doses and lead to fewer patient side effects, but also impose manufacturing challenges due to their toxic, highly potent and sensitising nature that can produce adverse health effects with either acute and chronic exposure. Their manufacture requires a specialised approach to manufacturing processes, equipment selection and facility design to achieve desired levels of containment, minimise operator exposure, and ensure worker protection and safety.
Designing the Building for Containment
Too often buildings are designed first and then the process is shoe-horned into the available space. This creates problems with regulatory compliance and workflows. It is also an issue if the equipment and room containment are not aligned.
PharmOut designs the process first and the equipment is specified with the appropriate containment system level. Then the facility including room containment is built around this and should never rely on personal protective equipment.
Feasibility and Conceptual Development Studies
PharmOut have developed a simplistic but standardised and streamlined approach to containment during feasibility and conceptual development studies where limited information and time are available. This containment control strategy adopts room containment levels throughout the facility.
These levels have been adapted from the levels of protection described in the ISPE Oral Solid Dosage Forms Baseline Guide and the OEB type classification.
Note that the focus is shifted from protection of product to operator protection from hazardous materials.
Table 1: Room Containment Levels
|-||Room containment level||Description|
|C3||Open and exposed product/ hazardous materials are present in the space.|
|C2||Spaces where manufacturing processes are closed (not exposed) and where there is the potential for accidental product/ hazardous materials exposure.|
|C1||Spaces where there is minimal risk for product/ hazardous materials exposure such as areas where raw materials and packaging components are in their received packaging, final product is fully contained and protected by its completed shipping packaging.|
|C0||These areas are physically separated from GMP manufacturing areas where there are no product/ hazardous materials. These are typically support functions (e.g., offices, canteen) for the facility.|
This approach simplifies the gowning and conceptual HVAC approach. Where possible, C3 areas are avoided by using appropriate isolation and containment.
In the past we have used this notation and approach for facilities manufacturing penicillin, beta lactams, cephalosporin, on the same site, at high level helps understand all the possible cross contamination risks and vectors.
Preliminary and Detailed Design Stages
The initial containment control strategy adopted during feasibility and conceptual development studies is reviewed and a complete assessment of all chemical and activities conducted during the subsequent design stages.
During the preliminary and detailed design stages, PharmOut follow an exposure assessment methodology adapted from that developed by Extract Technology. The Extract Technology approach is modified to better suit each application and the technologies expected to be utilised. The methodology recognises that hazards posed by any specific process are a result of several interrelated factors. All of which require assessment to define the most appropriate containment control strategy.
Throughout this process, PharmOut works with the client and other specialists such as toxicologists, occupational hygienists and risk management consultants.