Secondary containment
Even when robust primary containment is implemented, a residual risk of exposure remains. To address this residual risk, secondary containment should be implemented as a facility-level engineering control within the overall containment strategy.
Secondary containment limits the spread and impact of highpotency compounds in the event of an unintended release, thereby extending exposure control from the source to the surrounding environment and providing a critical additional layer of protection. The required level is defined through a risk-based approach that considers the assigned OEB, the quantity of material handled, the primary containment used and the nature of the activity performed.
The secondary containment used is achieved through a combination of local exhaust ventilation, HVACbased segregation, pressure cascades, HEPA filtration and controlled airflows that establish a directional air flow from clean to potentially contaminated areas. High-potency operations are conducted within dedicated areas physically separated from other activities. Airlocks with defined material and personnel flows are implemented to maintain spatial and functional separation and to support the defined gowning procedures.
Use of PPE & extra containment
During facility design, several key considerations are integrated to ensure sustained secondary containment performance. This includes provisions for effective cleanability, as well as enabling maintenance activities to be executed under contained conditions. In parallel, the design incorporates preventive maintenance and continuous monitoring of critical parameters like airflow directionality and pressure differentials to ensure containment systems remain within their qualified state during routine operation.
The human factor
Tertiary containment combines operational and organisational measures such as clearly defined procedures, training, controlled access and the appropriate use of task-specific PPE. In alignment with the hierarchy of controls, these measures are applied as a complementary layer to primary and secondary containment.
Despite engineered controls, loss of containment is frequently linked to human factors, particularly during atypical manipulations or deviations from predefined methods. Therefore, emphasis on the consistent and correct use of containment is equally important as having it. This requires a workforce that that understands not only how to execute tasks, but also why containment is essential for protecting both operators and patients.
As technical proficiency and containment behaviour are equally important personnel should be both trained in the correct execution of process operations as in the fundamental principles governing containment and exposure control. The training approach should incorporates thorough training of the applicable procedures and hands-on simulations that replicate high risk tasks, The training should extend beyond manufacturing personnel to all relevant operational functions. During training, particular attention should be given to gowning and degowning procedures required for high potency operations.
In addition, structured and thoroughly trained procedures should be in place to address accidental spills, loss-of-containment events and other emergency situations. If primary containment is compromised, the affected area must have a defined decontamination and verification process, with release for further operations permitted only after visual and analytical confirmation demonstrate that predefined cleanliness and exposure-control criteria have been met.
Embedding cleaning & change-over
For any multi-product CDMO, cleaning and change-over operations are a critical part of the containment strategy, as exposure and crosscontamination risk can increase during equipment opening, disassembly or manual access. These activities must therefore be designed and executed under controlled conditions to maintain containment integrity as much as possible throughout the cleaning lifecycle.
Following each production campaign, equipment needs to be cleaned in accordance with validated and scientifically justified compoundspecific cleaning procedures. Cleaning effectiveness should be continuously verified through validated analytical
20 SPECIALITY CHEMICALS MAGAZINE ESTABLISHED 1981