Case Study 10:
Potent Pharmaceutical Compound Containment
Description of Operation
Pharmaceutical manufacturing operations require the mixing, blending, and processing of multiple compounds to obtain finished drug products. Increasingly, new active drug compounds are becoming more potent thus increasing their toxicity to workers who may be exposed to the substances during manufacturing. One area of potentially high exposure to workers is the dispensing of pharmaceutical ingredients during various stages of the manufacturing process. Traditionally, dispensing was performed by carefully hand scooping powders into containers or directly into process equipment.
With the increasing potency of new drug entities, companies are finding that high levels of personal protective equipment are required to meet minimum protection requirements. As drug research has identified even more potent compounds, respiratory protective equipment with Assigned Protection Factors (APF) as high as 1000 have been found to be insufficient to provide adequate employee protection. In this case the manufacturer recognized that the use of powered air-purifying respirators (PAPR) with an APF of 1000, although currently sufficient, would not effectively protect operators from the new generation of drug substances being developed. It was determined that containment technology needed to be developed that would allow for the accurate measurement and dispensing of powered drug compounds but that would also protect workers from potent compound dust exposures.
The company formed a team to determine a dispensing method that incorporated the necessary parameters to optimize the combination of manufacturing accuracy, quality control, cost control, and employee safety and health. The team determined that using flexible containment glove bag technology verses fixed containment systems was the most effective solution to control dust exposures during dispensing operations.
Impacts of the Intervention
The intervention achieved all of the necessary requirements of the project. The glove bag technology lowered the exposure risk by a factor greater than 1000 with the actual exposure measures being significantly less than 10% of the established Occupational Exposure Limit (OEL). As a result of the intervention there was no longer a need for operators to wear respiratory protective equipment. Used glove bags are required to be incinerated after use however the overall volume of hazardous waste for incineration was reduced by 75% since the need to dispose of PAPRs was eliminated.
As a result of the intervention operator confidence in the level of protection being provided is extremely high.
The project resulted in a 5-year net present value of $27,585 with an internal rate of return of 98%. The discounted payback period for the project was 0.9 years. No capital investment was required since the glove bag equipment was already available at the facility. The savings in respiratory protective equipment, labor time to don the RPE, and disposal costs of the RPE more than offset the planning time associated with the project and the cost of purchasing and disposal of the glove bags.
The intervention also demonstrated a level of containment that satisfies the requirements of EU and US pharmaceutical regulatory agencies with regard to the cross-contamination of active pharmaceutical ingredients. The alternative to the solution provided by the intervention would have required a segregated facility to dispense compounds. Such a facility would have cost several millions of dollars in capital expense. These costs were not considered in the financial metrics listed above.
The project showed containment projects can result in improvements in employee health exposures and savings in labor and waste disposal costs. This case demonstrated an example where containment projects require little incremental capital investment to accomplish significant results.
The project not only addressed the current challenge of employees wearing cumbersome respiratory protective equipment but also addressed the developing concern about the existing RPE providing ineffective protection for newer and more potent pharmaceutical compounds.