Description of Operation

The operation where the intervention occurred is a process step in the manufacturing of active pharmaceutical ingredients which are subsequently formulated in various drug products.  The current operation was an open process involving the repack of resin columns using an acetonitrile (ACN) slurry.

Hazard Identification

The current operation involved the addition of ACN into an open manway of a process tank. During the operation two operators were exposed to levels of ACN ranging from 60-100 parts per million (PPM).  Operators were required to wear powered air-purifying respiratory protective equipment to protect against airborne ACN exposures that were created during the solvent charging process.

Hazard Intervention

To reduce exposure an engineering control consisting of purchasing and installing a high containment valve was implemented.  By using the high containment valve for charging the tank, airborne exposures of ACN were virtually eliminated.

Impacts of the Intervention

Due to the installation of engineering controls the airborne levels of ACN were reduced from the 60-100 PPM range to less than or equal to 1 PPM.  The resultant exposure level eliminated the requirement for operators to wear respiratory protective equipment (RPE).  As a result there was a cost savings associated with the elimination of the RPE as well as the associated time required to properly don/doff the RPE.  Prior to the intervention the process step required three operators, which was subsequently reduced to two operators after the implementation of the containment project thus significantly reducing overall labor costs associated with the operation.

Although no quality deviations had been previously associated with this manufacturing step the containment and enclosure of the open process were also recognized as a quality control improvement.  In addition, containing the process also eliminated foaming issues sometimes noted during the operation of the process, but the benefit of the reduction has yet to be fully evaluated.

The process change also reduced by one third the amount of ACN lost to the environment during the operation thus allowing a small material savings and a corresponding lowering of volatile organic compound (VOC) air emissions.  The enclosed process would require additional Leak Detection and Repair (LDAR) monitoring points to be added to the environmental monitoring schedule, but the incremental cost was minimal.

Another benefit of the project was the elimination of the need to dispose of used RPE as hazardous waste. As a result one drum of hazardous waste per month and the associated disposal costs were eliminated.

Financial Metrics

The financial metrics associated with the intervention indicated that the project yielded a 5-year net present value (NPV) of $23,629 with an internal rate of return of 14%. The project had a discounted payback period of 3.8 years.  Therefore in addition to the benefits of lower employee ACN exposures, improved quality, reduced air emissions and reduced hazardous waste the project also yielded a competitive rate of the return on the organization’s investment. The project also resulted in some improvement in employee morale due to eliminating the need for the wearing of respiratory protective equipment.

Lessons Learned