METHYLENE CHLORIDE EXPOSURE EVALUATION DURING ACTIVE PHARMACEUTICAL INGREDIENT MANUFACTURING

摘要

A manufacturer utilizes methylene chloride (CH2Cl2) (CAS 75-09-2), also known as dichloromethane, to manufacture active pharmaceutical ingredients. Methylene chloride is specifically regulated by the Occupational Safety and Health Administration (OSHA) under 29 Code of Federal Regulation (CFR) 1910.1052. Evaluation and documentation of employee exposure to methylene chloride is required to comply with OSHA regulations. In addition to OSHA compliance, it is also important to evaluate employee exposure levels to determine if respiratory protection, regulation of the work area, and medical monitoring are necessary.This industrial hygiene report describes an investigation into the risks of exposure to methylene chloride. This report includes evaluation of employee exposure to methylene chloride during the manufacture of active pharmaceutical ingredients. During the manufacture of active pharmaceutical ingredients, employees transfer methylene chloride from small containers to a large reactor. After the desired reaction has taken place and allowed to separate, different layers of the solution which contains methylene chloride are drained from the reactor into small containers. Employees have the potential for exposure to methylene chloride during the transfer and collection processes.The results of the occupational exposure sampling indicate employees are exposed to levels of methylene chloride above the permissible exposure limit (PEL) and the action limit (AL). The regulatory standard requires medical monitoring when employees are exposure above the AL. Regulation of the work area and respiratory protection is required at the PEL.Recommendations to reduce exposure include identifying a substitute solvent that is less hazardous. To control exposure through an engineering control, an evaluation of the current localized ventilation system would be valuable in determining existing capabilities for reducing exposure to methylene chloride vapors. If this is not possible with the current ventilation system, other ventilation options could be explored. An engineering control to reduce exposure during methylene chloride transfer from pails to the reactor may be achieved by applying nitrogen pressure to the bucket to force methylene chloride from one container to the reactor vessel from a remote location. Reduction of exposure during transfer from the bottom of the reactor to collection pails may be achieved by attaching a hose to the bottom of the reactor and channeling discharge into a closed top container. The implementation of either of these controls would necessitate additional exposure monitoring to evaluate the effectiveness.