Development of a cleaning process should include a review and risk assessment of residue characteristics. Review the process development or historical cleaning data, if information is available, to determine the physicochemical characteristics of the residue. Information may also be leveraged from products having similar characteristics or the same products having different cleaning methods.
Consideration should be given to the API; however, in some cases, the API will not be the hardest-to-clean active or the most prolific component in the formulation. For that reason, a thorough review should include any raw materials, excipients, impurities, degradants, or by-products that may contribute to a harder to clean or more toxic residue.
The API should be assessed by reviewing pharmacological (represented by the ADE/PDE/HBEL as available) and solubility data, along with its strength or percentage in the formulation.
Review and understand the manufacturing process including processing temperatures, process hold times, and environmental temperatures to understand how these may impact the residue characteristics. Soil condition on the equipment and MOC function together and should be considered when developing the cleaning process. The amount of soil on the equipment should be consistent among batches to ensure consistently adequate cleaning. Depending on the equipment, this can be accomplished using a clean-out step at the end of manufacturing. Scraping and/or vacuuming the equipment can remove the majority of the soil. This serves two purposes: providing a consistent soil level for cleaning and reducing the amount of soil flushed down the drain into the wastewater treatment facility.
Develop an equipment matrix to understand grouping, design, and product contact MOC.
Determine available cleaning process options since there may be limitations with utilities, waste requirements, and automation. Review and understand any restrictions that may influence the cleaning method.
- pH restrictions due to MOC or waste stream limitations
- Temperature restrictions due to MOC or waste stream limitations
- Decontamination step that may change the characteristic of the residue
- DHT constraints
Additional considerations for cleaning process development include: contribution to microbial growth, equipment availability, and manufacturing schedule needs.
