Quality Risk Management in Pharmaceutical Manufacturing Operations: Case Study for Sterile Product Filling and Final Product Handling Stage

Abstract

In the highly regulated pharmaceutical industry, significant risks to products/processes must be formally identified, reduced, and controlled to minimize potential negative impacts on patients. Failure Modes and Effects Analysis (FMEA) is one of the well-recognized risk-management tools which is effectively used by the pharmaceutical industry to document and communicate risk control. International Conference on Harmonization (ICH) guideline Q9, Quality Risk Management (QRM), represents the first internationally recognized guideline specifically addressing QRM for the pharmaceutical and biopharmaceutical industries. However, Q9 does not provide details on how to use FMEA in real-world pharmaceutical situations. Authors have previously presented a real case study through which various risks were identified and controlled in an early stage of sterile manufacturing process, including (i) procurement/supply chain, (ii) logistics/warehousing, and (iii) raw materials dispensing. This study represents a modeled risk mitigation approach for professionals or regulators in the industry field associated with sterile pharmaceutical production processes such as (a) glass bottle washing and handling, (b) rubber stopper washing and handling, (c) product filling process, (d) final product receiving and handling. The benefits of this case study include providing a proactive means to identify, control, and communicate risks associated with various vital steps, thereby improving decision making and reducing regulatory non-compliant risk. In this study the outcomes of risk assessments associated with every defined step highlighted all critical hazards with risk priority number (RPN) scores equals to or above 105. These hazards are given the priority to be treated and put under control to reduce the RPN to acceptable levels. Although every manufacturer’s product and process are unique, and risk tolerance varies among manufacturers, some processes are generic in nature, and the associated risks are similar. Therefore, our case studies and examples can fit every circumstance in pharmaceutical manufacturing.