Biological Contamination Management In Aseptic Environments: Requirements And Expectations

By James Drinkwater

Bio-contamination found in critical zones within processing environments can affect the whole process and sterility of the final products, potentially putting patients at risk. This can lead to significant financial costs and impact operational resources. This white paper examines the regulatory environment around processing in a GMP and hospital pharmacy environment and looks at the importance of root cause investigation into biological contamination.

Biological contamination management requires a formal process of root cause analysis (RCA), microbiological identification (at species level) and correction and preventative action (CAPA) to avoid reoccurrence. Root causes of why the biological contamination is present are not always easy to identify as they are often the result of complex environmental interactions. The outcome of a root cause investigation would be expected to identify at least the most probable cause if the actual cause cannot to be fully identified. Investigations and CAPA implementation can be time consuming and interfere with production operations. Failure to understand why the loss of control occurred can lead to in-depth QA/regulatory scrutiny thereby significantly increasing the QA work load.

There are clear regulatory expectations for the total particulate and microbiological control levels (GMP Annex 1) in aseptic processing and aseptic preparation environments. Different processes have different levels of risk relating to biocontamination. For example, there are more risks where sterile medicinal products or ingredients are opened and exposed in a Grade A/ISO 5 aseptic process environment than those that where closed containers of sterile products and closed transfers are used in the same class of environment. In ‘closed systems’ the risks are at the sterile interfaces and aseptic connections.