Biopharmaceutical plant commissioning, that period between start-up and validation, is too often treated as an isolated part of the plants project life cycle, ignoring the impact that commissioning decisions can have on subsequent project phases.
A Commissioning Master Plan (CMP) is a practical way to define commissioning goals and align them with overall project goals. The alignment and integration of the plants commissioning teams objectives with those of the plant project team can improve quality and save both time and money.
During commissioning, the capabilities of the systems including process, utility, HVAC and electrical are tested to assure proper functioning and adherence to design criteria. Any discrepancies are identified and the necessary remedial actions are taken. During this phase, the manufacturing team can be trained in the operation of the plant systems. So, at the end of commissioning, direct-impact systems are turned over to qualification, and indirect- and no-impact systems are turned over to system owners.
The validation team will confirm that the equipment and systems perform in accordance with the Functional Requirements Specifications (FRS) and Detailed Design Specifications (DDS), reliably and with repeatability. In a successfully commissioned facility, it is expected that a minimum number of deviations will arise during the Installation and Operational Qualification (IQ/OQ) and Performance Qualification (PQ) execution phases of validation. By minimizing the number of validation-phase deviations, commissioning can help to reduce the overall validation duration, and consequently the overall project timeline and cost.
Trends in Commissioning Biopharmaceutical Plants
The process of commissioning biopharmaceutical plants is evolving in response to excessive deviations found during the IQ/OQ/PQ execution phases of validation. These deviations cause the repetition of some validation activities, resulting in unanticipated project schedule delays and costs. Commissioning has evolved to help reduce the time required for commissioning and validation by discovering and correcting discrepancies before the validation phase starts. Additionally, there is a trend towards integrating commissioning and validation to minimize the duplication of activities.
Even as late as the mid-1990s, commissioning was not well-defined. Some viewed it merely as mechanical startup after the plant utilities were connected or as repeating Factory Acceptance Tests (FAT) at the site and calling them Site Acceptance Tests (SAT). Still others viewed it as the phase that occurred between start-up and validation. It was treated much less formally, without the aid of a CMP to define the purpose, scope and expectations of commissioning. Too often, inadequate effort was put into defining the objectives of the commissioning phase and insufficient time was allowed for verifying how well the design requirements were met. These factors led to excessive deviations during the qualification phases of validation.
Planning for Commissioning
Having a formalized and documented commissioning strategy ensures that commissioning goals are met. The first step is the writing of the Commissioning Master Plan (CMP) by a designated commissioning leader. The CMP is written based on the agreements formed between different functional groups, such as Validation, Manufacturing (Owner), Engineering, Quality, Commissioning and Construction. The inclusion of the manufacturing team helps ensure that the plant will meet manufacturings needs. The validation team helps make certain that the turnedover systems are truly ready for validation, and that they meet agreed-upon acceptance criteria backed by system turnover documentation packages.
The CMP must define the boundaries of systems that will be commissioned, and must categorize each of the systems as having a direct, an indirect, or no impact; it must also specify the roles and responsibilities of project personnel and how to coordinate commissioning and related activities for a project.
The CMP needs to detail the steps of the commissioning process, such as:
- Commissioning Test Plan (CTP) development;
- System checkout prior to commissioning;
- CTP execution;
- Review of the executed CTP;
- Turnover of the executed CTP to Validation/Manufacturing.
Typically, only the CTPs for the direct-impact systems require QA/Validation before and after post-execution approval.Therefore, the direct-impact system CTPs often have the look of draft IQ/OQ protocols, having been modeled after the validation documents, which ensures a minimum number of deviations during the IQ/OQ and PQ execution phases of validation.
Determining the right makeup of the commissioning team is important to reduce post-validation changes and assure that input is obtained in a timely manner so any required changes have the least impact on schedule and cost. The commissioning engineers need to be familiar with the design intent, process requirements and validation expectations. Having process engineers knowledgeable in the plant design intent and experienced in troubleshooting will help resolve errors correctly and in a timely fashion. The manufacturing personnel bring their invaluable operating experience and are well qualified to determine the ease of operability and safety of the system design.
At the same time, the commissioning team must evaluate the suggestions made by plant operators to ensure that they are not based on personal preferences. The automation engineers are required to perform automation verifications of automated systems. For an automated system, three-quarters of the commissioning time is spent in automation verification or automation documentation upkeep, therefore it is important that automation engineers stay on schedule. Using experienced automation engineers who are wellversed in process control-loop tuning will save considerable time.