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Process validation is the name given to specific validation activities performed on a manufacturing process. (As opposed to cleaning validation, for example, which is the name given to validation activities that prove that the equipment used to make a drug product is clean and will not contaminate the drug product being made).
Process validation follows a rigorous set of inspection requirements (called a protocol) that includes instructions on how to make the drug product and the type of equipment validation to be used.
Process validation can be broken down into three phases:
Phase 1 – Process Design
Phase 2 – Qualification Facility Design, Utilities and Equipment Qualification (Installation Qualification, Operational Qualification, Performance Qualification), Process Performance Qualification
Phase 3 – Continued Process Validation
Before we take a closer look at each of these parts, it’s worth acknowledging that some of these phases contain multiple parts and can be a little confusing.
Process design is the initial phase of any process validation protocol.
The ultimate goal of the process design phase is to develop and document a manufacturing process that can be used for commercial manufacturing to consistently produce a quality drug product every time.
The "commercial manufacturing" bit is important. The process needs to be able to produce enough drug for a lot of patients, not just a few. Many of the key factors considered throughout the process design phase, called critical product attributes, are determined during early product development activities.
During these early phases, only small quantities of the drug are produced and tested on patients during clinical trials. The goal of these trials is to demonstrate that the drug is safe to use and effective in treating patients.
The challenge at this stage (because the drug has already gone through a lot of development and testing) is to maintain the quality of the drug established during the small-scale manufacturing process, now to produce it in larger quantities. During the process design phase, the small-scale manufacturing process is designed and tested to confirm that it is suitable to consistently produce a drug that meets all the necessary quality requirements.
This phase is usually conducted in the laboratory. Manufacturing drugs can be very complex, and many different experiments may be required to get them to work.
Although these experiments are not usually conducted under GMP conditions (as they would be in commercial manufacturing), they will be strictly following good scientific principles and will be carefully documented.
While conducting the experiments in the laboratory, the scientists will already be thinking about the types of equipment that can be used when the process is scaled up for commercial production of large quantities of the drug. This approach will provide the greatest chance of successfully controlling the manufacturing process (reducing any variability compared to small batch manufacturing).
In turn, this control helps ensure that the critical quality attributes of the drug are consistently achieved. Completion of this phase will involve testing the quality and consistency of the drug being made, as well as the equipment used. Examples of conditions that might be documented at this stage include:
The temperature at which the drug is being made
The pressure in the container in which the drug is being made
The time it takes to make
In addition, any factors that influence how decisions were made about the process should also be documented.
For example, one might want to document the risk management tool that informed the scientific decision to do something in a certain way, and how the safety of the patient who will ultimately take the drug was considered. Once the process has been successfully completed and each step/condition carefully documented, the process design can be sent to the next stage.
It is important to note that all conditions throughout the process must be documented in order to be able to move to the next stage. Those who were not there initially must then be able to look back at what was done and understand why.
