While reasonably straightforward in principle, poor implementation may lead to uncertainty which in the worst case can result in costly field actions.
So how do you determine which process to validate and what are the keys to good process validation?
One of the main assumptions made during the product design phase is that the manufacturing process will be capable and stable to assure that the product remains safe and performs as intended.
In order to do this:
- the product should be designed to withstand variations in the manufacturing process and
- the manufacturing process should provide assurance that the product can be produced to its predetermined specifications.
Often, this results in a very interactive process between the product development and manufacturing stages.
Process validation entails exactly that; it aims to “demonstrate” that, when a process (e.g. manufacturing, testing) is operated within specified limits, it will consistently produce products that comply with their predetermined specifications.
And you have heard this before… if there is a need to “demonstrate”, there is a need to document!
Which process to validate? (or why some processes are “Special”)
Regulatory and quality system requirements state that every process that cannot be verified by subsequent monitoring or measurement shall be validated. If you can’t confirm the output with a direct test or measurement of the product – then you have a “special process” and must validate. Good examples of special processes are sterilisation (where doing a sterility test will destroy the sterility barrier) or glued joints – where you can only test the joint by pulling it apart.
Simply put, think about providing control over those variations or issues that may only become apparent after the process output is produced (or when the finished device is in use).
Variations that affect the product quality are a particular area of concern for the Medical Device industry as even a small change in performance can have a direct impact on treatment efficacy and patient safety.
As process variations can also occur at any stage of the product manufacturing, the need for process validation should be considered at each level: individual component, sub-assemblies and final finished device manufacturing.
Depending on the device complexity, this translates into a potentially large number of processes affected by validation. GHTF and other sources discuss common examples of processes requiring validation:
- Sterilization process
- Sterile packaging sealing process
- Injection molding
- Additive manufacturing (3D printing)
- Automated assembly lines, test stations
- Software interfaces
- Destructive testing
A manufacturer may also decide to validate a process or its parameter voluntarily: Validation may be particularly useful during production scale up or automation where it is used as a tool to improve reliability, quality, manufacturing yield, reduce production time and in certain cases even reduce cost of manufacturing (e.g. by cutting down on continuous verification or inspections)!
The steps to effective validation
A good validation program involves a series of activity taking place over the product and process lifecycle. These steps typically include:
Step 1: Production planning
The quality system regulation requires establishment of procedures and work instructions for the control and monitoring of production processes. While control and monitoring has a broad definition, implementation of procedures and instructions for process validation is also necessary.
The regulation is however unspecific as to whether validation procedures shall be general or established for individual processes and both approaches may be suitable depending on your organizational needs. Whichever the case is, validation activities shall be planned, responsibilities for the validation process defined and the output of each stage documented.
Step 2: Process design
this phase includes collection of data on the product specifications and process to gain an understanding of the manufacturing controls required to meet the desired output. A multi-disciplinary team (e.g. QA, Manufacturing, Design, Testing, Clinical, Procurement) is typically required to ensure all factors that can impact the product or process are incorporated in the design.
The manufacturing process design requires:
- Understanding the product quality attributes or critical parameters. These become the goals of the process.
- Understanding the manufacturing process and its limitations. For example, what equipment will be used? What are the limits imposed by the equipment manufacturer?
- Understanding the possible sources of variations (i.e. “what could go wrong?”) in the process and their impact to product.
Variations can be identified via process experimentations or pilot studies but this process more effective if integrated within your risk management program. For example, the use of tools such as Process FMEAs will inform you on the impact and relevance of the variation.
- Implementation of a process control strategy/plan. Process control measures shall be commensurate with the risk of its variations and their impact to product quality. This assessment is typically based on experience but reliance on robust statistical rationales is important. The resulting controls may include product or process examinations, equipment monitoring (e.g. calibration and maintenance), implementation of sampling methods, additional procedures, staff training and of course, qualification of the relevant process parameters.
Step 3: Process Qualification
Qualification activities must be conducted in accordance to a pre-defined protocol. In the Medical industry, process qualification typically involves three distinct phases “IQ, OQ, PQ”. All or part of this phasing applies to the selected process:
Installation Qualification (IQ) – the IQ phase is the confirmation of correct equipment installation. Describe the equipment installed, the installation conditions, the recommended maintenance and calibration activities and as well as their frequency or schedules (part of the process should be to enter the equipment and the relevant components in your equipment register), review and collect the relevant documentation (e.g. equipment manual and procedures), establish spare parts lists etc.
This activity may be conducted by the organization where the equipment is installed or by the original equipment manufacturer. Both would be acceptable so long as activities remain within your supplier control policies and the relevant records are collected as part of this process.
Operational Qualification (OQ) – this is the phase during which the selected process parameters will be challenged. The pre-established protocol shall define the “what/how/how many” to measure as well as the acceptance criteria for each parameter. Execution of the protocol shall always ensure that the challenge test performed represents the “window of operation”, that the worst-case condition is identified and its impact on the product understood.
Parameters to be considered during qualification include process control limits (such as temperatures, pressures, time, speeds, pixelization), raw material specifications, operating procedures in use, training of staff. And if such qualification involves software, use of workflow and fault-tree analyses can be helpful in identifying the possible issues that can affect product quality.
Performance Qualification (PQ) – the last step of the process is to demonstrate that the process output is reproducible under normal operating conditions. The process should be challenged over a period of time, using actual production conditions of product, procedures and resources with the aim of performing capability studies and measuring process deviations. A process found to be unstable may highlight that inputs such as product design specifications require review or that additional process controls should be implemented to mitigate the observed deviation.
Step 4: On-going monitoring
On-going monitoring and measurements of process such as trending of data show if the process remains within the defined parameters. When monitoring shows a negative trend, a root cause investigation should take place, use your Corrective/Preventive Action (CAPA) system to control the change and evaluate the need for re-validation as part of this process. Note that part of ensuring that that the process remains under its validated conditions involves execution of calibration and maintenance activities per the defined schedule.
Step 5: Re-validation
The need for re-validation may arise during the product or process life cycle. Re-validation may be required as a result of a change in the product specifications (whether on the finished device, sub-assembly or raw material), supplier change, infrastructure and building changes, process (e.g. transfer or equipment change) or even as a result of post-market activities (e.g. complaints and adverse event reporting). Manufacturers should have the necessary processes to identify when re-validation may occur and the criteria for re-validating impacted processes.
Validation still daunting? Whether you require, training, consultation on a specific case or auditing of your validation processes, we are here to help! Contact us by email firstname.lastname@example.org or call +61 0 9906 2984. We would be pleased to discuss how we can help supporting your projects.