Introduction
A manufacturing process is a series of steps and operations used to transform raw materials into finished products. It involves using equipment, reagents, tools, labour, and technology to produce items to specified standards and requirements. Manufacturing processes are designed in the Design Transfer stage of Design Controls (Design and Development), which translates design outputs into products.
Medical device manufacturers must ensure their manufacturing processes incorporate the necessary controls to produce safe products that comply with all user, technical, and regulatory specifications. Process controls, verification and validation are essential to achieving this assurance.
- Process Controls provide the tools and methods to monitor and manage the manufacturing process.
- Process Verification uses these controls to check individual steps and components against specifications.
- Process Validation ensures that the entire process, supported by these controls, reliably produces products meeting all requirements.
Together, they create a robust system that ensures medical devices are manufactured to the highest safety and quality standards.
Production and Process Controls
Production and process controls are the mechanisms, procedures, and techniques used to regulate the manufacturing process. They are implemented to ensure that the manufacturing process consistently maintains product quality and prevents defects.
Process controls include activities like monitoring, measuring, and adjusting process parameters to maintain product quality and compliance. Developing process controls involves a structured approach to identifying critical aspects of the manufacturing process and implementing measures to monitor and control them.
During design transfer, the detailed specifications and requirements of the product are communicated to the manufacturing team. Process controls are then established based on these specifications to ensure that the manufacturing process consistently produces products that meet the design criteria. Effective design transfer with robust process controls leads to a reliable, reproducible, and compliant manufacturing process, ensuring the production of high-quality medical devices.
Key elements of process controls include:
- Standard Operating Procedures (SOPs): Detailed, written instructions to achieve uniformity in the performance of a specific function. Design transfer includes the development of Level 2 and Level 3 QMS documents based on the product design. These documents outline the necessary process controls and provide detailed instructions to ensure that the manufacturing process is followed correctly.
- In-Process Controls: Monitoring and controlling manufacturing processes to meet product specifications consistently. These are measures and checks performed during manufacturing to monitor and control the process parameters. Their primary aim is to ensure that the process operates within specified limits and that intermediate products meet defined criteria before moving to the next production stage. The purpose is to detect and correct deviations from specified process parameters immediately to prevent defects from occurring in the final product.
- Quality Controls The measures and tests conducted on the final product or at the end of the production process to ensure it meets all specified quality standards and regulatory requirements. These controls focus on the final output rather than the process itself. The purpose is to verify that the finished product meets all quality, safety, and regulatory standards and to identify and remove defective products from the supply chain before they reach the customer. QC Activities:
- Incoming Inspection: Testing raw materials and components upon arrival to ensure they meet predefined specifications.
- In-Process Testing: Conducting tests during manufacturing to monitor the process and ensure product quality.
- Final Product Testing: Inspecting and testing the finished product to confirm it meets all specifications and regulatory requirements.
- Stability Testing: Evaluating the product’s stability over its shelf life to ensure it maintains its quality and efficacy.
Process verification and validation
As part of design transfer, process verification and validation are conducted to demonstrate that the manufacturing process, supported by the implemented controls, can consistently produce products meeting the design specifications. In the context of medical device manufacturing, process verification and validation are two crucial steps to ensure that the devices are safe and effective. They serve different purposes and occur at different stages of the manufacturing process.
Process verification confirms that the manufacturing process can produce products that meet specified requirements under controlled conditions. The primary goal is to ensure that the process, when followed correctly, consistently produces results within predetermined specifications.
Process verification occurs during the development of the manufacturing process and periodically during production to ensure ongoing compliance. A verified process demonstrates that it can consistently operate within established parameters and produce conforming products.
Verification focuses on confirming that each step in the process meets defined standards and ensuring that the process inputs and outputs are within acceptable limits.
Typical Activities:
- Conducting tests on samples from the production process.
- Using statistical methods to assess process capability.
- Inspecting and calibrating equipment.
- Reviewing documentation and records.
Documentation: Verification involves inspection reports, test results, and calibration records.
Process validation is the documented evidence that a process consistently produces a product meeting its predetermined specifications and quality attributes. The primary goal is to establish and provide objective evidence that the manufacturing process, when operating within established parameters, can perform effectively and reproducibly to produce a product that meets its specifications and quality attributes. A validated process provides documented evidence that the process will consistently produce products that meet all specifications and quality requirements.
Validation focuses on the entire production process and the end product to ensure long-term process stability and capability. It examines the process under real-world production conditions and variability.
Validation activities occur at several stages of manufacturing:
- Before releasing a new product to the market (pre-market validation).
- Whenever there are significant changes to the process or product.
- Periodically, as part of ongoing quality assurance.
Typical Activities:
- Conducting process design studies.
- Performing installation qualification (IQ), operational qualification (OQ), and performance qualification (PQ).
- Running process validation batches to demonstrate consistency.
- Collecting and analysing data from the process to demonstrate control.
Documentation: Validation involves comprehensive studies, protocols, and reports that document the entire validation effort
Verification and validation activities should be based on sound scientific principles, risk-based approaches, and statistical analysis techniques, with clear acceptance criteria defined a priori.
Process validation studies
Once the design is finalised, manufacturing processes must undergo rigorous validation to ensure consistency, reliability, and compliance with regulatory standards. Process validation, a critical aspect of manufacturing in the medical device industry, involves demonstrating that manufacturing processes consistently produce products that meet predetermined specifications and quality attributes. Process validation is performed when verification is inappropriate or unfeasible for a particular process step and to evaluate the entire process.
Process qualification involves executing the manufacturing process under normal operating conditions to demonstrate its reproducibility and capability to produce products that consistently meet quality requirements. This typically involves conducting process performance qualification (PPQ) studies, where process parameters are systematically varied to assess their impact on product quality.
- Installation Qualification (IQ): Verifying that equipment and installations meet the required specifications.
- Operational Qualification (OQ): Confirming that equipment and processes operate correctly under defined conditions.
- Performance Qualification (PQ): Demonstrating that processes perform effectively and reproducibly in real-world conditions.
Process validation protocols must be meticulously designed, executed, and documented to ensure compliance with regulatory requirements and industry best practices.