FDA Process Verification Versus Process Validation
18 Dec 2024
The medical device manufacturing industry is heavily regulated worldwide. This stringent oversight ensures that every device produced and marketed meets consistent standards. Two key approaches in achieving this are process verification and process validation. While they may seem similar, understanding their distinct purposes is crucial to selecting the method for specific circumstances. Both processes are essential for both regulatory and quality perspectives.
Process Verification from the Perspective of FDA’s Quality System Regulation (QSR)
The FDA defines verification in QSR 820.3(aa) as:
“Confirmation by examination and provision of objective evidence that specified requirements have been fulfilled.”
When a manufacturer needs to ensure that a process works as intended, they must provide objective evidence. For instance, such evidence can be generated through tests or measurements. This evidence shows that the process outcome meets the manufacturer’s specified requirements.
Process verification involves a quantitative approach to confirm that specifications have been met. For example, if a manufacturer specifies a width of 25 mm for a component, they can verify compliance by measuring the part against this specification.
Process Validation from the Perspective of FDA’s Quality System Regulation (QSR)
The FDA defines validation as:
“Establishing by objective evidence that a process consistently produces a result or product meeting its predetermined specifications.”
While the definition appears similar to verification, there is a key distinction: process validation does not involve testing or measuring the final product against its specifications. Instead, it confirms that the process itself consistently yields results meeting the required criteria.
According to QSR 820.75(a), process validation is required:
“When the results of a process cannot be fully verified by subsequent inspection and test.”
In certain cases, process verification alone cannot confirm that a process works as intended. Examples of such processes include:
- Aseptic filling
- Injection molding
- Sterile package sealing
- Welding, soldering, heat treating, and painting
For example, consider sterile package sealing. To prove its efficacy, opening the package to inspect the seal would destroy the sterile barrier, rendering verification efforts ineffective.
Stages of Process Validation
Process validation is performed in three key stages:
Step 1: Installation Qualification (IQ)
A documented process to verify that equipment or systems are correctly installed according to design specifications, manufacturer instructions, and regulatory requirements.
IQ ensures that the installation of equipment, piping, and services complies with the manufacturer’s requirements. This step verifies that all components have been installed correctly before testing begins. Key activities during IQ include:
- Cross-checking the contents of packages
- Inspecting devices for damage
- Verifying proper installation at designated locations
- Confirming connections to other equipment or systems
Step 2: Operational Qualification (OQ)
A documented process to verify that equipment or systems perform as intended within specified operating ranges under controlled conditions.
In this stage, equipment is tested to determine worst-case scenarios, process control limits, action levels, and potential failure modes. OQ verifies that the equipment operates as intended within the prescribed range. Common parameters tested include:
- Humidity and control systems
- Operational capabilities of display systems
- Activity triggers
- Timers
- RPM of fans or motors
- Temperature fluctuation controls
Step 3: Performance Qualification (PQ)
A documented process to confirm that equipment or systems consistently perform as intended under real-world conditions.
PQ aims to demonstrate that the process consistently produces acceptable results under normal operating conditions. It is conducted in a real-world setting, using trained personnel, control procedures, utilities, and equipment in an actual facility. PQ verifies process consistency and safety over time.
FDA’s Recommendations for a Written PQ Protocol
The FDA recommends manufacturers develop a comprehensive written PQ protocol that includes:
- Raw materials used, manufacturing conditions, and operational parameters
- Data collection methods and evaluation plans
- Tests performed on equipment, along with acceptance criteria for each test
- Sampling plans to ensure batch-to-batch quality
- Scientific and risk-based decision-making criteria to assess process efficacy
- Personnel training and qualification status
- Facility design and suitability
- Validation status of analytical methods used for measuring processes and products
- Protocol review and approval by the quality team and relevant departments
Importance of Sequential Validation Steps
To ensure thorough validation, manufacturers must perform and document all three stages of process validation—IQ, OQ, and PQ—in order. Skipping or altering the sequence can compromise the reliability of the validation process, potentially leading to regulatory non-compliance or quality issues.
By understanding and implementing both process verification and process validation correctly, manufacturers can ensure their processes are robust, compliant, and capable of producing high-quality medical devices.
Process Verification vs. Process Validation: Where to Use Them?
In the earlier example of sterile packaging, it is more practical to use process validation instead of process verification. However, choosing between the two is not always straightforward.
To make an informed decision, manufacturers should consider the following questions:
- Can the process’s output be verified? If not, the manufacturer should either validate the process or redesign it to enable verification.
- Is verification cost-effective and sufficient? Will verification alone eliminate unacceptable risks?
While some processes may technically be verifiable, manufacturers might find it more practical to validate them. Scenarios where validation might be preferable include:
- Certain filling and cleaning processes
- Numerical control cutting processes
- Specific human assembly tasks
Seeking Expert Help!
Performing process verification and validation can be challenging, but experts at TSQ & E are ready to help. As outlined in this guide, these processes are intricate but essential for regulatory compliance. Medical device manufacturers aiming to meet all regulatory requirements can consult our team of professionals. Our experts will assist you in ensuring that your processes meet all regulatory guidelines, making it easier to bring your medical devices to market.
