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5 Elements for Success

Medical device manufacturers are facing increased customer and regulatory scrutiny regarding process validation. Process validation is a regulatory requirement per 21 CFR Part 820.75 and ISO 13485:2003 Section 7.5.2. For example, at least 37 FDA warning letters have been issued to date in 2013 related to process validation for medical device manufacturers.

Process validation applies to all production and service performed by the MDM which cannot be subsequently verified. Typical examples of processes which must be validated include sterilization, cleaning, welding, bonding and heat treating. MDM’s may decide that process validation is preferable to verification because it increases the confidence in the process and can reduce routine monitoring requirements.

Below are 5 key elements medical device manufacturers should consider during planning and execution of process validation projects:

1) Fully Defined Requirements – In many instances, process requirements are inadequately defined. Important questions include: What are the outputs of the process? Are there regulatory or customer requirements? Is valid justification provided? The requirements should be justified, measureable, clearly communicated in the validation protocol, and reflect customer/regulatory input. Historical process data may be evaluated, but is not a valid basis to justify the process requirements.

2) Risk Management –  Risk management should be implemented throughout the planning and execution of process validation. Consider supporting and documenting decisions based on risk management, among other considerations. Creation of a risk management plan and process FMEA (pFMEA) in the early stages of a validation is highly recommended. The pFMEA should be reviewed and updated as required during the validation, in accordance with the risk management plan.

3) Feasibility – Failures during process validation tend to be expensive and time consuming. Validation runs often require relatively large sample sizes and laboratory testing. Therefore, any failure which requires additional validation runs can add significant time, expense and may be difficult to explain during an audit. Consider the use of feasibility testing during the early stages of process validation. One approach is to perform operational qualification (OQ) in two phases. During Phase 1, feasibility can be investigated. This is an appropriate stage to perform Design of Experiments (DOE), Taguchi methods or other screening experiments. In addition to reducing the risk of failures during validation runs, feasibility studies are also an opportunity to improve process efficiency. Significant process inputs can be identified and the process parameters can be optimized. After Phase 1, the OQ can proceed to Phase 2 where the limits of the process are validated using a statistically valid sample size.

4) Gaging –  Gaging is often overlooked as part of process validation. However, the validation success is highly dependent on measurement of the process inputs and outputs. During installation qualification (IQ), measurement equipment should be calibrated to traceable standards. In addition, Measurement System Analysis (MSA), including Gage R&R studies, should be conducted to assess the measurement equipment capability. There are often many process inputs which could potentially be monitored during routine production. The pFMEA and DOE results can provide guidance to the MDM on what process inputs are significant.

5) Routine Monitor and Control – The validation report is often overlooked as the basis for routine monitoring and control. In many cases, engineering judgment or historical data is relied upon to determine monitoring requirements. During performance qualification (PQ), consider implementing limited-effectivity work instructions which include monitoring and control requirements. Operators should be trained on these work instructions prior to executing the PQ. When the final validation report is approved, the limited-effectivity work instructions can be implemented permanently. If the process is demonstrated to be stable and capable, loosening the monitoring requirements can be considered, depending on the medical device manufacturer’s risk tolerance.

Each process validation project presents unique challenges. Consider incorporating this guidance into your next validation project to reduce the potential for costly failures, reduce regulatory risk, and to optimize the operational efficiency of the process.