FDA Validation Requirements for Medical Devices...

FDA Validation Requirements for Medical Devices
The FDA validation requirements for Medical Devices are based upon the US FDA Code of Federal Regulations, (particularly section 21 of the CFR’s, part 820). These define the Quality System Regulations (QSR’s) applicable to the design, manufacture, release and post market follow-up for medical devices.
The quality system regulations define when a product or process needs to be validated, or alternatively where verification may be sufficient. The validation requirements are just one aspect of the QSR’s.


“where the results of a process cannot be fully verified by subsequent inspection and test, the process shall be validated”


The FDA expect that a manufacturer, will be able to confirm the compliance of a medical device to all critical quality, safety and efficacy attributes before release to the market. This confirmation may be via recording and maintaining test records (verification activity) or where verification is not possible then product and process validation will be required. Clearly, the FDA cannot stipulate up front, exactly when a manufacturer needs to perform a validation, it is up to the manufacturer to define their process controls from the design through processing and onto the release stages and in doing so, the manufacturer needs to identify the validation and verification activities.

“Each manufacturer shall establish and maintain procedures for monitoring and control of process parameters for validated processes to ensure that the specified requirements continue to be met.”


Therefore, once validations have been performed, the FDA expect the manufacturer to continue to control the validated processes to ensure they remain in control. The FDA also state that documented records of such controls shall be retained.

“When changes or process deviations occur, the manufacturer shall review and evaluate the process and perform revalidation where appropriate.”

Once a process has been validated and the controls established as a result of the validation have been defined, implemented and are effective, the manufacturer of the medical device must revisit the original validation where any product or process changes are to be implemented. Revalidation may not be necessary for all change (for example changing the color of a medical device may not require revalidation), however, the manufacturer needs to assess if the original validation and original validation controls could be compromised by the planned product or process change and determine if a new validation is necessary. When a revalidation is necessary, then this needs to be completed in advance of any change being implemented.


Examples of when products or processes should be validated are:


i) where the end product testing would be deficient or lacking in sensitivity to confirm the required safety and efficacy of the product,
ii) where end product testing would not confirm all variations in safety or efficacy which may arise in the product,
iii) where clinical or destructive tests are necessary to confirm the achievement of all required attributes in the product,
iv) where the capability of the process is deficient or unknown.

The types of validation that may be performed are, a) prospective validation, where the validation is pre-planned in advance, b) concurrent validation, where the validation is based on data collected during actual performance of a process already implemented in a manufacturing facility, c) retrospective validation, where production has been commenced, but has not been validated according to a prospective protocol and concurrent validation is not a realistic option and d) laboratory-and pilot-scale validations, where planned production processes cannot be carried out in a production facility.

The optimum approach and most widely applied is prospective validation.

When performing a validation program, the manufacturer of a medical device will normally have in place a Validation Master Plan, which will outline the overall approach to validation, detail the lower level documents, identify the processes for creation and approval of specific validation protocols. The validations themselves will be controlled via validation protocols, these will define the objectives of the validation study, location of the study, the responsible personnel, a description of any applicable equipment, applicable SOP’s (standard operating procedures), reference standards to be applied and define the criteria for the relevant products and processes including acceptance criteria.

When implementing a validation program, a manufacturer needs to include risk assessment (and management). The risk assessment will identify the areas of greatest risk (to the patient, user, etc..) and therefore the areas of focus for the validation program. The risk assessment is a critical stage in the overall approach to validation. It will be necessary to demonstrate to the FDA, that the intensity of the validation activities are proportional to the potential risks.

The Quality Management System will need to comply with the QSR’s. Many manufacturers obtain ISO 13485 approval of their manufacturing facilities as a means of demonstrating that their QMS is substantially equivalent to the QSR’s as there are many similarities between the international standards and the FDA’s QSR’s.

Medical Device.

FDA Device classification database: http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpcd/classification.cfm
FDA Medical Device Panels: http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/Overview/ClassifyYourDevice/ucm051530.htm
FDA Medical Device Exemptions: http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpcd/315.cfm