Your medical device has been performing well, but you want to make it better. The FDA and the EU both require that all changes to medical devices be reviewed, verified, validated (as appropriate), and approved prior to implementation - but what does this actually mean? Let’s break it down:
Reviewed
Proposed changes to medical devices must be reviewed to determine their impact on existing product performance, safety, and documentation. This includes evaluations of requirements, production processes, testing, and risk management. Specifically, it should include determinations of whether:
·Any new user needs, design inputs, design outputs, equipment, and/or manufacturing process requirements are needed to account for the new features or functionality being added
Any modifications to existing user needs, design inputs, design outputs, equipment, and/or manufacturing process requirements are needed to account for the changing features or functionality
Existing design verification and/or design validation testing will still be applicable to the modified medical device or whether all or part of design verification and/or design validation testing must be repeated
The production equipment and processes (including inspections) for the modified medical device will still be operating within their validated ranges, whether equipment qualifications must be repeated, and whether process performance qualifications must be repeated.
New production processes must be developed and whether new production equipment is required along with what qualification activities are needed for these new equipment and processes
There are any new or changes to existing risks or benefits
Any changes to labeling are needed to discuss the new or changing features or functionality or disclose the risks associated with them
Any regulatory notifications or submissions are required for the change in any region
Once you’ve determined the impact on existing product performance, safety, and technical documentation, you can weigh this against the estimated business benefit of making the change to determine whether pursuing this design change is worth it. If you still want to pursue this change, you’ll need to verify, validate, and approve it.
Verified
If the design features being changed could impact the results of design verification testing, design verification testing must be repeated on the modified medical device. Only tests whose outcomes could be impacted by the proposed change need to be repeated.
Verification must also occur for the design features being changed during the production process. This typically means repeating any inspections associated with changes to the production process as well as that impact the production processes accompanying the design change.
Validated
If the design features being changed could impact the results of design validation testing, design validation testing must be repeated on the modified medical device. Only tests whose outcomes could be impacted by the proposed change need to be repeated.
Additionally, the production processes used to manufacture and inspect the modified device must be re-validated if they change (e.g., modification of a CNC program for a size change) or if the device design could impact the outcome of the production process (e.g., sterilization).
Approved
The results of the review (i.e., determination of what work must be done to support the design change) as well as the work itself (i.e., updates to requirements, completion and documentation of verification and validation testing, updates to risk management documents) must be approved prior to implementing the design change. It’s not enough to say that you understand the work that is required to execute a design change, you actually have to complete that body of work prior to making the modified medical device available to customers.
Case Study
Let’s walk through a case study for a hypothetical medical device change. This case study will go over the activities required to complete each step of the process to implement the new sterile fracture plate.
ABC Orthopedics sells a non-sterile version of an orthopedic fracture plate in the US and EU. Recently, some customers have been requesting that the fracture plate also be sold sterile, so ABC Orthopedics has decided to pursue selling a separate sterile fracture plate that is sterilized via gamma irradiation. ABC Orthopedics does not have sterilization capabilities in house and must engage a supplier to perform the gamma sterilization.
Review
Since the need for a sterile packed fracture plate was previously unknown, a new user need for a sterile fracture plate must be created. This user need must be translated into new design inputs that establish requirements for sterility assurance level, sterile packaging, and sterile shelf life.
New sterile packaging must be developed.
New part numbers must be assigned for the sterile fracture plate.
New production processes for sterile package sealing and gamma sterilization must be developed.
Risk management documentation must be updated to include the risks and benefits associated with the sterile fracture plate as well as the sterile packaging and gamma sterilization processes.
New labeling on the carton and sterile packed device must be developed with the new sterile fracture plate part number as well as an indication that the product is sterile and the method of sterilization
Regulatory applications must be submitted to the US and EU.
Verified
Design verification testing for sterility assurance level, sterile packaging, and sterile shelf life must be completed to confirm that the fracture plate is sterile and remains sterile for at least its stated shelf life.
Distribution design verification testing must be repeated on the new sterile configuration.
An inspection to confirm completion of gamma sterilization must be added to the production process for the sterile parts.
Validated
New sterile package sealing equipment must be qualified.
A new sterilization supplier must be qualified.
Production processes for sterile package sealing and gamma sterilization must be developed.
A periodic revalidation schedule must be established for the sterilization and sterile package sealing processes to ensure these high risk processes remain within their validated state.
Irradiation dose and bioburden monitoring programs must be established ensure that the sterilization process continues to be effective.
Approved
The following must be approved:
Updates to user needs and design input documentation
Sterile package specifications
Updates to risk management documentation
Design verification reports
Supplier qualification reports
Equipment qualification reports
Process validation reports
Periodic revalidation schedules
Dose audit and bioburden monitoring programs
Manufacturing and inspection work instructions
Labeling
In addition, regulatory clearance or approval of the change must be received prior to making the updated medical device available to customers in that region.
