Validation and verification are inextricable from product development and process design for the manufacturing of medical devices. To satisfy regulatory standards, reduce risk, create efficiencies and ensure outcomes, manufacturers have ever-evolving validation and verification procedures. New testing methods, automated solutions and documentation tools are frequently introduced to make this part of process development as streamlined and pain free as possible.
Validation is a process of testing and analyzing operations to guarantee the output they produce will consistently fulfill the end user’s needs and provide the intended medical benefit in actual-use conditions.
Verification is a process of testing and inspecting products during and after production to collect objective evidence that each one meets all regulatory requirements, fulfills all predetermined specifications and is ready for use.
The FDA lays out the current good manufacturing practice (CGMP) ordinances in their Code of Federal Regulations which describes the purpose of validation. The CGMP principles require that “manufacturing processes be designed and controlled to assure that in-process materials and finished products meet predetermined quality requirements and do so consistently and reliably.” In the FDA QSR 820.75(a) it states: “Where the results of a process cannot be fully verified by subsequent inspection and test, the process shall be validated with a high degree of assurance and approved according to established procedures.”
These are indispensable components of the production process for medical device manufacturers and yet, don’t always get the attention they deserve.
The FDA does not quantify what “fully verified by subsequent inspection and test” specifically is, but, to illustrate their seriousness about this requirement, they have censured a company for not “fully verifying” products on the basis that the company was not doing 100% testing on all products during production.
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The censured company was using an ultrasonic cleaning step and a passivation treatment on medical devices, but there was only process validation done prior to implementation. The product testing being done was only conducted on a few samples that went through the manufacturing process.
The actual letter from the FDA, that includes a response to the company’s insistence that they satisfied verification requirements, states this:
“Failure to validate a process whose results cannot be fully verified by subsequent inspection and test, and approve the validation according to established procedures, as required by 21 C.F.R. § 820.75(a). For example, you have not validated the static ultrasonic cleaning and passivation process, or the tumbling, cleaning and passivation process...
We have reviewed your response, which lists several other manufacturing processes (for example, your CNC processes and polishing) that you state do not need validation because you perform in-process and final inspection/tests. We have concluded that your response is inadequate because you are not testing every device to assure it meets specifications, and the results are not fully verified. All of these processes must be validated to ensure the specifications are consistently met or you must test all devices.”
In this regard, “fully verified” can be taken to mean every single product that goes through an unvetted process must be inspected and tested to authenticate that they were all completely cleaned and assembled according to the prescribed requirements.
One of the reasons this is difficult for companies to do, even though the idea of not going through the comprehensive and expensive process validation proceeding is very attractive to manufacturers, there are not many testing methods suitable for use in a production setting. Typical testing methods are little more than visual tests that have no meaningful correlation with testing accomplished in laboratories.
Contact angle measurements can be key in bridging the gap between the laboratory and the production line. With technology designed to make testing surface energy easy, fast and consistent on real products at any critical point during production, manufacturers can use a proven testing method in a new and effective way for product verification.
A major hurdle for manufacturers has been the difficulty of testing on the unique geometries of their products. With an automated, in-line contact angle measurement system, almost any curved, angled, or grooved surface can be tested on due to patented ballistic deposition of the probe fluid. When the volume of the fluid is controlled, essentially allowing for extremely tiny drops to be deposited in places that have heretofore never been able to be tested for cleanliness before, then the measurement can be done on any surface.
Medical balloons, populated circuit boards, catheters of nearly all diameters, metal components with recessed channels and even diagnostic wells can be tested to substantiate that process requirements were met throughout production using contact angle measurements.
Contact angle measurements can also be used to determine if a hydrophobic or hydrophilic coating has been uniformly applied to a wire, catheter, or medical device (i.e. the surface needs to repel or attract fluids). Inconsistent contact angles over the entirety of a surface can indicate the coating was not uniformly applied. Using contact angle measurements for coating inspection correlates well to coefficient of friction testing and could enhance or replace common testing methods. Being able to characterize an entire surface is one of the reasons taking measurements in batches to map out the quality of a whole surface is extremely useful. This information can help identify ways coating deposition equipment might be inconsistent or indicate that treatment processes require optimization.
Contact angle measurements can be done with liquids other than water. Even highly-purified water can have unacceptable endotoxin levels. But endotoxin-free water is available for processes where sanitization needs to be maintained. The portable and automated contact angle measurement devices utilize touchless inspection heads so the pure liquid is all that comes into contact with the surface, preserving its pristine condition. Product verification often leads to a tremendous amount of scrap for manufacturers since the tests they currently use are destructive to products that need to maintain very specific levels of cleanliness and sanitation. A nondestructive test like a contact angle measurement is the perfect replacement for methods that increase the cost of manufacturing.
In a manufacturing field like medical device engineering, failure isn’t an option and assurance that everything will proceed the way it was designed to is paramount. The only way to accurately predict the successful performance of medical devices is to have data-driven inspection and continuous monitoring at every point in production where the material surfaces can be altered, either intentionally or unintentionally, with good or bad outcomes. These places in the manufacturing process are called the Critical Control Points (CCP). When the inspections of these CCPs correlate perfectly with analytics from the research and development lab then there isn’t a regulatory guideline in the world that these measurements wouldn’t fulfill.
Some medical device manufacturing CCPs include:
Contact angle measurements are also powerful supply chain control tools. Manufacturers can quantify the quality and cleanliness of incoming components from suppliers to certify that every aspect of production is falling within the designated specifications. Some companies require contact angle measurements as mandatory quality tests from their suppliers and then verify the data their vendors provide with a subsequent check of all incoming materials. Measuring incoming parts also allows manufacturers to detect undisclosed changes in the material, shipping process, or cleaning prior to shipping that could throw off their highly calibrated production process.
Creating a common language through shared quality measurement techniques eliminates barriers to smooth, quick problem solving and stopping issues before they get very far. With inspection equipment that can take contact angle measurements and share the data in real time, this kind of quality assurance can be done remotely and potential issues can be flagged and handled from anywhere in the world, saving companies millions of dollars in carting engineers all over the globe.
To learn more about how to shore up your medical device manufacturing process with data-driven process checks, download our eBook about ensuring predictable process outcomes. Get your free copy of How to Streamline Process Design to Production for Medical to gain insight into the best ways to create a fully verified production process.