Validation is crucial in assessing test results. In a fast-paced world where immediate answers are required, there is a temptation to prioritize technological innovation to deliver rapid results, often bypassing essential protocols for quality control, verification, and validation. I work in the medical lab industry, and from my experience, continuous regulatory compliance is maintained through proficiency testing (PT) as mandated by the College of American Pathologists. PT acts as an external quality assessment that confirms the accuracy and reliability of the testing process.

Theranos claimed to use the Edison machine for less than 10% of its tests; however, they were actually using off-the-shelf equipment from Siemens and Roche for analytical tests. Their understanding of regulatory compliance and quality practices was lacking. A 2014 article titled "Hot Startup Theranos Has Struggled With Its Blood-Test Technology" highlighted significant issues with how Theranos conducted their tests and the absence of proper validation.Despite these concerns, the FDA allowed Theranos to operate without a necessary post-market safety monitoring program, which is critical for special controls. This leniency was attributed to the prototype being unique or unprecedented in the innovation process, which resulted in a series of regulatory deficiencies, particularly in design control. Consequently, Theranos was able to circumvent standard regulatory compliance protocols.

The key takeaway from this regulatory issue is that device development must ensure accuracy and integrity. The broader challenge in the healthcare industry is the demand for rapid results without sufficient validation, which can lead to poor patient safety outcomes.

Balancing innovation with regulatory compliance requires a proactive approach that integrates compliance into each stage of product development. By not addressing it early, companies set themselves up for delays, regulatory setbacks, and high costs. Implementing a Regulatory Affairs and Quality Assurance team (RA/QA) is a great strategy for maintaining that balance. Embedding regulatory experts within R&D teams ensures compliance with the FDA, ISOs, and EU requirements. There are many other strategies that can be implemented, such as pre-submission meetings with regulatory agencies like the FDA, following verification and validation testing, i.e. does the devise meet design inputs / does it meet user needs as seen in the slides for this week. What are some other strategies that can be used?

An important factor to consider which is equally important as pre-market approval is post-market surveillance of medical devices. A rigorous and well-made pre-market portion of a medical device project is essential for the approval and success of the device. An equally important post-market approval phase is critical for long-term success of the device. For example, utilizing metal-on-metal for hip and knee joint implants in the past was seen as an "innovation" that met all regulatory requirements. The metal implants were biocompatible and regulatory agencies saw no issues with it. However, we now know that metal-on-metal joints cause significant wear that creates metal debris within the body and should be reconsidered. This led to inflammation, pain, and eventually the failure of the early prosthetics. We now have other implants that are made of a combination of metal, plastics, and ceramics that take into account the debris accumulated through wear. This shows the importance of having a well-developed post-market plan. If something were to go wrong with a medical device long-term, it could cause damage to the reputation of the company in the public's view, and legal repercussions are almost certain to occur.

Ensuring compliance with regulations is essential for the innovation of medical devices, as it ensures that new technologies are safe, effective, and ready to be captured in the marketplace. Absent of a robust compliance strategy, even the most spectacular innovations can be delayed from market access, suffer recalls, or fail completely. The most compelling reason to prioritize compliance is faster access to market and regulatory approval. Early alignment with FDA, ISO 13485, and EU MDR requirements saves costly redesigns and re-submissions, therefore enabling companies to bring products to market more readily. Compliance also earns the trust of healthcare professionals and patients, increasing the safety and reliability of a device.

A key challenge is how to ensure the speed of innovation while ensuring compliance with regulations. Very strict processes can delay development, while letting too much slack can result in failures or rejection post-market. Bringing on board regulatory specialists at the onset of R&D, performing adequate risk-analysis, and keeping compliance filing helps ease compliance that stifles innovation. How do you believe companies should navigate the debate between the speed of innovation and compliance? 

Unfortunately, without regulatory compliance there is no innovation. I do not necessarily agree that there is a balancing of innovation and regular compliance. Regulatory compliance is far more important than innovation, as with any violations a project or company can be shut down regardless of how small the impact may be. For example, one of the warning stories we were told at one of the companies I previously worked at was that at one of the smaller sites, the FDA was presented with unoriginal, forged, and backdated documents, when the documents had been requested but could not be found. The FDA eventually found the original documents later in their inspection, forcing the site heads to reveal what had happened. This is a massive GMP violation and puts every piece of documentation the company presents in question, which did result in a major fine and an order to cease production due to the nature of the documents in question. That being said, the best way to maintain regulatory compliance is to ensure that there are no violations or risks present in the first place. This requires early and constant communication to regulatory experts within a company as well as to applicable regulatory boards as well. Although regulatory boards can be slow with communication, it is important to keep them well-informed so if they do not agree with any decisions or action taken, they can interject prior to violations occurring. Patience is essential. Internally, it is also important for a company to maintain a strong quality management system that aligns with ISO standards. This can help ensure that any design, manufacturing, and post-market surveillance processes conform to relevant regulatory boards and there is no potential for issues to arise through inspections and audits. On the topic of audits, internal audits are also a fantastic way of maintaining regulatory compliance. They can be done via site personnel, or personnel from other sites and global departments. This helps ensure that violations are not occurring and in the case of an audit from a regulatory board, everyone is prepared and everything is up to par. 

I think in order create an innovative design that passes all regulatory compliance, it should have an effective Validation Plan. The validation method is required to test the device's safety and effectiveness, and the results to prove its safety and effectiveness.

In cases where the Validation test method was not thorough enough, the innovative design could be too risky and fail FDA Approval. Change Requests can be made to change validation protocols, design inputs, or verification tolerance levels.