Embracing quality and creating a mindset around quality best practices is the common thread among the companies we work with that are successful at avoiding regulatory issues and are adept at getting to market quickly. These organizations all use an effective quality management solution (QMS) that allows them to catalog, review and act upon every aspect of the product lifecycle. Specifically, they use a QMS to address and manage these things:
- Reviewing quality procedures through an effective methodology for conformance to established regulatory requirements.
- Quality verification of product development records, including samples, test results, analysis and other data.
- Management review processes that includes quality audits, training requirements, and procedural guidelines.
- Submission processes for communication and submission of information to the FDA when changes to testing and product processes have happened.
- Ability to assess product claims, submission data and other relevant information that is part of the product lifecycle.
- Evaluation of necessary processes and procedures that pertain to identification, documentation, evaluation, segregation and submission to governance bodies.
- Implementation of effective quality control processes that verify and validate all activities in the product development lifecycle.
- Manage documents that can be used for future product development or used for validation during FDA review.
- Create and manage complaint and corrective actions procedures and catalog all pertaining activity.
With a QMS in place, we find that all these activities can be addressed in their appropriate place during the product lifecycle, and when problems arise, they can be quickly rectified. Ultimately, the QMS can be used to help device manufacturers bring their products to market as much as five times faster and improve their ability to be effective solution providers.
Interesting news coming out of the FDA today, where the agency released a rule that amends its regulations on the definition of a custom device so as to include new statutory requirements under the Federal Food, Drug, and Cosmetic Act (the FD&C Act) as amended by the Food and Drug Administration Safety and Innovation Act (FDASIA).
With this updated revision, a device that meets the qualification of a custom device is now exempt from 510(k) and Premarket Approval (PMA) submissions.
The FDA is saying with this ruling that the new definition of a "custom device" will ensure clarity and consistency among manufacturers who may not be fully aware that some devices do not meet the original definition. Many of these are, and have been, subject to premarket review.
A device will qualify as a “custom device,” FDA says, by meeting new statutory requirements, including, among others, that each device:
Because life sciences companies must have FDA approval to sell their products in the United States, they have to agree to inspections of their facilities, processes, and documents. When FDA officials inspect the facility of a company or review its documentation and processes, they're looking for issues with how a company complies with regulatory requirements. When the FDA finds issues, they will issue a 483 letter which documents and communicates concerns discovered during these inspections.
No one wants to be on the receiving end of a 483 letter, but fortunately the FDA provides a protocol for correcting mistakes and reporting updates. The FDA will ultimately determine whether or not an organization can bring their product to market, so it is wise for recipients of a 483 letter to respond and address their issues. The first thing to understand is that the FDA seeks quality in how companies develop and deliver life sciences products; quality is how those products are created, how documentation and tracking is handled, and how the product is tested and ultimately prepared for the market. The emphasis on quality is where many companies fall short of the FDA's requirements.
While fixing quality issues will delay product development, it is important that, in the process of rectifying their issues, the offending company take measures to respond appropriately in a way that will enable them to continue with their work. It is recommended that the first thing life sciences companies do is address quality as a foundational element of the way they work. That said, some companies will find themselves in a position of neglecting quality issues; hence the 483 letter.
Problems can be fixed, but communication with the FDA must happen first. We strongly encourage life sciences companies to consider the following in how they approach their written response to the FDA:
- Put time on your side: Once you receive the 483 letter, your organization has 15 days to reply in writing. That's plenty of time as long as you create a timeline for how you will respond. This means you must create a timeline, assign tasks for who will provide necessary data in the response, and ensure that reviews and approvals are done so you do not miss the 15-day deadline.
- Be direct, but be humble: You just got served a warning, so it is in your best interest to first acknowledge the reality of the situation. Then, address each issue individually and very clearly. This is not your opportunity to get pedantic or solve problems. Simply detail the problems and show an indication that you are aware of them and eager to fix them.
- Prioritize: As you go through each issue, you should know your business and product well enough to be able to prioritize the issues and communicate that you will address them accordingly. The FDA likes to see that you've given serious thought to their findings and will look more favorably upon your situation if you are candid about what needs to be fixed.
- Accentuate the positives: It is important to emphasize where you're going, not necessarily where you've been. To that end, let the FDA know that you are taking steps to remedy the issues they are concerned about. Include relevant documentation that demonstrates not only a willingness, but actual execution towards finding a resolution.
- Don’t play the blame game: Clearly some problems have been uncovered, hence the letter. However, there's no need to take rehash it all. Simply emphasize the corrective action you will take, and be detailed. This indicates you are working on making things right. If you start to accept fault, you will likely be under even more scrutiny.
- Get on the mend: Be specific about the steps you'll take to correct the issue(s). This should communicate that you are already working on fixes and that you're serious in your efforts to complete product development and testing. An indication of thoughtfulness and purpose will help the FDA understand that you are capable of getting past your hurdles.
- Dispute when necessary: It certainly may be the case that a mistake was made by the inspector. If you think you were unfairly evaluated, explain that in your response. Be diplomatic, and be thorough. Explain the issue that was discovered, provide some background on what you feel may have been missed, and offer something similar to an agreement. Perhaps you'd like to be re-evaluated. Maybe you can provide documentation or proof that the issue in question is actually just fine in its current state. Be direct but tactful.You can also file an official dispute; the one for the pharma industry is straightforward and helpful.
- It actually is all about you: The purpose of a 483 letter is not just to get you to correct problems. If issues exist, it is incumbent upon you and the organization to take a critical look at your processes and correct them so they don't happen again. Consider the 483 letter as a reason to reevaluate how you manage quality, and then improve upon those things that have been problematic. The FDA's Operations Investigations Manual is a helpful tool in learning what they look for and how they expect organizations to adhere to quality standards.
- Ask for help: It may be that you're at a loss for how to move forward. Maybe it's because your quality management processes are not adequate, or perhaps it has to do with being unable to fully understand the scope of the needed corrections. Either way, you only have 15 days to get a response, so you should immediately seek help by contacting FDA headquarters in order to get clarification.
- Plan ahead: After submitting your response, you will need to wait for feedback from the FDA before you can officially move forward. There's clearly going to be a lag, but you should spend that time preparing for the different possible scenarios. You may get the green light to return to business as usual, or you may need to adapt your plans and processes to adhere to a different way of working. Spend time with your team, plan for next steps, and be prepared to retool and re-engage.
It's been a busy few weeks as the FDA continues to approve and release new drugs and various pharmaceuticals products. In recent weeks, the organization has provided updates and approvals for drugs related to Crohn's disease, arthritis, Duchenne muscular dystrophy, as well as alerts and news on a host of related topics.
Some noteworthy items include:
FDA grants accelerated approval to first drug for Duchenne muscular dystrophy: DMD is a debilitating genetic disorder that is manifested in progressive muscle deterioration. Approval for a new drug to treat the disease, Exondys 51, has been granted approval by the FDA.
Avoiding pharmaceutical scams: Interesting video that provides a warning to those in the pharma industry about how to avoid scams.
Amjevita approved to treat inflammatory diseases: Last week, the FDA approved Amjevita (adalimumab-atto) as a biosimilar to Humira (adalimumab) for multiple inflammatory diseases.
Updates on recent drug shortages: A variety of drugs have been discontinued due to shortages, while other previously at-risk situations have been resolved.
Last month, the US Food and Drug Administration (FDA) released a document that provides guidelines and compliance information for companies that manufacture wellness devices. As opposed to devices that are invasive or provide extensive screening or testing capabilities, wellness devices are in a category the FDA considers "low risk", and outlines the classification within the document.