Predictions for the New Year: A Crystal Ball Insight into Path to Market

As a business owner in the medical device industry who works with a range of clients developing a variety of devices, I wish I had a crystal ball I could consult for each one. I’d pierce the veil of mystery covering the path to market and foresee every potential pitfall to ensure quick and speedy success for all of the wonderful people I work with.

Sadly, my crystal ball is in the shop. Instead of psychic abilities, I rely on my 20-plus years in the medical device industry and the work I’ve done for and with the U.S. Food and Drug Administration (FDA) when telling clients what they can reasonably expect on their orthopedic device development journey. So I can accurately predict that almost all of them will express concern that the FDA will be one of the most significant roadblocks they’ll encounter along with issues pertaining to reimbursement.

But the FDA is only one part of the process, and reimbursement is a topic worthy of its own article. Through the Empirical family of companies, we deal with a range of entities in the medical device industry: FDA, ASTM International, the Entrepreneurs in Residence Program (EIR 2012-2013), the Experiential Learning Program (ELP in 2015), and various other training and conference opportunities.

From what I’ve seen in the orthopedic/spine division and 510(k) clearance pathway, the FDA has worked hard to change the paradigm and perception of being a roadblock in the clearance process. Reviewers and other team members are an integral part of the success of safe and effective devices entering the market. There is a constant evolution of tools including guidance documents, feasibility programs, feedback mechanisms, and more that offer medical device manufacturers transparency and consistency in the clearance and approval process.

So in a sense, the FDA is offering us a crystal ball by sharing with us common mistakes, easy paths, and current topics/technologies. For example, the FDA compiles and shares information about the Refuse To Accept (RTA) and submission process. Similar information exists for special 510(k) submissions and premarket approval (PMA) applications as well. If you have a device that falls into one of those categories, look up the appropriate reference information or contact me directly so I can help you find it.

For the 510(k) program under Medical Device User Fee Amendments (MDUFA) III, a 510(k) submission has multiple general steps in the process: RTA decision, interactive review and/or official correspondence, and final decision. It does not take a brain or orthopedic surgeon to master that process. Here is the FDA’s list of most common mistakes:

• Include a copy of the checklist with page numbers.¹
• Make sure the 510(k) summary meets 21 CFR 807.92 and includes appropriate product codes.
• Cite any relevant previous submissions (if there are none, state “NONE”).
• For the device description, provide a complete list of compatible components and accessories (instruments) with the corresponding 510(k) number in a table format.
• For sterilization validations, be clear about which components are sterile vs. nonsterile and indicate that the validation complies with the relevant standards.
• When addressing device shelf life, always include the proposed shelf life (with a summary of the methods used to establish said shelf life) or a statement that no shelf life is proposed for nonsterile devices.
• For performance data, provide data that correlates to the specific device or cite the guidance documents for characterizing the device.

Before receiving a substantial equivalence decision for your device, there may be an interactive review and a receipt of deficiencies on your submission. Bear in mind, your reviewer only knows what you present. We’re not the only ones wishing we had crystal balls. The more detail you can provide to help the reviewer understand the background, scope, and depth of your device and processes, the easier that person’s job will be and the better your review will likely go. For an interactive review, know the types of communication you will receive from your reviewer² and how much time you have to resolve the issue at hand (a sponsor typically has about five days to respond to any remaining deficiencies). The top three most common 510(k) deficiencies include: non-equivalent preclinical testing results as compared to the predicate device (your device is not as strong as the predicate device); discrepancies in the device description, parts listing and/or engineering drawings; and sterility and cleaning issues.

The devil is in the details, not in our imaginary crystal ball. The most predictable issues to be reconciled in a submission include:

• Substantial equivalence comparison between devices in different classifications (e.g., intervertebral body fusion devices and vertebral body devices);
• Lack of dimensional and technological comparison between the subject and predicate devices;
• Lack of justification for the worst-case component testing (how you determined the size you tested represents the worst case for the family of devices); and
• Unsubstantiated and/or ambiguous claims.

One advisor at the FDA told me most of the pitfalls for sponsors they encounter are issues of common sense. I strongly encourage all of my clients to perform a gross reality check on the submission before sending it off to be scrutinized by its most important reader.

The FDA is an evolving organization composed of human beings and learning is continuous. Processes, presentations, and information from the past—whether 30 years, three years, or even three months ago—may not be applicable today. Just because you were successful with a similar submission a year ago does not mean the same information will now be sufficient to establish substantial equivalence. This doesn’t mean the rules are changing at the FDA; it means the FDA is applying knowledge gained to improve device and/or patient safety. It’s constantly synthesizing new information via clinical outcomes, evaluation of new technologies, publications, etc. It’s also constantly evaluating and publishing information about new tools (such as pre-submission meetings³ and guidance documents⁴ in an effort to be transparent and approachable in this process of working together with sponsors. But as a sponsor, can you meet the requirements of a repeatable process? Are you asking the right questions about the specific topic of discussion?

There are a few topics pinging on the FDA radar, but the crystal ball gets a little cloudy here. My sources at FDA tell me currently they’re scrutinizing:

• Cleaning and sterilization validation: What methods and materials were used in your validation?
• Color additives: Colors change regularly (due to other industries), and a color additive from the past may no longer exist. Its current counterpart may no longer be biocompatible.
• MRI compatibility: Think about the questions you are asking and make sure that you, as the sponsor, are taking proper steps to ensure the patient and other personnel in the room are not at risk during an MRI procedure. Specify if your device is safe, conditional, or not tested.
• Unique Device Identification (UDI): Yes, this is happening. Communicate with the FDA and understand your responsibilities and options. Timelines for this are closing in and as the sponsor, you are responsible for the UDI activities of your implants and instruments.
• 3-D printed devices (including custom devices): Understand that if you change the material properties, the system has to be reevaluated; processes have to be revalidated and shown they are reproducible. If there is a mix and match of materials, corrosion is something else that has to be evaluated. If, as the sponsor, you use 3-D printed materials as a custom device, you must have an informed consent from each patient as you collect data. It would be wise to assess the pros and cons of this regulatory approach.

So what is our imaginary crystal ball really showing us? Use sound science, FDA resources, and common sense. Be aware of common mistakes in submissions and avoid them. Know the latest conversation topics at the FDA. Stay current with available tools and new guidance documents published by the FDA. The agency’s reviewers want sponsors to be successful, and everyone wants safe and effective devices on the market to extend and improve the lives of end users. When we all work together, that’s what we achieve. 

Footnotes

1. http://www.fda.gov/downloads/medicaldevices/deviceregulationandguidance/guidancedocuments/ucm315014.pdf
2. http://www.fda.gov/RegulatoryInformation/Guidances/ucm341918.htm
3. http://www.fda.gov/downloads/medicaldevices/deviceregulationandguidance/guidancedocuments/ucm311176.pdf
4. http://www.fda.gov/RegulatoryInformation/Guidances/

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Dawn Lissy is a biomedical engineer, an entrepreneur, and an innovator. Since 1998, the Empirical family of companies has operated under Lissy’s direction. She has been responsible for all Empirical operations, including designing test fixtures and protocols, running test protocols, and writing complete reports. She holds an inventor patent for the Stackable Cage System for Corpectomy and Vertebrectomy. She is a member of the Biomedical Engineering Society, Society of Women Engineers, the American Society of Biomechanics, and the ASTM. She holds an M.S. in biomedical engineering from The University of Akron, Ohio. She can be contacted at [email protected].