Avomeen understands submitting a PMTA can be a challenging process. So much of it is uncharted territory and with so many viewpoints, where can e-liquid manufacturers and distributors look to receive accurate, non-biased information?
Avomeen recently spoke with Marc Sanchez, an attorney who specializes in FDA and USDA regulations, to help break down a PMTA submission. In addition to speaking to Sanchez for a legal perspective, we spoke to one of Avomeen’s in-house subject-matter-experts, Derek Beauchamp, Ph.D. With both a legal and scientific perspective, we aim to shed more light on the full PMTA submission process.
Key Components of the PMTA
The top and most important components of a PMTA submission according to Marc Sanchez is a literature review in lieu of clinical data, the analytical testing component, an environmental assessment and information in various modules describing the device (or e-liquid) and providing any necessary details or specifications in regards to manufacturing.
The analytical testing component includes:
- HPHC Testing
- Looking for a defined list of chemicals provided by the FDA that may be present in an e-liquid.
- Stability Testing
- Testing of HPHCs over the relevant shelf life of your product. This ensures the product is the same throughout the entire lifecycle of the product.
- Extractables and Leachables Testing
- Testing the components of the packaging, container, and container closure to ensure no components find their way into the product as it is consumed by the user over the life of the product.
Data generated throughout analytical testing above by the lab is used to not only support those specific sections but also supports sections such as the toxicology review and potentially the environmental assessment.
The Manufacturer’s Role
The manufacturer too is a key part in submitting a PMTA. “Working with manufacturers has definitely been a learning curve. There are good manufacturers who communicate extremely well, provide necessary information quick and efficiently,” says Sanchez, “Some manufacturers are a lot slower and need more handholding which can slow down your submission.”
Derek Beauchamp also adds, “Making sure the manufacturer is good at communicating is more important than some may think. If they’re bad at communicating to you, imagine how tough it is for the lab to work with them to get the necessary information to complete your testing.”
A lot of details come from the manufacturer including specifications or schematics related to your product or device, how your product is made from beginning to end, and one of the FDA’s most sought-after pieces of information, how manufacturers control quality.
Open Versus Closed Device Filing
Sanchez mentions the skepticism towards closed, disposable devices from the FDA, stating that “because they’re newer and the overall marketing towards youth is a big deal. It’s the main difference in an open versus closed device filing.”
Youth prevention is one of the main requirements of a closed device filing. Simply because the FDA believes these types of devices are more accessible and attractive to youth, whereas open devices demographics are more of people seeking showmanship or overall vape connoisseurs. However, there are challenges that come with open systems. The unlimited amount of customization, particularly with various modifications or accessories is a variable that worries the FDA.
E-Liquids Versus Device Filing
Filing for e-liquids is completely different than filing for devices and devices sold that include an e-liquid is different than devices altogether. “In an e-liquid application you will have more information and data relating to the formulation, whether it is to be used in an open or closed device and the differences in manufacturing,” says Sanchez.
Sanchez also noted that many custom vape shops who create their own blends struggle to submit PMTA’s. Those custom blends or create your own in shops all require PMTAs. As much as it is both challenging and costly, he’s seen it done before.
Pre & Post 2016 Market Status
Companies that started creating products after the 2016 Maryland ruling are in a gray area. According to Sanchez, “the FDA will not put you on the safe list (like pre-2016), but they have not formally pushed to remove companies in non-compliance from the market.” Whereas, pre-2016 companies are allowed to stay on the market for at least one year while they wait for the review of their PMTA submissions. Sanchez does believe that it is still early and that the FDA may more strictly enforce compliance in the future in regards to PMTA submissions.
“Regardless of when your company was founded, your PMTA submission will be the same and treated equally,” says Sanchez. The PMTA isn’t going anywhere and each company will be treated the same during the review of their submission.
Preparing My Submission for the CTP Portal
Although submitting through the CTP Portal is an option, it is preferred by the FDA compared to a paper or thumb drive submission. First and foremost, make sure you request access to the CTP portal. To request access, you have to agree to follow the rules of behavior and sign a document stating you have the legal right to sign on behalf of the company you’re submitting for.
Once you receive access, it’s not like an email where you can click and attach. The submitted file must be an e-submitter validated zip file. The e-submitter program walks you through while files are needed. It then validates your files and zips up the folder to be uploaded to the CTP portal. Sanchez does warn about using any special characters in file names including exclamation points or scientific symbols. “It won’t validate if you use any of those, so be careful,” says Sanchez.
Once you’re ready to submit, log in to your CTP account and upload to the designated area. If you’re filing on your own without the help of an attorney, consultant, or lab, do not be in a rush. Sanchez jokes, “The programs are a bit clunky, a bit dated and can be tricky at times. Even getting access to the portal itself may take weeks, so plan accordingly.”
Beauchamp mentions that even though the attorney or consultant is largely responsible for submitting on the CTP, testing labs are responsible for the tobacco product master file or TPMF. “The TPMF contains our analytical methods, validations, validation reports, and any other confidential information that is proprietary to the lab completing the testing,” states Beauchamp. “This information is used by the FDA to understand and interpret the data resulting from our testing.”
I Submitted, Now What?
You will first receive confirmation from the CTP or a confirmation that your delivery has arrived at the FDA. Then there are two phases of review before the actual decision-making review.
- Acceptance Review
Acceptance review makes sure it is a product that falls within the boundaries of the PMTA. This is a very high-level review.
- Filing Review
During a filing review, your submission is double-checked for the contents such as the environmental assessment, a literature review, etc. Sanchez suggests including a cover letter with a summary and a table of contents to help out the FDA. This allows them to quickly confirm the submission is all there.
After those two steps, your submission is sitting with a reviewer for at least six months, maybe longer, for a substantive review. The FDA will follow up with any possible questions or requests for additional information or data needed. Whether you get an acceptance or refuse to accept, the FDA will reach out either via phone or via overnight carrier. If you get a refuse to accept, the FDA will most likely contact you to fix the issues in hope of an approval.
Finding the Right Partner for Your PMTA Submission
What’s the difference in a good lab? How do you find the right partner? Derek Beauchamp has a few tips and tricks to finding the best fit for your submission.
He says, “Working with a lab, such as Avomeen, that has strong expertise as well as relevant and necessary experience is crucially important. Having the experience in the analytical product testing space, but as well with interactions with the FDA helps expedite the testing process and aid in remedying any potential deficiencies or questions.”
Labs that have experience with the FDA and submitting PMTAs should be your top priority when looking for a partner. Additionally, he believes the first question you should as a potential partner is their background on these types of products and the testing. Seeing examples of their work, hearing about their relationship with the FDA and making sure they understand the data requirements for the PMTA are all a very good start.
Beauchamp also says to make sure the team of scientists working on validating these methods and working with the data have the correct experience to benefit your project. The lab should be in it for the long haul, not just completing the testing and sending over your numbers.
“A thorough lab will be there for questions, additional work and most of all, there to support your PMTA application through the very end,” says Beauchamp.
Worried about receiving a deficiency letter from the FDA? We’ve got you covered! Check out our blog, FDA Deficiency Letters: What Do I Need to Know?
Interested in learning more about the analytical testing Avomeen provides their PMTA clients? Our On-Demand Webinar, PMTA Strategy: A quick and effective approach to product selection, may be of interest to you.
If you haven’t received marketing authorization for your product yet, read up on our blog: FDA Issues Warning Letters for E-Liquid Products without Marketing Authorization.