Tag: PMTA

  • FDA Asked to Extend PMTA Grace Period

    FDA Asked to Extend PMTA Grace Period

    Photo: Grispb

    The U.S. Small Business Administration (SBA) has urged the FDA to allow nicotine products to remain on the market for another year while their premarket reviews are in progress, reports Vaping 360.

    In a letter sent to the FDA on June 7, the SBA Office of Advocacy asked the agency to seek a court order extending for an additional year the current freeze on enforcement actions against small vape manufacturers who submitted premarket tobacco product applications (PMTAs) before last year’s Sept. 9 deadline.

    In the current situation, manufacturers who submitted PMTAs on time may leave those products on the market until Sept. 9, 2021. The SBA advocacy office is asking the FDA to request that U.S. District Court Judge Paul Grimm allow the agency to extend the deadline until September 2022.

    Considering the large volume of PMTAs submitted—the FDA says it received more than 6 million applications—It is unlikely that the agency will be able to process all submissions before manufacturers are required to pull their products off the market.

    “Small ENDS manufacturers cannot afford to have their products pulled from store shelves while the FDA continues to review the timely submitted PMTAs for millions of ENDS products,” the SBA writes. “Most small ENDS manufacturers do not have the resources to absorb the losses from having their products pulled from the marketplace for several months or more. Once the FDA orders small ENDS manufacturers’ products removed from the market, those small businesses will close permanently.”

    The letter also urges the FDA to end its current practice of processing PMTAs in order of manufacturer market share. By doing so, the FDA all but guarantees that small vaping companies will be unable to have their reviews completed in time to remain on the market, according to the SBA.

    The SBA is a federal agency that represents the views of small businesses to the various branches of government.

  • FDA Publishes List of Marketing Applications

    FDA Publishes List of Marketing Applications

    Photo: alotofpeople

    The U.S. Food and Drug Administration’s Center for Tobacco Products has introduced a new webpage on its site entitled “Deemed New Tobacco Product Application Lists.” The webpage lists and features 17 MS Excel files that include over 6 million deemed new tobacco products for which a premarket application was submitted to the FDA by Sept. 9, 2020.

    A court order provided for a one-year period during which time such products might remain on the market pending FDA review. If a negative action is taken by the FDA on the application prior to Sept. 9, 2021, the product must be removed from the market or risk FDA enforcement. If a positive order is issued by the FDA on a product in the below lists, the product will be listed on the positive marketing orders page and may continue to be marketed according to the terms specified in the order letter.

    The FDA stressed it has not independently verified the information provided by applicants about the marketing status of their products. In addition, the list excludes entries of products from companies that did not provide information on current marketing status of their products to the FDA so that the agency could determine whether the existence of the application could be disclosed. 

    “It is important to note that the lists are not comprehensive lists intended to cover all currently marketed deemed tobacco products that a company generally might manufacture, distribute or sell without risking FDA enforcement,” the FDA wrote on its website.

    Companies that submitted their application by the Sept. 9, 2020, deadline can keep their products on the market for one year pending FDA review.

    If a negative action is taken by the FDA on the application prior to Sept. 9, 2021, the product must be removed from the market or risk FDA enforcement. If a positive order is issued by the FDA on a product in the lists, the product will be listed on the positive marketing orders page and may continue to be marketed according to the terms specified in the order letter.

    The publication of the list likely signals the start of enforcement. The FDA has already issued 111 warning letters to vapor companies in 2021.

    Stakeholders in the nicotine business have been anticipating the FDA list for months. In September 2020, the FDA stated that it would publish a list of vapor companies that had submitted PMTAs by the Sept. 9, 2020, deadline. The news came just one week after several retail groups submitted a letter to the agency asking for a published list of applicants.

  • FDA Sends its 69th PMTA Warning Letter

    FDA Sends its 69th PMTA Warning Letter

    Photo: Pixabay

    The U.S. Food and Drug Administration (FDA) issued three more warning letters to vapor companies on March 19. The latest announcement brings the count to 69 letters this year for companies selling vapor products without gaining regulatory approval through the agency’s premarket tobacco product application (PMTA) process.

    The latest letters were issued to Arizona-based Vapor Outlet, Vapor Tech Hawaii and the Vaporium in Illinois. In its letter to Vaporium, the FDA stated that the company continues to “manufacture, sell and/or distribute to customers in the United States The Vaporium 6 mg Red White and Blue 70/30 30 mL e-liquid product” without a marketing authorization order.

    “Your firm is a registered manufacturer with 19,860 products listed with FDA. It is your responsibility to ensure that your tobacco products comply with each applicable provision of the FD&C Act and FDA’s implementing regulations,” the letter states. “Failure to adequately address this matter may lead to regulatory action, including, but not limited to, civil money penalties, seizure and/or injunction.”

    Companies that receive warning letters from the FDA have to submit a written response to the letter within 15 working days from the date of receipt describing the company’s corrective actions, including the dates on which it discontinued the violative sale and/or distribution of the products. They also require the company’s plan for maintaining compliance with the FD&C Act in the future.

    Many of the FDA’s letters so far have gone to local vape shops that manufacture their own e-liquids in the store. For example, Vapor Tech Hawaii’s letter states that the FDA has determined that it “manufacture[s], sell[s] and/or distribute[s] to customers its Vapor Tech Hawaii Waikikiwi 100 mL 3 mg e-liquid product” without a marketing authorization order.

    On March 12, the U.S. FDA sent warning letters to 13 firms that manufacture and sell unauthorized e-liquids.

  • FDA Accepts Halo Market Application

    FDA Accepts Halo Market Application

    Photo: Nicopure

    The U.S. Food and Drug Administration has accepted all Halo products’ premarket tobacco product applications (PMTA) for the substantive scientific review phase. 

    Just over six months after submission, Nicopure Labs’ PMTAs for Halo Turkish Tobacco E-liquid, Halo Triton II Starter Kit, Halo ZERO Starter Kit and all supporting consumable components have been accepted and advanced to the final phase, substantive scientific review, by the FDA.

    Halo’s first round of products was accepted and advanced three days after submission.

    “Halo’s more than 12 years of commitment to producing the highest quality vaping products available for adult consumers has been our organization’s mission for more than a decade,” said Jeffrey Stamler, co-founder of Nicopure Labs, in a statement.

    “We believe in science, and we believe in transparency; we are honored to continue to work with the FDA, and as always, in the best interest of the industry and the most important thing of them all, our loyal customers.”

    Halo FDA accepted premarket tobacco product applications include:

    • Halo Tribeca Tobacco e-liquid
    • Halo SubZero Menthol e-liquid
    • Halo Turkish Tobacco e-liquid
    • Halo Fusion Unflavored Tobacco e-liquid
    • Halo Triton II Starter Kit (and supporting consumable components)
    • Halo ZERO Starter Kit (and supporting consumable components)
  • Vapor Voice Publishes PMTA Tracking Tool

    Vapor Voice Publishes PMTA Tracking Tool

    Thousands of vapor companies submitted premarket tobacco product applications (PMTAs) to the U.S. Food and Drug Administration (FDA) by the Sept. 9, 2020, deadline to keep their products on the U.S. market. But which products exactly are under review and how all those submissions have fared in the process is less clear. A comprehensive list promised by the FDA has yet to materialize.

    In the absence of an official database, Tobacco Reporter’s sister publication, Vapor Voice, decided to create its own tracker. As a news outlet, Vapor Voice already receives many press releases relating to PMTA submissions. In addition, its editors continuously monitor corporate websites, social media platforms and other industry sources. Individually, the pieces of information gathered during those endeavors make for interesting news announcements; taken together, they provide a coherent dataset to track PMTAs.

    Of course, this approach has its limits. The data is self-reported, and at present, Vapor Voice cannot fully verify the veracity of all claims made in the announcements used to compile the list. The quality of the information that reaches the magazine also varies greatly, from exact counts in all list categories to more general statements on a brand or brand family without further elaboration. As per Vapor Voice’s protocol, these issues are noted in the list.

    While the dataset should not be taken as a representative sample, it paints as coherent a picture as possible. Vapor Voice recommends using this tool to gain a directional understanding and as a starting point in a comprehensive due diligence search regarding products.

    Check out the Vapor Voice PMTA tracker here.

  • FDA Sends Fresh Round of Warning Letters

    FDA Sends Fresh Round of Warning Letters

    Photo: Jhvephotos | Dreamstime.com

    The U.S. Food and Drug Administration issued warning letters to 18 manufacturers selling unauthorized e-liquids. The companies did not submit premarket tobacco product applications (PMTAs) by the Sept. 9, 2020, deadline.

    The companies that received warning letters include Square Vape Labs, The Vapor Emporium, Tally Ho Vapor Tonic, The Vape Corner., Dripco d/b/a Dripco Vape Co., VaporIce, Vapor Maven E-Juice, Vapor City Plus, Vapor Invasion, Vaporatory, Chuckin’ Clouds Vape Shop, Black Dog Reserve, California Vaping Company, The Chubby Baker, Smooth, Bulldog Vapor, Adore eLiquid and E-Cig Outlet.

    While each warning letter issued cites specific products as examples, collectively these companies have listed a combined total of more than 234,000 products with the FDA.

    Per a court order, applications for premarket review for certain deemed new tobacco products on the market as of Aug. 8, 2016—including e-liquids—were required to be submitted to the FDA by Sept. 9, 2020. For companies that submitted applications by that deadline, the FDA generally intends to continue to defer enforcement for up to one year pending review unless there is a negative action taken by the FDA on the application.

    The FDA recently published an update on its progress on the processing and review of the applications received by Sept. 9, including a list of companies that submitted timely applications.

  • Gold Nuggets

    Gold Nuggets

    Photo: Stokkete | Dreamstime.com

    Gaining insights from the FDA’s final PMTA rule

    By Willie McKinney and Cheryl K. Olson

    On Jan. 19, the U.S. Food and Drug Administration finalized a “foundational rule” about the “minimum requirements for the content, format and review of premarket tobacco product applications (PMTAs).” Within days, before many of us had a chance to download the 516-page document, let alone read it, the rule disappeared. The link says, “page not found.”

    Don’t worry. This is part of a normal review by the incoming Biden administration of recent rules from the old regime. Given that little FDA staff turnover is expected, their thinking, and the rule, will probably stay the same. The document will be back, nicely formatted.

    What to do while we wait for the final-final rule to appear on the FDA’s site? Well, the bulk of the document addresses “about 1,000 comments” (!) the FDA received on the proposed rule issued in 2019, including many questions from industry folks confused about PMTAs.

    Understanding the subtleties and subtext of the FDA’s responses to comments can dramatically increase your chances of getting a marketing granted order. Ignoring them can lead to a significant waste of time and money.

    Let’s wade into the FDA’s responses and see what gold nuggets of insight we can pan. What fuzzy areas affecting your strategy are now clear? What costly studies or paperwork might be trimmed or skipped?

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    A PMTA is not a box-ticking exercise

    We can begin with how the FDA thinks and what that means for PMTA strategy. Remember, interacting with tobacco product makers and sellers is still relatively new for the FDA’s staff and consultants. As they read comments, held conversations and began reviewing the recent flood of PMTAs, they realized that companies couldn’t figure out what the FDA was asking for. We know this because the PMTA rule lays out, much more clearly than in previous documents, what the FDA needs from companies. There are details on required content and format. The rule contains dozens of “musts”—must list, must include, must state and so on.

    The FDA also says what can happen if you don’t meet minimal requirements: Do this, and we won’t accept or file. Or: This will slow the review process. Think of it as a series of red lights (“FDA will refuse to accept a PMTA … where it lacks constituent testing information required by § 1114.7(i)(1)(v)”) and yellow lights (“FDA may refuse to accept or file an incomplete application for review”). All of this is welcome clarity.

    That doesn’t mean, as we’ve heard it described, that having a PMTA accepted and filed is a check-the-box exercise. Parts of a PMTA are like that, but the substantive review of data definitely is not.

    Many of the comments to the FDA hint at frustration. “Why can’t they just tell me what studies to do so I can market my product?” The short answer is that a PMTA is partly a checklist of required information, but it’s also a narrative. You’re telling a story about why your product is appropriate for the protection of public health (APPH), illustrated by data. An effective PMTA is driven by story—explaining why your product on balance is likely to benefit public health—and merely organized by the PMTA format. 

    If you try to follow the rule document like a cookbook recipe—add a cup of pharmacokinetics (PK) studies and a tablespoon of label comprehension, and it’s baked—you will likely fail. That’s because the rule is descriptive but not prescriptive; it doesn’t tell you how to deliver. Why? First, because each product is different, with its own particular characteristics and target customers and therefore a distinctive set of potential public health benefits and risks that need to be demonstrated or mitigated. Second, a how-to list would tie the FDA’s hands as they make and rethink decisions about what is APPH. In Response 105, the agency notes that “Due to the nature of the Federal rulemaking process … FDA may not be able to update such standards in a timely manner.”

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    Expect APPH to evolve

    APPH is about relative health risks; it’s about “net benefit to the health of the population as a whole.” A definition like that, based on comparing ever-evolving tobacco products, will create a moving target. See FDA’s Response 123: “Because market conditions will change over time, what might be APPH at one point in time may no longer be APPH in the future.”

    A static approach for granting marketing orders means the FDA couldn’t keep riskier products off the market, “thus undermining its core statutory mandate to reduce the harm caused by tobacco product use.” Basically, if you can show that your novel tobacco product is less risky than today’s cigarettes, that’s great. But as more tobacco users move to reduced-risk products, both the comparators and the risk equation will change. And if your tobacco product has, say, slightly more of a potentially harmful chemical than others in its category, adding your product to (or keeping it among) consumers’ options is not reducing harm.

    Save with bridging, bundling and master files

    Another reason the FDA “declines to require that an applicant conduct a list of new studies as part of every application” (Response 59) is that shortcuts are allowed. Applicants can also “provide scientific data to inform FDA’s review” through bridging. Rather than generating all new data on your product, you can sometimes leverage the research literature to show your product is APPH. Just a little new data connects you to more.

    Suppose you show from chemistry that your product releases nicotine in the same way and has the same nicotine concentration as another product already tested in published literature. That may let you bridge to their PK and abuse liability studies, saving you hundreds of thousands or even millions of dollars. In Response 62, the FDA “declines to define” bridging but instead gives useful examples of how to do it.

    Another cost-saving and time-saving shortcut is bundling or combining applications. Let’s say that you have four flavors or two nicotine strengths. The FDA sees them as separate products. But the FDA allows you to submit one PMTA for all of them. A bundled PMTA includes “a single, combined cover letter and table of contents across all products” (Response 19).

    You still need to provide unique information about each product, but you can collect and present it more efficiently. For example, you might conduct and present one bundled perception and intention survey that asks noncustomers about perceptions of the labeling of each of your four flavors in turn. But be aware that the FDA will break up your bundle for review, so list in tables which parts of the PMTA apply to which products. 

    Bundling isn’t always best. Are your harm reduction story and target audiences the same across products? A high nicotine vape may appeal to a heavily addicted smoker, but it has different health implications than a lower nicotine sister product. Combining the two into one PMTA might muddy your case for APPH status.

    A third PMTA shortcut to know about is called a tobacco product master file (TPMF). A master file contains information you can reference again and again for multiple applications. In Response 17, the FDA defines a TPMF as “contain[ing] trade secret and/or confidential commercial information about a tobacco product or component that the owner [e.g., manufacturer, ingredient supplier] does not want to share with other persons” but is willing to share with the FDA. That’s useful if your new tobacco product uses an e-liquid made by a manufacturer who doesn’t want to share their formulation but who will give you a letter of authorization to cite their master file in your PMTA. 

    There are other TPMF options. “When companies want to rely on the same pool of data, FDA encourages the use of shared resources, such as tobacco product master files, where appropriate” (Response 18). This might be the fruits of a thorough literature review on a particular topic. Rather than cite and submit 150 articles over and over, you can reference the master file.

    More information is not always better

    PMTA applicants now need to provide “only high-level marketing plan information” (Response 30) rather than detailed consumer research. The FDA’s main concern is youth exposure. It emphasizes descriptions of intended audiences and how they’ll be targeted. Note, however, that if you have already done consumer research, “the results of such research will be required” to go to the FDA. 

    As Comment 14 notes, “the tobacco industry has a history of marketing its products to … vulnerable populations,” which may include low-income communities, racial/ethnic minority group members, rural residents and youth, among others. Your PMTA story should include how your product might improve (or not worsen) the well-being of some of these vulnerable populations. Harm and benefit to subgroups that are more likely to start, less likely to stop and/or more likely to get sick from using tobacco products “are an important part” of the FDA’s APPH calculations. Groups of interest “will vary depending on type of tobacco product and may change over time.”

    However, the FDA does not clearly state that conducting research with some of these subgroups is unethical or unsafe. This includes people under the age of 21 and women “who are pregnant or trying to become pregnant.” (The document mentions the need for special attention to vulnerable populations, including children and incarcerated persons, when discussing FDA plans to issue future regulations concerning use of Institutional Review Boards for tobacco product clinical studies.)

    In Response 79, the FDA allows for “studies using individuals under the minimum age of sale” with extra protections and parental consent but “does not require it [or] anticipate that it will be necessary.” Don’t go there. Instead, over-sample young adults in your studies as a proxy for youth. Report, for example, whether intentions to use your product were different for people under age 25 compared to the rest.

     

    Cheryl K. Olson is a California-based public health researcher and consultant who specializes in behavioral health issues. She spent 15 years on the faculty of Harvard Medical School.
    Willie McKinney is the founder of McKinney Regulatory Science Advisors. He’s held senior regulatory roles at major tobacco product companies and served for three years as the industry representative on the FDA’s Tobacco Products Scientific Advisory Committee.
  • FDA to Prioritize Bestsellers’ PMTAs

    FDA to Prioritize Bestsellers’ PMTAs

    Mitch Zeller (Photo: David Parker)

    In reviewing premarket tobacco product applications (PMTAs), the U.S. Food and Drug Administration is prioritizing products with the greatest market share where scientific review will have the greatest public health impact, the agency said in a Feb. 16 update on its website.

    As of mid-January, the FDA had completed the processing step of applications for more than 4.8 million products from over 230 companies. “We have accepted applications for about 84,000 products and refused to accept applications for about 3,100 products submitted through the PMTA pathway,” wrote Mitch Zeller, director of the FDA Center for Tobacco Products. “As of mid-January 2021, of the applications submitted by Sept. 9, we have filed applications for about 29,000 products and refused to file applications for about 1,650 products submitted through the PMTA pathway.

    According to Zeller, the agency’s progress has been slowed by the great variety of ways in which applicants submitted their PMTAs. For example, some applicants provided information on one product per submission while other applicants provided information for all of their products within one submission.

    The FDA is prioritizing enforcement against electronic nicotine-delivery devices (ENDS) that continue to be sold and for which the agency did not receive a product application. To date, the FDA has sent warning letters to 30 firms selling ENDS products, specifically e-liquids, without premarket authorization.

    The agency also stated that the likelihood of the FDA reviewing all the applications by Sept. 9, 2021, is low. Because of the sheer number of applications, the agency has set aside the products with the greatest market share and will push those products through the process more quickly. “[We will] focus resources on products where scientific review will have the greatest public health impact, based on their market share, while also committing to providing an opportunity for review to all companies,” Zeller wrote.

    The FDA could not confirm when it would release a list of products that are approved to be on the market. Zeller wrote that the agency continues to work on processing submissions and verifying the dates of initial marketing and current marketing status of products that submitted a timely PMTA.

    “We have already verified this information for around 86,000 products received through the PMTA pathway,” he wrote. “Due to the size and volume of the PMTA submissions and the variable quality, format and presentation of these submissions, processing these submissions and verifying this information will take more time.”

  • Hall Analytical Offers PMTA Webinar

    Hall Analytical Offers PMTA Webinar

    Photo: Bacho | Dreamstime

    Hall Analytical is offering a virtual seminar on Feb. 11, 5-6 pm GMT about the U.S. Food and Drug Administration’s premarket tobacco product application process.

    E-liquid and device manufacturers will have an opportunity to take part in a live Q&A session with subject matter experts.

    Panelists include David Lawson, CEO, Inter Scientific; Patricia Kovacevic, founder and principal, Regulation Strategy; and Sally McGuigan, principal scientist, Hall Analytical

    This session is limited to the first 50 registrants, and therefore places will be offered on a first come, first served basis.

    Participants can register here.

  • Broughton Publishes Summary of Final Rule

    Broughton Publishes Summary of Final Rule

    Illustration: Broughton Nicotine Services

    Broughton Nicotine Services has published a summary of the U.S. Food and Drug Administration’s rule for the premarket review of new tobacco products.

    Released on Jan. 19, the FDA’s final rule makes amendments and recommendations to the previous rule and helps ensure that PMTAs contain sufficient information for the agency to determine whether a marketing granted order should be issued for a new tobacco product.

    The purpose of the rule is to improve the efficiency of the submission and review of PMTAs as well as providing applicants with a better understanding of the information a PMTA must contain.

    Amongst other topics, the rule addresses:

    • The submitting of detailed information regarding the physical aspects of the new tobacco product and full reports of information regarding investigations that may show the health risks of the new tobacco product.
    • Whether the product presents the same or different risks compared to other tobacco products. The FDA requires the submission of these health risk investigations to ensure it understands the full scope of what is known about the potential health risks of a new tobacco product.
    • Electronic submission of the PMTA.
    • Post-market reporting requirements for applicants that receive marketing granted orders.
    • Retention of records requirements for PMTAs
    • Procedures by which the FDA reviews a PMTA

    Broughton Nicotine Services summarized the 516-page recommendations and requirements report into a digestible guide, which is available for download here.