Tag: Broughton Nicotine Services

Best Practices
Photo: doidam10
How to approach environmental assessments for the best chance of success
By Adam Bonin and Antony Jones
An Environmental Assessment (EA) is an analysis prepared in accordance with the U.S. National Environmental Policy Act (NEPA) to determine if a product’s approval would significantly affect the environment. It applies to all federal actions in the U.S., including regulations, policies, projects, licensing and permission granting. The assessments give insights into potential risks associated with a product’s manufacture, use and disposal and help manufacturers develop effective mitigation strategies to reduce or avoid possible environmental consequences.
EAs therefore help regulatory agencies identify potential adverse environmental impacts from the manufacture, use and disposal of electronic nicotine-delivery systems and oral nicotine products. They are a small yet important part of premarket tobacco product applications (PMTAs) and modified-risk tobacco product submissions. The U.S. Food and Drug Administration requires manufacturers to submit EAs for each individual tobacco product, or stock-keeping unit, within a PMTA.
An inadequate or absent EA will result in either a “refuse-to-accept” or a “refuse-to-file” order from the FDA. In 2021, the FDA rejected 4.5 million vaping applications on the grounds that they “lacked an adequate environmental assessment.” With companies spending millions on PMTA submissions, they cannot afford to miss out on approval due to such a small part of the process. So, what does a good EA look like?
What to Include in an Environmental Assessment
In general, an EA includes an executive summary, applicant details, description of the proposed action and purpose and need of the proposed action. Further EA sections include the identification of alternatives, including the proposed action and no action alternative, potential environmental impacts of the alternatives (affected environment [or existing conditions] and environmental impacts), cumulative impacts and mitigation measures. An EA is appropriate for submission if it is determined that the impacts of the proposal will not be significant or the FDA concludes a finding of no significant impact. Mitigation measures may be recommended if impacts are anticipated, to reduce them below the significance threshold.
The initial stage of the EA process is building a well-defined project description, covering the purpose and need for the regulatory decision (marketing granted order) that triggers the requirement for an EA under the NEPA. The applicant will also need to include details of product components, product formulation (where applicable) and predicted sales projections for the first and fifth years. It is particularly important to include the mass of individual metals in product hardware components (e.g., devices, pods) to assess potential impacts at the end of life.
A good EA includes a thorough screening and comprehensive modeling of product components (e.g., e-liquid ingredients), with all conclusions and results backed up with hard data. The evaluation of the potential release of materials to the environment should be quantitively assessed, with the resulting potential concentrations in the environment explicitly stated and compared with relevant ecotoxicity standards to determine the possible impact.
Throughout, it is important to appropriately manage confidential information. EAs include both confidential and nonconfidential appendices, and it is important that these are prepared correctly. For example, if there is proprietary information in the e-liquid formulation, this would be best listed in the confidential appendices, as would sales and marketing projections. It can be difficult to know which information is appropriate for inclusion in the confidential apprentices, and working with an experienced team offers the best chance of success.
Determining the Possible Impacts
E-liquids typically consist of a mixture of ingredients, including propylene glycol, vegetable glycerin and nicotine. The formulation can be screened using a predictive tool to determine which ingredients are of most ecotoxicological concern and should be carried forward into the analysis. The selected ingredients can be assessed for estimated acute and chronic aquatic toxicity for aquatic organisms, including plants, fish and invertebrates, and then be assessed in subsequent fate and transport modeling.
The EA should analyze the plausible scenarios for the impact of the identified substances being released into the environment, including quantitative release modeling. For example, this could include the possible impact of the material being released into surface water or soils at quantities considered reasonable based on predicted sales data.
The project supply chain should also be documented, including details of manufacturing and shipping to retail entities. The environmental and social resources around U.S. manufacturing facilities require characterization to provide an understanding of the affected environment (existing or baseline conditions). The potential impacts of projects can then be evaluated based on changes to the baseline conditions—for example, if chemical mixtures or raw ingredients are accidentally released into surface water or chemicals are released down the drain during manufacturing.
It is important that the EA is realistic. In our experience, the inclusion of conservative analyses appears to be the soundest approach. It may be tempting to conduct modeling for a wide variety of release scenarios, but if they are deemed unlikely by the FDA, you may receive a deficiency for evaluating unreasonable scenarios.
Tips and Tricks
Start early. Considering the EA process early in the application can improve efficiencies, particularly for characterizing natural resources around U.S.-based facilities and engaging with manufacturers and other vendors to understand product supply chains.
Use a robust standard operating procedure. In an EA, it is vital that every section includes explicit information that satisfactorily evaluates the product against FDA requirements.
Choose an experienced team. Many businesses do not have employees with sufficient NEPA experience; in this case, we recommend working with a consultancy. NEPA-specific jargon and other regulatory nuances can be challenging for new practitioners.
Stay up to date. Attending FDA and NEPA meetings can be a great way to stay up to date with any changes in the guidance. In addition, manufacturers can engage directly with an FDA project manager if they receive deficiency comments.
Adam Bonin is a senior consultant at Broughton with over 22 years of scientific consulting experience. He earned a Bachelor of Science degree in environmental management from the University of Rhode Island and a doctorate in environmental microbiology from Portland State University. Bonin also completed a postdoctoral appointment in microbial ecology at Oregon Health and Science University.

Antony Jones is a managing consultant at Broughton with more than 22 years of experience in risk assessment with a focus on characterizing and reducing risks across the pharmaceutical, biotechnology, food, nicotine and environmental industries. He earned a Bachelor of Science degree in biology from the University of York and a doctorate in molecular biology and microbiology from Newcastle University. Jones also completed a postdoctoral appointment at King’s College London.

Broughton is a global scientific consultancy-based Contract Research Organization serving industries in pharmaceuticals, next-generation nicotine-delivery products and cannabinoids. Its team has developed a robust and proven approach for preparing defensible NEPA-compliant EAs for the FDA PMTA. For more information, visit www.broughton-group.com/us-pmta-and-mrtp-nepa-environmental-assessments-ea.
July 1, 2023
Broughton Restructures for Growth

From left to right: Paul Moran, Nveed Chaudhary and Chris Allen
Contract Research Organization Broughton is restructuring its operations to prepare for growth.
Founder and CEO Paul Moran will transition to the role of executive chairman to further grow Broughton’s global capacity, focusing on expanding the company’s existing U.S. team. Co-founder and Chief Scientific Officer Chris Allen will become CEO on Jan. 1, 2022. Chief Regulatory Officer Nveed Chaudhary will take up the position of chief scientific and regulatory officer.
‘’Since 2006, our focus has always been to help our clients succeed,” said Moran. “With a passion for enhancing societal health and wellbeing, our expertise across harm reduction and next generation products now covers the broad life science industries of pharmaceuticals, nicotine containing products and cannabinoids. This next phase of our expansion is part of our natural evolution to grow capacity and capabilities. I’ll continue to focus my energies on new markets and early initiatives.”
“The recent changes to our management team reflect our continued commitment and ambition to become the most trusted integrated services provider in the world,” said Allen. “Our additional investment plans into global operations will enable us to expand our services for clients across the nicotine, pharmaceutical and cannabinoids markets, always with a focus to help clients deliver life-enhancing products to market.”
December 16, 2021
Rules Of The Road
Photo: DW labs Incorporated
What manufacturers should know about the medical route for vapor products to the U.K. market.
By Lloyd Smart
E-cigarettes, and the regulations surrounding them as medicinal products, were thrust into the national spotlight in the U.K. with the news that the National Health Service (NHS) could look to prescribe them to smokers in the future.
The U.K. has set a target to be smoke-free by 2030, and supporting smokers in switching to less harmful methods of nicotine delivery has largely been met with a positive reaction.
Yet, the opportunity to register nicotine-containing products as medicines in the U.K. has always been in existence.
Broughton was involved in the first electronic cigarette to be licensed in the U.K. as a medical product in 2015, the Voke. The e-cigarette, which underwent testing at our facility, was a milestone in the electronic nicotine-delivery systems (ENDS) world but was never launched.
The recent press release by the Medicines and Healthcare products Regulatory Agency (MHRA) underlines the medicinal route for manufacturers and sets out the guidance on offer for those who want to take it. The expanded guidance is a positive step to encouraging larger take-up that could lead to general practitioners (GPs) prescribing e-cigarettes—and greater numbers of people quitting tobacco completely. Of course, the outcome of a GP appointment lies in the choices made by the GP or nurse practitioner, and it may be that work needs to take place to change perceptions of ENDS products within the NHS.
It is interesting to note that Brexit has paved the way for the U.K. to somewhat diverge from European legislation, a clear indication that the U.K. is pioneering this approach and moving forward on its own.
The requirements of the MHRA’s application process are stringent but well understood, with timelines for the approval as a medicine likely longer than a consumer product. Yet there are benefits to be had for those whose products make it through this pathway.
While it may be a more detailed route, classing a product as a medicine comes with confidence for the end user that it meets defined standards of quality, safety and efficacy, and this layer of trust could make the difference in attracting more smokers to make the switch, which is undoubtedly a positive.
The medicinal route allows for a much higher strength of nicotine too, not to mention the ability to market products slightly differently.
The MHRA authorization may also arguably result in a price premium for those products that make it through the process, making it an attractive prospect for manufacturers.
Certainly, a holistic view of the available regulatory pathways should be discussed upfront, something an integrated consultancy such as Broughton builds into every project, and certainly before data begins to be generated or submissions compiled.
So, what do manufacturers need to know about the MHRA’s updated guidance?
Overall, the guidance has been expanded somewhat from about 14 pages to nearly 17, and the MHRA has provided expectations in the key areas of quality, safety and efficacy.
The overriding message is still that “The MHRA seeks to encourage the licensing of electronic cigarettes (e-cigarettes) and other inhaled NCPs [nicotine-containing products] as medicines and aims to support companies to submit marketing authorization applications for these products.”
There are other changes for potential applicants to consider:
The guidance name has been updated to “Guidance for licensing electronic cigarettes and other inhaled nicotine-containing products as medicines” and now clearly references other inhaled NCPs outside of e-cigarettes.
References throughout have been updated to U.K.-specific articles/regulations, for example, UKCA marking is now mentioned, and the U.K. Human Medicines Regulations (2012) replaces EU Directive 2001/83 for the legal basis.
The U.S. premarket tobacco product application (PMTA) pathway (via the Food and Drug Administration) is now specifically noted, and the MHRA states, “For applicants with products undergoing the U.S. FDA premarket tobacco product application (PMTA) process, the MHRA can discuss what data may be relevant for a U.K. marketing authorization application.” There is, therefore, potential to share/bridge data from other applications.
The new 150-day (national) accelerated procedure for the assessment of high-quality applications is noted. This could potentially shorten the processing time from 210 days down to 150 days, excluding clock-stops, for the marketing authorization application (MAA).
Updated references to test equipment and methodology for a “vaping machine” have been replaced with BS ISO 20768:2018.
There are clear expectations to provide “analytical chemistry data” to confirm the compounds present in the vapor produced by an e-cigarette device under its normal operating conditions.
The nonclinical safety is further expanded to ensure the applicant considers repeat-dose toxicity and how read-across end points, such as PK modeling, adverse outcome pathways and post-marketing surveillance, can all assist in the nonclinical assessment.
Guidance on clinical aspects (safety and efficacy) has been strengthened from three quarters of a page to nearly three pages. The underlying principle of the studies has not changed and remains in line with the legal status of the application. However, the MHRA has provided comments on how an applicant may look to design such studies, including the number of participants, sampling points and times, whether the comparison to a combustible cigarette can be excluded, how to address further nicotine concentrations and additional flavors.
An application and successful product registration as a medicine does come with an increased regulatory expectation on the marketing authorization holder, which applicants will need to consider. Example areas of consideration would include:
Applicability of Good Manufacturing Practices
Qualified person mandatory role
Medical device marking aspects, i.e., UKCA or CE
Pharmacovigilance system and qualified person for pharmacovigilance
Good Distribution Practices in the supply chain
Ongoing stability
Life cycle maintenance of the license
Working with established partners in the pharmaceutical space will ensure that the above list, which is certainly not exhaustive(!), is not an overburdening one.
The MHRA is making a clear stance as a global regulatory leader in the registration of electronic cigarettes as medicinal products, and that is only to be welcomed.
Lloyd Smart is the head of regulatory affairs at Broughton Group.Broughton’s focus is to ensure its regulatory knowledge is contemporaneous by swiftly reviewing and adapting to changes in the expectations or requirements as a result of any revised guidance.Broughton’s team has a deep understanding of the pathway for registration of medicines, including electronic cigarettes in the U.K., and is well placed to provide full consultancy in this area.
December 2, 2021
Broughton Moves Into New Markets

Photo: Broughton
Broughton has unveiled a rebrand that reflects its evolving service offerings to support clients through their whole product life cycle journey. The company states that it is on a mission “to help our clients deliver life-enhancing products to market, by providing the most trusted integrated services in the world.”
Building on years of experience in the pharmaceutical and next generation nicotine products space, Broughton offers its clients fully integrated scientific and regulatory consultancy, combined with comprehensive in-house laboratory services. The launch coincides with the announcement that the business is expanding its services into the rapidly evolving cannabinoids industry.
Moving forward the company will focus on accelerating life-enhancing products to market within strategic markets including pharmaceuticals, nicotine and cannabinoids. Its combined expertise in formulation science, device technology, software applications and aerosol science makes Broughton the ideal strategic outsourcing partner to support client pipeline portfolios of future next generation products, according to the company.
“The launch of the Broughton brand formalizes our rapidly developing position as a full-service solutions provider to the life sciences sector,” said CEO Paul Moran, who founded Broughton Laboratories in 2006. “We will continue our commitment to investing further into global operations delivering scientific and regulatory consultancy combined with comprehensive product development and laboratory services.
“This next phase of our expansion is a natural evolution to grow capacity and capabilities into the broad life sciences sector as technologies improve to target unmet market needs.”
“One exciting aspect of this change is that it facilitates the expansion of our existing pharmaceutical quality and product stability services to support providers of pharmaceutical inhalation products,” said Broughton Chief Scientific Officer Chris Allen. “With expertise in device optimization, human factor studies, navigating complex regulatory pathways for combination products and a track record of quality compliance, our broad expert team can support device development from concept to commercialization.’’
“The expanding team at Broughton hold extensive knowledge of their specialist fields,” said Moran. “This rebrand brings together this expertise with a fresh focus on the journey of our clients’ products to meet an unmet market need. This is an exciting time for the business that will enable us to continue to innovate as we contribute to global health and wellbeing.”
As part of its rebranding, Broughton has created a new website at www.broughton-group.com.
October 20, 2021
PMTA Deficiency Letters
Photo: Tobacco Reporter archive
Common causes and how to prepare for them
Contributed
Paul Hardman
In this article, Broughton Nicotine Services Head of Scientific Affairs Paul Hardman outlines the factors that can lead to data gaps in premarket tobacco product applications (PMTAs), what prompts a deficiency letter and how you can respond quickly and appropriately.
What is a deficiency letter?
Deficiency letters are sent to those who have submitted a PMTA with incomplete or insufficient data for the U.S. Food and Drug Administration to make a decision on whether the product is “appropriate for the protection of the U.S. public health.”
Why have I received a deficiency letter?
There are common causes of deficiencies that prompt the arrival of a letter. These could include a PMTA that lacks information that was mistakenly considered unimportant by the electronic nicotine-delivery systems (ENDS) company but is actually required by the FDA.
Applicants may also have been rushed to meet last year’s Sept. 9 deadline, leaving the company submitting the PMTA with insufficient time to collate and provide the required data. Similarly, the timeframe required to submit the application may not have left enough time to complete stability studies of the required length to provide a range of data. The FDA is, understandably, keen to understand the stability of a product over its expected shelf life.
Other reasons include:
A lack of integration between different studies—often submissions provide extensive data for some workstreams but are light in others. It is important that appropriate data is provided for all product analysis, nonclinical and human subject studies—and that data and approaches are integrated across all areas.
Different interpretation of “scientifically justified”—many elements of the PMTA guidelines indicate that approaches applied need to be justified by scientific data. However, as all products differ, there is a level of ambiguity in terms of what this looks like and what is required.
Poor “bridging” of data—the FDA welcomes the bridging of scientific data between similar products where appropriate. However, bridging that is not, in the opinion of the FDA, sufficiently scientifically justified will be highlighted and raised as a deficiency.
What will be in a deficiency letter?
Despite the name, it won’t just be a letter. The deficiency packs issued by the FDA are very detailed, outlining positive aspects about your application and areas for improvement and attention.
There will be multiple pages covering different points, with sections covering all products or particular products in a bundled PMTA and perhaps highlighting deficiencies for particular timepoints.
What is the aim of the deficiency letter?
Once a PMTA application has been accepted for filing, the next stage is substantive scientific review, which results in either a deficiency letter, a request for environmental information, a market order granted or a market order denied. The FDA will notify the submitting company when their application enters substantive scientific review.
The FDA intention of the deficiency letter pack is to support you in providing the required information. Each will typically cover what you need to do to remedy the deficiency and what data you need to provide to allow the FDA to carry on with a substantive scientific review—and the FDA has confirmed that, for deemed products (those on sale in the U.S. on or before Aug. 8, 2016), you will only receive one deficiency letter based on the agency’s current high workload with the many applications in process. The FDA has said this may be reviewed in the future once the backlog is cleared. Generally, for deemed products, you will have only 90 days to respond to the deficiency letter with all the relevant data that has been requested.
Information could include examples of what meets the FDA’s requirements and advice on how you could better explain or justify the information provided. There is no set response to a PMTA application. The FDA has received an extensive number of applications, which are reviewed by a team of people, so inconsistencies may arise between different responses. Also, take note that answering all the queries in a deficiency letter does not necessarily guarantee that your application will eventually be granted a marketing order.
How can I prepare for a deficiency letter?
As an ENDS company, you might have a good idea of possible data gaps within your submission and understand whether you are likely to receive a deficiency letter. Or, you may believe that what you have provided is appropriate and adequate. Either way, it is best to be prepared.
Steps can be taken to ensure you are ready for any eventuality, the most important one being to ask for help. Scientific and regulatory ENDS specialists can undertake gap analysis to identify any possible deficiencies so that steps can be taken now to provide what is required.
You can also ensure you fill any missing data gaps. If there is information that is clearly missing or inadequate, put studies in place to collect the data now. Remember, there are only 90 days to respond to a deficiency letter, which may not be sufficient time to obtain the information required.
Another piece of advice would be to start stability studies now if you are in any doubt that the stability data you provided may not be sufficient in terms of duration. Putting studies in place now will help you stay ahead of the game if this aspect of your submission is questioned.
Finally, you should always cross-check requirements. It is surprising how many companies miss out key sections, such as an executive summary or environmental assessment. Although omission of key sections is likely to lead to the FDA refusing to accept or refusing to file the application prior to reaching the substantive review phase, it makes sense to compare the detail of what you have provided with the list of requirements from the FDA to check if you have overlooked anything.
Recently, the FDA confirmed that addendums of additional data can be submitted to them before the commencement of the substantive scientific review stage for the process. This is fantastic news for manufacturers who had submitted dossiers that were not as comprehensive as they would have liked; if your application has not yet entered substantive scientific review, you now have the opportunity to submit additional data at no penalty to your application. However, if you plan to do this, it is important to contact the FDA and describe the anticipated plan of data generation and submission—and be quick. If you leave this too late and your application does enter substantive scientific review, you run the risk of any addendums being detrimental to your application and a shortening of the FDA’s enforcement discretion.
How can I be prepared for, or minimize the chance of, receiving a deficiency letter?
ENDS companies most prepared to respond appropriately will be those that are expecting the letter and have the required data ready or those that avoid receiving a letter altogether by providing information upfront. Companies such as Broughton Nicotine Services can help at any stage of the process, either prior to submission or during substantive scientific review, troubleshooting when there is a refuse to file/accept decision and also helping with preparation for and response to deficiency letters.
Broughton Nicotine Services can help you undertake a gap analysis on your submission and generate the required information. Contact our regulatory consulting team to book a meeting so that we can help you advance a smoke-free future.
This article was supplied on behalf of Broughton Nicotine Services.
August 5, 2021
Paul Hardman to Lead BNS Scientific Affairs
Broughton Nicotine Services (BNS) has appointed Paul Hardman as head of scientific affairs, the latest in a series of senior level appointments, as it continues to expand its services.
The business, which has helped electronic nicotine device companies bring noncombustible products to market, is currently expanding its full-service regulatory consultancy into modern oral nicotine products, heated-tobacco products and cannabidiol products.

A scientist with extensive experience in inhaled product development across pharmaceutical and consumer products, Hardman will have the task of growing the scientific affairs team to enable the business to grow and offer a premium consultancy experience for clients in the industry.
“We’re delighted to have welcomed someone of his caliber into this new role,” said Nveed Chaudhary, chief regulatory officer of Broughton Nicotine Services. “His addition to the Broughton team will strengthen the business further as we look to expand our full-service regulatory consultancy. Paul will take responsibility for delivering product development and optimization activities, drawing on his years of industry leadership and experience.”
Prior to joining Broughton, Hardman was scientific lead with Imperial Brands, where he was responsible for designing the testing strategy for the chemistry of inhaled and oral next-generation nicotine products, from assessing a variety of prototypes at the early stages of development through to characterization of products for submission through the U.S. premarket tobacco product application process.
He began his career working at a specialist pharmaceutical company where he gained experience of dry powder and metered dose inhaler development, including for the treatment of local lung conditions and systemic absorption. Hardman also has experience leading the quality control department in a multinational pharmaceutical company involved in the production of generic nicotine lozenges.
Paul’s addition to the Broughton team will strengthen the business further as we look to expand our full-service regulatory consultancy.
Nveed Chaudhary, chief regulatory officer, BNS
“I am passionate about the opportunity to work with multiple clients and really get to the heart of their products so that Broughton Nicotine Services can best serve these businesses by championing those points in their regulatory submissions,” said Hardman.
“My role will involve growing the team to enable us to deliver a highly effective offering as Broughton moves into new areas, and I am eager to build on the success the business has already achieved.”
May 5, 2021
Broughton Launches Blue-Sky Thinking Hub

Photo: BNS
Broughton Nicotine Services (BNS) has launched its Blue-Sky Thinking Hub, an “open innovation community” for companies to collaborate and develop ideas within the electronic nicotine-delivery system (ENDS), pharmaceutical and cannabis markets.
BNS is a contract research organization with more than 10 years’ experience helping ENDS companies bring tobacco-free nicotine-delivery products to market.
The company has recently added services aligned with a number of new product categories, including modern oral nicotine products, cannabidiol (CBD) and cannabis-delivery devices and work with clients based in the U.S., China, U.K., Europe and the Middle East.

The Blue-Sky Thinking Hub seeks to engage companies with innovative ideas.
Nveed Chaudhary, chief regulatory officer, BNS
The Blue-Sky Thinking Hub encourages manufacturers and regulators to build strong relationships to overcome product development and regulatory challenges and work toward total harm reduction. An additional benefit is around considering solutions to potential regulatory concerns as part of the product development.
“Broughton Nicotine Services is dedicated to helping manufacturers meet regulatory requirements and delivering reduced-harm products to market,” said Nveed Chaudhary, chief regulatory officer at BNS.
“The Blue-Sky Thinking Hub seeks to engage companies with innovative ideas, which could be anything from new formulations to plastic-free or biodegradable products, technology to discourage and reduce youth access or even alternative charging for devices.
“Broughton helps these ideas to come to life by providing expert scientific and regulatory advice, contributing to the end goal of global total harm reduction.”

We invite industry professionals to discuss, debate and develop their ideas for new products aligned with regulatory requirements and to hopefully help influence and shape new policies.
Paul Moran, chief executive, BNS
“We are delighted to be launching the Blue-Sky Thinking Hub, which is the first of its kind in the industry,” said Paul Moran, chief executive at BNS.
“We invite industry professionals to discuss, debate and develop their ideas for new products aligned with regulatory requirements and to hopefully help influence and shape new policies.
“Together we can achieve total harm reduction and a smoke-free future.”
April 1, 2021
Nveed Chaudhary Joins Broughton Nicotine Services

Nveed Chaudhary (Photo: BNS)
Broughton Nicotine Services has appointed Nveed Chaudhary as chief regulatory officer.
This appointment is the latest in a series of high-profile additions to the team at the contract research organization specializing in electronic nicotine-delivery systems (ENDS) as it embarks on its next phase of growth.
Having built a leading reputation for advancing a smoke-free future by helping ENDS companies bring noncombustible products to market, the business is now also moving into modern oral nicotine products, heated-tobacco products and cannabidiol products.
“We are absolutely delighted to have brought Nveed on board,” said Paul Moran, CEO of Broughton Nicotine Services. “He is one of a small number of experts in the industry to have developed scientific and regulatory strategies that have delivered the highly sought-after marketing order for both premarket tobacco product applications (PMTA) and modified-risk tobacco product (MRTP) applications. Nveed’s depth of knowledge and experience will further help Broughton’s clients shape the future of next-generation nicotine products.”
Previously head of harm reduction science at Imperial Brands and director of strategic communications at Philip Morris International, Chaudhary was a core team member of the successful IQOS PMTA and MRTP regulatory submissions and director for the Myblu PMTA submission program. He is a recognized expert in the nicotine sector, author of over 25 peer-reviewed publications and speaker at international lung disease and tobacco harm reduction conferences.
“My career goal has always been to reduce the burden that lung disease has on patients, society and public health,” said Chaudhary. “To combat the harm effects caused by smoking, it’s important to offer consumers high quality, rigorously tested and regulated noncombustible products.
“Broughton Nicotine Services acts as the bridge between the industry and global regulators. By applying experience and knowledge, we partner with manufacturers to help them secure marketing orders for safer next-generation products.
“It’s clear that the business shares my drive to accelerate the creation of a smoke-free future, and I’m excited to be part of the team.”
February 18, 2021
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.
February 4, 2021
A Journey, Not a Destination
Photo: BNS
Navigating successful post-market requirements for ENDS products
By Yvonne Wilding
This month marks the deadline for submitting premarket tobacco applications to the U.S. Food and Drug Administration (FDA). Many organizations have worked diligently to ensure their submissions are as complete and robust as possible. Their goal is to ensure that they are sufficiently complete to allow acceptance for filing and, following substantive review, that the product may be granted a market order by the FDA, allowing it be sold in the United States. By early September, hundreds of PMTAs for electronic nicotine-delivery systems (ENDS) had been submitted to the FDA, and a number are currently undergoing substantive review.
However, in this article I will remind applicants that their obligations do not stop at PMTA approval but persist for the entire life cycle of the product in market—and products can be removed from market potentially more easily than they can be brought to it.
During its PMTA review, the FDA extensively evaluates the provided experimental data to make a risk-benefit assessment of the new product and ascertain its suitability to be designated as “appropriate for the protection of public health” (APPH).
This includes scrutinization of the quality and compliance aspects of the manufacturing processes and review of extensive research information generated on the specific product to allow the FDA to evaluate any potential public health risks associated with the product. The research aspects are compiled by the applicant into different modules of the eTobacco Technical Dossier and include chemistry and manufacturing, toxicology risk assessment and clinical and human experience evidence.
There will be a series of investigations in human volunteers to look at the pharmacokinetics (PK) of the product and its delivery of nicotine compared to comparator products. The PK profile of a product has the potential to affect the abuse potential—i.e., how easily someone may become addicted to nicotine. In addition, there will typically be several human behavior studies to check that the users can operate the device safely and effectively and to assess their preference for this product against competing products. Additionally, there is a significant amount of research done in never-smokers to ascertain how likely they are to start smoking with this product. The numbers of volunteers in the studies are often very large and care is taken to look not only at a representative U.S. population from their demographics but also to incorporate a significant number of young adults in order to be able to make extrapolations to a youth (11–18 years of age) population.

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The research data provided to the FDA also includes extensive data on the performance of the device in laboratory-controlled conditions and its delivery of nicotine in each puff under different device settings and different coil components. Stability of the product on storage and extractables and leachables are measured, and quantitative data on the discharge of harmful and potentially harmful constituents (HPHCs)—a list of 33 chemicals of most toxicological concern detailed in the FDA guidelines) is collected. The toxicology and the chemistry data are linked to consumer behavior information and topography data to indicate how a consumer will use the product, enabling the estimation of the likely exposure to potentially hazardous aerosolized constituents and hereby the risk-benefit of this new product can be ascertained.
Assessing the actual product though, is only part of the information required. The product must also be assessed for risk-benefit alongside data from existing relevant tobacco-containing products, much of which is obtained from scientific publications. These comparator products would typically be combustible cigarettes or similarly performing ENDS. It would be wrong to assume that ENDS are without risk, but in a PMTA, the risk relative to other comparator products, e.g., combustible cigarettes, is described. Based on this assessment of these actual and relative risk estimates, the FDA will decide on whether the product is APPH. This approval process can be considered the first step of the journey.
There are several regulatory documents published by the FDA Center for Tobacco Products (CTP). These include Guidance for Industry and Proposed Rule, both of which have sections on post-marketing requirements, although most detail is provided in the Proposed Rule (Federal Register Vol. 84, No. 186, 25 Sep. 2019, Subpart D – Postmarket Requirements section, $1,114.39–$1,114.41).
Having been granted a market order from the FDA, there is an explicit ongoing commitment for each approved SKU to collect and provide information and submit it for regulatory review. Following each review, the FDA will consider whether it is appropriate that the product is maintained in market. Reasons why the FDA may decide to remove a product from market could include any of the following: the product is no longer considered to be APPH; there is inaccurate representation of factual data, the applicant has not set up a system for maintaining records and/or fails to make appropriate records and submit reports.

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The post-marketing updates required by the FDA can be put into three main categories: changes to manufacturing processes and controls; changes to the health risks associated with the product; and sales, distribution and marketing information.
Periodic reports need to be submitted to CTP within 60 calendar days of the reporting dates which will be specified in the applicant’s marketing order and must include the following:
Manufacturing and processes
A description of changes to the manufacturing, facilities or controls during the reporting period
An explanation of why the changes were made and why these change do not result in the generation of a new tobacco product that is different from the one for which the original order was granted
Health risks
An inventory of ongoing and completed studies by or on behalf of the applicant that have not previously been reported
Full reports of information published or known, or which should be reasonably known, to the applicant concerning scientific investigations and literature about the tobacco product that have not been previously reported
Significant findings from publications not previously reported
A summary and analysis of all serious and unexpected adverse experiences reported to the applicant or that the applicant is aware of
A statement of any changes to the overall risk associated with the product and a summary of the health risks, including the nature and frequency of the adverse experience and potential risk factors
Sales, marketing and distribution
A summary of sales and distribution of the tobacco product for the reporting period to include:
Total U.S. sales and demographic characteristics of purchaser
Specimens of labelling and detail of any changes
Full-color copies of all advertising material used with dates of dissemination
A description of advertising and marketing plans
Actions taken to restrict youth access and limit youth exposure to labelling, advertising or promotion
Use of social media
Use of partners, influencers or bloggers
An assessment of the impressions left by advertising and audience demographics
In addition to the above categories, there is also a requirement to provide any additional information specified or any additional requests under the terms of the marketing order and an overall assessment of how the product continues to be APPH.
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As well as the requirement for regular submission of post-marketing reports, if there are any serious and unexpected adverse events reported to the applicant, these must be reported to CTP’s Office of Science via the Health and Human Services Safety Reporting Portal within 15 days of the applicant having received the report.
There are strong concerns among the public, health policy makers and government that the potential health benefits of switching smokers from combustible cigarettes to a less harmful way of accessing nicotine may be dramatically offset by young nonsmokers being attracted to vapor devices and through use of these devices drive an increase in nicotine addiction in youth. Smoking volumes of combustible cigarettes have been falling for many years across the world, which will ultimately lead to significant improvements in health, although the evidence will take several years to become apparent. Understandably, there is much enthusiasm that the scourge of tobacco smoking-related diseases may be, if not eliminated, significantly reduced in future generations.
It is in the interest of consumers who may wish to move to a safer form of nicotine intake that PMTA applicants are fully compliant with the post-marketing requirements and continue to work with the FDA and lobbyists to contribute to and maintain an appropriate balance of risk reduction and health benefit realization. If these products, stated to be APPH, are no longer available to consumers, then the consumers’ opportunity to potentially improve their long-term health outlook is diminished.
Many of the larger companies manufacturing ENDS products may have specific regulatory compliance staff and sales and marketing departments that are fully trained, equipped and resourced to deal with the FDA requirements, but for the smaller organizations, without such infrastructure, this resource requirement, skill set, potential complexity and the associated costs, particularly if the organization has a large number of SKUs, can be particularly onerous.
The cost and resource requirements of maintaining established products in market has been recognized in the pharmaceutical industry for a very long time. As pharma companies typically prefer to invest in novel medicine development or in the enhancement of existing medicines to provide patent life extensions, some older, established products are still very successful and so the maintenance of the post-marketing requirements of these products from a regulatory and pharmacovigilance perspective is often outsourced to specialist contract research organizations (CROs) who collect and report this data on behalf of the pharma companies. These CROs can provide the necessary resources, expertise and experience to make this a cost-effective solution.
It will be interesting to see how many ENDS products are successful in receiving a positive market order decision from the FDA only to be subsequently removed from the market as they fail to satisfy their post-market approval requirements, causing these products to be potentially as ephemeral as the aerosols they disperse.

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Yvonne Wilding is director of product safety and compliance at Broughton Nicotine Services (BNS). BNS operates exclusively in the ENDS sector. Its team of scientific and regulatory experts, backed by its in-house, custom-built contract research organization facility, understands customers’ specific challenges and opportunities. With expertise across the U.S. and EU for tobacco products, medical devices and pharmaceuticals, BNS is committed to working with customers to increase the value of their business and advance a smoke-free future. For more information, visit www.broughton.com.
September 1, 2020