Broughton Head of Scientific Affairs, Paul Hardman outlines factors that can lead to data gaps in Premarket Tobacco Product Applications (PMTA) and what level of instruction or guidance to expect from FDA.
Companies in the Electronic Nicotine Delivery Systems (ENDS) sector selling products in the US are waiting to see if they will receive a deficiency letter from the Food and Drug Administration (FDA). Deficiency letters are sent to those who have submitted Premarket Tobacco Product Applications (PMTAs) with incomplete or insufficient data for FDA to make a decision on whether the product is appropriate for the protection of the public health.
Here we outline factors that can lead to data gaps, what level of instruction or guidance to expect from FDA and how to improve your ability to respond quickly and appropriately.
Common causes of deficiencies
- Information mistakenly considered unimportant – Aspects required or considered priority by FDA may differ from those understood to be important by the ENDS company.
- Rushed applications – Some companies may have pushed through PMTA applications before last year’s September 9 deadline, with insufficient time to collate and provide all required data.
- Insufficient time for stability studies – The FDA is understandably keen to understand the stability of a product over its expected shelf life. However, it may not have been possible to run a stability study of sufficient duration to provide the range of data required.
- 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, non-clinical and human subject studies – and that data and approaches are integrated across all areas.
- Different interpretation of ‘scientifically justified’ – Many elements of PMTA guidelines indicate that approaches applied need to be justified by scientific data. However, as all products differ, there is a certain 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 scientifically justified will be highlighted and a deficiency raised.
What will be in a deficiency letter?
Well firstly, it won’t just be a letter.
The deficiency packs issued by FDA are very detailed, outlining positive aspects about your application and areas for improvement and attention.
They are likely to be multiple pages covering different points. Sections may focus on all products, or some particular products, and may highlight deficiencies for particular timepoints.
The FDA intention of the pack is to help and support you in providing the required information. Each will typically cover:
- What you need to do to remedy the deficiency
- What data you need to provide. This may include examples of what could be included to satisfy FDA’s requirements
- How you could better explain or justify the information provided.
However, be aware that due to the extensive number of PMTA applications submitted, applications are reviewed by a team of people at FDA, so inconsistencies may arise between different responses.
How can I prepare for a deficiency letter?
Many ENDS companies will have a good idea of possible data gaps within their submission and understand whether or not they are likely to receive a deficiency letter. Others may not and may believe that what they have provided is appropriate and adequate. Either way, it is best to be prepared.
Steps that can be taken now, in advance of a deficiency letter arriving, include:
- 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.
- Fill missing data gaps – Obvious really. 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 to obtain the information required.
- Start stability studies – If there is any doubt that the stability data you provided may not have been sufficient in terms of duration, put studies in place now so that you are already ahead of the game if this aspect of your submission is questioned.
- 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 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.
Helping you to be prepared?
ENDS companies most prepared to respond to a 90-day deficiency letter appropriately and within the timescale will be those who are expecting the letter and have the required data and information ready. We can help at any stage of the process, either prior to submission, troubleshooting when there is refuse to file/accept decision, and also with preparation for and response to deficiency letters.
To discuss undertaking a gap analysis on your submission and preparing the required information, contact us to book a meeting with our regulatory Consulting team, so that we can help you advance a smoke-free future.
Can we help you?
Broughton have deep CRO capabilities and an experienced team of scientific and regulatory professionals to manage full service global regulatory projects. Our knowledge of global regulatory pathways offers significant insights that can be incorporated into your project plans. Our mission is to accelerate safer nicotine-delivery products to market; advancing a smoke-free future.
Book a meeting with us today to discuss your requirements.