FDA issue finalised PMTA guidance

What does the FDA’s finalised PMTA guidance mean for your testing?

On 11th June 2019 the FDA issued their final guidance on PMTA submissions. An area that saw significant changes from the initial draft guidance (released in May 2016) was section VI.H, relating to ‘Scientific Studies and Analyses’. Having studied the guidance in depth, we have written up a detailed interpretation of the document.

What should I test for?

Some of the main changes to this section were made to the list of ‘Harmful or Potentially Harmful Constituents’ (HPHC’s). There were several compounds omitted from the initial draft guidance. Constituents that were traditionally tested for in combustible cigarettes (such as ammonia and benzo[a]pyrene) have now sensibly been removed. Likewise, there were several new flavour based HPHCs added to the list in the finalised guidance. Below is a comprehensive list of the HPHCs and where they featured on the initial draft guidance from 2016, compared to the finalised guidance from June 2019.

The new guidance also states that you should test:

“Other constituents, as appropriate for your particular product. For example, you might want to consider whether you should test for flavorants that can be respiratory irritants such as benzaldehyde, vanillin and cinnamaldehyde”.

This is best done on a case-by-case basis and the rationale for choosing the analysis will need to be submitted as per the guidance document.

How much testing should I carry out?

Another noticeable alteration to the FDA’s guidance is the number of tests that you are required to carry out. The initial draft guidance stated that:

“…data sets should span a minimum of three different batches with a minimum of 10 replicates per batch, with date and time sampling points”.

This has been replaced in the new guidance which now advises that:

“Data sets that can reliably reflect the product and its manufacturing. For example, FDA recommends data sets spanning different batches (generally three or more) with multiple replicates per batch (generally seven or more), depending upon the variability demonstrated in the method validation, with date and time sampling points”.

The potential reduction in the number of replicates required for your submission could save you a reasonable amount of time and money. However, as with any testing strategies for PMTA submissions, we would strongly recommend that you receive approval from the FDA for your testing strategy prior to beginning testing.

A further requirement to consider is the need to carry out testing under two regimens. In both versions of the guidance it is advised that:

“Evaluating new tobacco products under a range of conditions, including both non-intense (e.g., lower levels of exposure and lower volumes of aerosol generated) and intense (e.g., higher levels of exposure and higher volumes of aerosol generated), enables FDA to understand the likely range of delivery of emissions. The two regimens are expected to provide the Agency with information about possible different deliveries of constituents, including the range of quantities of constituents.”

Bridging – What is it and can I do it?

The submission of a PMTA application requires an incredible amount of work, not to mention a lot of money. Therefore, the FDA are suggesting to ‘bridge’ between like products to alleviate some of these costs. The FDA state that:

“Ideally, a PMTA will include studies conducted using the new tobacco product; however, bridging of data from one product to another may be feasible for a subset of products or for certain types of studies”.

A good example of this would be if a particular flavour of product was available in a range of nicotine strengths. It’s logical to assume that you could test the low, medium, and high strength versions and bridge that data for all the other concentrations in between. However, before deciding to do any bridging on your project we would strongly recommend that you get approval from the FDA for this approach. PMTA applications cost a lot of money and you would not want your submission to fail due to a lack of data. Likewise, bridging can save you a lot of unnecessary expenditure. So please do engage with the FDA at the earliest opportunity and make sure that your strategy has their approval before starting any HPHC testing.

What should I look for in a lab partner?

As per section VI.H.1, your PMTA submission must contain the accreditation of your chosen laboratory partner. You should take great care when choosing your approved lab partner — working with reputable labs who are accredited and have a reputation within the industry is vital. Likewise, using accredited methods would be very beneficial to your PMTA submission.

PMTA submissions must contain “Validation information and rationale for selecting each test method, including any relevant voluntary testing standards”. Therefore, using methodology that has been accredited will allow you to have greater faith in the integrity of your data and potentially give your findings greater weight.

How can Hall Analytical help you?

Head over to our PMTA regulatory compliance page where you can download a PDF of our simplified 4 phase/9 step approach to a PMTA submission or to sign up for a free consultation call.