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The Use of Bridging Studies in the PMTA

The Use of Bridging Studies in the PMTA

In the initial PMTA guidance from the FDA published in August of 2016, no mention of bridging studies appeared in that version of the guidance. However, in the new the June 2019 final guidance for PMTA submissions, the FDA specifically refers to bridging studies.

FDA widely mentions and accepts bridging studies for a wide range of other submissions for pharmaceutical and medical devices, such as 505(b)2 applications, also known as new drug applications, or NDAs. In short, bridging studies are frequently included in FDA regulatory submissions and applications, and the type of data generated from bridging studies is familiar to the FDA.

What is a Bridging Study?

A bridging study can be defined simply as a supplemental study that is performed to allow for the extrapolations of generated data to be used to support other products or studies. Bridging studies are primarily performed on:

  • Clinical data on efficacy
  • Safety
  • Dosage and dose regiment
  • Related Products

How Does Bridging Data Relate to the June 2019 FDA PMTA Guidance for Vape Products?

In the June 2019 final guidance for PMTA submissions, the FDA specifically calls out bridging studies as being allowed and also provides more clear definition and direction for the use of bridging studies in a PMTA. Bridging studies may now be included in a PMTA submission for toxicology and clinical data.

Additionally, bridging studies may be completed to support the analytical testing section of the PMTA for e-liquids at different nicotine strengths. The FDA will allow bridging studies for all nicotine strengths, provided that 3 nicotine strengths are tested:

  • Low strength
  • Mid strength
  • High strength

What Does an E-Liquid Bridging Study Look Like?

To provide some context, we’ll explore an example vape liquid PMTA bridging study. E-liquid “Manufacturer X” has 5 nicotine strengths of a vape juice product:

  • 3 mg/mL nicotine
  • 6 mg/mL nicotine
  • 12 mg/mL nicotine
  • 18 mg/mL nicotine, and
  • 24 mg/mL nicotine

E-cigarette “Manufacturer X” would need to test a low, middle, and high nicotine strength, and given their product offerings, the following would be analyzed:

  • 3 mg/mL nicotine (low)
  • 12 mg/mL nicotine (mid), and
  • 24 mg/mL (high) strengths

Provided all three strengths (low, mid, and high) pass analytical testing (ex. HPHCs, stability etc.), this data could be bridged to the untested 6 and 18 mg/mL strengths and could be submitted in a PMTA package.

How Will a Bridging Study Help My PMTA Submission?

In summary, when the low, mid, and high nicotine strengths pass analytical testing, the data supports that untested strengths which fall in the spectrum between the low, mid, and high strengths would also pass analytical testing. For the company in our example, “Manufacturer X”, because 3 out of the 5 product nicotine strengths passed analytical testing, all 5 could potentially receive a favorable outcome from the PMTA application, because the 2 untested strengths fell within the range of concentrations analyzed.

As the example has shown, bridging studies can maximize the cost effectiveness of a regulatory submission, and can reduce the need for large amounts of additional data.

How Can Avomeen Help?

Avomeen is an independent testing lab proudly serving e-cigarette, vape juice, e-liquid, e-juice, and ENDS manufacturers, distributors, consultants, other laboratories, entrepreneurs, and companies of all sizes. We are experienced with new testing standards pertaining to the e-liquids/e-cigarettes and the FDA’s Premarket Tobacco Application (PMTA) requirements.

We customize our approach for every customer we serve and offer full support for your projects. Our regulatory consultants can aid your team in their efforts to gain FDA approval, both during and after a project is completed. Get in touch with us to discuss your project.

Additional Resources

To help you understand some of the important methods and relevant equipment required for e-liquids testing, we’ve put together some Cliff Notes to help you navigate this complicated environment.

Want to know more about the new PMTA guidelines? Check out our blog, What You Need to Know About the FDA’s New PMTA Guidance.

We’ve outlined the major similarities and differences between the 2016 and 2019 PMTA guidance in our blog, Overview of Premarket Tobacco Application (PMTA) FDA Guidance for ENDS.

The 9 most commonly asked questions about PMTA requirements are answered in our blog, 2019 FDA PMTA Guidance FAQs.

Is finding the right lab to partner with stressing you out? Our blog, Choosing the Right Lab for PMTA Compliance, offers some guidance.

Extractables & Leachables (E&L) testing is required in the new PMTA guidance. Our blog, E-Liquids Extractables and Leachables Testing for the PMTA, outlines what you need to know about this integral part of the submission.

With the court ruling on July 11, 2019, the deadline for submissions has been moved up significantly. For more information, check out our blog, ENDS Industry Faces Tighter PMTA Deadlines with May 2020 Fast Approaching.

FDA is actively enforcing PMTA guidance. Check out our blog, FDA Issues Warning Letters for E-Liquid Products without Marketing Authorization, for more details.

We’ve outlined some common regulatory strategies that have emerged amongst leading ENDS manufacturers in our blog, Will my E-Liquid Product Receive PMTA Authorization?

Concerned about state-led e-liquid bans? Check out our blog, Proposed E-Liquid Bans and the PMTA, for insight into how state-led policies are impacting submission strategies.

 

 

Our expert blogger is Dr. Derek Beachamp, Avomeen’s Senior Technical Director of Analytical Sciences. He is an expert in a wide breadth of characterization techniques, and has years of experience with pre-formulation development of small molecules and their physical properties. 

Learn more about Derek’s expertise and experience.