Top Four Potential Issues with Methacholine Bronchoprovocation (MBPC) Challenges

Partly in response to potential inhaler shortages arising due to treatment of COVID-19, the U.S. Food and Drug Administration (FDA) approved the first generic version of Proventil HFA (albuterol sulfate) in the U.S. in April 2020. Dr. Stephen Hahn of the FDA, commented in a press release, “The FDA recognizes the increased demand for albuterol products during the novel coronavirus pandemic.”

This approval could provide an incentive to generic drug companies to develop or prioritize a program for albuterol sulfate. CROs may see new requests from clients regarding albuterol sulfate bioequivalence (BE) studies. When evaluating such a drug program, it is vital to bear in mind the complexities of this type of BE study. Four potential issues are outlined below.


1. Variability in Spirometry Data

When MBPCs are conducted across multiple sites, as would be required for a pivotal BE study, variability in the spirometry data that is the primary outcome measure for MBPCs can be introduced.


2. Incorrectly Characterized or Outdated Equipment

The equipment used in MBPCs has changed extensively in the years since the first MBPC guidance was published, particularly with regards to nebulizers and dosimeters, and much of the earlier equipment is no longer available.


3. Study Design Flaws

Another complexity of conducting an MBPC study is determining a workable protocol while integrating the FDA guidance on albuterol sulfate. While the guidance provides the minimum requirements for protocol design, familiarity with the model shows that further refinements can be the difference between failure and success.


4. Variability in Methacholine Dilutions

Perhaps the most complex of all considerations for this type of trial is the methacholine chloride dilutions required for the MBPCs. While it might seem as if clinical sites could dilute the methacholine themselves, this can introduce a level of variability into the data that would yield inconclusive results.

MERIT is an innovative specialty CRO providing clinical trial data collection and interpretation in the ophthalmology and respiratory disciplines. Our portfolio of solutions offers deep clinical expertise, unique technology, and exceptional service for our partners, sponsors and CROs.

To read about MERIT’s solutions for these potential issues, download our white paper Methacholine Bronchoprovocation in Bioequivalence Studies: MERIT Has Your Solution.