Fortrea, a leading global contract research organization, has announced a strategic collaboration with Emery Pharma to address a critical regulatory challenge in drug development. The partnership will provide rapid lot-by-lot testing of rifampin for 1-methyl-4-nitrosopiperazine (MNP) impurity levels, ensuring compliance with FDA guidelines for drug-drug interaction (DDI) studies.
The collaboration comes in response to regulatory scrutiny that has limited the use of rifampin, a widely used antibiotic that has traditionally served as a key tool in DDI studies. In 2021, the FDA discovered that all tested rifampin batches contained MNP levels exceeding previously accepted limits, prompting researchers to explore alternative drugs for these critical studies.
Addressing a Critical Regulatory Gap
Drug-drug interaction studies represent a cornerstone in the development of new therapeutics, and rifampin has long been the preferred agent due to its safety and tolerability profile as a CYP3A4 isoenzyme inducer. However, the discovery of MNP, a nitrosamine impurity in rifampin, created significant challenges for clinical researchers.
"The substitutes come with safety concerns and slower activation times," according to the companies' announcement. This limitation has created delays and complications in early-phase clinical trials, where DDI studies are essential for understanding how new drugs interact with existing medications.
The FDA updated its guidance in 2023, raising the acceptable MNP limit for rifampin, creating an opportunity for the pharmaceutical industry to resume using this preferred agent with appropriate testing protocols.
Strategic Partnership Benefits
Dr. Oren Cohen, chief medical officer and president of Clinical Pharmacology Services at Fortrea, emphasized the collaboration's impact on study design and participant safety. "By enabling use of rifampin through our collaboration with Emery Pharma, we're helping sponsors de-risk early-phase trials, accelerate timelines and enhance data quality," Cohen stated.
The partnership leverages Emery Pharma's specialized capabilities in analytical and bioanalytical testing, conducted under current Good Manufacturing Practice (cGMP) and Good Laboratory Practice (GLP) standards. The company's expertise in liquid chromatography-mass spectrometry (LC-MS/MS) and high-resolution mass spectrometry (HRMS) enables precise quantification of trace-level nitrosamine impurities in complex matrices.
Technical Capabilities and Regulatory Compliance
Emery Pharma, based in Alameda, California, has established itself as a pioneer in nitrosamine detection and validation. The company's cutting-edge analytical platforms can accurately measure MNP levels alongside other nitrosamine impurities, including NDSRIs and NDMA.
Dr. Ron Najafi, chief executive officer of Emery Pharma, highlighted the collaboration's significance for drug development. "Our team's strength lies in solving complex analytical challenges and ensuring studies meet the highest regulatory and scientific standards. We're excited to contribute to safer, faster and more effective drug development."
Industry Impact
The collaboration addresses a significant bottleneck in pharmaceutical development that has affected the industry since 2021. By providing a reliable pathway for rifampin use in DDI studies, the partnership could help restore efficiency to early-phase clinical trials and reduce development timelines.
Fortrea's global clinical programs will now have access to this innovative rifampin impurity testing approach, with flexible study designs that meet FDA requirements. The company's extensive network spans more than 20 therapeutic areas across approximately 100 countries, positioning the collaboration to have broad industry impact.
The partnership combines Fortrea's three decades of clinical development experience with Emery Pharma's specialized analytical capabilities, creating what Cohen described as "an ideal collaboration for the testing of rifampin for use in our DDI studies."
This strategic alliance represents a significant step forward in addressing regulatory challenges that have complicated drug development processes, potentially benefiting pharmaceutical sponsors seeking to conduct more efficient and compliant clinical trials.
