18 months after opening its draft guidance to public comment, FDA has published its final industry guidance for chemistry, manufacturing, and control (CMC) information in early clinical trials with live biotherapeutic products (LBPs). The guidance outlines the CMC data required to substantiate Phase I trials of LBPs, which include the myriad product candidates containing bacteria, yeast, and other microorganisms.
The focus of Phase I studies has always been on patient safety, and the new guidance reminds the industry that, “During Phase I studies, emphasis should generally be placed on elements to assure the safety of subjects. This should include identification and control of the raw materials and the drug substance, stability assurance, and, where appropriate, nonclinical safety assessments.” In addition to the obvious benefit of establishing patient safety as the initial and most important priority of early clinical studies, this method also may allow companies to delay investments in full blown quality control and assurance until later in the clinical development cycle. This is critical for many early-stage companies that are strapped for cash.
Failure to sufficiently meet Phase I CMC requirements at the Investigational New Drug (IND) stage will most likely result in FDA’s delaying the proposed investigation (another company-killer). Among the most common causes of these delays are submissions lacking information about processes, facilities, and stability. The guidance outlines CMC data required to avoid delays, including a stability test protocol showing product integrity over trial duration, a “flow chart [showing] the steps in production, equipment and materials used, the room or area where the operation is performed, and a complete list of in-process controls and tests performed on the product at each step.”
To read the complete set of CMC data requirements in the final guidance, click here. Need help with clinical trial material production, vendor assessments, supplier oversight or CMC regulatory filings? Contact Pearl.