In the final guidance the US Food and Drug Administration (FDA) explains how to do CMC (chemistry, manufacturing, and controls) for Phase I trials of live biotherapeutic products (LBP), such as those that contain bacteria.
“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”, the FDA wrote.
Companies can then refine quality control and assurance as the product moves through the phases of clinical development. This approach has the added benefit of saving companies from investing in quality control early in development only to see the compound perform badly in a clinical trial.
Dodging delays
Information that should be included at the IND (investigation new drug) stage includes a stability test protocol showing the integrity of the product for the planned duration of the trial. The FDA also asks for a complete list of the in-process controls and tests performed on the product at each step.
In a 2010 presentation at the New York Academy of Sciences Cara Fiore from the FDA said the most common CMC shortcomings relate to a lack of information about processes, facilities, and stability. Failure to provide suitable CMC information can lead to the FDA delaying a proposed investigation.
Final guidance comes 18 months after the FDA published its draft document. The FDA said it received ‘a few comments’, one of which is available here, and these prompted the addition of text related to the scope, definitions, and background section. Changes to improve clarity were also made.