By: Mark A. Lynch, VP – Management, PAREXEL® Consulting & Robert Iser, VP – PAREXEL® Consulting
Who would not want the fastest possible approval of a new drug to treat a significant disease condition and improve patients’ lives? Certainly the FDA has recognized the need for “Fast Track” and other “Expedited Approval” Options in order to address critical needs. U.S. FDA has developed the expedited approaches and pathways to address urgent patient needs. FDA has published a Guidance for Industry on Expedited Programs for Serious Conditions – Drugs & Biologics [https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM358301.pdf] which lays out a number of considerations for companies developing products that may fill gaps in unmet patient needs (e.g., accelerated pathways, breakthrough designations, etc.). Sponsors may also utilize additional options, such as developing products with an orphan drugs status or tapping into advice available through FDA Oncology Center of Excellence.
However, shortened timeframes for the drug approval process puts additional pressure on manufacturers and sponsors to assure they are ready for the key steps in the process, especially from the perspective of quality systems and CGMP compliance of manufacturing and testing facilities. For example, one key step is the manufacture of clinical materials in a both a consistent and high quality manner. If sponsors do not have manufacturing facilities themselves, they are forced to look for and negotiate arrangements (i.e., Quality Agreements) with suitable contract manufacturing facilities. These contract manufacturing organizations (CMOs) may or may not have the technical expertise or an adequate quality system to make the sponsor’s new drug in a consistent manner. Many sponsors use the expertise of competent consultant organizations to assist them in due diligence audits and help in setting up an effective Quality System infrastructure and Quality Agreement to approach the controls needed not only in production of clinical trial materials, but also commercial production as the regulatory process moves forward. It is essential that sponsors pay attention to the clinical material and planned commercial material manufacturing environment and controls, so that this does not become an obstacle to approval and critical patient access.
PAREXEL Consulting has found that many times sponsors leave evaluation of production and control facilities to the end. PAREXEL Consulting’s experts counsel against this strategy and urges sponsors to evaluate facilities before submitting the drug application, especially if the sponsor has limited experience with the facility. If not done until after drug application submission, sponsors can be caught between the rapidly, shortened approaching PDUFA date and the time needed for corrections and improvements to assure facility readiness. Readiness pertains not only to the condition and controls of the facility, but also to the capabilities of the personnel to manage a regulatory inspection. This activity is too important to leave to chance, since it is well understood that facilities and personnel, who practice inspection-like activities and refine their processes, technical skills, and communications, yield fewer issues when investigators are performing an on-site inspection
PAREXEL Consulting has helped many sponsors navigate this territory through training, mock audits, and participation in actual inspections to help assure effective communication and agency readiness. We have experienced technical experts ready to help companies wherever you are along the drug development pathway.