Over a decade ago, the FDA issued a final report on Pharmaceutical Quality for the Twenty-First Century. As time moved forward, this led to the FDA’s Center for Drug Evaluation and Research through the creation of the Office of Pharmaceutical Quality, to launch “FDA Pharmaceutical Quality Oversight: One Quality Voice” (here), which attempts to develop the stated desired state as: “A maximally efficient, agile, flexible pharmaceutical manufacturing sector that reliably produces high-quality drug products without extensive regulatory oversight.” While there has been significant progress towards that goal, nevertheless, there have been repeated indicators from industry of significant product quality defects that has led to a number of drug shortages and product recalls.
In an attempt to address these concerns, in 2015, FDA issued a draft guidance, “Request for Quality Metrics” and opened a Docket asking for comments (here). The initiative has generated 113 comments, two (2) ISPE Quality Metrics Pilot Projects (Wave 1, Wave 2), a St Gallen Metrics Research Final Report, numerous Webinars and industry meetings, and a revised draft guidance. Later, FDA has apparently learned that implementing a uniform standard for Quality Metrics across all players in the pharmaceutical industry is not a simple task, judging by their notices in today’s Federal Register of two (2) new programs, the Quality Metrics Feedback Program and the 2018 Quality Metrics Site Visit Program.
Modernizing Pharmaceutical Quality Systems; Studying Quality Metrics and Quality Culture; Quality Metrics Feedback Program is meant to encourage NDA holders to request Type C formal meetings, and ANDA holders to submit pre-ANDA requests to discuss Quality Metrics. In addition, FDA is initiating a pilot study to gain feedback from those establishments for which Type C formal meetings or pre-ANDA meetings do not apply (e.g., Active Pharmaceutical Ingredients (API) establishments, contract manufacturing organizations, over-the-counter (OTC) monograph products establishments, or marketed unapproved finished drug products establishments). Participation is voluntary.
FDA is looking for nine (9) or fewer firms using the following selection criteria:
- Company must be a covered establishment engaged in the manufacture, preparation, propagation, compounding, or processing of a covered drug product.
- Company must have an existing Quality Metrics Program that has been developed and implemented by the Quality Unit, and that is used to support product and process quality improvement.
Specific details about what FDA is looking for in the internal Quality Metrics Program can be found in this Federal Register notice of June 29.
FDA asks interested companies to submit a written request to participate in the program by July 29, 2019. The requests should be labeled as “Type C Meeting–Request to Participate in the Quality Metrics Feedback Program.” Pre-ANDA applicants or sponsors planning to submit an original or supplemental pre-ANDA should submit a pre-ANDA meeting request to OPQ-OS-Quality Metrics@fda.hhs.gov and label it as “Pre-ANDA Meeting–Request to Participate in the Quality Metrics Feedback Program.”
To be considered for the voluntary Quality Metrics Pilot Program, a company should submit a statement of interest for participation to OPQ-OS-QualityMetrics@fda.hhs.gov . Further information regarding this statement of interest can be found in the FR Notice.
The second Federal Register Notice published today, announcing the Quality Metrics Site Visit Program for Center for Drug Evaluation and Research and Center for Biologics Evaluation and Research Staff clearly demonstrates that, based on the feedback received from industry, FDA feels that they need to visit companies to observe their internal practices. This is an announcement of a CDER and CBER staff Experiential Learning Site Visit Program, whereby CDER and CBER staff will observe how Quality Metrics data are gathered, collected, and reported to management. FDA anticipates 5-10 FDA representatives who are involved with development of FDA’s Quality Metrics Program, would participate in a site visit to volunteer companies for a 1-2 day period. FDA feels that this program will provide stakeholders with opportunity to explain the advantages and challenges associated with implementing and managing a robust Quality Metrics Program.
The FR Notice invites pharma companies that are interested in participating to submit a Quality Metrics Site Visit Proposal. The details of what they would like in the proposal can be found in the FR Notice.
FDA is particularly interested in visiting companies that are:
- Manufacturer of brand, generic, biotechnology, APIs, and non-application product(s) marketed under the over-the-counter (OTC) monograph system, and any combination of these products;
- Contract development and manufacturing organizations;
- Establishments with small and large portfolios; and
- Establishments with past or current product availability issues (e.g., history of a drug supply issue, recall)
Companies that are interested in offering a site visit, or learning more about this Site Visit Program should respond by submitting a proposal directly to Tara Gooen Bizjak (Tara.Gooen@fda.hhs.gov) or Stephen Ripley of CBER by mail (address is in FR Notice).