FDA Proposes New Quality Metrics for Drug Manufacturing

With an eye on manufacturing modernization and a mission to protect public health, the Food and Drug Administration (FDA) this week released a draft of its Request for Quality Metrics, a guide for the pharmaceutical industry. The document, which currently contains non-binding recommendations, outlines a set of measurements to evaluate the quality of the facilities and the processes that manufacturers use to make regulated drugs and biologics.

According to the document, quality metrics are used to develop compliance and inspection policies and practices in order to improve the FDA’s ability to predict and possibly mitigate future drug shortages. Shortages of drugs and biologics pose a significant public health threat, the FDA says, as it delays critical needed care for patients. To that end, the agency has found that the majority of drug shortages stem from substandard manufacturing facilities that may result in quality defects that require remediation efforts to fix the issue. This, in turn, interrupts production and causes a shortage.

The FDA will use the metrics as a tool to encourage the pharmaceutical industry to implement state-of-the-art quality management systems, and ultimately provide peace of mind to patients, healthcare professionals, and caregivers who will be assured medications are available and made with the highest quality methods.

The guidance includes an explanation of how the Center for Drug Evaluation and Research (CDER) and the Center for Biologics Evaluation and Research (CBER) intend to collect data and use quality metrics to help ensure that their policies and practices support continuous improvement and innovation in the pharmaceutical manufacturing industry.

Manufacturers are expected to maintain a state of control over the life of the drug production process, even as materials, equipment, the production environment, personnel, and manufacturing procedures change. That means pharmaceutical companies will need programs in place to collect and analyze information to evaluate the state of control throughout the process.

In addition, the FDA is encouraging some optional metrics around a “quality culture.” The agency is proposing that manufacturers have senior management engagement measured by their authority to implement change related to product quality, and their ability to share knowledge throughout the manufacturing organization. Another metric evaluates corrective and preventative action (CAPA) effectiveness. And, the use of statistical process control as a tool to understand and manage variability in both product and processing.

The FDA is asking for comments on the draft guidance from patients, prescribers, and the pharmaceutical industry. The feedback collected will be reviewed and discussed during a public meeting next month and used to finalize the guidance.

The International Society for Pharmaceutical Engineering (ISPE) issued a statement that it is reviewing the document as it relates to its own data gathered through its Quality Metrics Pilot Program, which supports FDA efforts to develop guidance on quality metrics.

Developing standards, too, will be critical to the success of a quality metrics program. According to ISPE, “routine company metrics include number of lot release tests, out-of-specification results, and lots attempted, rejected, reworked, and reprocessed. However, each company tends to collect data in its own way for its own internal use, using a range of definitions and sampling plans. How firms measure and define “batch,” “lot,” and even “rejection” can differ among companies in different sectors, in the same sector, and even within the same company. Standardization is needed to ensure that the metrics reported to the FDA are defined and measured the same way by all.”