Overview of the Quality Metrics Guidance

In July, the U.S. Food and Drug Administration (FDA) released   draft  guidance detailing the FDA’s plan to collect quality metrics for the pharmaceutical industry in order to monitor quality control systems and processes within the industry.  As we explained in an earlier post, the goal of the metrics collection is to drive continuous improvements in the drug development and manufacturing sectors.  While the pharmaceutical industry groups state that they support the guidance generally, they are reportedly concerned about the resulting cost and time burdens on the industry, the implementation timeframe, the use of a draft guidance versus the use of a rulemaking process for the requirements, and the lack of clarity about the agency’s intended use of the collected data.  As an overview, the data to be collected include:

• The number of lots attempted of the product;
• The number of specification-related rejected lots of the product, rejected during or after manufacturing;
• The number of attempted lots pending disposition for more than 30 days;
• The number of Out-of-Specification (OOS) results for the product, including stability testing;
• The number of lot release and stability tests conducted for the product;
• The number of OOS results for lot release and stability tests for the product that are invalidated due to lab error;
• The number of product quality complaints received for the product;
• The number of lots attempted that are released for distribution or for the next stage of manufacturing the product;
• If the associated Annual Product Reviews (APRs) or Product Quality Reviews (PQRs) were completed within 30 days of annual due date for the product; and
• The number of APRs or PQRs required for the product

The FDA plans to use the quality metrics data to schedule its risk-based inspections more effectively, where there will be fewer inspections for those manufacturers who produce timely and thoughtful  reports proving highly controlled operations to the agency. Therefore, the  benefit to the industry from the agency’s quality metrics collection is the possibility of less frequent inspections and increased opportunity to self-regulate.

Industry Response

Cost and Time Burdens on Industry

Pharmaceutical groups are concerned about the amount of time and investment that will be needed to meet the FDA’s requirements in the draft guidance. The Pharmaceutical Research and Manufacturers of America (PhRMA) has commented that the “FDA is substantially underestimating the burden that manufacturers will encounter in collecting and reporting such information” required in the draft guidance. PhRMA stated that the industry’s collection and organization of metrics data from numerous sites in the supply chain will challenge the industry. Furthermore, many pharmaceutical groups will have to change their practices to be in compliance and maintain consistency with the FDA’s expectations in the guidance, which may prove costly and time consuming for the industry. The FDA also stated that it plans to begin requesting and collecting the metrics data as soon as the guidance is finalized.

Phased Approach to Implementation

Due to the numerous changes that the industry will have to implement in a short timeframe to meet the guidance’s requirements, industry groups such as PhRMA, the Biotechnology Industry Organization (BIO), and the Generic Pharmaceutical Association (GPhA) have called on the FDA to implement the metrics guidance in phases. Specifically, the organizations ask the FDA to begin with a voluntary two-year trial program that includes an assessment of the program’s performance before mandating the quality metrics reporting requirements.  PhRMA stated that a phased approach would “prevent any unintended consequences that can arise when embarking on such an innovative and transformative approach to regulation” and “provide ample opportunities for evaluation and optimization of the quality metrics program.”

Statutory Authority

Industry groups call on the FDA to propose rules to implement the quality metrics requirements, challenging the quality metrics program in the draft guidance under the Administrative Procedures Act.  The GPhA released a statement calling the draft guidance “legally flawed in that it proposes requirements that exceed the agency’s statutory authority, is contrary to law, and fails to consider important aspects of the problem it seeks to address.” According to industry groups, the draft guidance is not the correct mechanism to impose binding quality metrics collection and reporting requirements, and under a draft guidance, the FDA would not have a legal basis to initiate enforcement actions against companies who failed to comply with the requirements, wasting both the agency’s and the industry’s time and efforts.

PhRMA raised the issue that the FDA’s failure to use a rulemaking process would make the quality metrics program “vulnerable to legal challenge” after industry companies will have invested millions of dollars and significant time in efforts to comply with the program’s requirements.

Instead, groups suggest that the FDA go through a notice-and-comment rulemaking procedure to allow industry an opportunity to voice its input and concerns in a comprehensive and organized manner.

Need for Clarification

There is also worry among the industry groups regarding the FDA’s use of the collected metrics data. BIO released a statement expressing its concern that “it is unclear whether FDA would use low-quality metrics as an indicator to increase inspections at a particular entity” or to take compliance actions  against a company.  Moreover, PhRMA stated that while the FDA has released the type of data it wants to collect from groups, it has not shared any of the science behind the FDA’s metrics analysis, the framework for evaluating the data, and the type of statistical analysis that will be applied to the data collected.

While there are benefits to the industry to be gained from the creation of the quality metrics collection program in the draft guidance, there are still many aspects of the program and its requirements that may need improvement to alleviate the industry’s concerns.