Slow down on the quality metrics push, drugmakers advise the FDA

The FDA needs to apply the brakes on its headlong rush to adopt quality metrics for the manufacturing of drugs, the agency was told Monday.

Industry groups speaking at a public meeting on a draft quality metrics guidance released last month were unanimous in urging the FDA to "start small, learn and revise" before dashing into a full-blown metrics program that could drive drugmakers and the agency itself into a sinkhole of data with no clear methodology for how it would be used.

Before issuing a final guidance, the FDA should provide more of everything, various industry groups said, including more time for comments, more definitions, more transparency, more clarity and more consideration for the burden specific metric requests would impose on drugmakers.

In opening the meeting, the FDA's Janet Woodcock made the case for a quality metrics program that's part of what she called a "quality revolution." With more than 13,000 facilities around the world producing drugs and pharmaceutical ingredients for the U.S. market, the FDA is facing some steep challenges to its current inspection program. Thus, each manufacturing site needs to have a quality system in place to ensure the ongoing quality of drugs coming to market, Woodcock said.

The guidance, developed through a series of meetings with industry, proposed four quality metrics to start with – the lot acceptance rate, quality complaint rate, invalidated out-of-specification rate, and the annual product review or product quality review on-time rate. It also suggested optional metrics, such as senior management engagement and the effectiveness of a company's corrective and preventive action programs, which could be added later.

The data required for the metrics would have to be submitted annually, if not more frequently, and would be considered part of a pre-inspection request, making noncompliance subject to the same penalties as refusing an inspection. The data would then be used to develop objective measures of drug and site quality.

This is a learning process, said Ashley Boam, acting director of the FDA's Office of Policy for Pharmaceutical Quality. She added that companies are already collecting the data needed for the metrics.

Industry groups begged to differ with her, with several recommending that the quality metrics program start slowly until the agency knows what it's doing.

"The process seems unduly rushed considering the significance," said David Gaugh, senior vice president for sciences and regulatory affairs at the Generic Pharmaceutical Association. Like others at the meeting, he raised concerns about the unintended consequences of a guidance that "imposes binding, rigid rules" and increased inspection penalties for failure to report "voluntary information."

Although the FDA worked with industry in formulating the guidance, what was issued had a lot of surprises, Gaugh said. He questioned the agency's authority to require manufacturers to generate new records and to implement certain provisions, especially under the guise of a guidance.

Gaugh also noted that the agency underestimated the burden the program would have on drugmakers. "What the guidance specifies is not reasonable," he said.

Diane Hagerty, representing the International Society for Pharmaceutical Engineers, agreed that the FDA had significantly underestimated the burden, especially for companies that would have to change their information technology systems to capture new data and incorporate additional reviews.

She advised the agency to start with a voluntary program that would allow for a phased approach so the agency could understand just how much data would be coming in. Hagerty also called for greater transparency on how the data will be evaluated and used.

In a webinar on the proposed guidance, FDA staff indicated that after the agency begins collecting the data, it will need to refine its definitions and improve its understanding of how best to interpret and use the metrics. Those things need to be done before the program starts, industry officials asserted.

USING THE DATA

The FDA has touted the metrics program as a way to better use its limited resources by allowing it to:

• schedule risk-based inspections;

• identify potential risks of drug shortages;

• improve the efficiency and effectiveness of inspections;

• improve the agency's evaluation of drug manufacturing and control operations.

The big plus for drugmakers is the possibility of reducing the number of inspections they face as the FDA moves from a "blame-and-shame" enforcement model to a model of improving quality management, Woodcock said.

While the public meeting was supposed to be a time for stakeholders to comment on the guidance, several groups had questions for the agency, especially about how the guidance would impact contract manufacturers.

Their questions remained unanswered. Unless the FDA heeds the requests to give stakeholders more time to comment on the draft guidance, comments are due by Sept. 28. In concluding the meeting, the FDA's Russell Wesdyk said the agency will continue to work with stakeholders as it finalizes the guidance.

"Publishing a final guidance is a high priority," he said, adding that the final version won't be released this year.

Prior to issuing that guidance, the FDA intends to conduct an internal and international outreach program with updates.

Meanwhile, the agency has been working on a quality metrics framework that includes a technical performance guide and technical specifications, both of which are in the clearance process, said Ron Fitzmartin, an FDA senior adviser.

The performance guide is intended as a "living document" that explains how to submit the metrics data and describes the various data elements.

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