Back to the drawing board for FDA’s revised quality metrics plan?

Regulatory NewsRegulatory News | 13 June 2022 |  By 

The US Food and Drug Administration’s (FDA) revised plan to collect quality metrics data from manufacturers drew criticism from one major pharmaceutical industry group on the metrics the agency is proposing, as well as its methods for developing the program. Others complained that the proposed program lacks focus, while two industry groups also expressed serious misgivings about the purpose of the overall program.
Yet on a positive note, one industry group and major manufacturer praised the plan’s flexibility in allowing manufacturers to decide which metrics to report.
FDA issued the calls for comment in releasing its revised quality metrics proposal in March. (RELATED: Quality metrics: FDA wants feedback on pared-down program, Regulatory Focus 8 March 2022)
The proposal is FDA’s attempt to revive its earlier stalled efforts to obtain manufacturing quality data to reduce potential drug shortages. The comments were a bit more supportive of the flexibility of this plan compared to previous iterations. (RELATED: Industry Wants FDA to Hit the Brakes on Quality Metrics Program, Regulatory Focus 30 March 2017).
The agency stressed in an announcement that this program would be different from the original quality metrics draft guidance unveiled in 2015, as well as the revised draft guidance issued in 2016.
FDA identified four areas, with individual metrics within each of the areas, as appropriate for reporting: manufacturing process performance, pharmaceutical quality system (PQS) effectiveness, laboratory performance, and supply chain robustness. The reporting establishment would select the most appropriate metrics from each practice area and inform FDA how it was calculated. FDA also sought feedback as to whether reporting at the establishment level is appropriate.
Flexibility praised
Both Pfizer and the Parenteral Drug Association (PDA) supported the flexibility of the proposed quality metrics program.
Pfizer said, “in principle we agree with the proposed direction of FDA’s QM reporting program and the flexibility on what metrics are reported, as well as the allowance for each estosehemnt to be able to define how to calculate the metrics.”
Yet, Pfizer noted that “the program introduces potential ‘incentives’ but does not address specific regulatory and oversight incentives, such as possible lowering inspections frequency.”
PDA also supported the proposal’s flexibility. The group writes that “allowing a site to select the metrics from within a specified practice area that is most appropriate to their operations and best characterize the maturity of their site or the opportunity for improvement is a positive development for the industry.”
ISPE calls for increased engagement
In its comments, the International Society for Pharmaceutical Engineering (ISPE) said FDA needs to solicit more outside engagement with industry in developing the program.
“The current approach of issuing guidance, piloting programs, commenting on docket requests, and responding to polls during the FDA conferences provides limited opportunities for dialogue. Expertise that all parties could provide to develop this important initiative could be better leveraged,” ISPE wrote.
In addition, the group said its members did not support any of the four practice areas suggested by FDA.
For example, members told ISPE that supply chain robustness “may be relevant to business performance for some companies, however, there was not a high level of support for these metrics in our survey with many strong comments that they were out of scope of a quality metrics reporting program.”
Bristol-Meyers Squibb also expressed concern about including supply chain robustness as a metric. “BMS is concerned with the inclusion of the supply chain general practice area as it may be redundant or duplicative of other initiatives such as the CARES Act volume reporting requirement.”
ISPE also said that its members were “polarized” on FDA’s recommendation to report process capacity values, and therefore, “Cannot recommend inclusion of this metric.”
The group said that the number of batches manufactured within a reporting period “may be insufficient to support calculation of process performance as well as the variable and inconsistent setting of specification acceptance criteria.”
In addition, ISPE said the PQS effectiveness metric was not supported by its members. ISPE also recommends moving the laboratory performance metric to the manufacturing process performance area and removing the invalidated/overturned out-of-specification (IOOSR) metric from the list of potential metrics.
AAM and PBOA have serious misgivings
Two groups, the Association for Accessible Medicines (AAM) and the Pharma & Biopharma Outsourcing Association (PBOA), a trade association representing contract manufacturers, expressed reservations about the program.
AAM said FDA’s proposals are not aligned with the group’s proposal outlining five key quality metrics reporting principles in a 2021 while paper. These principles include the following: quality metrics must be within bounds of clear statutory authority, quality metrics data should be collectible and participating must be feasible, quality metrics should be formalized by product types and product risk and quality metrics should not create “perverse” incentives.
AAM wrote that FDA’s proposed quality metrics program is not aligned with any of these principles, and “in many respects moves even further away from them than some of FDA’s previous quality metric reporting program proposals.”
The group adds, “We are concerned FDA’s proposed potential new direction for a quality metrics reporting program may still lack appropriate statutory authority, may incorporate metrics that have not been validated and that may not be relevant to quality, and would incentive the submission of metrics that are not meaningful and that would not advance public health.”
Along these same lines, PBOA complained that FDA’s proposal lacks focus, and recommends the agency “more clearly define its purpose and the intent behind this initiative.”
“Without collecting data in a focused way and with clarity of purpose, our members are concerned about how these metrics will be interpreted and how they may incorrectly reflect the state of quality maturity or focus of a site. PBOA is also concerned that the metrics collected will vary dramatically depending on site versus product metrics, development status of drugs being measured, annual manufacturing demand, and age of the manufacturing product/process.
The group also wrote that “there is no clear, positive incentive for CDMOs to participate in the program, only negative ones. The incentives that FDA has cited in the past have been discussed are focused on sponsor’s/MAH’s goals.”
Establishment site metrics supported
In other areas, BMS said it supports the inclusion of establishment site metrics. The use of these metrics “will allow reporting of metrics that are meaningful to the establishment’s operations. Metrics should be selected to allow an establishment to monitor its own operations and drive continuous improvement.”
BMS also recommended that the agency take a phased approach to rolling out the program.
Biologics not adequately addressed
In terms of specific products covered by the plan, the Biosimilars Council said the quality metric program is not tailored to biologics manufacturers.
The proposal does not “adequately account for inherent differences between specific product categories (i.e., biological products versus chemically synthesized small-molecule drug products). Namely due to the complexity of biological products, it would be inappropriate to compare metrics data from a biological site to other incomparable sites, such as those for a simple oral solid. For example, bioassays can have high invalid rates as compared to a typical high performance liquid chromatography (HPLC) analytical method.”
The council said, “Because FDA intends to use quality metrics data to develop compliance and inspection policies and practices, biological products could face inequitable treatment if these differences across product categories are not considered. Consequently, biosimilars manufacturers may therefore choose not to participate in the program.”
Comments on quality metrics


© 2023 Regulatory Affairs Professionals Society.

Tags: FDA, metrics, quality

Discover more of what matters to you