Pharmaceutical industry groups say they support the US Food and Drug Administration's (FDA) plan to request quality metrics from drugmakers, but they also call on the agency to clarify what it wants and implement a phased-in approach.
In July, FDA released its long-awaited draft guidance, Request for Quality Metrics, which outlined the agency's plans to collect quality metrics to "further develop FDA's risk-based inspection scheduling."
While the draft guidance revealed FDA's general approach to quality metrics and detailed 10 initial metrics the agency plans to collect, it left many areas open for input.
FDA says it intends to use quality metrics data to schedule its inspections more effectively, and foresees fewer inspections for manufacturers with "highly controlled" operations as a result of the initiative.
FDA says it has authority to request quality metrics under current good manufacturing practices (CGMP) and section 704(a)(4)(A) of the Food, Drug and Cosmetic Act, which allows the agency to gather records "in advance of or in lieu of" an inspection. Accordingly, FDA's draft guidance indicates that manufacturers that do not provide the agency with quality metrics "within a reasonable timeframe, drugs from the facility may be deemed adulterated."
Clarifying FDA's Approach
While industry groups have generally voiced their support for FDA's plans to collect quality metrics, both the Pharmaceutical Research and Manufacturers of America (PhRMA) and the Biotechnology Industry Organization (BIO) say FDA needs to release more specifics on how it plans to use the data it collects.
PhRMA writes that "the draft guidance shares none of the 'science' of FDA's metrics analysis, [and the agency] has provided no framework for evaluation, nor has it given a tentative description of the statistical analyses to be applied."
In the draft guidance, FDA says it plans to begin requesting quality metrics as soon as its guidance is finalized.
PhRMA, BIO and the Generic Pharmaceutical Association (GPhA) all said this would be too short a timeframe, and call on FDA to take a phased approach to implementing its metrics guidance.
All three organizations say FDA should begin with a voluntary two-year trial of the program that includes an assessments of the program's performance before making quality metrics reporting mandatory.
Responding to FDA's question on whether to include a free-text field for manufacturers to explain specific metrics, PhRMA, GPhA and BIO agreed it would be critical for manufacturers to provide context to the agency on specific results.
While PhRMA and BIO both commented that FDA should limit the quality metrics to the 10 listed in the draft guidance, GPhA and the International Society for Pharmaceutical Engineering (ISPE) requested FDA to initially limit the program to three metrics.
GPhA also called on FDA to exclude active pharmaceutical ingredient (API) manufacturers from the program "until the metrics process has matured."
GPhA and ISPE also questioned how quality metrics reporting requirements would apply to contract manufacturing organizations (CMOs). GPhA and ISPE argue that it would be impractical to report this data from CMOs, as quality metrics data are not "routinely gathered/shared" between CMOs and license holders. Likewise, BIO said FDA's draft guidance does not make it clear whether license holders or CMOs are responsible for reporting quality metrics, saying it would prefer data from CMOs to ultimately be reported to FDA by license holders.
PhRMA and GPhA are also challenging FDA's statutory authority to gather quality metrics in the manner proposed in the draft guidance, saying the agency's actions would go against the Administrative Procedures Act.
While FDA has the authority to collect records from covered establishments under the FD&C Act, PhRMA and GPhA challenge FDA's authority to require companies to "generate quality metrics data in the precise categories and format dictated by the draft guidance."
Both groups say that FDA should instead go through notice-and-comment rulemaking procedures to allow industry more "meaningful input on the definitions and format to be used by FDA."
PhRMA cautions that if FDA proceeds with its plans to require quality metrics data through guidance the program could face legal challenges "months or even years [after] implementation resources have been expended by both FDA and industry."
In its draft guidance, FDA asks whether it should consider requiring "high-risk excipient producers" to provide the agency with quality metrics data.
Responding to this question, the International Pharmaceutical Excipients Council of the Americas (IPEC-Americas) says that FDA should apply its guidance to finished drugs and active pharmaceutical ingredients (APIs) before looking at excipients.
Furthermore, IPEC-Americas says that there is no accepted definition of what constitutes a "high-risk" excipient. The group says that excipients' risks are mostly dictated by their use in high-risk drugs rather than from quality issues related to manufacturing.
The group says FDA also needs to clarify how its guidance would affect atypical actives, or excipients used as active ingredients, since the guidance would apply to API manufacturers.
Request for Quality Metrics Public Docket