Gil Roth, President, Pharma & Biopharma Outsourcing Association09.16.19
Shortly before Labor Day weekend, the FDA extended the deadline for its Quality Metrics Feedback Program by four months,1 giving license holders and manufacturers the opportunity to talk with the agency about their forays into measuring key quality attributes of products and facilities.
According to the agency, the Quality Metrics (QM) Initiative is intended both to promote quality at drug manufacturing facilities—under the notion that measuring quality empowers companies to improve their quality systems—and to help the FDA refine its risk-based inspection program, as well as to help predict manufacturing-related shortages.
PBOA has been involved in the industry response to the QM Initiative since a public meeting FDA held in 2015, which led to the establishment of our Quality Technical Group (QTG) and our involvement in a cross-industry consortium on QM. Our members have significant concerns about the QM Initiative, the massive new regulatory burden it may create, how it can be inadvertently biased against CDMOs, and the flaws in using it to rank facilities, rather than product-specific ratings, among many other issues.
While it’s been invaluable for PBOA’s QTG to submit written comments to FDA’s QM docket (you can find our docket submissions at pharma-bio.org), there’s a lot of value in direct feedback and interaction with the agency, especially with a subject as complex as Quality Metrics.
Last year, members of PBOA’s Quality Technical Group met with FDA’s QM team to talk about our concerns with the initial visions of the program, as well as some of the realities of how the CDMO sector works. I’ve written previously about the importance of the latter, but I can’t stress it enough: CDMOs are not the same as in-house pharma—be it innovator or generic—and often our regulators and legislators aren’t aware of how those differences mitigate against a one-size-fits-all model and the language of “drug manufacturers.” Our member companies aren’t averse to the idea of measuring quality across time, but we explained some of the differences between, for example, a pharma facility dedicated to a single product and a CDMO site with a dozen or more customers and dozens of SKUs: they can both be high quality sites that pass surveillance inspections with flying colors, but the in-house, single-product site is almost by definition going to be in greater control of its more limited set of product processes.
The FDA team seemed legitimately surprised about aspects of how CDMOs work with their customers. Our members talked about the, shall we say, suboptimal tech transfers that sometimes occur with decades-old products, and how as CDMOs it’s their job to make the product effectively, but that any improvements to the process they develop could get rejected by the customer, who may not want to go through with filing a change to that product with the FDA (and with every other regulator in other regions where it may market that product).
We also talked about the challenges around how CDMOs can generate a consistent set of metrics for FDA’s consumption when CDMO customers apply key terms inconsistently. When an FDA representative asked about metrics related to batch records, one of our members replied, “How do you define ‘batch’? Because I have five customers at one facility who have five different definitions of what a batch is, and that means they may each report batch-related metrics that don’t reconcile with other products at the same facility.” Rather than clutch their pearls and faint in horror, the FDA staff was interested in how common terms and definitions could get refined and implemented across the industry.
That meeting was filled with candid but not confrontational conversation about the QM Initiative and how our members work with their customers, FDA and other regulatory bodies to ensure quality therapeutics reach patients. Our members took back input from FDA just as they heard our concerns. While our docket submissions can be comprehensive responses to guidance documents, sessions like this can provide room for conversation and learning.
FDA’s Quality Metrics Initiative is a very complex and controversial issue for all of pharma and for CDMOs in particular. Hiding from the agency and hoping it will never get implemented is no way for a mature, responsible, quality-oriented sector like ours to behave. It’s my hope that CDMOs engage the FDA through the Feedback Program and help shape and inform the agency’s next steps.
References
Gil Roth
President, Pharma & Biopharma Outsourcing Association
Gil Roth is the President of the Pharma & Biopharma Outsourcing Association (www.pharma-bio.org). He can be reached at gil.roth@pharma-bio.org.
According to the agency, the Quality Metrics (QM) Initiative is intended both to promote quality at drug manufacturing facilities—under the notion that measuring quality empowers companies to improve their quality systems—and to help the FDA refine its risk-based inspection program, as well as to help predict manufacturing-related shortages.
PBOA has been involved in the industry response to the QM Initiative since a public meeting FDA held in 2015, which led to the establishment of our Quality Technical Group (QTG) and our involvement in a cross-industry consortium on QM. Our members have significant concerns about the QM Initiative, the massive new regulatory burden it may create, how it can be inadvertently biased against CDMOs, and the flaws in using it to rank facilities, rather than product-specific ratings, among many other issues.
While it’s been invaluable for PBOA’s QTG to submit written comments to FDA’s QM docket (you can find our docket submissions at pharma-bio.org), there’s a lot of value in direct feedback and interaction with the agency, especially with a subject as complex as Quality Metrics.
Last year, members of PBOA’s Quality Technical Group met with FDA’s QM team to talk about our concerns with the initial visions of the program, as well as some of the realities of how the CDMO sector works. I’ve written previously about the importance of the latter, but I can’t stress it enough: CDMOs are not the same as in-house pharma—be it innovator or generic—and often our regulators and legislators aren’t aware of how those differences mitigate against a one-size-fits-all model and the language of “drug manufacturers.” Our member companies aren’t averse to the idea of measuring quality across time, but we explained some of the differences between, for example, a pharma facility dedicated to a single product and a CDMO site with a dozen or more customers and dozens of SKUs: they can both be high quality sites that pass surveillance inspections with flying colors, but the in-house, single-product site is almost by definition going to be in greater control of its more limited set of product processes.
The FDA team seemed legitimately surprised about aspects of how CDMOs work with their customers. Our members talked about the, shall we say, suboptimal tech transfers that sometimes occur with decades-old products, and how as CDMOs it’s their job to make the product effectively, but that any improvements to the process they develop could get rejected by the customer, who may not want to go through with filing a change to that product with the FDA (and with every other regulator in other regions where it may market that product).
We also talked about the challenges around how CDMOs can generate a consistent set of metrics for FDA’s consumption when CDMO customers apply key terms inconsistently. When an FDA representative asked about metrics related to batch records, one of our members replied, “How do you define ‘batch’? Because I have five customers at one facility who have five different definitions of what a batch is, and that means they may each report batch-related metrics that don’t reconcile with other products at the same facility.” Rather than clutch their pearls and faint in horror, the FDA staff was interested in how common terms and definitions could get refined and implemented across the industry.
That meeting was filled with candid but not confrontational conversation about the QM Initiative and how our members work with their customers, FDA and other regulatory bodies to ensure quality therapeutics reach patients. Our members took back input from FDA just as they heard our concerns. While our docket submissions can be comprehensive responses to guidance documents, sessions like this can provide room for conversation and learning.
FDA’s Quality Metrics Initiative is a very complex and controversial issue for all of pharma and for CDMOs in particular. Hiding from the agency and hoping it will never get implemented is no way for a mature, responsible, quality-oriented sector like ours to behave. It’s my hope that CDMOs engage the FDA through the Feedback Program and help shape and inform the agency’s next steps.
References
- Federal Register: “Modernizing Pharmaceutical Quality Systems; Studying Quality Metrics and Quality Culture; Quality Metrics Feedback Program; Reopening of Submission Period” https://www.federalregister.gov/documents/2019/08/30/2019-18771/modernizing-pharmaceutical-quality-systems-studying-quality-metrics-and-quality-culture-quality
Gil Roth
President, Pharma & Biopharma Outsourcing Association
Gil Roth is the President of the Pharma & Biopharma Outsourcing Association (www.pharma-bio.org). He can be reached at gil.roth@pharma-bio.org.
