Whether or not you agree with the FDA in its determination to collect “quality data” directly from all drug manufacturers – including contract manufacturing organizations (CMOs) – if the agency moves forward, then the real question is this: Should that data, and any rating the agency might assign to individual manufacturing plants for quality standards or “quality culture,” be kept internal at the FDA or made public?
Originally at Outsourced Pharma West San Diego in August, and continuing through our just concluded conference in San Francisco, we’ve discussed this topic of quality metrics openly, and indeed with some passion. Particularly spurred by a panel in San Diego led by Timothy Scott, president, Pharmatek, it was decided we would take the FDA up on its Request For Quality Metrics Guidance for Industry DRAFT GUIDANCE. You can find our submittal here.
Below is further analysis and background.
If You Collect, You Must Communicate
The debate over the FDA moving towards an enhanced oversight at manufacturers, in an effort to further promote what it calls a culture of quality, certainly goes on. Many in the against column believe it’ll be doubly onerous if as a part of this new initiative judgments on the quality of facilities, or quality culture of organizations, are made public.
This is understandable for a variety of reasons. For one, there’s the real possibility of data or metrics being misunderstood or misconstrued by everyone from the FDA to the general public, or by customers and competitors, perhaps particularly in the case of CMOs. There’s also the challenge of quantifying the qualitative (e.g., a “quality culture”), and measuring evenly or comparatively across product, platform and plant.
It’s probably safe to say those concerns are acknowledged – and shared. Also shared is the opinion that debate on all issues continues. At the same time, as the FDA’s (once extended) deadline for comments approaches, and although the form and practice of this new quality initiative appears still very much in flux at FDA, we’ve decided it better to take the side of at least some level of public disclosure of any process, resultant data, and metrics derived as a part of this new initiative. Taking from the comments submitted to the FDA, this would:
(a) Enhance the ability of all drug discovery and development organizations and sponsors (e.g., academia-based investigators; virtual and start-up companies; established biotechs; Specialty and Big Pharma) to select the most “quality reliable” manufacturing locations. Public disclosure would help increase quality standards for projects at all sponsors, and reinforce the need for obtaining the highest – and measurable – “culture of quality” at all manufacturers and service providers, and ultimately and positively affect patients.
(b) Further bring CMOs and all third-party drug discovery, development and manufacturing organizations into the public awareness, aiding an already growing understanding of the increased utilization of these organizations in all facets of production of patient medicines, and again promote higher quality standards throughout the industry and for those patients.
On our quality panel in San Diego, Julia O’Neil, principal, Tunnel Consulting, articulated this positive attribute of the FDA metrics initiative itself: “I was in the [Outsourced Pharma West San Diego] session this morning on how sponsors should measure their CMOs. The ideas sounded very similar to the quality metrics guidance coming out from the FDA. I wonder if it’s possible that the FDA, requiring quality metrics in reporting on a standard basis, could actually simplify the work of evaluating and measuring CMOs. Relative to continued process verification, most CMOs want to be good partners, and provide proof of their quality records. But every sponsor asks for a report in a different format with different requirements, creating complexity for those who want to comply with continued process verification. So I wonder if this new guidance from the FDA could serve to standardize on the quality metrics side.”
With the vantage points above of transparency (public disclosure) and simplification (standardization), if this new FDA quality initiative is indeed inevitable, then there is an increased potential the entire drug industry could end up benefiting from it.
An Element Of Self-Improvement In Controversial Initiative
It appears there is no quarter in disagreement with the need for and goal of improving quality in drug development and manufacturing. In fact, also surfaced at our Outsourced Pharma conferences in 2015, was an active call for a global coming together on quality standards and shared SOPs of the drug development and manufacturing outsourcing industry itself.
“There was much more feedback at our conference than this issue on transparency at the FDA,” says Tim Scott, who moderated the quality-metrics session. “Panelists and attendees provided a significant amount of thoughtful and comprehensive review of the Guidelines. But while much of the feedback involved regulatory aspects, transparency of findings is a public policy issue that kept coming up. It’s also an important first step: A deeper focus on developing quality culture is critical to the CMO industry successfully regulating itself. So transparency at the FDA is important so long as quality data is standardized and meaningful.”
So again, while recognizing such issues as the burden of more regulation; the difficulty in FDA making accurate assessments of quality above and beyond specific inspections; the real risk of misinterpretation of metrics by the public (or potential customers of CMOs); we’re in favor of the following:
1. The FDA make available – even if in an abbreviated or abridged format – information it obtains from new reporting guidelines for manufacturers, including contract service providers (CMOs), regarding the development and manufacture of drug substance and drug product at their facilities, as it relates to quality metrics.
2. In the case where the FDA adheres to a policy of keeping internal the submitted quantitative and qualitative information from manufacturers and CMOs, since the agency has implied it intends to assign “grades” to each individual manufacturing plant or facility, that at least those grades – or any other rating – along with a scale and detailed description of those grades, be made public.
We’re interested in hearing what others think.
A thank you to Tim Scott, CEO, Pharmatek, and Julia O’Neill, Principal, Tunnell Consulting, for their efforts on behalf of Outsourced Pharma West (both Sand Diego and San Francisco), and with the recommendation submitted to FDA.