Industry Remains Divided on Quality Management Maturity Proposal

At the 2022 FDA Pharmaceutical Science and Clinical Pharmacology Advisory Committee Meeting, November 2-3, CDER’s quality management maturity (QMM) program proposal was presented along with interested party public comments on the program. The committee’s vote was a unanimous ‘yes’ that CDER should establish a QMM program to incentivize investment in mature quality management practices. However, this positive recommendation was not fully supported by industry speakers.

In follow-up discussions with members within the industry at the meeting, there was support and opposition to FDA’s QMM program. Some of the concerns expressed were the level of transparency (and the necessary context) regarding the QMM ratings to external stakeholders (e.g., payors, physicians, patients), a lack of clarity on possible incentives provided to companies that adopted QMM and voluntarily provided data to the FDA, and specifically how the FDA will use the data in their evaluations. Moreover, while it is known that some companies are assessing QMM within their facilities, these were some of the concerns voiced that seem to be holding back the industry’s support regarding a QMM program.

Presentations from past PDA/FDA joint regulatory conferences have described some suggested incentives related to QMM ratings. One, in particular, is reducing the submission requirements for post-approval changes based on the QMM assessment ratings and compliance history to relieve the regulatory burden on companies, aiding the continuous improvement of their drug products and manufacturing processes to maintain an available supply of products for patients. Discussions with members of the QMM Task Force echoed this theme of providing incentives to the industry to develop a win-win scenario for both the industry and the regulators, encouraging more drug manufacturers to adopt QMM practices and the reporting of data.

Based on the discussions with members in the industry, the following suggested incentives were mentioned as ones that should be considered:

• Regulatory flexibility regarding submission of post-approval changes (PAC). Allow a post-approval change to be implemented across all companies’ manufacturing facilities with only one PAC submission and reduced reporting requirements for specific types of post-approval changes, with some reportable changes allowed to be evaluated and implemented through the quality system without reporting.
• Increasing the use of waivers for both PAI/PLI surveillance inspections or records requests in lieu of inspections.
• Allowing companies with low QMM ratings to meet with the FDA to address quality issues in real time and leverage FDA’s expertise to help these sites solve quality issues before they lead to inadequate products being distributed to patients. This incentive could also apply to improvement recommendations for the companies’ QMM program.
• Adopting proactive interactions with drug manufacturers to address quality issues in real time will assist the FDA solving issues such as drug product recalls and drug shortages.
• Greenlighting the FDA’s quality profile data for facilities to be used by the Health and Human Services, Centers for Medicare & Medicaid Services and Department of Defense procurement offices will allow for flexible price incentives to drug manufacturers that demonstrate elevated levels of quality management maturity.

The base assumption is that providing incentives would be based on an evaluation considering the QMM rating, Knowledge Aided Assessment and Structured Application (KASA), and the facility’s quality profile, including the facility’s compliance history.

On the other side of the discussion, members in the industry were concerned about:

• The extra resources required by a company to administer the program and reporting would divert resources from focusing on the manufacturing operations.
• The FDA's inability to correctly interpret the data that would be collected, creating significant additional work as companies spend time responding to questions that provide little value. In addition, less scrupulous drug manufacturers may try to manipulate the system with the information provided to the FDA that may be incomplete or fraudulent (not being representative of the actual situation) with the goal of supporting a higher quality maturity ranking, creating ramifications that will lead to damaged relations between the FDA and the industry as a whole, followed by the elimination of incentives.
• Overflow of variability and subjectivity in audit programs utilized to assess QMM. Without training and a certification program to standardize the QMM assessments, it would be extremely difficult to develop a reliable score. PDA has established training programs and an assessment tool that could provide the basis for developing such a training and certification program.
• The program's effectiveness, which depends on multiple regulatory agencies need to recognize the QMM program and rating system. Furthermore, it would need to be a part of the MRA, PIC/S or ICH discussions to maximize the benefits of global companies serving patients around the world.

So, what does this all mean? From my discussion with the industry's members, it is clear that we are on a profoundly important journey, but one with an outstanding amount of work left to do.