SUPPLEMENTARY INFORMATION:

I. Background

QMM refers to the extent to which drug manufacturing establishments implement quality management practices that prioritize patients, drive continual improvement, and enhance supply chain reliability through the strategic integration of business decisions and manufacturing operations with quality practices and technological advancements. CDER is in the process of developing a voluntary program to promote QMM at drug manufacturing establishments, which would encourage drug manufacturers to implement or improve their quality management practices.^[1]

Between October 2020 and March 2022, CDER conducted two pilot programs to assess the QMM of drug manufacturing establishments. The first pilot program evaluated the maturity of seven domestic manufacturers of finished dosage forms for the U.S. market.^[2] The second pilot program evaluated the maturity of eight foreign manufacturers of active pharmaceutical ingredients (APIs).^[3] Each pilot program was conducted by a different contractor. These pilot programs provided valuable insights for CDER to develop a protocol to assess establishments' QMM, understand assessor behaviors during interviews of establishment personnel, and gather participant feedback on assessment questions, reports, and outcomes.^[4]

Using the findings from these two pilot programs, a review of the literature on quality management, evaluations of existing external programs assessing elements of quality culture or pharmaceutical quality, surveys of external stakeholders, and feedback from partner offices and centers within FDA, CDER developed a prototype assessment protocol to evaluate an establishment's QMM.^[5] This prototype assessment protocol included a series of questions in five practice areas: management commitment to quality,^[6] business continuity, technical excellence, advanced pharmaceutical quality system, and employee empowerment and engagement. Within each practice area, the prototype assessment protocol explores key elements of the establishment's QMM. Examples of some topics covered under the practice areas include management review and resource management (management commitment to quality), supply planning and demand forecasting (business continuity), continual improvement ^[7] (advanced pharmaceutical quality system), data governance and process optimization (technical excellence), and rewards and recognition (employee engagement and empowerment).

In 2024, CDER evaluated nine establishments in the voluntary QMM Prototype Assessment Protocol Evaluation Program.^[8] CDER used the prototype assessment protocol to collect information on each establishment's practices, behaviors, and responses to specific questions in five practice areas. The information collected was evaluated using an objective rubric. Trained assessors conducted 5-day assessments and provided establishments with a QMM report following the assessment. Each QMM report highlighted the establishment's strengths and opportunities for improvement. Feedback from voluntary participants indicated that engagement with the QMM assessment team and the QMM reports were favorably received and provided value to the establishments. However, participants also indicated that certain aspects of the prototype assessment protocol were repetitive and suggested that the protocol should be streamlined.

The 2024 QMM Prototype Assessment Protocol Evaluation Program provided CDER with experience in the successful application of the prototype assessment tool across a group of volunteer establishments that reasonably reflected the diversity of the industry. The rubric effectively differentiated the maturity of quality management practices across the nine establishments assessed in 2024. Using the feedback received and insights gained from 2024, CDER modified its prototype QMM assessment tool to be clearer and more concise and updated the rubric. We also modified how some of the questions are framed for greater clarity. CDER intends to evaluate these improvements and further refine the prototype protocol as necessary by continuing the voluntary program and offering the opportunity to establishments that wish to volunteer to participate in 2025. This notice announces CDER's intent to continue the voluntary QMM Prototype Assessment Protocol Evaluation Program, outlines the types of establishments CDER is seeking for participation, and describes the process for submitting a request to participate in the program. ( printed page 17071)

II. Participation

A. Establishment Characteristics

CDER will consider the following establishment characteristics when identifying potential participants for this voluntary QMM Prototype Assessment Protocol Evaluation Program:

• The potential participant is an establishment as defined in21 CFR 207.1 that registers with FDA under section 510 of the Federal Food, Drug, and Cosmetic Act (FD&C Act) and manufactures, prepares, propagates, compounds, or processes drugs, or APIs used in such drugs, subject to approval or licensure under section 505 of the FD&C Act or section 351 of the Public Health Service Act, or that are marketed pursuant to section 505G of the FD&C Act without an approved application under section 505 of the FD&C Act (often referred to as over-the-counter (OTC) monograph drug products).
• The establishment has received at least one human drug surveillance inspection.^[9]

• The current inspection classification for the establishment at the time of the request to participate is No Action Indicated or Voluntary Action Indicated.
• The establishment manufactures, prepares, propagates, compounds, or processes at least one CDER-regulated drug (API or finished drug product) that is currently in commercial distribution in the United States.
• The establishment is willing to participate in an onsite or hybrid assessment.

B. Requests To Participate

Drug product manufacturers that meet the establishment characteristics described in Section II.A and are interested in participating in the voluntary QMM Prototype Assessment Protocol Evaluation Program should submit a request directly to Conchetta Newton (see FOR FURTHER INFORMATION CONTACT ). To be considered for this program, a request should include all the following information:

(1) A contact person (name and email).

(2) Manufacturing establishment address.

(3) FDA Establishment Identifier and Data Universal Numbering System Numbers.

(4) A brief description of the business operations ( e.g., manufacturing, testing, re/packaging, re/labeling, sterilizing, storing, distributing, or salvaging) conducted at the establishment. Please indicate whether you produce APIs, generic drugs, innovator drugs, OTC drugs, biological drug products, and if you are a contract manufacturing or contract testing organization.

(5) Confirmation that the establishment features the characteristics discussed in Section II.A of this notice.

To be eligible to participate in this 2025 program, establishments should submit a request to participate within the request acceptance period as discussed in the DATES section. This applies to all establishments regardless of whether they previously submitted a request to participate in the 2024 QMM Prototype Assessment Protocol Evaluation Program.

C. Selection Process

CDER intends to select participants that reasonably reflect the diversity of the industry. CDER intends to notify each establishment of a decision on their request to participate within 45 days after the close of the request acceptance period as discussed in the DATES section when this notice closes. CDER intends to select up to nine volunteer participants for this program.

D. CDER-Participant Interactions

CDER intends to notify participants of their selection and confirm participation. This notification would include information about a virtual orientation session in which CDER would share additional information with participating establishments including the program timelines, milestones, and expectations. Participating establishments would also receive a pre-assessment questionnaire, which provides specific topic areas that would be addressed during the assessment, help to prepare in advance of the assessment, and help determine which personnel would be most appropriate to provide supporting information. CDER intends to provide each establishment with options for dates to schedule the 5-day assessment.

Teams of three assessors would conduct each assessment. The QMM assessment team would be composed of CDER staff not including personnel from FDA's Office of Inspections and Investigations charged with the responsibility of ensuring compliance with current good manufacturing practice. In advance of the assessment, the establishment would receive an agenda to ensure the appropriate people are present at the requested times. The entire leadership team would not need to be present for the full assessment. If necessary, personnel may participate remotely.

Following completion of the assessment, each participating establishment would receive a report that provides, for each practice area: their score, a narrative, areas of strength, and opportunities for improvement. After reviewing the report, participating establishments would meet with the QMM assessment team to discuss any questions or comments they have regarding the report.

In the post-assessment phase of this program, participating establishments will be encouraged to select at least one opportunity to improve from the QMM report and develop an improvement plan with defined goal(s) based on that opportunity. Approximately 3 months after receipt of the QMM report, participating establishments will share their improvement plan with CDER and meet to discuss their plan and path forward. Approximately 6 months after receipt of the QMM report, CDER will schedule a final meeting with the participating establishment to discuss any progress made toward achieving their improvement goal(s). CDER will also solicit feedback from each participating establishment on the assessment, the report, and any suggestions or input they wish to share. This information will help CDER evaluate use of its QMM assessment tool and process to determine whether it enables a meaningful assessment of the establishment's quality management practices and if the feedback provided to the establishment was useful.