Quality Metrics in pharmaceutical industry
Quality metrics are used throughout the pharmaceutical industry to monitor quality control systems and processes and drive continuous improvement efforts in drug manufacturing.
Quality Metrics play an important role in the desired state of pharmaceutical quality and regulation
– minimal but effective regulatory oversight that results in quality drugs available for patients
• Development of the FDA program is a journey that has reached an important next step
• In collaboration with participating industry stakeholders, we will incorporate learnings from this initial phase of the program to more fully realize the potential of quality metrics.
These metrics can also be used by FDA: to help develop compliance and inspection policies and practices, such as risk-based inspection scheduling of drug manufacturers; to improve the Agency’s ability to predict, and therefore, possibly mitigate future drug shortages; and to encourage the pharmaceutical industry to implement state-of-the-art, innovative quality management systems for pharmaceutical manufacturing.
• Pharmaceutical Quality for the 21st Century
• Why Quality Metrics (QM)?
• Initial draft of the QM Guidance
• Key Features of the QM Revised Draft Guidance
• Phased-In Approach and Benefits to Participants
• How FDA Intends to Use Metrics Data
“A maximally efficient, agile, flexible pharmaceutical manufacturing sector that reliably produces high-quality drugs without extensive regulatory oversight.”
Desired State of Manufacturing • Manufacturers have extensive knowledge about the critical product and process parameters and quality attributes
• Manufacturers strive for continuous improvement
• FDA role: Initial verification, a subsequent audit
• Minimal manufacturing supplements needed for postapproval changes.
Encourage the use of modern, more efficient manufacturing technologies
- Develop approaches to increase regulatory flexibility for postapproval changes.
- Focus on robust analytics and surveillance techniques to monitor the state of manufacturing in the pharmaceutical industry.
- Quality Metrics reporting program.
- Emerging Technology Team.
- Participation in ICH Q12.
- New Inspection Protocol Project.
Existing Quality Metrics Programs
Many manufacturing establishments currently use quality metrics as a part of the process validation lifecycle and pharmaceutical quality system (PQS) assessment.
• Current good manufacturing practice (CGMP) for human drugs requires manufacturers to have an ongoing program to maintain and evaluate product and process data that relate to product quality
• Continued process verification includes a Periodic Product Review (PPR):
– conducted at least annually
– data collected includes relevant process trends and the quality of incoming materials or components, in-process materials, and finished products
• Programs should be tailored to include those metrics that the manufacturer finds useful in performing these products- and establishment-specific evaluations.
Robust Product/Site Measurement Program:
Other Metrics Likely to be Useful
- Lot acceptance rate
- Invalidated and validated OOS rate
- Product quality complaint rate
- Deviations without assigned root cause
- Periodic Product Review
- Quality culture
- Process performance and capability
- Senior management commitment to quality.
- CAPA effectiveness (retraining, preventive actions).
- Reliability of drug availability.• Unplanned/planned equipment/facility maintenance rate.
Quality Metrics Programs Indicators of Maturity
Identifying existing problems vs. predictive analytics
• Importance of quality culture
• What are useful product- and site-specific metrics?
• How committed is senior management to overall quality?
• How committed is the entire staff to quality culture?
• Does the program improve over time?
Why Quality Metrics?
• Enables continual improvement of process performance and product quality
• Supports continual improvement of the pharmaceutical quality system
• Important element of oversight and controls over the manufacture of drugs to ensure the quality (section 501 FD&C Act)
• Additional insight into the state of quality of product and facility
• More quantitative and objective measure of quality at the product, site, and system levels
• Enhance risk-based surveillance inspection scheduling model
• Improve the effectiveness of inspections
• Help to identify factors leading to supply disruption
• Gain insights/trends regarding the state of quality across the pharmaceutical industry
• More reliable patient access to important therapies.
– Commitment to ongoing improvement by the industry leads to more robust manufacturing processes
– Fewer recalls
– Fewer quality-related drug shortages
Request for metrics data
• Product reports
• FDA would use the data to calculate metrics:
– A lot Acceptance rate
– Product Quality Complaint rate
– Invalidated Out-of-Specification (OOS) rate
– Annual Product Review (APR) or Product Quality Review (PQR) On Time rate
• Public comment requested on several optional metrics
– Senior management engagement
– CAPA effectiveness
– Process capability/performance
Mandatory → Initial Voluntary Phase
• Product- OR site-based reporting
• Limited set of 3 metrics related to batch manufacturing, laboratory robustness, and the voice of the patient or customer (quality complaints)
• Technical edits and examples
• Incentives for participation
Submission of Information is Voluntary
During the voluntary phase of the reporting program,FDA does not intend to require the submission of this
• FDA does not intend to take enforcement action based on errors in a quality metrics data submission
made during this voluntary phase of the reporting program provided the submission is made in good faith.
Voluntary vs. Mandatory
The extent to which FDA can achieve its goals for the QM the program will be largely driven by the extent of
– Large body of data is needed to draw the most meaningful conclusions about the quality of a site or product
• Developed additional incentives for reporting.
Benefits of Participation
Opportunities for participants to provide feedback and additional comments, as well as share knowledge from
ongoing, industry-driven quality metrics programs
• FDA working informally with establishments toward an early resolution of potential quality problems.
• Improved inspection effectiveness (e.g., more focused inspections)
• Enhance premarket and postmarket review program (e.g., consider the use of calculated metrics as an element of the postapproval manufacturing change reporting program)
• Reduction in inspection frequency
• Inclusion on the Quality Metrics Reporters List
Vision Remains the Same
Focus the use of resources on areas of highest risk to public health
– Establish a signal detection program as one factor in identifying establishments and products that may
pose a significant risk to consumers
– Identify situations in which there may be a risk of drug supply disruption
– Improve the effectiveness of the establishment inspections
– Improve the FDA’s evaluation of drug manufacturing and control operations
Quality Metrics in the Short Term
Test and improve the electronic portal submission process
Incentives for establishments going “above and beyond” – Additional opportunities for feedback from participating establishments
– Quality Metric Reporters List.
– Enhance pre-market and post-market review programs.
– Reduction in inspection frequency based on reporting.
Improve and mature the program based on feedback and analytics.
– Publish a summary of initial reports.
Ensure the program supports, not deters, emerging technology.
Continuing discussions with external groups
- Measuring and assessing quality culture
- Ongoing improvement in definitions and examples
- Continuing discussions with a range of industry groups/representatives
- Non-application products
- Contract manufacturers
Active ingredient manufacturers
– Evaluate additional sources of data to study quality metrics.
Quality Metrics in the Long Term
– Correlation with FDA data (e.g., inspection outcomes, recalls, FARs)
– Drug supply disruption
• Continue to recognize participating establishments
– Quality Metric Reporters List (?)
– Enhance premarket and postmarket review program (e.g., postmarketing change reporting program)
– Potential reduction in inspection frequency based on data
• Continue to encourage emerging technology
• Other incentives?
Voluntary reporting alone may not be sufficient to accomplish FDA’s goals for the program
• Greater net benefit for FDA and industry likely to result from a fully operational program
– Incorporate initial learnings
– Fuller participation
• Continuing to plan for notice and comment rulemaking.