Quality Metrics An FDA Perspective PDA Dinner and Dialogue. Melissa Seymour VP, Corporate Quality DRAFT

Transcription

1 Quality Metrics An FDA Perspective PDA Dinner and Dialogue Melissa Seymour VP, Corporate Quality DRAFT

2 Agenda How does industry use Metrics? FDA Challenges and Requirements and Use Complexities of Implementation (Industry Feedback) What does it all mean??? Presentation to the Board of Directors 10 February

3 Presentation to the Board of Directors 10 February Industry use of Metrics

4 Application Data Overload? Vendor Data Specification Data Validation Data Knowledge Management Support development, manufacturing, compliance and flexibility M Sources (primary) RM Sources (tertiary) Exception Data Quality Management System Learning Items Training Data Product Data Integrate QRM into process Make Use of data and use QRM to convert data to information OOS Data egulatory Filing Data Change Control Data Efficiency Data Regulatory Intelligence Regulatory Guidance Regulatory Quality System Know what comes next Predict what will happen Document rationale Create Understanding Raw Facts Filter Risks Learning Data Information Knowledge Understanding Put the facts in a context Guidance For Action What to use for what purpose Presentation to the Board of Directors 10 February

5 Metrics and Trending Key in Risk identification systematic use of information to identify potential sources of harm (hazards) referring to the risk question or problem description [ICH Q9 / Definitions] Enables the detection of potential problems as early as possible to plan corrective and preventive actions Provides indication that controls are losing effectiveness Important in achieving problem resolution and problem prevention Another important concept of modern quality systems is the use of trending to examine processes as a whole. Presentation to the Board of Directors 10 February

6 RISK AND ESCALATION Management Review Cost of Quality Analysis Recall Committee Material Review Board Process Improvement Efficiencies Monitoring Trending Action Visibility RISK VISIBILITY Management Review Stability Trending Annual Product Review Product Complaints Deviations OOS QA Self Inspection QUANTITY Presentation to the Board of Directors 10 February

7 FDA Challenges and Requirements Presentation to the Board of Directors 10 February

8 FDA Vision for the 21 st Century A maximally efficient, agile, flexible pharmaceutical manufacturing sector that reliably produces high quality drugs without extensive regulatory oversight Presentation to the Board of Directors 10 February

9 FDA Challenges What about Quality? FARs have increased Recalls have increased Shortages have increased Lack of common measuring stick What about flexibility? Supplement trends continue unabated What about workload Significant increases in application numbers Increasingly complex Increasingly global What about focus? More on review (predicting) than on post market surveillance Compliance or quality? Presentation to the Board of Directors 10 February

10 Potential Regulatory Mechanism FDASIA Title VII Sec 705 requires FDA to do risk based inspection (i.e site stratification schedule) Currently have limited practical access to most meaningful data Sec 706 allows FDA to collect informatino that would have been available on inspection in advance or in lieu of an inspection Potential regulatory mechanism Identify metric available on inspection Collect under 706 Utilize for 705 Potential draft guidance on mechanism Presentation to the Board of Directors 10 February

11 Potential Ask of Industry Each FEI site reports the following (per CY) stratify by product and/or application number # of lots attempted # of lots rejected # of lots reworked or reporcessed # of lot release tests conducted # of OOS results # of lot release results invalidated Early 2013 FDA Reached out to Industry for Feedback Assess industry feedback Q Collection of first data 2015 Engage industry including PDA/FDA conference Dec 2013 Initial industry request Q Presentation to the Board of Directors 10 February

12 How will FDA Use Metrics? Assist to segment sites for risk based inspection schedule Risk based inspection schedule required under FDASIA, Title VII, section 705 Assist to segment products (and/or processes) and individual product manufacturers based on risk Potentially predictive of future drug shortages Basis of structured (objective) component of inspection and review Only one element of risk assessment Not to issue restaurant style grades Where do you stand relative to industry groupings Presentation to the Board of Directors 10 February

13 Complexities of Implementation (Industry Feedback) Presentation to the Board of Directors 10 February

14 Complexities Many existing metrics are lagging indicators as opposed to leading indicators Clarity of Definitions among highly diverse contingent (API, small molecule, large molecule, etc.. Concerns around cultural impacts of reporting metrics CMO Management (Product vs. Site) Virtual companies and expectations Global Implications (reporting requirements from other countries/language implications) Presentation to the Board of Directors 10 February

15 PDA/FDA Quality Metrics Conference December 9-10, Conference Participants 150 companies Wide range of responsibilities Quality, engineering, manufacturing, reg. affairs Multiple industry sectors Generic, OTC, CMO, pharma, biotech, large and small molecule, APIs and drug products Presentation to the Board of Directors 10 February

16 Quality Culture Quality Culture plays a key role Open and honest communication Clear vision and belief in quality Management leadership/sponsorship Listening Training and implementation of Continuous Improvement Presentation to the Board of Directors 10 February

17 Industry Recommended Metrics All groups recognized the potential benefits and endorsed the initiative. PDA Trend Metrics Collected per Product Confirmed Product Quality Complaint rate by Product Batch Reject Rate by Product Confirmed OOS Rate (DS and DP) by Product Trend Metrics Collected per Site Confirmed OOS Rate (DS and DP) by Site Batch Reject Rate by Site Provide explanations/interpretations Focus on Trends and Variability Pilot Program to Start BIO Error Rates % Critical Non Conformance Rate Confirmed OOS Metric Manufacturing Success Rate % Manufacturing Success Rate Complaint Rate Critical and Confirmed complaints Avoid public consumption of data Coordinate between CDER, CBER, CDRH, etc.. Pilot Program to Start PhRMA Site Information Products, size, change information Quality Metrics Batch reject rate Confirmed OOS # media fill failures (for sterile facilities) Product Quality Complaints Quality System Inspection metrics from global authorities Use metrics already reported (Recalls, FAR, BPD, drug shortage) Use a phase in approach with suggestions of other metrics Coordinate between CDER and other FDA Offices Global Implications should be considered ISPE Identified Metrics Batch Rejection Rate Rework and Reprocessing Rate Confirmed OOS Rate Unconfirmed OOS Rate Critical Complaints % APQRs complete on time Includes clear definitions of each metric Provide raw numbers and rates Do not set any numerical targets Include a Pilot Program Presentation to the Board of Directors 10 February

18 Other Metrics being considered Process Capability CpK, PpK, etc. Critical Investigations Rate CAPA Effectiveness Rate Quality System Effectivness Environmental Monitoring Rate AE Rates Deviations Rates Recall Rate Repeat CAPA rate Right first Time rate Unplanned Downtime Indicators of ongoing investment/maintenance Presentation to the Board of Directors 10 February

19 BENEFITS RISKS Benefits and Risks Greater visibility and transparency between industry and regulators Ability to identify drifts earlier to drive audit/inspection schedules Risk based approach to inspections Increasing consistency of metrics Driving wrong behaviors and unintended consequence Establishing excessive or overly complex metrics Comparing data that is not consistently defined or comparison of single data values Using metrics as a quality surrogate Presentation to the Board of Directors 10 February

20 Next Steps FDA is currently evaluating feedback Anticipate more information in Q2 of this year ISPE participating in a pilot with FDA and small subset of companies discussions to occur at June ISPE/PDA meeting. Presentation to the Board of Directors 10 February