ISPE Annual Meeting 29 October 1 November 2017 San Diego, CA. Need systems approach to pharmaceutical manufacturing

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1 Aligning Quality Excellence with ICH(Quality Systems Management) Prabir K Basu Need systems approach to pharmaceutical manufacturing Pharmaceutical manufacturing needs to be approached as a system that regards the organization as comprising of three purposefully designed parts that are interconnected viz. input, process and output. A systems approach makes an organization to function as a unit despite being a complex entity that's subject to changes from within and outside. This approach allows analysis of problems in a systematic fashion identifying the factors affecting the system and its various components thus allowing the design of proactive solutions to overcome problems and reduce risks to the operation and product quality. Pharmaceutical manufacturing is a system which has a set of parts that interact and affect each other, thereby creating a larger whole of a complex thing. Pharmaceutical manufacturing is complex and is growing more complex everyday with globalization globalization often brings uncontrollable risks to supply as well as quality. The old ways are inadequate for our dynamic world. Systems thinking will allow a model of decision making that will help pharma manufacturing effectively deal with changes and adapt. A maximally efficient, agile, flexible pharmaceutical manufacturing sector that reliably produces high quality drug products without extensive regulatory oversight Dr. Woodcock, 2005 Prabir K Basu 1

2 Lack of a systems approach to CGMP makes it difficult to comply GMPs provide guidance on the manufacture and control of pharmaceutical product, but GMPs do not address the systems needed to bring a quality product to market The guidance provided by GMPs is mostly on how to address problems after the fact, such as CAPA, change control, etc. but do not profess proactive continual improvement GMPs, as it is, provide a discrete set of instructions that involve many actors and many independent systems it is difficult to see the big picture without a proper systems approach. GMPs do not drive a lifecycle approach to quality and there is no concept of continuous improvement in GMPs Issues where an action impacts (or is affected by) the environment surrounding the issue (including people, equipment, culture, etc.), cannot be solved without a systems approach. This is particularly important in this global environment. GMPs only touch on management responsibility and employee participation in quality. There is no specific reference in the GMPs on the necessity of a robust quality culture in an organization Without a systems approach, problems reoccur and are made worse by past attempts to fix them. Systems thinking would allow people to make their understanding of GMPs more explicit in a manner similar to how engineers use engineering principles to analyze and improve their understanding of mechanical systems. Prabir K Basu 3 FDA Industry effort to implement a Quality Systems Approach to cgmp Regulation since early 2000 GMPs originated in 1970s and have been only incrementally added to. The ISO Quality Management thinking was not embedded in the GMPs. In 2002, FDA issued a report titled Pharmaceutical CGMPs for the 21st century a Risk Based Approach In 2006, the US Food and Drug Administration issued a document entitled, Guidance for Industry: Quality Systems Approach to Pharmaceutical Current Good Manufacturing Practice Regulations. This document represented FDA s efforts to encourage the pharmaceutical and biotechnology industry to adopt...modern quality systems and risk management approaches... to management of GMP compliance. The idea was that a system of management controls can serve to support and maintain a company s GMP compliance status. The establishment of management controls is a concept that is embodied in the FDA guidance and has also been advanced by FDA in other contexts in recent years. Since then, there has been multiple FDA Industry efforts to implement Quality Systems approach to pharma manufacturing 2

3 Lawrence Yu, CDER Update: Quality Metrics, Quality Culture, and other Initiatives, 15th ANNUAL PIA PR REGULATORY CONFERENCE Innovation and Compliance as an Enabler of Quality System Robustness, JUNE 22, 2017, Ritz Carlton Hotel San Juan PR My goal today is to show that CDER s Quality Journey is synergistic with the evolution of the OPEX model at St. Gallen s Around , the OPEX team in Switzerland, along with its industry collaborators independently embarked upon developing a systems approach to manufacturing and quality in pharma St.Gallen Operational Excellence Model provides analysis of pharma manufacturing based on a systems approach 3

4 The St. Gallen OPEX Model is a Total Quality Management System OPEX model comprises of sub systems that are critical and they reinforce each other TPM represents equipment effectiveness and overall efficiency of a comprehensive productive maintenance system TQM represents the rigorous problem solving process which should be in an operation where Total Quality and Continuous Improvement are key objectives. Six Sigma and Lean approaches are very much aligned to this concept. JIT represents optimization of manufacturing operations and ultimate customer satisfaction. It is one of the key elements of Total Quality Management and is possible only when good processes, systems and a culture of continuous improvement is in place. Management System incorporates other key elements of Total Quality Management such as management commitment, employee participation, continuous improvement and training. St. Gallen OPEX framework contains different blocks How efficiently fixed assets are being managed while effectively using new process technology? The TQM System is a measure of quality performance (e.g. reduce variability, scrap rates, complaint rates etc.). TPM TQM JIT Foundation The main objective of the foundation elements is to support the deployment of TQM, TPM and JIT principles. Elements Effective Management System Enablers Prabir K Basu The main objective of JIT is the reduction of working capital (incl. inventories) by simultaneously increasing service levels. The main objective of an effective Management System is a learning organization that is managed by clear objectives. 8 4

5 St. Gallen OPEX Framework enables continuous improvement Preventive maintenance Stabilize the Underlying System TPM Process management TQM Customer integration Cross funct. Effective Supplier Planning Housekeeping product Layoutoptimization technology quality adherence development usage management Standardized Standardized Standardized equipment processes replenishment Stable running machines Stable processes Low inventory Self directed High continuous Low abseentism teams improvement rates & fluctuation Effective Management System Set up time reductions Low absenteeism & fluctuation Direction setting Management commitment and company culture Employee involvement & continuous improvement Functional integration & qualification Manage the Flow & Reduction of Waste JIT Pull system Flexible workforce Operational Performance Continuous Improvement Management & Leadership Source: University of St.Gallen Operational Excellence (OPEX) and Quality management have similar objectives The ultimate objectives of both OPEX and Quality are to reduce variation, streamline operations, minimize chances of errors and thus achieve a State of Control and manage the risks of noncompliance and wasteful operations. Risk management (ICH Q9) can be defined as the identification, assessment, and prioritization of risks to minimize uncertainty in processes, operations and ultimately quality. Project prioritization activity should be both cost and risk driven both are really the same in fact, risk to quality should have a priority over cost to prevent quality deterioration. In order to implement a risk informed decision making approach, risk management activities should be embedded into organizational structures and processes at both the operational and strategic levels. Prabir K Basu 10 5

6 Similarities between OPEX and Quality Management programs System based approach with focus on establishing effective systems Both attempt to standardize systems to increase reliability. Both aim to develop closed loop processes that enable continuous improvement. Proactive risk management that goes beyond compliance. Generating actionable data from key performance indicators (KPIs). Performance measurement is key to success in both programs. Collaboration among cross functional teams. Management commitment and employee participation is key in both programs. Requires documentation and knowledge management OPEX approach can be a measure of a robust Quality System Operational Excellence (OPEX) efforts are generally aimed as business goals which seek to reduce inefficiencies and increase quality. They have all the elements of an effective quality system built in. OPEX is a process that involves taking care of customers' needs, keeping the employees motivated and empowered, and continually improving the current activities at the workplace. The important components of a true operational excellence program (OPEX) are striving for stable operations, minimizing variations, continuous improvement, management commitment, and employee participation. These are also key components of any successful Quality Management program. Therefore, one should be able to use similar metrics for OPEX implementation and Quality in a pharmaceutical plant Prabir K Basu 12 6

7 The OPEX framework incorporates and has the ability to measure the core elements of Quality Management Quality Management Requires: Systems and Techniques formal system of operations and quality management should be in place Processes Analysis of processes and continuous improvement is a focus. Look after the process and the product looks after itself. (Hutchins, 1990) Management This is a way of life for a company and management must be committed and lead the effort People ongoing education and training supports drive to quality and efficiency. Employees must be encouraged to take responsibility and communicate effectively Teamwork everyone works individually and as a team Culture a radical change in culture and way of work in an organization Metrics built into the model allowing actionable responses OPEX captures performance relative to a standard, allows and encourages comparison, and supports a Quality Operations Excellence strategy. Prabir K Basu 13 Common Architecture for Quality Management & Operational Excellence Operational/Quality Management/Excellence (Quality & Cost) Stable Operations Continuous Improvement Facilities & Equipment Quality Systems Personnel Development Knowledge Management Commitment Employee Participation Technology Prabir K Basu 14 7

8 These are also the chapters of an important document issued by the FDA in the last decade Chapter 1: Pharmaceutical Quality System Chapter 2: Management Responsibilities Chapter 3: Continual Improvement of Process Performance and Product Quality Chapter 4: Continual Improvement of the Pharmaceutical Quality System Chapter 5 : Glossary Which is this document? Prabir K Basu 15 Guidance for Industry Q10 Pharmaceutical Quality System Additional copies are available from: Office of Communication Division of Drug Information Center for Drug Evaluation and Research Food and Drug Administration New Hampshire Ave.,Bldg. 51, Room 2201 Silver Spring, MD (Tel) Office of Communication, Outreach and Development, HFM-40 Center for Biologics Evaluation and Research Food and Drug Administration 1401 Rockville Pike, Rockville, MD (Tel) or U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER) Center for Biologics Evaluation and Research (CBER) April 2009 ICH 8

9 Vision of ICH Q10 Quality Systems Develop a harmonized pharmaceutical quality system applicable across the lifecycle of the product emphasizing an integrated approach to quality risk management and science. (Brussels July 2003) ICH Q10 describes one comprehensive model for an effective pharmaceutical quality system. (ICH Q10) Prabir K Basu 17 Key Elements of Q10 Q10 emphasizes systems approach to Quality Management by establishing and maintaining a state of control and continuous improvement as key elements as is in any systems approach to process/operations management Q10 is based on a set of stated Objectives, supported by specified Enablers which support continual improvement of product quality and the Quality System itself. It relies heavily on the concept of Management Responsibility and Employee Participation for the Quality Systems 9

10 Pharmaceutical Quality System(ICH Q 10) Achieve Product Realization Establish & Maintain State of Control Facilitate Continual Improvement Stable Operations Stable Processes Quality Assurance Management Committment (Effective Management System) Knowledge Management (Prevention not Reaction) Quality Risk Management (Prioritization based not just on cost but also on risk) Prabir K Basu 10

11 ICH Q10 and Pharmaceutical Quality Systems were designed to address the gap in systems approach to GMPs Regulatory agencies and the pharmaceutical industry recognized this deficiency in approach to cgmps and thus in the recent years have proposed a systems approach to the cgmps. The overarching philosophy articulated in both the CGMP regulations and in robust modern quality systems is: Quality should be built into the product, and testing alone cannot be relied on to ensure product quality. Quality Systems Approach to Pharmaceutical CGMP Regulations, FDA, 2006 ICH Q10 aims to promote a paradigm shift from discrete GMP compliance procedures at each stage of the product lifecycle to a comprehensive quality systems approach over the lifecycle of the product Neil Wilkinson, ICH Q10 Pharmaceutical Quality System WCC PDA Dinner Meeting, Jan 2012 What is missing? Measuring Quality or Metrics A systems approach cannot be effective without an appropriate way to measure performance and continually improve Prabir K Basu 21 We need an integrated OPEX, Quality Systems Management, and EHS program Most companies use different teams and programs for OPEX, Quality, Quality Systems, EHS etc. Each group is trying to implement their own systems and measure performance in separate efforts These programs should be integrated into one and there should be a unified framework or system for all these programs. In addition to cost savings, quality and safety goals also can be achieved by an overall systems management and overall performance tracking and management system. FDA and industry are debating Quality Metrics. Why duplicate efforts? Determine how to measure the overall pharmaceutical Operations system and that will provide metrics for quality and safety also With minor adjustments to the work that St. Gallen is doing, we can make it s model acceptable to both the regulatory agencies and the industry. All the basic elements are already there in the OPEX model, and Quality Metrics is embedded in the already existing Operational Excellence programs of many pharmaceutical companiesaround theworld. Prabir K Basu 22 11

12 Pharmaceutical Production System Model The new Pharmaceutical Production System Model (PPSM) proposed by St. Gallen combines both OPEX and Quality Management goals. It was developed specifically for the FDA Quality Metrics Project. The model enables a structured analysis of the components of a Pharmaceutical Quality system. The St.Gallen OPEX Model as Basis for the PPSM A System Approach to Pharmaceutical Manufacturing TPM: Total Preventive Maintenance; TQM: Total Quality Management; JIT: Just in Time; PQS: Pharmaceutical Quality System 24 12

13 PPSM is a successful attempt to represent suitable metrics for the Pharmaceutical Quality System Human beings adjust behavior based on the metrics they're held against. Anything you measure will impel a person to optimize his score on that metric. What you measure is what you'll get. 1 Perhaps what you measure is what you get. More likely, what you measure is all you ll get. What you don t (or can t) measure is lost H. Thomas Johnson Thus the discrete metrics recommended in revised FDA Draft Guidance for Quality Metrics (2016) has obvious limitations. These are also inherently lagging indicators and do not reflect the effectiveness and efficiency of the quality systems. An effective performance measurement system should provide timely, accurate feedback on the efficiency and effectiveness of operations. 2 A Pharmaceutical Quality System is successful when it assures an ongoing state of control. 3 PPSM provides a structured and holistic depiction of the relevant data from the St. Gallen OPEX database which truly reflects the efficiency and the efficiency of the pharmaceutical operations/quality system. In addition, it also positions the three metrics, suggested in the revised FDA Draft Guidance (2016) within the broader context of holistic understanding. 3 Food & Drug Administration, Quality System (Drugs), you are what you measure 2 Kaplan, R., & Norton, D. (1993, September/October ). Putting the balanced scorecard to work. Harvard Business Review, pp Summary Pursuing operational excellence is both a challenge and a commitment. But for operations, willing to take it on, the result is improved performance across a range of outcomes, including product quality, safety, and ultimately, financial performance. Operational excellence is a journey, not a destination. It s also an iterative, cross functionalprocess bynature,involvingmultipledepartments,processes and stakeholders. Creating silos of quality, EHS, operations management creates roadblocks to achieving operational excellence, while an integrated system streamlines the path forward. ThesameistrueforFDA sapproaches. Individual approaches such as Quality by Design, PAT, ICH, Quality Metrics, etc. create more confusion among companies. They sometimes worry, what s next? Perhaps, if we wait long enough a new approach will be there? Operational excellence provides an unique opportunity and format to combine all of these diverse efforts into one and make it very effective and easy to adopt. 13