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Achieving Quality and Compliance Excellence in Pharmaceuticals
A Master Class GMP Guide
Madhu Raju Saghee Corporate Quality Gland Pharma Limited & Director – Indian Region Pharmaceutical and Healthcare Sciences Society (PHSS)
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ii Achieving Quality and Compliance Excellence in Pharmaceuticals
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Achieving Quality and Compliance Excellence in Pharmaceuticals
To P.V.N Raju An eminent entrepreneur, industrialist and chairman of Gland Pharma with 50 years experience in Pharmaceutical Industry who held various positions in various professional bodies and whose vision, dynamism and leadership about the health care business are inspirational to younger professionals like me.
An illustrious microbiologist and the force behind my success in professional life.
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& To Dr. Tim Sandle
PHSS and ISPE. His areas of expertise include all aspects of quality and compliance for systems. . particularly for sterile products. including PDA. All Rights Reserved. India. cleanroom contamination control and microbiology. Madhu has written many articles pertaining to regulatory compliance. Madhu is the co-editor of the books “Microbiology and Sterility Assurance in Pharmaceuticals and Medical Devices” and “Cleanroom Management in Pharmaceuticals and Healthcare.iv Achieving Quality and Compliance Excellence in Pharmaceuticals ABOUT THE EDITOR Madhu Raju Saghee is working in corporate quality department at Gland Pharma. facilities and operations for drug products. ensuring regulatory compliance and involved in qualification and validation of sterile and aseptic manufacture for parenterals. He is an active member of various industry associations. he is responsible for implementing a robust quality system. quality assurance. In this position.in and he can be reached at madhuraju. Madhu runs an online compliance blog http://cgmpcompliance. quality risk management.sagi@gmail.” Madhu has a Master of Science in Microbiology from Andhra University. Madhu is also a volunteer for Pharmaceutical and Healthcare Sciences Society (PHSS) and acts as Director for Indian region.blogspot.com Sample Chapter for Promotion © Business Horizons. a producer of small volume parenterals located in Hyderabad. processes.
Achieving Quality and Compliance Excellence in Pharmaceuticals v ABOUT THE AUTHORS Ajit Basrur Ajit Basrur is an experienced quality professional in Pharmaceutical and Medical Devices with sound knowledge on FDA. Root Cause Analysis using Problem solving tools.es Alok Ghosh Alok Ghosh is the President – Technical Operations of Lupin Limited. Singapore in the past for nearly 5 years. She is qualified as a Six Sigma Black Belt and lead projects on process improvement in manufacturing areas. ISO 13485. Alicia holds a B. Kolkata and has more than three decades of experience in R&D. India. he has worked with Schering Plough. Ajit is passionately involved with Elsmar Cove. In addition. Quality Management.currently at Nypro Healthcare as the Global Director – Quality & Regulatory Affairs (Asia) based in China. China and Singapore . Alicia Tébar Alicia Tébar is the Managing Partner of Development Team Consulting dTC and provides consulting services and training to pharmaceutical companies. His core strengths are Audit and Compliance. Technology Transfer. a website to provide responses to questions raised on quality systems. Sanofi and Dr Reddy’s in India for over 15 years. Training and managing customer and supplier relationships. She is a habitual lecturer and trainer and has also published some technical articles on specialized magazines. Mumbai. where he specifically focuses on Pharmaceuticals and Medical Devices. ISO 9001. She is a member of the Board of Directors of ISPEs Spanish Chapter. ISO 14971 and other related guidelines. He is also globally responsible for Drug Master Files for Nypro. He has a rich Asian working experience across India. . he is responsible for the quality and regulatory affairs function for medical devices across 3 plants in China and 1 in India for the last 6 years.S. European regulations. Since 2006 she has been blogging on Quality by Design http://www. In his current role at Nypro Healthcare. She is a strong believer of Quality by Design paradigm and since 2004 she has been involved in implementation projects as an external support to train manufacturing and development staff in QbD/PAT tools like risk analysis. design of experiments and statistics. Ajit can be reachedSample Chapter for Promotion at ajitbasrur@hotmail. All Rights Reserved. She can be reached at firstname.lastname@example.org/ in Spanish. Chemistry at the University of Barcelona and a postgraduate in environmental engineering. Alicia has over 20 years experience in pharmaceutical industry as quality control and analytical development manager. he has also worked with leading Pharmaceutical organizations like Fulford India.qbd-dtc. Alok has a Masters in Pharmacy from Javavpur University. Projects and Manufacturing.com © Business Horizons.
Atul completed Masters in Pharmacy from Haffkine Institute Mumbai in Regulatory toxicology supported with Diploma in Business and Marketing Management from IITC. regulatory due diligence. audits and documentation. both in India and abroad. In his present capacity. initiating and managing recalls. All Rights Reserved.S. Alok is a member of board of studies in Applied Pharmaceutical Sciences with Narsee Monjee Institute of Management Studies (NMIMS). and FDA guidance on pharmaceuticals produced with bioengineered plants. Kupchyk regulation of advertising and promotional activities. and biologic products. medical device. Delhi and carries a rich experience of working in the Pharma industry in various disciplines and capacities for nineteen years. value based GMP resource firm in India. Quality Management. and has been listed as a leading lawyer in biotechnology law by The Best Lawyers in America since 2008. Atul Shirgaonkar Atul shirgaonkar is the CEO of Insight Systems Inc. she was a three-time recipient of the FDA Commissioner’s Special Citation for Outstanding Achievement. Ms. Mumbai. Atul . import/export requirements. and supports litigation with the FDA involving the Administrative Procedure Act (APA). and was recognized for her role in developing a regulatory framework for human cellular and tissue-based products. and product Chapter for Promotion also specializes in the FDA Sample liability actions. During her time at the FDA. Kupchyk is a regular presenter at FDA in their CDER new employee training programs. Atul also works as course director with Insights Professional Management Academy firm engaged in offering distant learning courses in GMP. India and in the committee of TB care and control in India constituted by SEARPharm Forum. Also completed Diploma in Training and Development from ISTD. biotechnology. Areta Kupchyk Areta L. Additionally. Kupchyk is a partner with Nixon Peabody LLP who provides counsel to clients on the U. he is responsible for Lupin’s Global Manufacturing. Ms. use. Kupchyk has received numerous awards for her work. including FDA’s restrictions on off-label © Business Horizons. India. Insight Systems is pioneer and engaged in GMP training. an 18 years old. Technology Transfer and new Project implementation. responses to 483s and warning letters. Food and Drug Administration (FDA) regulation of drug. Mumbai. corporate matters and transactions. she assists clients with internal investigations and developing corrective measures in response to suspected wrongful conduct. and other issues.vi Achieving Quality and Compliance Excellence in Pharmaceuticals Alok has worked with leading Pharmaceutical Companies. Ms. Formerly an Associate Chief Counsel for Drugs and Biologics and Assistant General Counsel for Litigation at the FDA. cGMP inspections. Kupchyk advises clients on post-approval compliance and enforcement matters such as adverse event reporting. He is a visiting faculty member for several pharmacy colleges and management institutes. In addition. Ms.
along with other experts from the Indian Pharma Industry. Ananth Prabhu is a graduate of the then Bombay University. he briefly worked in the development laboratories of Colgate Palmolive India Ltd.net and URL www. He has been actively involved in the implementation of cultural change programmes. Also. After graduation he proceeded to Kansas University. Currently he is a visiting faculty at the NMIMS College for the management degree in pharma marketing and M. before he moved to the pharmaceutical Industry and worked for 25 years.Knoll and Abbott and retired from Arch Pharma Labs. for several years. He also taught synthesis of drugs. Subsequently these companies were successful in the regulatory inspection that followed. in developing the new Schedule M of the Indian Drugs Act. He worked for Glaxo-Wellcome. he became a GMPPromotion to several pharmaceutical Sample Chapter for Consultant companies.000 participants (from nineteen countries as well ) as on date.Achieving Quality and Compliance Excellence in Pharmaceuticals vii has conducted more than one thousand seven hundred fifty (1750+) training programmes till date in functional. Kansas. both in the primary and secondary manufacturing. Atul can be reached at insightsystems@vsnl. Atlanta. On his return back to India. and EMA) © companies and helped them rectify deficiencies observed during these audits. a meticulous and indepth auditor. After his retirement in 2007.Pharm degree in QA & Regulatory at Manipal College of Pharmacy and a consultant to 2 US pharmaceutical companies for their operations in India. documentation and GMP resource to various leading multinational firms in India and overseas. besides to 2 other Indian Companies Brian Szukala Brian Szukala is the Managing Director of Transfer Knowledge Partners. He also conducted several training programmes for companies as per their requirements. He co-authored a book on” Synthesis of Drugs—A Synthon Approach” which was very well received by the Indian pharmacy teaching fraternity He was a member of the Indian Pharmacopoeia 1986 and also has contributed substantially.Pharm degree students at Bombay College of Pharmacy.com. incorporating .Manipal College of Pharmacy. audits for several out pre approval regulatory (MHRA. Kalina. Presented views on pharmaceutical quality aspects at different national and international symposia.. US FDA.V. A.insightcgmp. technical and behavioural aspects of management and more than 100 GMP audits. USA for his doctoral degree and then did his post doctoral research for 2 years at Georgia Institute of Technology. Brian has over 20 years experience in the pharmaceutical industry.He was an examiner both at graduate and under graduate examinations in Pharmacy conducted by SNDT. and Mumbai University. All Rights Reserved. Boots. several as UK Head of Training for two of the world’s most successful pharmaceutical companies (Pfizer and Abbott Laboratories). A popular trainer and has traveled all over the country and overseas to train more than 40. for the M. He carried Business Horizons. Georgia. Prabhu Dr.
developed and delivered numerous training courses and the originator of the concept of behavioural Good Manufacturing Practice (bGMP®) and behavioural Good Pharmaceutical Practices (bGxP®). AAPS. (www. six sigma and modern quality management system design. His experience includes senior management positions in quality assurance at several pharmaceutical companies where he has been responsible for design and implementation of GxP training programs. David can be reached at David@gmptrainingsystems. Dave has served as an Editorial Advisory Board member for the Journal of GxP Compliance. David M. Institute for Validation Technology. Dave started his own pharmaceutical quality management consulting company. Lean Six Sigma.com. ISPE. David M. health and safety and other compliance topics. as well as serving currently as an EAB member for the FDA Compliance Digest and has published numerous articles on a wide variety of quality assurance and regulatory compliance topics and maintains memberships in PDA.com) a top tier provider of GMP training products and services. Inc. Quality Management at Onconova Therapeutiucs Inc. . www. NVQ Awarding Bodies. review and assessment of global regulatory filings and coordination of preparation activities for GCP and GMP pre-approval FDA field inspections. where he was responsible for GCP. Stephon Consulting. GLP and GMP quality management operations.fdagxpconsultant. Class A MRPII. Brian has designed and delivered courses in leadership. Presented at numerous seminars across the globe on a variety of performance improvement subjects. Dave served as the Vice President of Quality Management for Adolor Corporation. design and implementation of GxP vendor/CRO assessment programs. In 2010.uk David Markovitz David Markovitz is the Founder and President of GMP Training Systems. Dave received an Industry Recognition Award from the Institute of Validation Technology.GMPTrainingSystems. His most recent position in industry was Senior Vice President. Stephon has more than 25 years of experience in the pharmaceutical industry with in depth experience in regulatory compliance and quality management systems. Europe and the Middle East. Skills Academies) in helping to identify workforce development needs and supporting initiative implementation across industry.co. Brian can be reached at Brian@tknp. Prior to that. performance improvement.com David Stephon Sample Chapter for Promotion © Business Horizons.viii Achieving Quality and Compliance Excellence in Pharmaceuticals competency based performance management.. Designed. logistics topics and pharmaceutical compliance issues. values based leadership through to performance improvement initiatives (e. In 2002. He has presented numerous seminars on a wide variety of GxP topics to the pharmaceutical industry across North America. LLC. All Rights Reserved.g. ASQ and SQA. behavioural safety). Brian also has global experience of developing company training standards and has been involved with several UK public service bodies (eg Sector Skills Councils.
an international pharmaceutical industry consultant who has a Ph. Canada. which is a management consulting company specializing in regulatory affairs and quality issues pertaining to medical devices. regulatory submissions. Lincoln and Associates LLC. You can reach her at janet. and The External Quality Audit.S. She is a contributing author to the Clinical Trial Manual from Euromed Publications. editions 1 and 2. He has worked inReserved. and regulatory issues remediation and resolution. 162. John has worked with companies from start-up to Fortune 100 in the U. Mexico. Dr. and has taught English in university graduate and undergraduate programs. . editions 1 and 2. Jerry Lanese is president of The Lanese Group. including standard operating procedures. The Internal Quality Audit. he has been a consultant in the drug and medical device industries focusing on laboratory activities. Lanese was the quality representative on the team that started manufacturing operations in Puerto Rico for a major pharmaceutical firm.gough@gmail. defect and cycle time reduction. performing quality assessments and helping both small and large firms to achieve a higher level of compliance. Lincoln. Hosting A Compliance Inspection. China. He moved to industry where he has gained more than 30 years of quality control. in Analytical Chemistry from the University of Michigan. software documentation / validation. Lincoln John E. product clearance / 510(k)s. Dr.Achieving Quality and Compliance Excellence in Pharmaceuticals Janet Gough ix Janet Gough assists companies in designing and implementing document management systems for compliance with 21 CFR Part 11 and the predicate rules. research and development reports. quality/regulatory management.. Lanese is a member of the ASQ and the Editorial Advisory Board of Journal of GXP compliance. and journal articles. He specializes in client culture/systems change. Germany. president and principal consultant of J. and 164. Dr. France. Write It Down: Guidance for Preparing Effective and Compliant Documentation. She helps prepare documentation. FDA-regulated industries. E.S. All Rights large and small pharmaceutical firms managing Analytical Research & Development and QA & QC functions. 16 of which as president of his own consulting company.com Jerry Lanese Dr. For the past 17 years. He has over 30 years’ experience serving U.for Promotion and analytical research Sample Chapter quality assurance experience in the pharmaceutical industry. She trains staff in English as a second language and technical and medical writing. © Business Horizons. pharmaceuticals / drugs. She has been a director of technical communications for a biotechnical company. Electronic Record Keeping: Achieving and Maintaining Compliance with 21 CFR Part 11 and 45 CFR Parts 160. Answers to Questions You Didn’t Even Know to Ask. and Taiwan. He began his career teaching Analytical Chemistry at college level.D. RiskBased Software Validation: Ten Easy Steps. and nutraceuticals. John E. Lanese has been part of several teams working with firms under consent decree. She has authored over 35 journal articles and the following books: Managing the Document Maze. in product to market.
quality.D. . He writes an on-going medical device column for the Journal of Validation Technology. He is an active member of various industry associations. strategic business development and engineering and constructing manufacturing facilities.blogspot. All Rights Reserved. biohazards.” © Business Horizons. His areas of expertise include all aspects of quality and compliance for systems. quality assurance. he was Vice President of Manufacturing for Amgen.com Mark F. including PDA. quality risk management. Vice President. Madhu has written many articles pertaining to regulatory compliance. At Covance. senior manufacturing engineer. Most recently. Plant Manager. and conducts webinars. Manufacturing Operations for Covance Biotechnology Services. Madhu has a Master of Science in Microbiology from Andhra University. Madhu is the coeditor of the books “Microbiology and Sterility for Promotion Sample Chapter Assurance in Pharmaceuticals and Medical Devices” and “Cleanroom Management in Pharmaceuticals and Healthcare. and Mallinckrodt Medical. Witcher Mark is a Principal Consultant at IPS (Integrated Process Services) and an SME related to operational issues associated with engineering and construction of biopharmaceutical facilities. Inc. and validation. Madhu is also a volunteer for Pharmaceutical and Healthcare Sciences Society (PHSS) and acts as Director for Indian region.jelincoln. facilities and operations for drug products. training. in Chemical Engineering from the University of Massachusetts. and Director of EPOGEN® Manufacturing. Prior to joining Covance in 1995. a producer of small volume parenterals located in Hyderabad. he was a consultant to the biopharmaceutical industry for 14 years on operational issues related to: Process and product development. and workshops / training worldwide. he is responsible for implementing a robust quality system. Additional experience has been in government (civil and military). India. CAPA. start-up. Madhu runs an online compliance blog http://cgmpcompliance.com . working for such companies as Abbott Laboratories. he was responsible for the design. He has published numerous peer-reviewed articles on culture change. Director of QA/RA. Mark was with Amgen for nine years and held positions as Engineering Manager. and operation of Covance's contract manufacturing facility. Mark teaches courses on process validation for ISPE. In this position. construction. ensuring regulatory compliance and involved in qualification and validation of sterile and aseptic manufacture for parenterals.com Madhu Raju Saghee Madhu Raju Saghee is working in corporate quality department at Gland Pharma. particularly for sterile products.x Achieving Quality and Compliance Excellence in Pharmaceuticals John has held assignments as VP R&D. He has a BA from UCLA. senior QA engineer. processes.jel@jelincoln. www. Integra Life Sciences.sagi@gmail. regulatory affairs. aerospace and electronics industries. Mark received his Ph.in and he can be reached at madhuraju. PHSS and ISPE. He was previously the Sr. cleanroom contamination control and microbiology.
culminating in value added outcomes for all stakeholders. Leading GMP learning and Development for Pfizer in the UK was the last role undertaken.Pharma Business” of Excel Group of Industries (Mumbai) assisting Excel group of companies to design and install pharmaceutical manufacturing plant and develop Pharmaceutical business. Senior Validation Specialist.Achieving Quality and Compliance Excellence in Pharmaceuticals Michael Hopper xi Michael is the managing Director of GxPpro Ltd who are based in the UK but provide consultancy and training across the globe.uk or contact Michael directly via email: Michael@gxppro. working on many local and global projects. Michael has a wealth of experience of operating within both API and Drug product facilities. He was appointed as a Chair Person for New Product Selection Global Committee. China and Taiwan. ASolution Pvt. which included responsibility for the Watson API plants in India.uk Mitch Manning Sample Chapter for Promotion © Business Horizons. Having worked for Pfizer for over 30 years. and has been cited in the WHO’s WHO. He serves on the Board of IFPRESS India. Sastra University.gxppro. Michael gained valuable experience in senior roles in both Human Resources and business Development. Mitchell W. prior to starting GxPpro. For further information please visit: www. Additional information is available on LinkedIn. Mitch is a GlaxoWellcome retiree (now GlaxoSmithKline). He helped develop the criteria for the Malcolm Baldridge National Quality Award and served two times as an Examiner for the award. published number of patents and . Manning.co. where a 5 year plan was developed and delivered which incorporated knowledge and skills as well as behaviours. is the Chief Priorities Officer. All Rights Reserved. and Section Head of Regulatory and Technical Training. As well as managing his own consultancy. Ltd. Nandkumar Chodankar Nandkumar is currently “Group CEO. He is the Ex CEO & MD and shareholder of Sekhsaria Chemicals Ltd (which was later acquired by Watson Pharmaceuticals USA). He served as President of the API division. Michael works with a specialist Awarding Organisation in the UK and has written technical certificates for inclusion in the UK apprenticeship framework for Laboratory Analysts as well as conducting regular audits of NVQ centres throughout the UK and Ireland. won several prestigious awards. Positions held during his career are: Lead Chemical Processor. Priorities Limited. He also served two times as an Examiner for the President's Quality Prototype Award. Sr. Passionate about people and developing systems and teams has enabled a pragmatic approach to be taken when working with client organisations.co. Section Head of Employee Involvement (Project Teams). Initially having spent several years in Quality Control and Quality Assurance.
During his tenure he held several responsible positions with increasing responsibilities at the various manufacturing Quality units as well as the Corporate Quality function of GlaxoSmithKline in India and the South Asia region. for more than 32 years and retired in November 2007 as Vice President – Quality (South Asia). Nandkumar has been a volunteer of Drug Information Association (DIA) since in 1995 and he and his wife Laxmi Chodankar (Ph D) worked together and organized first DIA conference in India at Mumbai. participated in number of Annual DIA Conferences in the US. Mumbai. Leadership Edge. Raghunandanan R. Nilanjana Basu Nilanjana Basu is the Deputy General Manager in Corporate Quality Assurance of Lupin Limited. Nilanjana is heading the Technical Training Vertical for all the eight manufacturing plants of Lupin in India. R. IPA. Lean Sigma. the then apex body for formulating GMP and Quality standards. He actively participated in several international training workshops organized by GlaxoSmithKline in the areas of Aseptic Processing. she also is an MBA from All Rights Reserved. Ltd. Raghunandanan holds a Masters Degree in Organic Chemistry. moderator and Chair person. Kolkata andBusiness Horizons. He worked with GlaxoSmithKline Pharmaceuticals Limited.Calcutta University. that is currently involved in Research and Development and pilot scale manufacturing of Drug products. APIs and specialty products. Nandkumar has Doctorate (Ph D) in Chemical Technology from University Department of Chemical Technology (UDCT now ICT) Mumbai. He represented the region in GSK’s Global Quality Committee for several years. © Nilanjana has over 15 years of experience in Quality Assurance function and has worked in different capacities at various leading Pharmaceutical companies in India. Nilanjana has a Masters in Pharmacy from Jadavpur Sample Chapter for Promotion University. Microbiology. etc. Laxmi as a partner in Exmore Chemicals and as a Director at ASolution Pharmaceutical Pvt. He is involved in many Associations in India and abroad like ISPE. (ISPE) India Affiliate and the founder member of the Steering Committee for the ISPE . India. Nilanjana has been instrumental in setting up the Technical Training vertical in Lupin Limited and also has led the successful deployment of electronic Learning Management System in the organization. etc.xii Achieving Quality and Compliance Excellence in Pharmaceuticals scientific articles and continues to conduct management training programs and participates in several National as well International Conferences as a speaker. At her present capacity. as a speaker and as a session chair in three Annual US Conferences and many conferences in India. IDMA. Nandkumar supports his better half. Dr. Quality Audits. He served as a DIA Global Board Member and Chair of Advisory Council of India (ACI) since 2008-11 and continues as an immediate past chair and member of ACI of DIA. He continues as an Examiner and Reviewer of M Sc and Ph D Tech Thesis of Chemical Technology and Pharmaceutical Sciences students. Kolkata. He is currently a Director on the Board of International Society for Pharmaceutical Engineering. Process Validation. Total Quality Management.
the Regulatory Affairs Professional Society. Biochemistry. He received undergraduate and graduate degrees in Chemistry from St. Einig. 2008. he has consulted in the U. New Brunswick. Biochemistry. He teaches seminar courses on compliant API manufacturing for the Center for Professional Advancement in the U.. food. He had contributed substantially to the development of new GMP standards in India (Schedule M) along with several industry experts and senior regulatory officials. . Louis University. and internationally with innovator and generic dosage form companies. risk management. Einig participated in developing the PhRMA Bulk Pharmaceutical Committee's Guidance on Production of Drug Substance.S. Dr. consulting. API manufacturers. Bob holds an M. Richard Einig Richard G. B. Einig is a member of the American Chemical Society as well as a member and carries certifications from the American Society for Quality. and the Institute for Independent Business. He conceived and co-championed the ASQ Certified Pharmaceutical GMP Professional (CPGP). RAC. medical device. He can be reached at einig@APICM.Achieving Quality and Compliance Excellence in Pharmaceuticals xiii Community of Practice for Good Control Laboratory Practices. all from Rutgers. His employment experience spans over twenty years in senior management of quality. and B. dietary supplement.com. He is a member of the Expert Committee constituted by the Indian Pharmacopoeia Commission for final review and recommendation for approval of monographs of the Indian Pharmacopoeia.. S. All Rights Reserved. Pharma. Dr. and PhD from Missouri University. Since leaving corporate management. and medical device manufacturers. adopted by ASQ May 1. S. and Consulting speakers. and is an invited speaker at domestic and international meetings on quality and processingSample Chapter for Promotion of pharmaceutical products. regulatory. CQA is Vice-President and managing partner in API Consulting and Management (APICM). Europe. Currently he is a Pharma consultant based in Mumbai. with FDA. PhD.A. and © Business Horizons. He is Chair of ASQ FD&C’s Northeast Pharmaceutical GMP Conference. training in domestic or international pharmaceutical. He advises clients that are operating under adverse regulatory findings on remediation of quality systems.S. Robert Seltzer Bob Seltzer is President and Principal Consultant of “Worldwide GMP compliance Professional (WWGMPCP)” and provides auditing. He is also a consultant specializing in the pharmaceutical industry.. and/or cosmetic Good Manufacturing Practices and related regulations. Chem Engineering. and development units of large international companies and start-up “biotechs”. held annually in January. He is a member of the Technical & Regulatory Committee of the IDMA and is one of the panel members for selecting IDMA Quality Excellence Award winners. MBA from Webster University.
Tim Sandle is the Head of Microbiology at the UK Bio Products Laboratory. Sample Chapter for Promotion He possesses a Master’s degree in Pharmaceutical Technology and is currently pursuing his PhD.xiv Achieving Quality and Compliance Excellence in Pharmaceuticals Roger Janczak Roger Janczak is Director. Abbott is a diverse pharmaceutical and medical device corporation. a 100% subsidiary of Eisai Co. dosage form development and pre-clinical animal studies. scorecard reporting.lamba@gmail. he has proven adaptability with multi-cultural corporate environments while working with multinational pharmaceutical companies including Pfizer. a Masters degree in education. With more than 23 years of pharmaceutical industry experience. He is currently a Director on the Board of International Society for Pharmaceutical Engineering. USA. Tim serves on several national and international committees relating to pharmaceutical microbiology and cleanroom contamination control (including the ISO cleanroom standards). and others. at Abbott. He is associated with professional bodies like Indian Pharmaceutical Association and Parental Drug Association. Tim is an honorary consultant with the School of Pharmacy and Pharmaceutical Sciences. In his role in the global Quality and Regulatory group he is responsible for the Management Controls. He earned a bachelor’s degree in mechanical engineering and master’s degree in business administration. He is a committee © Business Horizons. Ltd. Japan. Merck Sharp and Dohme. . operations and R&D. Tim is a chartered biologist and holds a first class honors degree in Applied Biology.com Tim Sandle Dr. and a PhD in the safety testing of blood products. quality internal business data intelligence. Projects. All Rights Reserved. Sanjit Singh Lamba Sanjit Singh Lamba is the Managing Director of Eisai Knowledge Centre. CAPA and Complaints and Quality Systems. His role involves overseeing a range of microbiological tests. Northwestern University. Drug Regulatory Affairs. India Affiliate. Janczak developed a ten-year strategic plan for global R&D facilities including pharmaceutical discovery. and he has acted as a spokesperson for several microbiological societies. he manages programs including Executive Management Reviews. He can be reached at Sanjit. He is a member of the Parenterals Expert Committee constituted by the Indian Pharmacopoeia commission for final review and recommendation for approval of monographs of the Indian Pharmacopoeia. batch review. Currently. University of Manchester and is a tutor for the university’s pharmaceutical microbiology MSc course. Global procurement and Supply Chain Management etc. He has held a variety of management roles over the last 25 years at Abbott in both the US and abroad for both pharmaceutical. He has undergone a successful leadership program at Kellogg School of Management. Continuous Improvement. India. Lupin and Ranbaxy in various disciplines including Global Manufacturing. microbiological investigation and policy development.. In addition. medical products in quality. leading edge CAPA system.
. Tim has written over one hundred and fifty book chapters.blogspot. All Rights Reserved. Tim runs an on-line microbiology blog (http://www.Achieving Quality and Compliance Excellence in Pharmaceuticals xv member of the UK and Irish microbiology society Pharmig and editor of its newsletter. peer reviewed papers and technical articles relating to microbiology. In addition.com) Sample Chapter for Promotion © Business Horizons.pharmig. this includes co-editor of the books “Microbiology and Sterility Assurance in Pharmaceuticals and Medical Devices” and “Cleanroom Management in Pharmaceuticals and Healthcare”.
All Rights Reserved. © Validation by Tim Sandle Process Validation by Mark F. Raghunandanan Designing an Effective GMP Training Program by David Markovitz Behavioural GMPS (bGxP®): A New Paradigm in Compliance Management by Brian Szukala 169 7 207 8 251 9 287 10 295 11 317 12 325 13 349 . and Part 11 Compliance by Janet Gough Change Control and Management by R. Witcher Documents. Prabhu Effectively Incorporating Quality Risk Management into Quality Systems by Tim Sandle and Sanjit Singh Lamba Monitoring and Controlling Process Drift for Enhancing Quality by Nandkumar Chodankar 1 2 39 3 67 4 89 5 129 6 Sample Chapter for Promotion Qualification andBusiness Horizons. Raghunandanan Deviation Management by Alicia Tébar Pérez Internal Quality Assessments/Self-Audits by R. Records.V.xvi Achieving Quality and Compliance Excellence in Pharmaceuticals CONTENTS 1 Fundamentals of Global GMP Requirements by Atul Shirgaonkar Effective CAPA Management for Optimal Compliance by Michael Hopper Laboratory Compliance and Handling Out-of-Specification (OOS) Results in the Laboratory by John Lanese and A.
Achieving Quality and Compliance Excellence in Pharmaceuticals xvii 14 Supplier Quality Management by Ajit Basrur and David Stephon Understanding the United States Pharmacopeia (USP) by Robert D. Seltzer Meaningful Performance Metrics for Compliance by Roger Janczak Implementing ICH Q 10: A Pragmatic Approach by Alok Ghosh and Nilanjana Basu Compliance Aspects of APIs Manufacturing by Richard Einig Compliance Aspects of Sterile Manufacturing by Tim Sandle and Madhu Raju Saghee Domestic and © Business Horizons.S. All Rights Reserved. International U. Food and Drug Administration (FDA) Inspections by Robert D. Seltzer Avoiding FDA Enforcement Actions: An Optimal and Sustainable Compliance Program by Areta Kupchyk Developing a Master QMS Plan by John E. Lincoln Trends in cGMP Compliance by Mitch Manning Index 381 15 417 16 431 17 459 18 479 19 497 20 517 Sample Chapter for Promotion 21 561 22 567 23 581 24 629 641 . Seltzer Spotting Overall Weak GMP Compliance Systems by Robert D.
andChapter for Promotion many in the industry. Siegfried Schmitt. This picture is no longer accurate. This book not only encourages and details the application of these modern quality paradigms in a single guide. Thus. The changing regulatory environment encourages a risk-based and performance-governed compliance approach based on an agile quality framework. continually improve. a variety of countries in Asia. All Rights Reserved. into advanced. embrace advancement of science and benchmark themselves. it is also an aide and an encouragement for those in industry who wish to learn from the best. © Business Horizons. the Middle East and Central/South America have become providers of innovative. current and exceedingly high quality of the contents. UK . as many companies outside the USA and European Union have established industry best practices and leading edge technology. PhD PARAXEL. Such an approach is fundamental to maintaining competitiveness.e. I am certain that this publication will be read with Sample put to good use by great interest and pleasure. irrespective of location and cost base. high-value and into more basic low-cost regions. i. The pharmaceutical industry has long been perceived as being split between Western and Eastern hemispheres.xviii Achieving Quality and Compliance Excellence in Pharmaceuticals FOREWORD The publication of this comprehensive guide comes at a most opportune time. research-based pharmaceutical products that compete with the best in the world. The high calibre of the authors and the diligence of the editor assure comprehensive.
led to the formation of what is now known as ‘Good Manufacturing Practices’ (GMP). in varying from drug-to-drug and from country-to-country. In the wake of some appalling incidents which resulted in the deaths of many patients. to name but a few. For this task a number of leading international experts were approached and all accepted the task of shaping the understanding of twenty-first century compliance and applying it to modern pharma and healthcare. and improving upon cleanroom design and operations. medical devices and healthcare. which were discussed and debated in the mid-part of the twentieth century. Whilst compliance aspects of pharmaceutical drug development and manufacture have been enshrined most notably in the FDA Code of Federal Regulations and with the European Union GMPs. 10 and 11). All of working which will of medicinal products. both in the 1960s. extending out to drug distribution. a space within which Quality Assurancefor Promotion understand and develop new technologies and ways Rights Reserved. A series of developments in the twenty-first century has pushed this philosophy further and this has been captured within a raft of critical documents. this was erratic. and thus provide pragmatic advice for the industry. To this end a book has been produced which provides a comprehensive account of all facets of quality and compliance issues in Pharma. These are the FDA’s 21st century initiative and the ICH guidelines focused on quality risk management (ICH Q8.enhance the quality © Business Horizons. Pharmaceuticals and other health care products came first and whilst there was a concern with both the safety of the patient and proving the efficacy of the medicine. although the development of each of these has been at a different pace. and was not codified. The collective body of GMP evolved through the 1970s to the 1990s. It is not an over exaggeration to say that these documents. What underpins these documents is the importance of science based decisions and risk evaluation as the centerpiece of compliance policy and execution. drawing in aspects of operations management. reflecting a new philosophy. two pioneering acts in the USA and the UK. One of the key editorial requirements was that each chapter must balance the theoretical with the practical. and their philosophical underpinnings. . this book was developed. 9. So that quality personnel are better informed as to these changes and are able to place them within the context of the pharmaceutical organization. The idea was to put together something which would be of value to both the experience practitioner and those new to the pharmaceutical sector. there has always been the dimension of ‘c’ GMP (current Good Manufacturing Sample Chapter personnel are required to occupy in order to Practices). represent a paradigm shift in relation to the quality and compliance of pharmaceuticals.Achieving Quality and Compliance Excellence in Pharmaceuticals xix PREFACE Compliance and pharmaceuticals have a long association.
xx Achieving Quality and Compliance Excellence in Pharmaceuticals The editor is pleased to note that this task was achieved and he wishes to express his thanks to each of the contributors for taking the time and trouble. Antony Raj Gomes and T. I am indebted and grateful to Siegfried Schmitt. the world of Pharma. be of use to the reader. foremost. of training and auditing. of the key dimensions of quality and quality systems. India June. This has led to the creation of a truly global book which will be of use to all working within. Sample © Busines ACKNOWLEDGMENTS . Thus the book provides detail on global GMP. Madhu Raju Saghee Hyderabad. from APIs to steriles. and drawing upon many years of experience. In putting the book together. I would like to thank JPS Kohli for his patience and diligence in the production of this work. and applies these across different sectors. 2012 I would like to express my deep gratitude to the authors and contributors who have cooperated in preparation of this book amidst their busy work commitments. to produce unique and detailed chapters. the editor has not lost sight of the fact that book must. Raghunandanan. Rajesh for their insights in shaping this book into a master class guide. or who have an interest in. R.
manufacturing defects. The primary objective of this chapter is to help the reader in designing appropriate tools that can assess the health of the quality system and to find the problems. USA 17. This chapter provides a framework for establishing the right quality indicators/metrics for evaluating the performance of the quality system. There are typically. anticipates future needs and enables actions. An effective leadership team must develop. If you can't understand it. However. The effort needed to measure. collect data. collect and analyze information that provides current performance feedback. If you can't measure something. ideally before they mature into a quality defect and fix them. you can't understand it. supplier performance. All Rights Reserved.Meaningful Performance Metrics for Compliance 459 17 Meaningful Performance Metrics for Compliance Roger Janczak. Abbott.1 OVERVIEW OF PERFORMANCE METRICS “Measurement is the first step that leads to control and eventually to improvement. you can't control it. Successfully executing a strategic plan requires the development of an appropriate set of metrics. the development of any measurement system should take into account the following factors: Sample Chapter for Promotion H. If you can't control it. complaints. A well designed set of metrics enables managers to evaluate the performance of their business processes. not all of the data has the same value. James Harrington © Business Horizons. cycle times and many other internal or external processes. Data may pose a risk if the wrong things are measured or incorrectly analyzed. appropriate. It must be accurate.” Performance metrics are an essential element of the management review process. make decisions based on the evaluation and take action. and correctly analyzed. vast amounts of data available in any organization. Quality metrics may include elements such as customer satisfaction. According to Juran1. analyze and report must provide business value. timely. . you can't improve it.
An ideal organization uses accountability in a positive manner by focusing on the opportunity to improve. if any. Sometimes the easy metrics to collect offer little. They can also help avoid self-interest by elevating the objectives to the organizational level. value while more worthwhile information requires effort to establish a measurement process. Behavior – According to Eliyahu Goldratt. These measure the performance of a core set of compliance objectives that can be piloted quickly and iterated rapidly. Sample Chapter for Promotion Alignment – A core © Businessstrategy focused organization is to align the entire team on a objective for a Horizons. . Dean Spitzer described several key functions of performance measurement2. and I will tell you how I will behave. Metrics provide the common bond. This elevates the importance to meet performance objectives to the entire organization. common set of strategic objectives. Feedback – Metrics provide short and long term feedback on the effectiveness of projects and activities. Setting the right metrics drives the right behavior. This supports fine tuning implementation plans and supports continuous improvement. it is often best to start with a relatively simple set of metrics that can be closely aligned to organizational objectives. It is important to understand the intended and unintended consequences of a metrics system on an organization. Expectations – Metrics allow an entire organization a common understanding of what outcomes are most valued by leadership. People can be held accountable to deliver results. When accountability becomes negative it can drive behaviors associated with avoiding punishment. All Rights Reserved. Accountability – Metrics indicate how well an operation or project is performing against commitments. Metrics provide the feedback that enables faster responses to changing or emerging issues. author of The Goal. For emerging organizations. Performance metrics can be described as the central nervous system of an organization. This clarity enables people to stay focused on long term objectives on a daily basis.460 Achieving Quality and Compliance Excellence in Pharmaceuticals There should be a standardized meaning of the measurement The data should help the decision making process It should provide worthwhile information It should be easy to install It can be benchmarked or used elsewhere The challenge is selecting metrics that take into account each of these factors appropriately. What gets measured gets done. Attention – Metrics incorporated into management review provide a defined set of expectations of senior management and are reviewed regularly. all behavior can be predicted by what is being measured: “tell me how you measure me.
Metrics must be carefully chosen to ensure they align with strategy. An excessive number of metrics can be referred to as the trivial many. Having too many or the wrong metrics does not allow an organization to focus. the former CEO of General Electric. Make sure there is an understanding of The reason for collecting the metric. Objectivity – Metrics form the basis for a fact-based organization. it can be helpful to begin with the end in mind. They provide an orient point as people navigate continuous improvement. Metrics provide short and long term measurement of progress. hundreds of metrics are possible. referred to unfocused organizations as “measuring everything and understanding nothing”. . Other considerations in selecting metrics include the difficulty to measure or collect the data. 17.2 PRINCIPLES OF ESTABLISHING PERFORMANCE METRICS FOR COMPLIANCE “You measure your organizational capability by asking the right questions” 3 Larry Bossidy and Ram Charan When creating a performance measurement system. There can be increased visibility of small changes in performance that if unchecked grow into much bigger problems. Jack Welch. In a high performing organization. Think about the entire process from acting on the metric backwards to the data itself. It demonstrates their achievements and highlights the contributions made toward long-term business objectives. data reliability and the cost to collect. How will data be collected? By whom? Where will the records be stored (paper and electronic)? What is the data that you need? Sample © Busines To fully characterize a quality system. Many organizations have implemented strategy frameworks such as the 4 Balanced Scorecard described in the The Strategy Focused Organization . what gets measured gets done. How will it be used? By whom? How will the results be communicated the information gained from the metrics to all stakeholders? Analysis needed to transform the data into useful information. It enables senior management better insight to the inner workings of their business processes. Instead it is important to determine the crucial few metrics. Reaching those interim milestones can be highly motivating.Meaningful Performance Metrics for Compliance 461 Motivation – People like knowing their efforts are worthwhile. What data transformations are needed? Who will perform them? What tools (software) are needed? What are the validation requirements? The process to collect the data. analyze and report. Visibility – A common set of metrics used throughout an organization creates transparency. Problem Solving – Metrics enable management to uncover problems earlier. They provide early warning indicators to avoid a crisis situation. Establishing a large number of metrics in the hope of finding some that work wastes resources and distracts leaders. Implementation of too many metrics may not result in a compliant quality system and may actually impede quality progress. This objectivity promotes a positive environment within an organization.
Establishing predictive leading indicators can improve a quality system. Measuring the percentage of CAPAs closed within 60 days may predict the number that will be completed past due. The expected quality outcomes (the Y’s) are the outputs. the inputs. Time-based metrics are used to measure the duration of a process. However. Leading indicators provide information that may be able to predict future outcomes. Sample © Busines Quality Output(s): Y Process Input x1 Input x2 Figure 17. it might have been possible to avoid a performance decline. etc are the causative agents. Metrics such as the percentage of CAPAs completed on-time is an . Leading indicators x1. If there is a spike in the number of CAPAs initiated in a particular month (say 25% percent increase compared to the typical run rate) then it would be expected that there might be an increase in the number of days to complete the investigation. quality or quantity/cost. it is also important to consider whether the metric measures time. if they had responded to the leading indicator (CAPA Initiations) and rebalance investigation resources. a typical CAPA organization has a fixed number of resources to investigate and implement resolutions. it is possible to focus on impacting drivers which will ultimately change the outcomes. etc can be inputs into the process or interim measurements of the process. More mature organizations will typically have a greater ratio of leading to lagging metrics. As metrics are developed for an organization. Most compliance metrics are inherently lagging indicators and are typically easier to define.1: Cause and effect relationships In addition to looking at leading and lagging metrics. In business excellence terminology. they could find their metric has trended adversely. For example. It is necessary to understand the cause and effect relationships. x2. By understanding the cause and effect relationships. this is notated as Y = f(x) where Y is the outcome and x1. Lagging indicators measure the outcomes of what already happened. This can be illustrated using a process diagram (below). it is often possible to begin developing metrics with lagging indicators and then ask what actions or conditions cause this outcome to brainstorm leading indicators. An organization that has an internal goal for investigation completion timeliness. x2.462 Achieving Quality and Compliance Excellence in Pharmaceuticals A good metrics system is built with a combination of leading and lagging indicators.
Cost of Quality metrics have not been included in the Compliance Metrics section. All Rights Reserved.Meaningful Performance Metrics for Compliance 463 example. In the interest of understanding the how well batch records are documented. These types of issues can often be addressed through feedback loops between the reviewers and the operators who prepare the batch records without a formal elevation process. looking to further enhance their effectiveness. In a balanced scorecard these could include the cost of the process. focus the organization and develop the buy-on necessary in order to implement. However. Measuring the frequency that a CAPA investigation reaches root cause can be an indicator of the quality performance of the CAPA system. Some regulators do not look favorably on compliance decisions based on cost and using financial metrics for compliance is not recommended. This could be a perfectly value added metric in an operation where there has been a significant issue with recording keeping. Compliance metrics should focus on effectiveness and measure that the right things are being done correctly. Too often the focus of metrics is on efficiency which often is measured in financial terms. Quality objectives will support one or more elements of a strategic plan.1 Selecting the right metrics Defining metrics Setting targets/goals Roll-up of metrics Maintaining metrics Selecting the Right Metrics Performance measurements should flow from and be aligned to strategy. An emphasis on effectiveness first will drive an organization to eliminate the waste which in-turn will improve efficiency. Quantity/cost metrics track the frequency or productivity of the process. metrics could be established to measure “right first time” accuracy for batch history records. It may also apply to Sample Chapter for Promotion a mature business © Business Horizons. Identification of metrics should be done with individuals from each level of the organization. As the system is being developed. Quality-based metrics are typically more difficult to establish for a compliance process.2. collecting documentation errors will require the reviewer to record the nature and details of each error. The records will need to be maintained under a record retention process. This dialog provides the opportunity to increase alignment. 17. Some metrics are easy to define but establishing a data collection process can be a significant hurdle. There should be dialog between levels and across organizations to establish metrics. they can provide excellent insight into the health of the quality system. then level of effort needed to establish and maintain the process may not have sufficient benefit. if the record documentation has not been a problem. Since detecting such errors is a manual process. The record keeping requires additional steps in process including data recording. . include representatives from each step in the process to make sure the data system is designed successfully. For this reason. A metric might be defined as the number of documentation errors made per batch. It could also distract management from other more pressing compliance issues. However. data verification steps and analysis.
A list of draft metrics supporting each strategic objective is developed. and divide it by the sum of the total CAPAs that were planned to be closed during this period. It is not necessary to fill out every time %. The value for this week will be (4+3)/10*100%=70% For complicated calculations sometimes it is necessary to have detailed explanation on the components of the formula. each of those actions should be reviewed to determine how could the outcomes of that action be measured. a cross functional team should discuss actions that should be taken to achieve the strategic plan. what question is to be answered?.464 Achieving Quality and Compliance Excellence in Pharmaceuticals Hoshin Kanri is an implementation system that can be used to deploy metrics from strategy through implementation. A well-documented metric provides a solid foundation to collect consistent metrics across departments and over time. Example: Are qualityrelated issues detected in audits resolved in a timely manner? Be specific about the formula that is used to calculate © Business Horizons. convert the result into percentage. 17. Example: Between the week of March 20.2 Defining Metrics Metrics definitions should be documented. What quality objective do we wish to achieve. They should also consider the drivers that influence the outcomes. Sum the CAPAs whose actual closure dates are earlier or equal to the planned closure dates. This is not an accumulative number so each CAPA (including the CAPAs that are open across multiple time periods) is only counted once. Example: Percentage of supplier CAPAs (Corrective and Preventive Actions) that were completed no later than the planned completion date. The table below can be used as a guide to building a complete definition. All Rights Reserved. Once the actions are defined. Example 90% Definition: Expected Benefit: Sample Chapter for Promotion Formula: Example: Breakdown of Metric Formula: Unit of Measure: Target: . Give a detailed example for the calculation.2. Be specific about the benefit. 2012 there are 10 CAPAs planned to be closed (these CAPAs may be associated with multiple audits). Example: % The achievable and desirable goal. 3 CAPAs closed on the planned dates: 1 CAPA closed on March 22 versus the planned date of March 20 and 2 CAPAs remain open. Example: Identify the number of CAPAs planned to close during a certain period. One full sentence with verb (avoid using only of three or four words as that can open to interpretation) explaining the Metric. #. There are 4 CAPAs closed in January. Using the strategic objectives as a starting point. The system includes planning. 2012 and March 24. etc. the metric. implementation and reviewing and 5 establishes a closed loop feedback system .
Accountable: Senior Audit Manager. some of which may call for action. Accountable: person(s) ultimately responsible for the metric performance. and Green) to indicate the levels of metric performance. and internal) The metric that is the next level down that feeds into this one. Any helpful information in explaining this metric. Green >/= 90% Where data is currently collected. Yellow. Example: none (in this case) Responsible: person(s) influencing the metric performance. Describe where the data will be reported or used. Example: Red </= 79%.1: Defining metrics .M. usually a senior figure but sometimes may be the same as Sample Chapter for Promotion the Responsible person. subcontractors. © Business Horizons. Quality Director. Rank benefit of collecting this metric Rank effort of collecting this metric RACI: Person Responsible for Metric Data Source: Reports Utilizing Metric: Additional Information: Benefit (H. Consulted: person(s) with knowledge in improving the metric performance.M. Example: Weekly The parent level metric that this one feeds into. Example: Responsible: auditors. Yellow 80 to 89%. Informed: person(s) likely to benefit from the updates on the metric performance.Meaningful Performance Metrics for Compliance The level of performance over an agreed-upon time frame.L): Table 17. Consulted: none. Example: Overall Audit Effectiveness (for suppliers. two-way communication. run Report #1 using the most recent Monday and select the department(s) to be reported The frequency at which the data are accumulated. Example: Audit Department Quality report (the parent metric "Overall Audit Effectiveness" will be in the Management Review report). Example: Weekly and Monthly 465 Baseline: Frequency: Status Indicator Rules: Data Sources (s): Capture Process: Capture Frequency: Metric next level up: Metric drill down: Use the colors (Red. All Rights Reserved. Person filling out KPI scorecard and person(s) providing the data source: Example: Person filling out KPI scorecard: Senior Audit Manager.L): Effort (H. persons providing the data source: auditors. Example: CAPA IT system Report #1 The detailed process of the report generation. Example: 2011 actual results The frequency to report. Informed Quality council. In the CAPA system. one-way communication.
17. Performance improvement can be measured against the baseline. metrics often include sales. A weighting is assigned to each metric based on its contribution to the index. but also based on realistic expectations.” W. The need to collect a metric may change over time. All Rights Reserved. Attainable. Realistic.3 COMPLIANCE METRICS “If you can’t describe what you are doing as a process. Adjustments to the metric definition should be done with caution. Manufacturing metrics often include manufacturing schedule adherence.5 Maintaining Metrics Sample Chapter for Promotion Once metrics are defined. Measureable. this chapter focuses on factors that have a more traditional © Business Horizons. Quality performance metrics should be established based on linkages to organizational objectives. as some changes may invalidate older measurements. The index value is the sum of the weighted values for each metric. 17. piloted and placed into operation it is important that the individual(s) assigned the roles as Responsible and Accountable monitor the metric collection process and the results to ensure the metric is performing as intended. After metrics are defined and data collection activities are in place. profitability. you don’t know what you are doing. . it should be removed and free up the resources it takes to collect and report. market share. Edwards Deming At the business level.2. Time-bound and Aligned. When setting targets consider using “SMART-A” targets: Specific.2. baseline data should be collected for several reporting periods to ensure the data can be collected and calculated as expected. delivery time accuracy.2. In cases where two or more different metrics roll-up into a single index value on the higher level scorecard. etc. If the metric is no longer adding value. Each metric result is multiplied by its weighting. Weighted calculations methodology should be defined using a definition form similar to the metric. However. such as the CAPA manager. Quality and compliance metrics are a subset of the total performance metrics in a typical company. etc. The quality function in organization should support strategic issues.466 17. For example.4 Rolling Up Metrics Metrics are rolled-up into a hierarchy as defined in their definitions. Often the person assigned as Responsible is the process owner for the quality system being monitored. This can be a starting point and improvement targets can be established. CAPA timeliness for a company is the sum of the performance of each department’s results. 17. cost variances.3 Achieving Quality and Compliance Excellence in Pharmaceuticals Setting Targets and Goals Targets and goals should be set in alignment with strategy. The baseline data establishes either the past or current level of performance. it is possible to use a weighted average.
Sample © Busines Audit Reports and Findings Quality documents(Quality manual. batch records etc. procedures etc) Audit & Inspection Process Qualified Personnel Figure 17.3. Internal audits provide on-going feedback on the health of the quality system. but provide a starting point for each organization.1 Audits and Inspections A basic indicator of compliance is performance against regulatory agency inspections and inspection authority audits. Unfavorable outcomes can result in significant business interruptions including loss of license to market products or manufacture products. The audit process is a periodic snapshot of performance by an independent inspector. Internal audits should be conducted more regularly and enable a proactive response to avoid an external finding. There are many variations and extensions to these metrics in the industry. but not an assurance of health of the quality system. By this guideline 80% of the quality problems in an organization are outside the control of the quality function. Quality goals should be shared and be applicable across the organization. and distribution system problems. Successful regulatory inspections are required for commercialization of products and for manufacturing authorization. Functional area self-audits offer an excellent opportunity for most proactive measurement. quality costs. 17. quality improvement and customer satisfaction. These inspections are conducted infrequently and can’t be relied on as a single indicator. ownership of the issue belongs to operating function. It has been stated that the Pareto principle applies to quality problems6. Internal quality problems may include lab test issues. They can also impact public perceptions and decrease the value of a company’s brand and image. The metrics described are not an exhaustive list. Favorable outcomes from these inspections and audits help confirm compliance and conformance. Feedback from all sources of quality data and review by management is needed to fully evaluate the system.Meaningful Performance Metrics for Compliance 467 quality base. The Quality and Compliance metrics described below represent some of those commonly implemented in pharmaceutical operations. While Quality metrics may be collected and reported by the quality function. These can be linked to product or service performance. Examples of organization wide problems could include supplier quality requirements.2: Audit and inspection process . Performance metrics against external inspections are very reactive metrics. auditing procedures and sampling procedures. R&D product designs. while 20% may be internal. They provide an important indicator. Quality Records (CAPA.
1. sometimes referred to as “hot topics”. An additional benefit of a pareto analysis by citation is for external benchmarking. Carefully examine trends of external findings frequency. This may indicate increased emphasis on emerging issues or heightened inspection focus on key quality system topics. The internal audit plan can be . This enables development of a pareto of finding by citations. There are frequent studies showing pareto analysis of finding by agencies such as the FDA. If internal audits do not identify similar trends in findings as external inspections there may be an opportunity to refine the audit program. inspection and audit actions auditors (comparative analysis) Number/percent of effectiveness checks that pass Trend Evaluate whether there are relative differences between departments or auditors (comparative analysis) Table 17. An organization can compare their findings to the benchmark and react accordingly.3.2: Audits and inspections metrics 17. The highest frequencies of findings should be the focus of global improvement efforts. This is frequently done according to regulation citation number being violated. Another benefit of this type of analysis enables a comparison or perhaps a calibration of an internal audit group to external authorities. departments or differences between © Business Horizons.1 Additional Considerations Further insight into the quality system can be gained by analyzing the findings according their nature and details. sites and functions Number/percent of open inspection and audit actions Trend Trend Trend Evaluate whether there are relative differences between departments or auditors (comparative analysis) Trend Evaluate whether there are relative Timeliness of closure of Sample Chapter for Promotion Trend All Rights Reserved.468 Achieving Quality and Compliance Excellence in Pharmaceuticals Outcomes Metrics Statistic Method Trend Other Considerations Evaluate whether there are relative differences between inspecting authorities or between external and internal performance (comparative analysis) Evaluate whether there are relative differences between sites or functions (comparative analysis) Evaluate whether there are relative differences between departments or auditors (comparative analysis) Percentage of inspections/audits that result in no adverse findings Frequency and severity of findings Process Metrics Timeliness of internal audits against schedule Indicators that audits covered all quality systems.
In addition. Investigations that are incompletely performed or open for an extended period of time are a red flag for a possible significant unresolved problem or an unresponsive management team. This is also true for potential non-conformances and planned deviations.2 Non-conformance and CAPA Systems The CAPA and Complaints quality systems are two of the most important windows to compliance and the health of the quality system. A high level of non-conformances or an increasing trend should be monitored. Two of the most common metrics are the number/rate of non-conformances and CAPA timeliness.3: Non-conformance and CAPA process . test failures. Other proactive measures include understanding whether an investigation successfully determines the true cause of the nonconformance and whether the planned verifications of effectiveness were successful. They are frequently a focus area for external inspectors.Meaningful Performance Metrics for Compliance 469 adjusted to include covering “hot topics”. The primary objective of the CAPA system is to take actions to avoid reoccurrence. audit findings. Inspectors look at CAPA data to understand whether CAPAs are addressed thoroughly and promptly. 17. It is crucial to develop appropriate metrics. yet many organizations fail to measure performance of reoccurrence. Sample C © Business CAPA Investigations Correction Actions Implemented Preventive Actions Implemented Exception Report Records Non-conforming events(defects. complaints confirmed as deficiencies etc) Potentially non-conforming events (adverse trends etc) Figure 17. Establishing a process to measure reoccurrence can provide an outstanding method to demonstrate the health of the CAPA process. internal groups can prepare for external and internal audits by preparations for the frequent inspection areas and hot topics.3.
cause. categorization by product family.2. Evaluate the percentage of investigations are completed in a fixed period of time. Consider whether there are any products. A red flag can be when a high frequency of problems are attributed to human error and the corrective action is to re-train because it indicates a potential failure to identify the true root cause therefore an effective action has not been taken. product. product. cause.1 Additional Considerations Further insight into the quality system can be gained by analyzing additional CAPA system information. In addition. It is also useful to monitor those non-conformances and CAPA that have been determined to have a higher level based on the risk evaluation. such as 60 or 90 days ) Evaluate any plans that are overdue for extended periods of time Evaluate the location of the event. supplier. cause.3: Non-performance and CAPA metrics 17. type of process. This could include categorization of the nature and details of the nonconformities. etc. The high risk events should be given priority for completion (and therefore timeliness) and confirmation . For example. process step Evaluate the location of the event. part number.470 Achieving Quality and Compliance Excellence in Pharmaceuticals Statistic Method Trend Outcomes Metrics Frequency of investigations which reach root cause Frequency of effectiveness checks that pass Frequency of nonconformance reoccurrence Process Metrics Other Considerations Confirm the level of reoccurrences. product. process step Trend Trend Trend Trend Frequency of planned deviations (process input) Table 17. processes or departments with a disproportionate number of issues. process step Evaluate the location of the event. insight can be gained by understanding the cause and resolution of problems. root cause and effectiveness and that there are not any adverse trends or patterns (current value against target. human error. For example. etc. such as 60 or 90 days Evaluate any investigations that are open for extended periods of time Trend Investigation timeliness Completion of action timeliness Frequency of non-conformances (process input) Frequency of potential nonconformances (process input) Sample © Busines Trend Evaluate the percentage of actions are completed overdue in a fixed period of time. equipment used. categorization by equipment failure. trending).3.
Meaningful Performance Metrics for Compliance 471 of the adequacy of the investigation and corrective actions. Adverse events have defined reporting timeframe expectations. Management needs visibility to the frequency and level of review taken when decisions are made to disposition nonconforming product as “accept as is” without correction. Investigators will look for complaints open for extended time periods as a flag that the complaint was difficult to resolve and this may be an indicator of a significant issue. such as recalls. 17. Complaint and Product Action process measures determine the timeliness of key process steps. Complaints must be evaluated. They may also indicate a lack of focus or resources. resolved and reported. Corrective actions related to product actions. Complaint intake from field Sample © Busines Complaint records Adverse Event records Recalls Regulatory Notifications Customer Notifications Adverse event intake from field Non-conformances leading to a recall Figure 17. and complaints should be given a heightened level of priority for completion and elevated review/approval. in an effective and timely manner.3 Complaints and Product Actions The effectiveness of the Complaints and Product Actions systems are closely evaluated by regulators because of their criticality to the product safety and the patient.3.4: Complaint and product action . The appropriateness of corrections made to address a nonconformance can be monitored. as appropriate. investigated.
finished dosage and third party manufacturers of finished products. Review of complaint categories across products may identify common failure modes across several products that might be undetectable in any single product.3.472 Achieving Quality and Compliance Excellence in Pharmaceuticals Statistic Method Trend Pareto Trend Outcomes Metrics Frequency of complaints confirmed as a nonconformance Frequency of product recalls Frequency of adverse events by product and category Process Metrics Frequency of complaints by product (process input) Frequency of complaints by nature of complaint (process input) Other Considerations Evaluate by product and product family Evaluate by product and product family Trend Pareto Trend Pareto Evaluate the percentage of complaints that closed in a fixed period of time. starting materials.3. mandate a rigorous quality system.1 Additional Considerations Sample Chapter for Promotion Additional Considerations As the number of product lines increase. indirect materials and miscellaneous products or services such as pest control. . The number of suppliers. API (active pharmaceutical ingredients). calibration. All 17. it becomes more important to look across product lines for trends that may have a common cause. or IT may be best served by separate performance measures and monitoring. © Business Horizons. such as 60 or 90 days Evaluate any complaints that are open for extended periods of time Complaints closure timeliness Trend Regulatory notification filing timeliness Trend Table 17.4 Supplier System The increasingly complex supply chain has increased the importance of performance metrics for supplier quality. the diversity of the products/services they provide and the broad geographic distribution. excipients. a defect bottle lot may be used in multiple products. chemicals. Other types of suppliers such as CRO (contract research organizations) for testing or clinical studies. 17.3. For the purposes of metrics. For example if there is problem with a commodity such as a bottle.4: Complaint and product action metrics Rights Reserved. drug product. we are defining suppliers as providers of direct manufacturing materials including commodities.
Typically. This scorecard could include metrics such as audit outcomes. Both perspectives should be monitored with performance metrics. In addition. lot failure rates. Performance against such a scorecard should result in a composite metric for each supplier. Internal and external non-conformance are examples of supplier driven issues. For example. delivery performance and responsiveness. The cumulative metric for all suppliers would be the summary of the composite metric from all supplier scorecards The supplier process metric evaluates how well we are managing the supplier network. Metrics can be established to set targets for a sub-set of suppliers.4: Supplier System Outcomes Metrics Frequency of non-conformances due to supplier Incoming testing failures In-process failures due to supplier Performance against scorecards Process Metrics Frequency of Quality Agreements established Timeliness of internal supplier audits against schedule Table 17. Supplier nonconformances Supplier metrics for scorecard Sample © Busines Supplier System Supplier Audits Supplier Scorecard Performance Recalls due to supplier Quality Agreements Figure 17.Meaningful Performance Metrics for Compliance 473 Suppliers are both a part of a company’s quality system and act within their own quality system. a target might be to have a quality agreement in place for all critical suppliers.5: Supplier system metrics Statistic Method Trend Pareto Trend Pareto Trend Pareto Trend Pareto Trend Trend Other Considerations Evaluate overall and by supplier Evaluate overall and by supplier Evaluate overall and by supplier . it is important to look at a supplier as a whole quality system. there are no regulatory requirements to have quality agreements or conduct on-site audits of the entire supplier base. A scorecard should be developed for each supplier. manufacturers take a risk based approach to establishing these. Today.
It is important to consider the implications of reporting two supplier metrics. This is not an exhaustive list. In all such cases. Data might be skewed if that data was included in the internal data. of Business Horizons. Another example is related to timeliness for suppliers to investigate non-conformances or close-out audit items. When tracking. All Rights • Calibration schedule conformance Cleanroom metrics • Frequency of cleanroom OOS (out of specification) Customer Satisfaction metrics • % Customer Satisfaction (survey) • Frequency of non-product related complaints Environmental metrics • Frequency of microbiological failures Equipment metrics • On-time performance of preventative maintenance • Available/downtime Information Technology • Frequency/severity of IT system issues Management Review metrics • Frequency of meetings held • Action item closure on-time . the effort to report the name in two ways might not be worth the effort to report separately. but provides points to consider. the effort/benefit analysis can guide appropriate reporting. systems might make it more difficult to separate and report both supplier and other non-conformances.474 Achieving Quality and Compliance Excellence in Pharmaceuticals Additional Considerations 17. For example.5 Other Metrics Compliance performance metrics can be established for additional aspects of the quality systems. 17. The following are examples of typical metrics. as a supplier metric and as a nonconformance.3.3.1 Supplier metrics can be reported as part of other quality systems. nonconformances/CAPA events will be reported in both the CAPA and Supplier metrics. Analytical Lab metrics • Frequency of OOS (out of specification) Calibration metrics Sample Chapter for Promotion • Frequency © calibration OOS (out of specification) Reserved.4.
2 Scorecards. When possible these roll-ups should be done more frequently than the formal management reviews to provide interim checks on performance and avoid surprises at management review. The data collection process can be time intensive. Many metrics need to be collected. such as audit results. Other metrics are reviewed less frequently. Scorecard reports are typically graphical reports that summarize key metrics.4.1 REVIEWS. Metrics are accumulated. metrics are not reported out of IT systems in a ready to use format. 17. there may be daily or weekly reviews held. or also said to roll-up. The frequency the roll-ups are done should be set according to the business. calculated and reported out manually. and Dashboards In many small to mid-sized companies. © Business Horizons. A detailed list of metrics should be reviewed on a routine basis in the functional area(s) involved. There should be a defined set of metrics that are reviewed by senior management at regularly scheduled management reviews. as well as in some multinationals. Whenever possible. Reports. these . into area or company level metric.Meaningful Performance Metrics for Compliance 475 Product Conformity • In-process rejects • Frequency of customer returns • Frequency of “accept as” concessions Sterilization metrics • Frequency of sterilization nonconformances Scrap • Yield Training metrics • Frequency of jobs with defined certification requirements • Frequency training that is completed on time Validation • % coverage of validation plans for systems • % validation master plans completed on-time • % validation protocols completed RFT (right first time) 17. reports and dashboards help turn a large amount of data into a graphical picture that enables managers to quickly recognize changes and patterns in the data. Management review is a process. for example for nonconformances. Well designed scorecards. For metrics closely connected to production.4 17. All Management Review Process Sample Chapter for Promotion Metrics are an important element of the management review process. SCORECARDS AND DASHBOARDSRights Reserved.4.
Try some combination of the above. Gather more data. when appropriate. Edwards Deming 17. This creates employee ownership of performance results and increases the commitment to achieve the goals set forth. In a dashboard. or suspension of marketing. For example. all others bring data. These reports can be a collation of all the lower level reports or just a summarization of accumulated results. An index value is calculated by taking a weighted value for each © Business Horizons. To avoid this problem. Using metrics Taking action on metrics: Do nothing. Take market action such as a field correction. all of the metrics may be reviewed directly by plant management. Based on that review they would elevate issues. Actions taken as part of management review need to be documented and tracked to closure.476 Achieving Quality and Compliance Excellence in Pharmaceuticals reports should be on display in appropriate. the content of the metrics varies according to the size of the organization.5 . Try a pilot corrective action and measure the results. As data rolls up from production line to department to company. Have a formal risk analysis performed. metric and summarized into the index.five CAPA metrics. At each level of the report metrics are accumulated from lower levels. recall. Actions should be taken at each level in the organization. visible locations in the operation. In a dashboard. For example if the complaints metrics tracks twenty five products. but not the entire report to executive management. In smaller companies. Often an executive dashboard is used. However. How metrics and data gathering affect some people Focus on Red vs Green OTHER CONSIDERATIONS “In God we trust. Try measuring something differently. an index can be created to summarize a set Sample Chapter for a CAPA index could be created consisting of metrics. As the organizational size increases in complexity it may be appropriate for functional areas to begin the process with a detailed review of scorecards for the function.” W. information in rolled-up reports should include both the accumulated data and reporting on sub-groups that have tripped a signal. only the most strategically important metrics are presented. All Rights Reserved. Promotion of three . At the executive level in the management review process. as data is accumulated there is the risk that problems may be masked due to dilution of the data. a multi-layered hierarchy is used. a spike in the complaint level on a small volume product can be invisible when rolled up into accumulated numbers consisting of much larger volumes.
Documentation and Audit are some of the most common modules within these systems. In addition to the modules in a QMS. Filtering data: Unless the definitions are precise. but often a regulatory expectation. it is important for design requirements to be established early for metrics calculation and reporting. Complaints. This enables better information management and richer quality system information. the EMEA updated the EU Annex 11 standard for computerized system validation. In addition.5. When such systems are being developments. there can be a rush to meet the numbers by pulling in activities from the next month.3 Data Verification and Validation Data integrity is crucial to the consumers of the reports. if a metric meets its objective. Some of the more common pitfalls include: Changing reporting periods: At the end of a month. Both QMS and PLM come at considerable cost and level of effort to implement. these complete systems including regulatory modules and linkages to materials management/production bill of materials systems.5.1 Typical Problems 477 There are a number of problems associated with implementing a metrics system. © Business Horizons. 17. the systems and tools need to be designed with verification and validation in mind. However. the analysis and proposed actions. Conversely. The connection isn’t clear between the metric and what is expected from the employee doing the work. there are a number of systems that manage quality from a product lifecycle management (PLM) approach. Easy targets: Targets might set at a level that is easy to reach. Reporting: Effective reporting simplifies the task of understanding the data. instead of stretch goals that drive improvement. Misalignment: There is a disconnect between what people are asked to perform and what they are being recognized Chapter for Promotion Sample (and measured) for. CAPA.Meaningful Performance Metrics for Compliance 17. sometimes people work to justify exclusions for certain situations and not report some of the data. there are numerous QMS (Quality Management System) IT solutions that provide the raw data needed and many provide good reporting tools. As the metrics system is being developed. In 2011. . 17. it is also possible to change the scale or use the wrong scale in graphs and dashboards. Significant time and expense can be avoided by developing the compliance metrics management system in parallel with system development.2 IT Systems An important consideration is the choice of an IT system. This is especially true when incentive (compensation) is based on goal performance. People can manipulate the metrics to “stay in the green”. Today. All Rights Reserved. work can be delayed into the next reporting period.5. FDA 21CFR 820 and 21CFR 211 have similar requirements.
7. and with training7. over the past six months there has been an noticeable increase in complaint rate for odor in several products that use the same excipient. new areas of future focus may come into view. 5.5. It is important to connect the dots between quality systems and the performance measurements. 17. eliminating unnecessary intermediaries. 4. The supplier promises to correct and there is no decision taken to restrict the supplier. there is an uptick in the failure rate during incoming inspection. 3. 6. They need to regularly be evaluated and kept current. in-process testing failures.4 Continuous Improvement Implementing Compliance Metrics is only the beginning of the journey. It is expected that the quality performance management system has sensitivity to detect a common cause between the odor on several products. capturing data electronically when possible. but the signal isn’t strong enough to require action. think © Business Horizons. incoming quality acceptance failures and supplier audits. Finally. Ellen Domb CMQ Primer III-51 Managing for Quality and Performance Excellence James R Evans and William M. 15 Bossidy and Charan in Execution: The discipline of getting things done The Strategy Focused Organization by Robert S.478 Achieving Quality and Compliance Excellence in Pharmaceuticals These regulations apply to both electronic and paper records. As improvement is seen on key metrics. Avoid changing the metrics too often. 17. each of the product complaint rates remained below action limits. the supplier audit. but again no cause to restrict supply. There are situations where an issue is identified in a quality system. For the same material. but the investigation was not able to determine cause. REFERENCES Juran 1993 QCI p. Data integrity can be improved by capturing data only once.6 1. Kaplan and David P Norton Beyone Strategy Vision: Effective Corporate Action with Hoshin Planning. During in-process batch testing occasional failure might be attributable to the excipient. Lindsay . potential for lack of controls. It may be also necessary to refine the metrics or the point in the process being measured to drive measuring earlier in the process to become more proactive. holding the data generators accountable for accuracy.5. there are findings showing of an excipient material. In All Rights Reserved. To Sample Chapter for Promotion illustrate this. Michael Cowley. However. III-48 Transforming Performance Measurement p. However. All these can drive the need for periodic change.5 All Sources of Quality Data It is expected that management should take a holistic view of the entire system. 2. Change may be driven by new strategic direction. 17. Time and effort are needed to implement metrics and too frequent changes to them can frustrate the organization. that issue can manifest itself in many places. Management is expected to have the tools to look across all quality data sources and identify the problem.
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