Introducing Product/Process Quality and Safety in Chemical Engineering Education and Research Henry Y. Wang The University of Michigan July 16th, 2014 Outline •  Innovation in Chemical Engineering (ChE) Education at UM (1898 - ) •  Renaissance in Chemical Engineering (2015 - )? •  Importance of ChE Product/Process Design •  New Regulatory Science and Innovation •  Product/Process Quality & Safety: Education and Research •  Need a Harmonized Global Quality System Chemical Engineering at The University of Michigan 1898 The Regents approve Dean Charles E. Greene's request for the first course of study at the University of Michigan leading to a bachelor of Edward Campbell science in Chemical Engineering. The coursework, second only in the nation, is directed by Professor Edward DeMille Campbell, with cooperation from the Chemistry Department. “A Century of Chemical Engineering at the University of Michigan” edited by J. Wilkes, 2003 G.G. Brown Alfred H. White Donald L. Katz 1950 http://www.scribd.com/doc/147591126/Unit-Operations-by-GG-brown 1930? http://www.worldcat.org/title/ heat-transfer-andcrystallization-a-series-ofpractical-articles/oclc/2062537 1963 http://deepblue.lib.umich.edu/bitstream/handle/2027.42/5898/bac5670.0001.001.pdf?sequence=5 New Frontiers in Chemical Engineering: Impact on UG/G Education •  Decade XII (2015 -2025) Renewable Feedstock Options Traditional ChE Molecular/Nano New Chem/Bio Product/Process Design Systems Analysis Transformations Multi-Scale Analysis Digital/Information Technologies (ICTs) Cloud Computing/Data Analytics ?? ?? ?? ?? New Knowledge Products Processes Skills Modified from Gulari (2004) http://pubs.acs.org/cen/hotarticles/cenear/960819/era.html Renaissance in Chemical Engineering •  Emergence of Shale and other more renewable feedstock options The ultimate chemical feedstock should be CO2? •  Technology driven innovation and design Molecular, Nano-, Bio-, IT-, Cyber- and others •  Product/process innovation and design to meet consumer expectation Health, Safety, Environment, & (Security), (HSE, EHS, SSHE) (Banholzer 2012) Various Consumer Driven Product Innovation and Technologies Converging Scientific Innovation and Technologies Genomics Bioinformatics Proteomics BIOTECH Pharmaceuticals Diagnostics Research/Info Tools Industrial Bioelectronics Microfluidics Nanabiotechnology Drug Delivery INFOTECH INFOTECH Hardware Hardware Software Software Communications Communications Biosensors Biochips Nanodevices Nanosensors Nanoelectgronics NANOTECH Electrical Structural Biomedical Energy & Environment Adapted from: Biology, Bioconvergence, Information And Enterprise: Taking the Broad of View May 20, 2004 10 Alan Barrell. Product/Process Innovation Cycle FDA regulatory challenges are having the greatest impact on VC investment decisions Factors Cited as Having the Highest Impact on VC Investment % of Respondents Regulatory Reimbursement Financial Capital Challenges Concerns Markets / Requirements (FDA) Availability of Capital to Invest *Unrelated to Regulatory Challenges NVCA MedIC Vital Signs Report, October 2011 Clinical Trial Issues* Firm / LP Changes or Requests Lack of Tax Incentives (Lasersohn 2012) Regulatory Science at FDA http://www.fda.gov/ScienceResearch/SpecialTopics/RegulatoryScience/ •  The science of developing new tools, standards, and approaches to assess the safety, efficacy, quality, and performance of FDA regulated products •  The critical bridge between the “too basic” scientific research discoveries and “too applied” science of manufacturing and marketing of regulated products •  Includes areas of preclinical and clinical research, manufacturing, processing, and translational science in a product development and approval process (“the cycle”) •  May improve regulatory affairs processes (Weichold, 2013) UM Regulatory Science and Engineering (RSE) Product Quality Innovation and Solution Environmental Health and Sustainability Regulatory Science and Engineering (RSE) Process Safety and System Security Wang (2012) Two Critical Attributes: Quality and Safety The Issue of Quality Driven by an increase in standard of living and intense global competition ASQ (2003) The Issue of Safety Driven by the public’s increasing concern with safety and risk-free products—and business’s responsibility to address this concern Product Quality Attributes: Some are obvious and others are not so clear Quality By Design (QbD) Quality Safety Biologics Design Risk Science Efficacy Drugs Discovery Devices Development Quality Engineering Quality defined in Regulatory Science and Engineering is to consistently uphold a product’s safety and efficacy standards throughout the product life cycle from Design, Discovery to Development, Manufacturing, and Global Supply & Distribution Multi-Scale System Analysis: Safety, Quality, Security and Sustainability Patient/Customer Safety/Needs Product Quality Process Reliability System Security Environment Sustainability •  •  •  •  •  •  •  •  Topics Relevant to Regulatory Science Regulatory Approval Roadmaps Product Benefit-Risk Assessment Target Product Profiles (TPPs) Establishing Bioequivalence/Biosimilarity Quality Risk Assessment Process Analytical Technologies Quality By Design Global Quality Systems (All these are relevant to ChE but require risk based decision analysis) Target Product Profile (TPP) (Quality Function Deployment (QFD) for consumer products) What is TPP? !  A set of elements that defines the product (e.g. drug, device) !  The target or goal set in advance !  A guide to Product Development What forms the basis for TPP? !  The RLD and its label (product specification) !  Applicable regulatory guidelines When to define TPP? !  At the start of development !  Knowledge gained in development may change some elements Elements related to product safety, efficacy, identity, purity and potency Target Product Profile (contd.) •  Think Creatively •  Consider All Aspects of the Product During Development –  The Bio/Environment System You’re Impacting –  Optimal Route of Delivery –  Who Will Use the Product (Patients, Health-care Providers, Consumers, Concomitant Meds, Etc.) –  Storage & Stability •  Build Quality into the Product (Design Controls) –  Raw Material Control –  Manufacturing Control –  In-process Quality Control •  Know the Regulatory System (or have good regulatory support) Diversity of Target Product Profiles, Users, and Settings Within the Spectrum of POC Testing Pai NP, Vadnais C, Denkinger C, Engel N, et al. (2012) Point-of-Care Testing for Infectious Diseases: Diversity, Complexity, and Barriers in Low- And Middle-Income Countries. PLoS Med 9(9): e1001306. doi:10.1371/ journal.pmed.1001306 http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1001306 Process Safety vs. Personal Safety •  All behavior influenced by context in which it occurs –  Both physical and social context –  Personal safety focuses on changing individual behavior –  Process (system) safety focuses on design of system in which behavior occurs •  To understand why process accidents occur and to prevent them, need to: –  Understand current context (system design) –  Create a design that effectively ensures safety Examples of Major Accidents Flixborough, UK, 1974 Bhopal, India, 1984 BP Texas City, USA, 2005 Piper Alpha 1988 Deepwater Horizon, 2010 24 Safety Performance by Industry Sector Injuries & illnesses per 200,000 hours worked (2002) Source: US Bureau of Labor Statistics (www.bls.gov/iif) Recent Incidents involved Chemicals West Texas Fer+lizer Plant Explosion – April 17, 2013 Williams Chemical Explosion – June 13, 2013 Geismar LA Lac-‐Mégan+c Train Derailment -‐ July 6, 2013 Major incidents drove Process Freedom Chemical spill – January 9, 2014 Safety regulations & Tigantourine gas facility -‐ January 16, 2013 changes in industry Cybersecurity – Boreas, Aurora, Stuxnet (new) Execu+ve Order (E.O.) 13650 -‐ Improving Chemical Facility Safety and Security Execu+ve Order (EO) 13636 -‐ Improving Cri8cal Infrastructure Cybersecurity R. Kane - April 11, 2014 Simplified Risk Grid Low Consequence High Typical Process Safety risks Our focus should be here. Typical Occupational Safety risks High Consequence Low Frequency (High Risk) High Consequence High Frequency (Very High Risk) Low Consequence Low Frequency (Very Low Risk) Low Consequence High Frequency (Low Risk) Low Probability High (Cross et al , 2014) Process Safety Consideration (elements of process safety management) 1.  Accountability 2.  Process Knowledge and Documentation (SOPs) 3.  Capital Project Review and Design Procedures 4.  Process Risk Management 5.  Management of Change 6.  Process and Equipment Integrity 7.  Human Factors 8.  Training and Performance 9.  Incident Investigation 10.  Company Standards, Codes and Regulations 11.  Audits and Corrective Actions 12.  Enhancement of Process Safety Knowledge CCPS: Guidelines for Technical Management of Chemical Process Safety Inherently Safer Design •  Options for Inherently Safer Approaches –  Minimize – Reduce the amount of hazardous materials involved –  Substitute – Replace hazardous materials with less hazardous alternatives –  Moderate – Change to less aggressive operating conditions –  Simplify – Design out problems rather that adding complex control schemes •  Link to the CSB video on inherently safer design: –  http://www.csb.gov/videoroom/detail.aspx?VID=66 ChE 487 Senior Design Project (W-14) Advancing Regulatory Science for Public Health (FDA) •  Rebuilding FDA’s small business outreach services (SBA). •  Building the infrastructure to drive and support personalized and precision medicine. •  Creating an expedited drug development pathway. •  Harnessing the potential of data mining and information sharing. •  Reducing the time and cost of medical device development, assessment and review. •  Training the next generation of innovators •  Streamlining and reforming FDA regulations. (Weichold, 2013) ChE Design and Lab courses in a typical UG Curriculum (UM) ChE 360 Chemical Engineering Laboratory I (4) ChE 460 Chemical Engineering Laboratory II (4) ChE 485 Chemical Engineering Process Economics (1) ChE 4xx Applied Statistical Learning ? ChE 487 Chemical Engineering Process Design ChE 488/489 Chemical Engineering Product Design (3) (5) (2/3) ChE 360 Safety training, uncertainty analysis, SOP writing ChE 460 Safety review, DOE, SOP writing/improvement ChE 487 TPP/QFD, process safety, sustainability & others Some Core Courses in Regulatory Science and Engineering at UM •  ChE/BME 5xx (2) F Technology Innovation, Law and Regulation (new) •  BME/ChE 588 (2) W Quality Systems and Regulatory Innovation •  NAME/MFG 582 (2) F Risk, Safety and Reliability Analysis •  IOE 460 (2) F Decision Analysis •  IOE 568 (3) W Statistical Learning and Quality Engineering •  IOE 536 (3) F Cognitive Ergonomics (Human Factors) •  NRE 557 (3) W Industrial Ecology •  EECS 598-008 (3) W Medical Device Security Regulatory Science Research for Product/Process Quality Evaluation and Safety Assessment 1.  2.  3.  4.  5.  6.  7.  8.  9.  TPP in Pre-clinical safety assessment (Greve) Quantitative pharmacology (Thurber) Human factors engineering for patient safety (Gosbee) Establishing bioproduct equivalence and similarity (Wang) Multivariate analysis for Quality by Design (Jin) Product registries in post-market surveillance (Hughes) Medical device security assessment (Fu) Global quality system to ensure product safety (Yadav) Others to be added FDA’s Strategic Plan for Regulatory Science The priority areas include: 1. Modernize Toxicology to Enhance Product Safety 2. Stimulate Innovation in Clinical Evaluations and Personalized Medicine to Improve Product Development and Patient Outcomes 3. Support New Approaches to Improve Product Manufacturing and Quality 4. Ensure FDA Readiness to Evaluate Innovative Emerging Technologies 5. Harness Diverse Data through Information Sciences to Improve Health Outcomes 6. Implement a New Prevention-Focused Food Safety System to Protect Public Health 7. Facilitate Development of Medical Countermeasures to Protect Against Threats to U.S. and Global Health and Security 8. Strengthen Social and Behavioral Science to Help Consumers and Professionals Make Informed Decisions about Regulated Products 9. Strengthen the Global Product Safety Net http://www.fda.gov/ScienceResearch/SpecialTopics/RegulatoryScience/ucm268095.htm Ensuring Safe Foods and Medical Products Through Stronger Regulatory Systems Abroad (2012) http://www.iom.edu/Reports/2012/Ensuring-Safe-Foods-and-Medical-ProductsThrough-Stronger-Regulatory-Systems-Abroad.aspx (Ghosh, 2006) How to incorporate Quality, Safety, Security and Sustainability concepts? Questions?