QUALITY SYSTEMS In BIOSCIENCE MANUFACTURING

QUALITY SYSTEMS inBIOSCIENCE MANUFACTURINGBIOMAN Conference July 2015Prepared by Gretchen Ingvason as part of NSF ATE Grant #1304474 -(National Science Foundation Advanced Technical Education)

AGENDA Concepts in Quality Quality Systems Quality Operations Investigations Bring it to the Classroom7/6/2015BIOMAN Conference2

MY BACKGROUND7/6/2015BIOMAN Conference3

BIOTECHNOLOGY. feeding, fueling and healing theworld.7/6/2015BIOMAN Conference4

CONCEPTS IN QUALITYWhat is Quality?Industry OverviewStandards & Regulations7/6/2015BIOMAN Conference5

QUALITY IN MANUFACTURING Quality is an important component ofcost of goods sold. Tracked through multiple measures. Lack of quality can lead to product andcompany failure.7/6/2015BIOMAN Conference6

WHAT IS QUALITYQuality is a product (or service) with the features andcharacteristics which determine desirability and can becontrolled to meet certain basic requirements. Who determines desirability of features and/orcharacteristics? Why are they desirable? What are the requirements that can be controlled? How is it known if the requirements are met?Quality is determined by the Customer (end-user)based on their expectation and needs.7/6/2015BIOMAN Conference7

Manufacturer(Supplier)7/6/2015BIOMAN Conference8

QUALITY ORGANIZATIONS Regulatory: Government organizations with legal oversight ofindustry– US FDA, European Union, etc. Independent: Organizations providing external review of industryprocesses– International Organization for Standardization (ISO)– ANSI (American National Standards Institute)– USP (US Pharmacopeia Convention) Trade: Organizations supported by industry representingcommon interests and processes– American Society for Quality (ASQ)– ASTM International (American Society for Testing & Materials)7/6/2015BIOMAN Conference9

COST OF QUALITY Internal– Scrap, Rework Appraisal– Material ReceiptMeasurement– In-process/Final Inspection Prevention– Improvement, Planning External– Returns, WarrantyQuality is a value that must be built into the product.Quality cannot be inspected into the product7/6/2015BIOMAN Conference10

Quality – Career Pathways Multitude of industries– Pharmaceutical, Biotechnology, Medical Device, Automotive,Aerospace, Plastics, Food and Beverage, etc. ASQ d Quality Improvement AssociateCertified Process AnalystCertified Quality InspectorCertified Quality TechnicianCertified Calibration Technician Career Path– Quality Engineering– Regulatory Specialist– Utilize (leverage) current experience Entry into Engineering Technology or 4-year degree7/6/2015BIOMAN Conference11

VARIOUS INDUSTRIES & SECTORS Manufacturing– Corporate offices, Plants– Controlled Environments Service– Corporate Offices– Field work7/6/2015BIOMAN Conference12

MANUFACTURING Aerospace Medical Devices & Supplies– Complete vehicles, components– Pacemakers, gurneys, filters BioTechnology Measurement Systems– Gages, Vision Systems, CMM Chemicals– Adhesives, paint, pesticides, soaps Computer & Electronics– Boxes, gift wrap, diapers Pharmaceuticals– Audio/video, components, etc.– Prescription, over-the-counter Fabricated Metal Products Rubber & Plastic Products– heat treating, engraving, nails,– Tires, hoses, bags, pipes Foods– Animal feed, seasonings, snacks Machinery– Mowers, HVAC, assembly equipment7/6/2015 Paper Products Transportation & Parts– Cars, trucks, boats, components Various Retail GoodsBIOMAN Conference– Toys, clothing, sporting goods13

SERVICE Construction Information Services– Buildings, Infrastructure, roofing– Publishing, archiving Consulting– Management, Scientific, technical Educational Inspection Services– Residential, Power plants, Electrical Retail– Training, K-12, Secondary– Department Stores, Auto Dealers Financial & Insurance Social Services– Banks, Mortgages, Brokers– Relief Services, Vocational Rehab Government /Public Admin– Judicial, security, fire protection Scientific / Technical– Testing Services, Engineering Firms Healthcare– Blood banks, diagnostic labs7/6/2015BIOMAN Conference14

BIOTECHNOLOGY - Careers Agriculture / Aquaculture Environmental Monitoring– Protect animals/crops from disease– Growing plants/animals in water– Lab methods (i.e. microarrays) used tomonitor air/water/soil Food Safety Biodefense– Protect air/food/water from pathogenicmicroorganisms Biofuels– Identify pathogens or chemical additives andtheir source– Track source of meat (illegal/poached) Forensics– Diesel/ethanol purified from naturalsources– Criminal investigations (DNA) Biopharmaceuticals Medical Diagnostics– genomics, vaccines– Various tests Cosmetics– Discover and manufacture components7/6/2015BIOMAN Conference15

QUALITY SYSTEMSISO and FDA7/6/2015BIOMAN Conference16

QUALITY SYSTEMS Quality is a product (or service) with the features andcharacteristics which determine desirability and can becontrolled to meet certain basic requirements. Quality System–––––7/6/2015Say what you do (documents)Do what you say (training)Record what you did (write it down, quality records)Check the results (analysis)Act on the difference (improvement)BIOMAN Conference17

QUALITY SYSTEMS International Organization of Standardization (ISO)– ISO 9001:2008 Quality Management Systems – Requirements– ISO 13485:2003 Medical Devices – Quality Management Systems –Requirements for Regulatory Purposes– ISO/IEC 17025:2005 General Requirements and Competencies ofTesting and Calibration Laboratories– ISO/TS 16949 (Automotive)– AS 9001 (Aerospace)7/6/2015BIOMAN Conference18

QUALITY SYSTEMS US Food & Drug Administration (FDA)– 21CFR (Code of Federal Regulations) Part 210/211 Pharmaceuticals Part 600/601/610 Biologics Part 820 Medical Device– International Counterparts Japan – Pharmaceutical & Medical Device Agency Europe – European Directives Canada –Health Canada7/6/2015BIOMAN Conference19

CODE OF FEDERAL REGULATIONS (CFR) CFR is the codification of the general and permanentrules and regulations (sometimes called administrative law) The titles are broken down into:Chapters, Parts , Sections , and ParagraphsExample: 21 CFR 820.30(d) (1)would read Title 21, Part 820, Section 30, Paragraph (d)(1)7/6/2015BIOMAN Conference20

CODE OF FEDERAL REGULATIONS (CFR)Title 1General ProvisionsTitle 18Conversation of Power & WaterResourcesTitle 35Title 2Grants and AgreementsTitle 19Customs DutiesTitle 36Title 3The PresidentTitle 20Employee's BenefitsTitle 37Title 4AccountsTitle 21Food and DrugsTitle 38Title 5Administrative PersonnelTitle 22Foreign RelationsTitle 39Parks, Forests, and PublicPropertyPatents, Trademarks, andCopyrightsPensions, Bonuses & VeteransReliefPostal ServiceTitle 6Domestic SecurityTitle 23HighwaysTitle 40Protection of EnvironmentTitle 7AgricultureTitle 24Housing & Urban DevelopmentTitle 41Title 8Aliens and NationalityTitle 25Title 42Title 9Animals and Animal ProductsTitle 26IndiansInternal RevenuePublic Contacts and PropertyManagementPublic HealthTitle 43Public Lands: InteriorTitle 10EnergyTitle 27Alcohol, Tobacco & FirearmsTitle 44Title 11Federal ElectionsTitle 28Judicial AdministrationTitle 45Emergency Management &AssistancePublic WelfareTitle 12Banks and BankingTitle 29LaborTitle 46ShippingTitle 13Business Credit and AssistanceTitle 30Mineral ResourcesTitle 47TelecommunicationTitle 31Money and Finance: TreasuryTitle 48Federal Acquisition RegulationsSystemsTitle 14Aeronautics & Space(aka Federal Aviation Regulations)(aka Treasury Regulations)Reserved(Formerly Panama Canal)Title 15Commerce and Foreign TradeTitle 32National DefenseTitle 49TransportationTitle 16Commercial PracticesTitle 33Navigation & Navigable WatersTitle 50Wildlife & FisheriesTitle 17Commodity and SecuritiesExchangesTitle 34Education7/6/2015BIOMAN Conference21

cGXP cGXP -- Current Good [ ] Practices– Manufacturing (cGMP) Pharmaceutical Medical Device– Laboratory (cGLP)– Clinical (cGCP)7/6/2015BIOMAN Conference22

cGXP cGXP -- Current Good [ ] Practices– Manufacturing (cGMP) Pharmaceutical Medical Device“ practices required in order to conform to guidelines recommended byagencies that control authorization and licensing for manufacture and sale of drug products, and active pharmaceutical products. These guidelines provideminimum requirements that a manufacturer must meet to assure that theproducts are of high quality and do not pose any risk to the consumer or public ” (Wikapedia.com)– Laboratory (cGLP)– Clinical (cGCP)7/6/2015BIOMAN Conference23

cGXP cGXP -- Current Good [ ] Practices– Manufacturing (cGMP) Pharmaceutical Medical Device– Laboratory (cGLP) (non-clinical)“.embodies a set of principles that provides a framework within whichlaboratory studies are planned, performed, monitored, recorded, reported andarchived. These studies are undertaken to generate data by which the hazardsand risks to users, consumers and third parties, including the environment, canbe assessed GLP helps assure regulatory authorities that the data submittedare a true reflection of the results obtained during the study and can thereforebe relied upon when making risk/safety assessments. “ (Wikapedia.com)– Clinical (cGCP)7/6/2015BIOMAN Conference24

cGXP cGXP -- Current Good [ ] Practices– Manufacturing (cGMP) Pharmaceutical Medical Device– Laboratory (cGLP) (non-clinical)– Clinical (cGCP)“ enforces tight guidelines on ethical aspects of a clinical study. Highstandards are required in terms of comprehensive documentation for the clinicalprotocol, record keeping, training, and facilities, including computers andsoftware GCP guidelines include protection of human rights for the subjectsand volunteers in a clinical trial. It also provides assurance of the safety andefficacy of the newly developed compounds ” (Wikapedia.com)7/6/2015BIOMAN Conference25

QUALITY OPERATIONSIncoming InspectionProduct ReleaseManufacturing Support7/6/2015BIOMAN Conference26

Manufacturer(Supplier)7/6/2015BIOMAN Conference27

PROCESS FLOW - MANUFACTURING7/6/2015BIOMAN Conference28

QUALITY SYSTEMS–––––7/6/2015Say what you do (documents)Do what you say (training)Record what you did (write it down, quality records)Check the results (analysis)Act on the difference (improvement)BIOMAN Conference29

INSPECTION Customers want expectations and needs met consistently– Fitness for use– Form is free of defect– Functions as intended Evaluate product quality by comparing measurementresults with specifications Inspection process:––––Measurement of sampleComparison against specificationDecision based on resultsCorrective action, if necessaryInspection is after the fact –materials used, product built, labor spent7/6/2015BIOMAN Conference30

Inspection ProcessProduct SampleMeasurementCompleteMeasurement EquipmentProduct SpecificationPart DrawingEtc.NoMeet SpecificationYesSort / ReworkShip ProductNon-Conforming ProductMaterial Review Board (MRB)Downgrade ProductScrap Product7/6/2015BIOMAN Conference31

MEASUREMENT Measurement is a method for evaluating a propertyor characteristic of an object and describing it with anumerical or nominal value.––––––7/6/2015Dimensional (e.g. length, diameter, volume)Functional (e.g. flow rate, tensile strength)Chemical (e.g. material type, pH, etc.)Service (e.g. time between calls, maintenance response, etc.)Attribute (e.g. color, clarity, etc.)etc.BIOMAN Conference32

ACCURACY vs PRECISIONAccurate butnot preciseNeither accuratenor precise7/6/2015BIOMAN ConferencePrecise butnot accurateAccurateAndPrecise33

METROLOGY PROGRAM Measurement Fundamentals– Methods, equipment Calibration System– Verification7/6/2015BIOMAN Conference34

METROLOGY PROGRAM Measurement apabilityEquipment specificationsEnvironmental ControlsStandards UsageConfidence (Uncertainty) ProgramsDataHow to trust the results7/6/2015BIOMAN Conference35