ISO SERIES.pptx

B.PHARM VI SEM

1. ISO ISO series, guide of pharmaceutical manufacturing facilities, productivity By : BALASUNDARESAN M 1 MBS 1

2. Contents 2 MBS Introduction. History. ISO: 9000 series. ISO:14000 series. Guide to Pharmaceutical Manufacturing Facilities, Productivity. References. 2

3. Introduction What are ISO 9000 Standards? ISO 9000 Standards Define the required elements of an effective quality management system Can be applied to any company Adopted by the United States as the ANSI/ASQC Q90 series. STANDARD BODIES 154 COUNTRIES Bureau of Standards Jamaica 3 MBS 3

4. ISO WAS FORMED FEBRUARY 23, 1947 IN GENEVA FIRST FAMILY OF QUALITY STANDARD RELEASED 1987 To eliminate country to country differences To eliminate terminology confusion To increase quality awareness FIRST ENVIRONMENTAL STANDARD RELEASED IN 1996 Background Who Created Standards 4 MBS 4

5. HOW DID ISO GET STARTED 1906 - International Electro-technical Commission 1926 - International Federation of the National Standardizing Associations (ISA) 1946 London - delegates from 25 countries decided to create a new international organization "the object of which would be to facilitate the international coordination and unification of industrial standards 1947 - ISO began to officially function 1951 - The first ISO standard was published "Standard reference temperature for industrial length measurement". 5 MBS 5

6. ISO 9000 CONSISTS OF 5 DOCUMENTS 6 MBS ISO 9000 Quality Management and Quality Assurance Standards ISO 9001 Quality Systems - QA Model for Design/Development, Production, Installation, and Service ISO 9002 Quality Systems - QA Model for Production and Installation ( no design ) ISO 9003 Quality Systems - QA Model for Final Inspection and Test ISO 9004 Quality Management and Quality System Elements - Guidelines 6

7. ISO 9000 Family of Standards 7 MBS ISO 9000-2 - Generic guidelines for applying ISO 9001, ISO 9002, and ISO 9003 ISO 9000-3 - Guidelines for applying ISO 9001 to the development, supply, and maintenance of software ISO 9000-4 Application for dependability management ISO 9004-2 Guidelines for services ISO 9004-3 Guidelines for processed material ISO 9004-4 Guidelines for quality improvement ISO 9004-5 Guidelines for quality plans ISO 9004-6,7- Guidelines for project & configuration management 7

8. What has ISO Accomplished? 8 MBS ISO film speed code TL9000 Standard format for telephone and banking cards ISO 9000 which provides a framework for quality management and quality assurance ISO 14000 series provides a similar framework for environmental management Internationally standardized freight containers Standardized paper sizes . Automobile control symbols ISO international codes for country names, currencies and languages AS 9100 the Aerospace Basic Quality System Standard 8

9. ISO 9000:1987 series International Organisation for Standards (ISO) adopted a series of quality standards, ISO 9000:1987 based on BS5750 strongly influenced by the US Department of Defence Military Standards (MILspecs). initial version was focused on quality control using retroactive checking and corrective actions. ISO 9000:1994 series ISO 9000 was revised in 1994 greater emphasis on quality assurance via preventive actions. required evidence of compliance with documented procedures tended to create a significant volume of associated procedure ("do it as you document it") manuals and bureaucracy . 9 MBS 9

10. Q S - 9000 Ford, Chrysler, General Motors and other automotive/truck manufacturers identified deficiencies in ISO9000:1994 undertook a re- interpretation and extension to develop QS- 9000 additionally addressed continuous improvement, manufacturin g capability and production part approval processes. ISO9000:2000 series 2nd revision of Quality Management System Requirement Standard from International Organization for Standards moved towards process performance metrics reduced the need for documented procedures where clear evidence exists that the process is working well. Replacement for previous ISO 9001 / 9002 and 9003 standards of 1994 MBS 10

11. ISO9000:2000 series standards provide criteria for companies to "certify" their quality management recertification is required every three years MBS achieve "registration" by third- party auditor. the system verifies practice and processes provides objective 3rd party validation enables benchmarking. TC 176, the ISO 9001 technical committee has started its review on the next version of ISO 9001 , which will in all likelihood be termed the ISO 9001:2008 standard , assuming its planned release date of 2008 is met. Early reports are that the standard will not be substantially changed from its 2000 version. Future Version : 2008 11

12. New ISO 9001 QMS Resource manage m ent Measurement, analysis & i m pro v ements Product Real i z a tion Management Responsibility Continual Improvement cycle MBS General require m ents General require m ents 12

13. I S O 9001 : M od e l CUSTOMERS S y stem 5.M an a gement Responsibility Quality Management 7. Product Rea l ization 6. Resource Management 8 . Measurement Analysis and I m provement R e q u ir e me n ts CUSTOMERS Satisfaction Continual Improvement of the Quality Management System C onsu m ption Product MBS 13

14. Principle Of New Standards Based on eight quality management principles System approach to Manageme nt Continual i m pro v eme nt Mutual beneficial supplier relationship Factual approach to decision making Customer focus MBS 14

15. Principles of new standard Customer focus Organization depends customers Understand current & future customer needs. Meet / exceed customer expectations Leadership Leaders establish purpose & direction of the organization Should create & maintain environment to achieve organization’s objectives Involvement of People People of all levels are essence of an organization Their full involvement for organization’s benefit Process approach Desired results are achieved more efficiently when activities and resources are managed as process MBS 15

16. Principles of new standard System approach to Management Identifying, understanding and managing interrelated process as a system contributes to the organization’s effectiveness & efficiency Continual improvements Continual improvement of the organization’s overall performance should be a permanent objective of the organization Factual approach to decision making Effective decisions are based on the analysis of data and information Mutually beneficial supplier relationships An organization & its suppliers are interdependent Mutually beneficial relationship enhances the ability of both to create value MBS 16

17. Expectations of the new Standard Avoid the application of systems that are separate from the organization’s business process Enable the development of a Quality system that is fully integrated into the normal operations of organization’s business Enable Continual improvements of the system for enhanced customer satisfaction Enable compliance to statutory & regulatory requirements MBS 17

18. Important changes MBS Criteria Previous version New Version Main focus Products Customer satisfaction Approach 20 quality elements Value adding processes Product requirements Requirements specified by customer / organization + Statutory & regulatory requirements Involvement of people What to do, When, Whom & How to do + Why it is to be done Improvements Maintain the system requirements Continual improvements should be achieved 18

19. Process approach Process definition Set of interrelated or interacting activities which transforms inputs into outputs Ensure continual im p ro v e m en ts I d entify the proc e s s es Do it for all value adding processes E s tabl i sh meas urin g criteria Identify the Interaction s to other processes Identify the Inputs & outputs MBS 19

20. Process approach – Continua l improvement s o f Process PDCA Cycle Processes in terms Of Added Value DO Continual improvements of Processes based on objective measurements ACTION Measure results of process Performance and effectiveness - Objective Measurements CHECK Understandings & meeting requirements PLAN MBS 20

21. System Requirements / Structure of the Standard Provision of resources Human resou rces I n f rastruct ures Work environment 6 ISO9000 structure II Resource Manageme n t General re q ui r e m e n ts Doc u m e n t ation Requirements Planning Customer related processe s Design & de v elo p m e n t Purchasing Production & service provision Mana g e m en t Commitment Customer focus Quality policy Planning Responsibility, authority & co mm u n ic a tion Mana g e m en t Reviews 5 ISO9000 structure I Management Responsibility 8 ISO9000 s t r u c t ure IV Measureme nt Analysis &im p ro v eme nt 4 Quality Ma n a g e m e nt System 7 ISO9000 structure III Product Reali z ati o n G e neral Monitoring & m easur e m en t Control of NCP Analysis of data Improvements MBS 21

22. 4 - Qualit y manageme n t system 4.1 General r e q u ir e m e nts I d entif i c a ti o n of processes required Criteria and methods to ensure Operation & control Availability of information & resources for operation & control Monitoring and Measuring of processes Continual impro v e m ents MBS 22

23. 4 - Quality management system 4.2 Document requirements Quality Policy Quality Objectives Quality Manual Procedures required by the Standard Procedures required for planning, operation & control of Organization activities Records MBS 23

24. 5 - Management Responsibility 5.6 Responsibility authority & c o mm un icate 5.4 Planning 5.1 M a n a g e m e n t commitment 5.2 Cu st o mer focus 5.7 M a n a g e me n t Review 5.3 Q u ality policy Quality objecti v es QMS planning General R e v iew inputs Review outputs Internal communication Management represe n t a t i v e R esponsibili t y & authority MBS 24

25. 5 - Management Responsibility Development, implementation and continually improvement of QMS Communication of importance of Regulatory & statutory requirements Meeting customer requirements Quality Policy & Quality objectives Responsibilities & authorities Appointment of Management Representative Conducting Management Reviews Providing required resources Establishment of Quality Policy Quality Objectives Identification of Customer requirements Top Manag e ment ’ s commitment MBS 25

26. 6 - Resourc e Management 6.4 Work E n vir o nm e nt 6.3 Infrastructures 6.2 Human R e so u rces General C o mp e te n c e , awareness & training 6.1 Provision of resources MBS 26

27. 6 - Resourc e Management Resources required to Implementing, monitoring & continual improvements Enhance Customer satisfaction by meeting customer requirements Human Resources Infrastructures Infrastructures needed to achieve product conformity Work environment Work environment needed to achieve product conformity Resource Man a g e men t MBS 27

28. 6 - Human Resources Competent on the basis of appropriate education, skill and experience Define competencies for people performing work affecting product quality Provide training or actions Evaluate effectiveness of the training / actions Employees should aware importance of the activity being performed 6.2 Human Resource s MBS 28

29. 7 - Product Realization 7.6 Control of m on it o ri n g measuring devices Co n trol Preservation of product Validation of processes Identification & traceability Cust o m e r property 7.5 Pr odu cti o n & service provision Verification of purchased products P urchasing process P urchasing information 7.4 Purchasing Design planning Design inputs Design outputs Design review Design Changes Design validation Design v er i f icat ion 7.3 Design and d e v el op me n t 7.1 Planning of product realiz a t io n Identification of customer requirement Review of customer re q ui r e m e n t Customer co mm u n ic a tion 7.2 Customer related p r o cesses MBS 29

30. 7 - Product Realization Quality objectives of Products Processes, procedures to realize product Verification, validation, monitoring, ins pection and testing of product Record to demonstrate conformance 7.1 Planning of Product realization MBS 30

31. 7 - Product Realization Review of requirements related product prior to acceptance / commitment to customers - ability to meet customer requirements Effective communication with customer in relation to Product information Sales order handling Customer feedback Customer complaints Identification of Customer / Market requirements Specified by customer Requirements taken for granted Statutory / Regulatory requirements 7.2 Customer related processes – (Sales) MBS 31

32. 7 - Product Realization Design inputs and outputs Review and verification, validation and control of changes Accuracy Potential hazards & faults Corrections Evaluations against lessons learned Planning Effective & efficient Expectations of interested parties 7.3 Design and Development – (Product) MBS 32

33. 7 - Product Realization Supplier evaluation Verification of purchased product – Inspection and testing Degree of control depends on effects of subsequent processes and effect on final product 7.4 Purchasing Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements MBS 33

34. 7 - Product Realization Product ch a ract e ristics Procedures and work instructions Suitable equipments to manufacture. Monitoring and inspection & testing Product release, delivery and post delivery Process validation Identification and traceability Customers property Material supplied by customers – e.g.. 3 rd party blending 7.5 Production and service provision Manufacturing / service provision under controlled condition to ensure conformity of product MBS 34

35. 8 - Measurement , analysis and improvement 8.2 Monitoring & measurements 8.4 A na l y s is of data 8.5 Improvement 8.3 Control of non co n f o rming product M easure m e n t of product Internal audits Customer satisf a c t ion M easure m e n t of processes Corrective action Pre v enti v e action Continual i m pro v e m ents 8.1 G eneral MBS 35

36. 8 - Measurement , analysis and improvement 8.1 - To demonstrate Conformity of the product Conformity to QMS requirements Continually improvements and the effectiveness of the system 8.2 - Monitoring and Measurements Customer satisfaction / perception Internal audits - conformity planned arrangements of QMS and ISO9001 Monitoring and measurements of processes – to determine / demonstrate ability of processes to achieve required results Monitoring and measurements of product – Conformity to product requirements 8.3 - Control of NCP To assure that NCP products are identified and controlled to prevent unintended use / delivery MBS 36

37. 8 - Measurement , analysis and improvement - Analysis of data Collection and analysis of data generated through QMS activities to verify suitability, effectiveness and continual improvement of the system Analysis shall provide information related to Customer satisfaction / perception Conformity to specs, requirements Trends of processes and products Opportunities for preventive actions Suppliers MBS 37

38. 8 - Measurement , analysis and improvement 8.5 - Improvements Continual Improvements QMS needed to be continually improved Corrective action Actions to prevent recurrence of NCP, NCR etc Includes reviews, determination of causes, need of action, implementation of action, review of action and maintenance of relevant records Preventive action Actions against potential non conformities to avoid their occurrence Includes identification of potential non conformities, cause, need for action, implementation of action, review of action and maintenance of records MBS 38

39. Criteri a fo r measurements – Internal audits Effectiveness & efficiency of processes Opportunities for improvements Use of data / information Effective & efficient use of resources Adequacy, accuracy and performance of measurements Relationships with customers/ suppliers/ other interested parties – Financial measurements Prevention cost Non conforming / failure cost Lifecycle cost Self assessment – Satisfaction surveys for customers and other interested parties Feedback on products Customer & market requirements System performanc MBS e 39

40. Criteri a fo r measurements –Process capability / process validation –Reaction time –Cycle time / throughput (Capacity) –Utilization of technology –Waste reduction –Cost reduction Products –Inspection and testing of incoming, in process and final product –Product verification –Product validation Pro c es s e s MBS 40

41. W h a t i s I S O 1400 ? Primarily concerned with Environmental Management Minimize harmful effects on the environment Continual Improvement of environmental performance The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series. The US Technical Advisory Group (TAG) for ISO/TC 207 (US/TAG for ISO/TC 207) represents the United States in international negotiation on ISO 14000 ISO 14000 EMS- General Guidelines on Principles, Systems and Supporting Techniques ISO 14001 EMS- Specification with Guidance for Use requires a substantial commitment of time and resources MBS 41

42. ISO 14004 EMS - General Guidelines on Systems, Principles and Supporting Techniques ISO 14010 EA- General Principles of Environmental Auditing ISO 14011 EA- Auditing of Environmental Management Systems ISO 14012 EA- Qualification Criteria for Environmental Auditors ISO 14013 Management of Environmental Audit Programs ISO 14014 Initial Reviews ISO 14015 Environmental Site Assessments ISO 14020 EL- Basic Principles of Environmental Labeling ISO 14021 EL- Self Declaration- Environmental Claims- Terms and Definitions 42 MBS 42

43. ISO 14022 EL- Symbols ISO 14023 EL- Testing and Verification Methodologies ISO 14024 EL- Practitioner Programs- Guiding principles, practices and certification procedures of multiple criteria (type1) ISO 14031 Environmental Performance Evaluation ISO 14040 LCA- General Principles and Practices ISO 14041 LCA- Goal and Definition/Scope and Inventory Assessment ISO 14042 LCA- Impact Assessment ISO 14043 LCA- Improvement Assessment ISO 14050 Terms and Definitions ISO 14060 Guide for the Inclusion of Environmental Aspects in Product Standards MBS 43

44. Guides To Pharmaceutical Manufacturing Facilities & Productivity MBS Quality Facilities and Equipment Materials Production Packaging/Labeling Laboratory Controls 44

45. N ee d o f gu i de li ne s i n pha r m a c eu t i c a l s facilities & productivity Detailed guidelines of a system so that the findings reflect the state of control in that system for every product (profile) class If one of the six systems is out of control, the firm is considered out of control A system is considered out of control based on GMP deficiencies which suggest lack of assurance of quality MBS 45

46. Quality System Quality must be built into the process Quality is not tested into the product Assurance of Quality comes from - Design of robust process based on thorough knowledge of that process and the sources of variability Effective Quality System in place Quality S y st e m MBS 46

47. Role of Management in QS MBS Management is responsible for: Organizational structure All Processes All Procedures Facilities & Resources In short, everything to insure product quality, customer satisfaction and continuous improvement 47

48. Quality System Responsibilties MBS Assures overall compliance with cGMPs Review and approval duties for : Product Quality Reviews ( at least annually ) Complaint reviews Discrepancy/ failure investigations Change Control CAPA (Corrective And Preventive Action) Reprocess/ Rework Validation/ Revalidation Rejects Stability Failures/ Out of trend data Quarantine products Documented GMP & Job Related Training 48

49. Laboratory Control System (I) Adequately staffed laboratories (supervisory and bench personnel) Written specifications for raw materials, intermediates, APIs, label s & packaging Written procedures for sampling, testing, approval or rejection of materials and for the recording and storage of data Method validation/ revalidation Validation and Security for computerized handling of test results and related data; system for assuring integrity of all lab data Laboratory Control System: Adequate lab facilities under the Quality Unit which is independent MBS from Production 49

50. Laboratory Control System (II) Reference Standards (primary; secondary) Laboratory controls followed and documented Calibration: written procedures, schedule, documentation Equipment Qualification Written procedure (SOP) covering out of specification “oos” results Laboratory Control System MBS 50

51. Laboratory Control System (III) Investigation of “oos” results conducted in a timely manner as per SOP and documented (complete records maintained). Conclusions from “oos” investigations documented and corrective actions/ need for addition investigation identified and implemented. “oos” review included in Product Quality Reviews Description of samples Identification of method used Raw data for sample/ standard preparation, reagents La b orator y Control System MBS 51

52. Laboratory Control System (IV) Date/ signature of second qualified person who reviewed original test records for accuracy, completeness and compliance with established standards Complete record of all data from testing Record of all calculations Statement of the test results; how compare with established acceptance criteria Laboratory Control System Signature of the person who performed each test; dates tests performed MBS 52

53. Pro d uction System (I) Contemporaneous, accura te and complete batch production documentation I m plementation and documentation of in-process controls, tests, and examinations Training (do c umen t e d; job- related) MBS 53

54. Productio n syste m (II) Adequate written procedures & practice for charge-in of materials Identification of equipment with contents, stage of manufacturing, status Equipment cleaning records Established time limits for completion of production steps/ stages Deviations investigated and documented contemporaneously with investigation MBS 54

55. Productio n syste m (III) Justification and consistency of in-process specifications and final product specifications Data/ information documented and available to Quality Unit for review (trending, investigations etc.) Process validation based on knowledge of process ( scientific basis for identifying critical steps/ critical process parameters/control points) MBS 55

56. Facilities & Equipment System Location, design, construction appropriate to facilitate cleaning, maintenance, operations Layout and air handling designed and constructed to prevent cross- contamination Flow of materials & personnel designed to prevent mix-ups or contamination Defined areas or other control systems to prevent mix-ups or contamination includes as: Facilities & Equipment System MBS 56

57. Facilities & Equipment System Incoming materials (id, quarantine) Sampling area (prevent contamination) Quarantine (intermediates, APIs) Released materials Reje c t i on b) EQUIPMENTS Appropriate design, size, location, non-reactive product contact surfaces Facilities & Equipment System MBS 57

58. Facilities & Equipment System Identification clearly marked Calibration Preventive Maintenance schedule and procedures Cleaning procedures and validation Records of use, cleaning, maintenance Clo s ed or c o ntained equipment. - Inspection prior to use Separate facilities or containment where needed (penicillin's, highly potent compounds etc.) Facilities & Equipment MBS S y stem: b) EQUIPMENTS 58

59. Utilities Qualified and appropriately monitored; drawings should be available Designed and constructed to prevent contamination or cross-contamination Recirculated air to production (same concern) Permanently installed pipe work should be appropriately identified Drains of adequate size with air break Utilities MBS 59

60. W at e r API to be used for incorporation into sterile dosage form – water used in later stages should be monitored and controlled for total microbial counts, objectionable organisms and endotoxins Process water at minimum meeting WHO guidelines for potable water Justify quality of water used to achieve stated API quality and establish specifications Water Water treatment facilities validation MBS 60

61. Materials System Written procedures for receipt, identification, quarantine, storage, handling, sampling, testing and approval or rejection of materials System to evaluate suppliers (critical materials) Purchased against agreed specification Change control process for changing suppliers Upon receipt check for correct labeling, seals Before co-mingling bulk material, id/test Assurances obtained from non-dedicated tankers Mat eria l s System MBS 61

62. Materials System Identification on large storage containers and associated manifolds, filling and discharge lines Code given to received batches; status identity At minimum, a specific identity test on incoming batches. Supplier evaluation should include three fully tested batches; one fully tested batch/year Written sampling plan with justification Prevent contamination of sampled containers Mat eria l s System MBS 62

63. Materials System Stored in manner to prevent degradation, contamination, no adverse effect on quality Drums, bags, boxes off the floor First in, first out Rejected materials identified and controlled under a quarantine system Established re-test/ re-evaluation periods Mat e ri a ls System MBS 63

64. Packaging & Labeling System Written procedures for receipt, identification, quarantine, sampling, examination and/or testing P&L P&L should conform to specifications Records maintained for each shipment (showing receipt, examination & result) Containers protective, clean, not alter product quality; if re-used, cleaned & labeling defaced Access to label storage area limited Written procedures for reconciliation; - investigation if discrepancy MBS 64

65. Packaging & Labeling System All excess labels with batch #, destroyed Obsolete labels destroyed Printing devices controlled to insure accuracy of label (against batch record) Print labels checked against master and a copy placed into the batch record Documented procedures to assure correct packaging materials/ labels used Operations designed to prevent mix-ups MBS 65

66. Packaging & Labeling System Labels: API name, batch #, storage conditions Shipped API: Name/ address manufacturer; special transport conditions; expiry/ retest date Documented clearance before operations Packaged/ labeled intermediates or APIs examined as part of packaging (documented) Seal employed to assure package integrity MBS 66

67. Benefits Certification demonstrates the recognition of quality throughout organization Decrease in wasted time, materials, and efforts. Inculcating values of excellence and best practices. Establish leadership role within organization. Increased recognition by international partners Ability to maintain standards of quality and excellence. MBS 67

68. References Lachman L. Lieberman A. Kanig JL. The Theory Of Industrial Pharmacy, 2nd edi, Varghese Publication House; Bombay-14 Gilbert s. Banker, Christoher T. Rhodes, Modern Pharmaceutics, 3rd edi, New York. Sharma P P . How T o Pra c tice GMPs, 2nd edi, Vandana Publication; Agra. www.kwaliteg.co.za.iso:9000.com www.fda.com MBS 68

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