1. ISO 9000 &14000VALIDATION Presented by – Varsha 1 st M. Pharm Dept. Pharmaceutics 1

2. ISO 9000 SERIES

3. INTRODUCTION I S O I S O International Standard Organization ISO in greek means “equal” and ISO wanted to convey the idea of equality – the idea that develop standards to place organization on equal footing.

4. DEFINITION OF ISO 9000:-  ISO 9000 is a set of universally understood and accepted quality / business practices which, when implemented, give customers confidence that suppliers can consistently meet their needs.

5. BIRTH OF ISO:-  In 1946, delegates from 25 countries met in london and decided to create a new international organization, of which the object would be “ to facilitate the international coordination and unification of industrial standards”. The new organization, ISO, officially began operations on 23 february 1947.

6. LOCATION OF ISO:- 1. Geneva, switzerland 2. 1, rue de varmbe, 3. Caste postale 56, 4. CH 12111 Geneva/ suisse, 5. Ph :41 22 749 0111, 6. Telex :41 22 733 3430.

7. FUNCTIONS OF ISO:-  It serves as a safety guard for the customer.  They make trade between the two countries.  They provide the technology to the government for health, safety, environment legislation.  They helps in transferring technology to developing countries.  They also helps in development, manufacturing, supply of product.

8. ADVANTAGES:-  Create a more efficient effective operation.  Increase customer satisfaction and retention.  Reduce audits.  Enhance marketing.  Improve employee motivation, awareness, and morale.  Promote international trade.  Increase profit.  Reduce waste and increase productivity.

9. SOME FACTS ABOUT ISO 9000:-  ISO 9000 is;  International standards for quality management.  Third party certification of QM.  It is evolutionary rather than revolutionary.  ISO 9000 is voluntary in nature.  Evolved as global standardization of quality management standards.  It certifies the process not product.  Exports not having ISO 9000 certification will have to face problem in world markets.  It provides the efficient and economic product.

10.  180 technical committees (TCs)  620 active sub committees (SCs)  The actual standards preparation is done by ISO Technical committees (ISO/TCs).  TCs are assisted by member country Technical Action Group (TAG).

11. There are 158 National members out of the 195 total countries in the World :  ISO has three membership category, they are: 1) Member bodies 2) Correspondent Member 3) Subscribers Member

12. ██ member bodies ██ correspondent members ██ subscriber members ██ other places with an ISO 3166-1 code who aren't members of ISO code who aren't members of ISO 12

13. ISO 9000 Quality Management Quality System Elements ISO 9004-1.-2,-3 Quality Assurance Models ISO 9001ISO 9002ISO 9003

14.  ISO 9000-1 : Guidelines for selection and use  ISO 9000-2 : Generic guideline for the application of ISO  ISO 9000-3 : Guideline for the application of ISO 9001 to development, supply, and maintenance of software  ISO 9000-4 : Guide to dependability program management

15.  ISO 9001 - Quality Assurance in design/ development, production, installation and servicing  ISO 9002 - Quality Assurance in production and installation  ISO 9003 - Quality Assurance in final inspection and test  ISO 9004 - Quality management and quality system elements

16.  ISO 9004-2 : Guidelines for services  ISO 9004-3 : Guidelines for processed materials  ISO 9004-4 : Guidelines for quality improvement  ISO 9004-5 : Guidelines for quality plans  ISO 9004-7 : Guidelines for configuration management

17. WORLD WIDE EQUIVALENTS OF ISO 9000 STANDARDS COUNTRY ISO 9000 Standard NISO 9000 Standard Nomenclature Australia Brazil Canada Denmark France Germany India Japan Mexico United State AS 3900 NB 9000 Z 299 DS/ISO 9000 NF EN 29000 DIN ISO 9000 IS 14000 JIS Z 9900 NOM – CC 2 Q 9000

18. Customer focus Leadership Mutual beneficial supplier relationship Continual improvement Factual approach to decision making System approach to Management Involvement of people Process approach PRINCIPLES OF NEW STANDARDS

19. Benefits : 1) Increased revenue & market share. 2) Improve customer satisfaction. Application: 1) Research work. 2) Understanding the customers needs, expectation, satisfaction. satisfaction.

20. Benefits : 1) Activities are evaluated. 2) People will be motivated towards organization’s goals. Application: 1) People accepting the ownership of problems. 2) People freely sharing knowledge & experience

21. Benefits : ) Innovation & creativity. 1) Innovation & creativity. 2) Motivated, committed, Involved People within the Organization. Application: 1) People accepting the ownership of problems. 2) People freely sharing knowledge & experience.

22. Benefits : 1) Lower cost & shorter cycle Times. 2) Improved, consistent, & predictable results. Application: 1) Systematically defining the activities. 2) Identifying the interfaces of key activities.

23. Benefits : Benefits : 1) Ability to focus the effort on the key processes. 2) Providing confidence to interested parties as consistency, effectiveness & efficiency of the Organization. Application: 1) Structuring a system to achieve the Organization’s objectives. 2) Continually improving the system through measurement & evaluation.

24. Benefits : 1) Increase the performance due to the improvement of the Organizational capabilities. 1) Increase the performance due to the improvement of the Organizational capabilities. 2) Flexibility to react quickly to the opportunities. 2) Flexibility to react quickly to the opportunities. Application: 1) Providing training to the people for the continual Improvement. 2) Establishing the Goals for continual Improvement. 3) Recognizing & acknowledging improvement.

25. Benefits : 1) Informed decisions. 2) Increased ability to demonstrate the effectiveness of the past decisions. 3) Increased ability to review. Application: 1) Making decision & action based on analysis. 2) Analyzing data & information using valid method.

26. Benefits : 1) Optimizing of cost & resources. 2) Flexibility & speed will increase in the market. Application: 1) Identifying & selecting key suppliers. 2) Clear & open communication. 3) Sharing information & future plans.

27. Documentation Review Pre- Assessment Registration audit Registration Decision Surveillance Audit

28. ISO 14000 SERIES  ISO 9001 and ISO 14001 are among ISO's most well known standards ever.  ISO 14001 helps organizations to implement environmental management.  They are implemented by more than a million organizations in some 175 countries.

29. Environmental management  ISO 14001 is for environmental management. This means what the organization does to:  minimize harmful effects on the environment caused by its activities,  to conform to applicable regulatory requirements, and to  achieve continual improvement of its environmental performance.

30. GENERIC STANDARDS ISO 9001 and ISO 14001 are generic standards. Generic means that the same standards can be applied:  to any organization, large or small, whatever its product or service,  in any sector of activity, and  whether it is a business enterprise, a public administration, or a government department.

31. PROCESS NOT PRODUCTS  Both ISO 9001 and ISO 14001 concern the way an organization goes about its work.  They are not product standards.  They are not service standards.  They are process standards.  They can be used by Product manufacturers and service providers.

32. PROCESS AND PRODUCTS(cont…)  Processes affect final products or services.  ISO 9001 gives the requirements for what the organization must do to manage processes affecting quality of its products and services.  ISO 14001 gives the requirements for what the organization must do to manage processes affecting the impact of its activities on the environment

33. Certification & registration  Certification is known in some countries as registration.  It means that an independent, external body has audited an organization's management system and verified that it conforms to the requirements specified in the standard (ISO 9001 or ISO 14001).  ISO does not carry out certification and does not issue or approve certificates,

34. Accréditations  Accreditation is like certification of the certification body.  It means the formal approval by a specialized body - an accreditation body - that a certification body is competent to carry out ISO 9001:2008 or ISO 14001:2004 certification in specified business sectors

35. Accreditation(cont…)  Certificates issued by accredited certification bodies - and known as accredited certificates - may be perceived on the market as having increased credibility.  ISO does not carry out or approve accreditations.

36. The ISO 14000 family  ISO 14001 is the standard that gives the requirements for an environmental management system.  ISO 14001:2004 is the latest, improved version.  It is the only standard in the ISO 14000 family that can be used for certification.

37. ISO 14000 Family (cont…)  The ISO 14000 family includes 21 other standards that can help an organization specific aspects such as auditing, environmental labelling, life cycle analysis…

38. Benefits of ISO 9001 & ISO 14001  International, expert consensus on state-of- the-art practices for quality and environmental management.  Common language for dealing with customers and suppliers worldwide in B2B.  Increase efficiency and effectiveness.  Model for continual improvement.

39. Benefits of ISO 9001 & ISO 14000 (cont.)  Model for satisfying customers and other stakeholders.  Build quality into products and services from design onwards.  Address environmental concerns of customers and public, and comply with government regulations.  Integrate with global economy.

40. Benefits of ISO 9001 and ISO 14001 (cont.)  Sustainable business  Unifying base for industry sectors  Qualify suppliers for global supply chains  Technical support for regulations  Transfer of good practice to developing countries  Tools for new economic players  Regional integration  Facilitate rise of services

41. VALIDATION  DEFINITION: A documented programme, which provides a high degree of assurance that a specefic process will consistently produce,a product meeting its pre determined specifications and quality attributes.

42. What does need validation?  Any drug manufactured f0r use by humans and animals needs to be validated.  A satisfactory inspection and approval by a regulatory inspector is required before a drug is released for sale. What is validated?  The process of manufacturing a drug

43. Principles of validation?  Document what is to be done.  Document how it is to be done.  Produce documented evidence that it was done in accordance with the specification.  Demonstrate that it remains in a state of control.

44. Regulatory requirements  Computerized systems installed in pharmaceutical companies are fit for their intended purposes (relevant to the GMPs) by considering :  Quality assurance of the development lifecycle.  Performance validation.  In use controls.  Accuracy and reliability.

45. Validation of equipment  Equipment is one of the basic components of the pharma processing.  If we want a pharmaceutical process to be validated then the equipment used play a very major role in the whole process.  Equipment validation process generally covers the following steps:

46. Validation of equipment(cont…)  1.customer requirements or requirement specifications.  2.preparation of design qualification and its certification.  3.installation qualification.  4.operational qualification.  5.performance qualification.

47. Process validation  DEFINITION: “ A documented program which provides a high degree of assurance that is specific process will consistently produce a product, meeting its predetermined specifications and quality attributes.”

48. Process validation(cont…)  Validation should be considered in the following situations. 1. Totally new process. 2. New equipment. 3. Processes and equipment, which have been altered to suit changing priorities. 4. Processes where the end product test is poor and unreliable indicator of product quality.

49. Process validation (cont…)  Process validation can be categorized in the following categories namely : 1. Prospective validation. 2. Concurrent validation. 3. Revalidation. 4. Retrospective validation.

50. Cleaning validation  DEFINITION: “Its may be defined as “a process of attaining and documenting sufficient evidence to give reasonable assurance given the current state of science and technology, that the cleaning process under consideration does,and / or will do, what it purports to do”.

51. Cleaning validation(cont…)  Cleaning and decontamination is one of the major and critical activity in pharmaceutical operations.  The 4 basic requirements of cGMP are: A. Identity B. Safety C. Strength D. purity

52. Validation of analytical methods  DEFINITION: It may be defined as “the process by, which it is established, by laboratory studies, that the performance characteristics of the method meet the requirements for the intended analytical application”.

53. Validation of analytical methods(cont…)  Typical analytical characteristics can be listed as follows: 1. Accuracy. 2. Precision. 3. Specificity. 4. Limit of detection. 5. Limit of quantitation.

54. Cont…  6.Linearity  7.Range.  8.Ruggedness.  9.Robustess.

55. Cont…  ACCURACY: “The closeness of test results obtained by that method to the true value. this accuracy should be established across its range”. PRECISION: “the degree of agreement among individual tests results when the method is applied repeatedly to multiple sampling of a homogenous sample”.

56. Cont…  SPECIFICITY: “The to ability to assess unequivocally the analyte in the presence of components that may be expected to be present, such as impurities degradation products and matrix components”. LIMIT OF DETECTION: “The lowest amount of analyte in a sample that can be detected, but now necessarily quantitated, under the stated experimental conditions “.

57. Cont…  LIMIT OF QUANTITATION: “ A characteristics of qualitative assays for low levels of compounds in sample matrices such as impurities in bulk substances and degradation products in finished pharmaceuticals. It is lowest amount of analyte in a sample that can be determined with acceptable precision and accuracy under the stated experimental conditions”.

58. Cont…  LINEARITY: “Its ability to elicit tests that are directly or by a well defined mathematical transformations proportional to the concentration of analyte in samples with in a given range”.

59. Cont… RANGE: “ Interval between the upper and lower levels of analyte that have been demonstrated to be determined with a suitable level of precision, accuracy and linearity using the method as written.the range is normally expressed in the same units as test results obtained by the analytical methods”.

60. Cont…  RUGGEDNESS: “ The degree of reproducibility of test results obtained by the analysis of the same sample under a variety of conditions such as different laboratories, different analysts, different instruments, different lots of reagents, different elapsed assay times, different assay temperatures, different days etc”.

61. Cont…  ROBUSTNESS: “A measure of its capacity to remain unaffected by small but deliberate variations in method parameters and provides an indication of its reliability during normal usage”.

62.  ISO 9000 – Brain Rothery.  Pharmaceutical quality assurance - Manohar A.Potdar  WWW. CENTRAL@ISOCS.ISO.CH

63. 63 Thank you