Pharmaceutical Quality Assurance

1. PharmaceuticalQualityAssurance

2. Quality Assurance • Extremely important nowadays! community pharmacies < hospital pharmacies << industry and distribution • It is impossible to learn it • It is possible to understand it (this course will help) • Bad news (as in the last Semester): Failure is also possible!

3. Quality Assurance Introduction trying to understand: what is it all about?

4. Let’s consult the literature Not the scientific literature like other times The best „literature” is not necessarily a scientific paper, but a fairy tale

5. Once, upon a time... • There were 4 friends called: Somebody, Anybody, EverybodyandNobody • There was a work that could doAnybody, butEverybodythought thatSomebodywill do it, thus, actuallyNobodydid it...

6. …and the consequence was that… • …Everybodybecame very angry blaming Somebody, for the work could be done byAnybody, but actually Nobodydid it… • =No quality assurance operated!

7. What to do to avoid such a situation?Introduce(the elements of)Quality Assurance!

8. QA introduced • Everybody knows his/her job (job description, substitution, etc.) • Working operations are described in Standard Operation Procedures in writing • The work is actually done according to these • The fact that an actual work has been performed is documented together with the result.Documents are archived

9. QA introduced – what it means? • My colleague retires (dies, etc.) • I say good bye (crying) • I go to his table, read the Standard Operating Procedure and his notes/records • And I can follow his work exactly where he left it! BYE!

10. Our classic: Murphy • Murphy’s laws: they emphasise that what can be defective that will be defective (as a rule, in the wrongest time!) • One example: • if a buttered bread is dropping, it will land with its buttered side looking to the carpet • if not, it means you buttered the wrong side!

11. Example(Our slogen: „Mr. Murphy may always be present…”) • Lecture with lap-top projection (as now) • Projector – where is it held, what happens if the key is left home, where is the spare key, who may land another projector, etc. • Are all these documented in writing?

12. Definition of the „QUALITY”

13. „Quality” • It is used in the everyday life, e.g. commodities of (good) quality • Whatever the quality means: we feel that it is a positive value • (It costs money!) • If it is value then it is valued • If it is valued: this depends on the concrete society

14. The quality in the sciences • …part of the real sciences • Decision on the value – it means we should measure the quality! • Galilei: „Measure everything what is measurable and make measurable what is not!”

15. What may have a „quality”? • Everything! • In general: commodities and services • Is there any quality of the • life? • society? (e.g. policy to help the poor, etc.!)

16. „Product” • It is used in the quality-oriented sciences in the very general meaning! • Everything is „product”, what is „consumed” during meeting some needs • In this meaning the services are also „products”! • (At this moment: the „product” is the knowledge I am just delivering to you!)

17. „Production” of the product In all cases: • product (to be consumed) • side-product (useful or not useful) • waste Also when the „product” is a service!

18. What may affect the quality of a product(using the natural definition) • performance • characteristics • reliability • general suitability (e.g. an electric device may be connected to the power supply) • durability • serviceability • esthetics (its appearance) • safety during use

19. What may affect the quality pf a service(using the natural definition of quality) • time and timeliness • completeness • politeness • continuity (you may have info about it) • availability (also price) and comfort • accuracy • readiness to incorporate new ideas

20. Quality from the point of view of the producer Quality defined through conformity • Ability of the technology to assure that the product will conform to the requirements specified duringplanning • It depends on several factors, such as • planning and organisation of the production technology • performance ofthe equipments and of the technology • the starting materials • training of workers and management’s control • level of final quality control based on statitical considerations

21. Quality of a product and its price • This evaluation is also important and needed • The producer’s interest to achieve the „quality” with affordable costs • It means that the price of the to-be product is also an important factor of the quality planning! • The quality characteristics of the product and the costs of its production must be in equilibrium

22. What is „quality”? Philosophical (natural) definition: suitability for the intended purposepapaverine: smooth muscle relactant with a given probability and its known side-effects with their known (lower) probability

23. According to this definition, Quality is a phylosophically determined term: to what extent is the product suitable for its intended purpose

24. Other quality definition • Quality = satisfaction of the stakeholders and the organisation itself = valued value • Generally accepted on the standardised field! • Subjective, for a) who are the stakeholders, b) they may not be satisfied at the same time!

25. Stakeholders Small retail shop • final costumers (who buy in the shop to consume) • other consumers (who buy in the shop to re-sell) • vendors whom the shop purchases • shop assistants („selling their working power”) • the Municipality (whom local tax is paid) • The State (whom the general tax is paid) • …

26. Stakeholders Travel agencies • those who want to travel • at the target country: hotels, restaurants • local guides • employees of the travel agency • the owner of the building, whom the travel agency rents the office • Municipality, State…

27. Guest orders Guest eats Guest pays 1st people orders 2nd people eats it 3rd people pays it Nonsense? Stakeholders and their interest in drug retail The restaurant example Doctor Patient Insurance company or the State

28. Different stakeholders • with perhaps different interests • If we want to measure the quality as stakeholder satisfaction, we should specify • points of view of the measurement • its methodology • the characteristics to be measured • the values (what is positive, what is negative)

29. Measuring quality? From„quality control”toconformity assessment

30. Dilemma of „measuring” the quality - definitions • Philosophical (suitable for the intended purpose) – difficult to measure • Stakeholders’ satisfaction? It seams to be much more measurable, but • „Who writes the novel, the writer or the reader?”

31. Product and consumer needs • They are interrelated! • The consumer needs what seems to be realistic on the market • The market is manipulated (advertising!)

32. Conclusion • The market not always reflects the real needs • There may be „value” also in cases when there is no consumers’ need • One may not relay on the „stakeholders’ satisfaction” as the sole quality determinant

33. We should measure the „suitability for the intended purpose” Galilei: „Measure everything what is measurable and make measurable what is not!”

34. Quality control? If the philosophical (natural) definition of quality applies, can we control it?

35. „Quality” and „conformity” • Do we control the Quality of products? Rarely(e.g. assessment of medicines before their registration, see the papaverine example before) • This „philosophical” quality should be „translated” to measurable characteristics (requirements with limits + control methods, e.g. legal requirements or standards), and the Conformity of the product to these requirements is analysed/controlled/measured

36. Actually… …speaking - both in the everyday life and in the profession - about quality control, this is the control of the conformity to certain measurable requirements (conformity assessment)

37. Conformity assessment It has different types! • analytical tests, measurements • on-the-spot inspection or documentation audit • exam (!) Finally: certification of the conformity

38. Introduction of the „assured” quality besides (or even instead of) „controlled” quality

39. The quality is, as a rule, not controlled but assured! • In the everyday life, there is no other possibility! • The master works in his own shop producing goods: this, as a rule, assures the quality • Small sclae manufacture: every manufactured batch is checked (cont’d)

40. The quality is not controlled but assured! • Large scale manufacture: control based on (statistical) smapling it has inherent problems • In addition to sample control also the control of the whole manufacturing process „manufactured-in quality instead of analysed-in quality”

41. Problems of the statistical sampling • Certain per cent of failures tolerated (depending on the statistics used) • The whole system is based on the theory that the distribution of the defective product units may be modelled mathematically (following certain rules) e.g. Gaussian distribution

42. Issues of the control based on statistical sampling, 2 As it is seen in the health-care industry There is a difference between statistics and health-care needs: „Only” 2 dirty infusion bottles among 10,000 „Only” 1 apple with mass phyto protector content among others - who is administered to with it or eats it represent „his/her 100%”

43. Proper attitude • Quality assurance (e.g. GMP) or terminal batch quality control (analysis according to a sampling plan)? Wrong attitude! • When GMP is not applied, the result of (statistically taken) sample analysis can not taken as reliable!

44. How the quality assurance does work? In general • We try to avoid failures (defects) • to find them as soon as possible or, at least, to prepare ourselves • to avoidAD HOC INTERVENTIONS!

45. Quality Assurance – its various levels and types do exists! • We think about the „quality” at all • We monitor the qualityand deal with its improvement (– this has a close connection with the managerial sciences): Total Quality Management • We prepare process flow technological documents, collect minimum requirements and standards relating to our activities, develop and assess performance indicators (what are they: see later) • We introduce ISO-based quality assurance and certification, although it is not mandatory in our case (see later) • Introduce mandatory quality assurance and certification • ISO and „standardised” certification systems • legally required systems: GMP, GDP, GLP, GCP

46. TQM • Total Quality Management • Characteristic to the fields where the quality is defined by the consumer satisfaction

47. TQM, definition Management of the total organisation with a view to every product and service that may be important for the consumer

48. TQM • The consumer determines the quality, his need is the highest priority • The Management’s priority must be the quality, not the quantity • Thus way,the quality becomes a strategic issue • The quality is the responsibility of allemployeees,independently from their position within the organisation

49. TQM • The Organisation should, in all procedures, focus to continuous improvement of the quality otherwiseit can not reach its strategic aims • Problem solving plus quality improvement uses statitical quality control methods • The quality problems can be solvedonly through collaboration of the employees and the management • Continuous education andtraining of all employees means the basis of the continuous quality development

50. From”thinking about the quality” to TQM How was it introduced and by whom?