for 3 rd yr pharmacy student

1. QUALITY ASSURANCE
PREPARED BY:
B.PUNITHA
M.SUGANESWARI
H.KALAIVANI
S.SASIKALA
L.SINDHUJA
M.SHANMUGAPRIYA
S.THILAGAM
1

2. INTERNATIONAL STANDARDS OF ORGANISATION (ISO)
INTRODUCTION
 In the 1970’s many organizations
published their own quality management
Standards(e.g. Ford’s Q101,the ministry
of Defence’s 05-20 series,etc.)
 This introduced the idea that confidence
in a product could be gained from an
approved quality management system
and quality manuals.
2

3. INTERNATIONAL STANDARDS OF
ORGANISATION (ISO)
 By the late 70’s it was decided that, there would
be a national standard on what constituted a
quality system.
 They promote the development of standard of
standardization and related activities in the
world to facilitating international exchange of
goods and services and to develop co-
operation in the sphere of intellectual,scientific,
technological and economic activity.
3

4. IMPORTANCE OF STANDARD:
 Zero defects states
 Responsible for long term benefits
 Essential requirement for business and helps
promoting products to foreign markets
 Viewed as position of strength during product
litigation
 GMP’s are automatically implemented 4

5. ISO 9000
 It is a family of standards for quality management
and quality assurance systems
 The ISO 9000 is an international set of documents
written by members of a world wide delegation
known as the ISO/ tech committee 176
 Members from America ,Canada, and Western
Europe were the first to prepare the ISO standards
5

6. ISO 9000
 It was first published in 1987 and updated every 5
years
 It defines the principle quality concept and provides
guidance for selecting appropriate standards.
 This calls for a quality policy statement from top
management.
6

7. QUALITY POLICY:
it provides overall quality objectives and direction of
organization pertaining to key elements of quality
(e.g. For use, performance safety)
QUALITY MANAGEMENT:
A function that establishes and
implements quality policy.
7

8. QUALITY SYSTEM:
The organizational structure responsibility,
procedures, process and resources used for
implementing quality management.
it also includes:
 A set of procedures that cover all key processes in
the business.
 Monitoring the processes to ensure they are
effective.
 Keeping adequate records.
8

9. QUALITY SYSTEM:
 Checking output for defects with appropriate and
corrective actions where necessary.
 Facilitating continual improvement.
A company or organization that has been
independently audited and certified to be in
conformance with ISO 9001 may publicity state that
it is “ISO 9001 certified” or “ ISO 9001 registered.
9

10. QUALITY SYSTEM:
certification to an ISO 9001 standard does
not guarantee any quality of end products and
services; rather, it certifies that formalized business
processes are being applied.
10

11. ISO 9001:
ISO 9001:2008 Quality management systems-
requirements is a document of approximately 30
pages which is available from the national
standards organization in each country.
Outline contents of ISO 9001 are as follows:
 Quality systems –Modal for quality assurance in
design/ development, production, installation and
servicing.
 It calls for the management to define document,
implement and maintain a quality policy.
11

12. ISO 9001
 The standard specifies six compulsory documents :
(1) control of documents
(2) control of records
(3) internal audits
(4) control of non-conforming products /
service
(5) corrective action
(6) preventive action
12

13. ISO 9002:
Quality systems-Model for quality assurance in
production and installation.
ISO 9003:
Quality systems-Model for quality assurance in
final inspection and test.
13

14. ISO 9004:
 Quality management and quality system eliminate
guidelines.
 this provides quality guidelines for quality
management as a way to prevent reduce or
eliminate quality deficiency.
14

15. CERTIFICATION PROCESS:
initial contact with certifying
body(ISO)
enter into the contract
manual revenue
Acceptable non-
acceptable
15

16. CERTIFICATION PROCESS
acceptable
pre-registration audit
assessment
acceptable non-acceptable
16

17. CERTIFICATION PROCESS
acceptable
certification
surveillance audit
acceptable non-acceptable(warning)
(3 yrs renewal) 17

18. STEPS OF IMPLEMENTATION:
 approval from the top management
 Training to all key persons for the implementation
 Establish policy objective
 Form resource group
 Evaluate and improve
 Provide training at all levels
 Commence writing the documents
 Implement system at work place
 conduct internal audit-improve compliance
 Get audited by external energy 18

19. CLAUSES OF ISO 9000 SERIES:
DESIGN CONTROL:
identification of responsibility for each
design and development and activity.
these activities are performed by
qualified staffs equipped with adequate resources.
it requires that the organizational and
technical interfaces between different groups are
identified.
19

20. CLAUSES OF ISO 9000 SERIES:
DOCUMENT CONTROL:
CGMP stresses on the master
production and control records for every drug.
ISO requires identification,
documentation and appropriate review and
approval of all designs, changes and modification.
these changes must be received and
approved by same organization that performs
original review. 20

21. CLAUSES OF ISO 9000 SERIES:
PURCHASE LEVEL:
ISO requires the firm to evaluate suppliers
quality system and select suppliers on the ability to
meet the firm’s quality requirements.
PRODUCT IDENTIFICATION AND
TRACEABILITY:
ISO requires that the product be identified
through out all stages of production, delivery and
installation.
21

22. CLAUSES OF ISO 9000 SERIES:
PROCESS CONTROL:
ISO requires identification and planning
of all the productions that has direct bearing on the
quality.
Prospective validation of process
equipments involves:
(a)installation qualification:
This ensures documented verification
that all key aspects of installation adhere to
manufacturer’s recommendation.
22

23. CLAUSES OF ISO 9000 SREIES:
(b)Operational qualification:
-Known as performance qualification
-This ensures documented verification
that the system/sub-systems perform as intended
throughout all specified operating ranges.
(c)Calibration:
Demonstrating that a measuring device
produces results with in specified limits of those
produce by a reference standard device over an
appropriate range of measurements.
23

24. CLAUSES OF ISO 9000 SERIES:
INSPECTION AND TESTING:
CGMP requires laboratory control written
procedures in the form of specification and
standards, sampling plants and test procedures,
which are used in lab for controlling components
and finished products.
ISO provides checking whether purchased
product need urgent release for production purpose
is being documented and recorded.
24

25. CLAUSES OF ISO 9000 SERIES:
INSPECTION, MEASURING AND TEST
EQUIPEMENT:
ISO requires that precision and accuracy of
all measuring and testing equipment be
determined.
INSPECTION TEST STATES:
ISO requires marking, stamps or tags
indicating the stage of the product.
(e.g. Under test, pass, rejected)
25

26. CLAUSES OF ISO 9000 SERIES:
CONTROL ON NON-CONFORMING PRODUCT:
ISO like CGMP regulation requires the
isolation of non-conforming products.
ISO requires that the causes of non-
conformation of products are investigated under
corrective actions needed to prevent re-currence be
taken.
HANDLING, STORAGE, PACKING AND
DELIVERY:
CGMP has regulation regarding sanitary
inspections.
26

27. CLAUSES OF ISO 9000 SERIES:
CGMP and ISO stresses on maintenance
and conformation to procedures regarding handling,
storage and packaging of pharmaceuticals.
ISO concerned with delivery of products up
to the consumer and acting on the feed back
received from the customer.
27

28. QUALITY RECORDS:
ISO requires establishment and
maintenance procedure of identification, collection,
indexing, filling, storage, maintenance and
disposition of quality records.
QUALITY AUDITS:
Internal audit to ensure compliance.
External audit carried out to analyze
the firm’s own quality performance.
Two types—system audit &
product audit.
28

29. CLAUSES OF ISO 9000 SERIES:
TRAINING:
ISO requires procedures for identifying the
training need of all personnel performing activities
affecting quality.
INDIAN CORRESPONDENCE:
Bureau of Indian standards (BIS) has
adopted ISO 9000 series and have brought about
the IS 14000 series (IS 14001, IS 14002, IS 14003
and IS 14004)
29

30. SPECIAL PRODUCTS:
ISO have 2 magazines:
1.ISO Focus-an overview of ISO’s
activities
2.ISO management systems published 6
times a year.
30

31. 31

32. TOTAL QUALITY MANAGEMENT(TQM)
INTRODUCTION:
 TQM is relatively new concept of quality control. It
is basically, management function involving the
direction of top management and co-ordination of
all quality related activities throughout the company
to achieve Zero defects and customer satisfaction.
 The topic is of contemporary interest to industrial
pharmacist, community pharmacist and to all those
who are conscious about quality.
32

33. INTRODUCTION:
 Since quality is a measure of the users satisfaction
provided by the product, it should include-
(i)Functional efficiency
(ii) Appearance
(iii) Ease of installation and operation
(iv) safety
(v) Reliability
(vi)Maintainability
(vii)Running and maintenance cost
33

34. INTRODUCTION:
 In this quality awareness begins at the very
continues during the various stages of its
development and manufacture and even its usage
to provide feedback from the users which is so
essential for quality improvement.
CONCEPT IN TQM:
it refers to the goal of an organisation which can be
achieved,
1.it requires the commitment of senior level
management and supervision of all departments,
operators, supplies and customers.
34

35. CONCEPT OF TQM:
* When every individual is associated with the
organisation directly committed to the quality
performance and activities in the organisation
should be of desired quality.
* Concept of this TQM is developed from
Inspection
Quality control Quality
assurance
Quality circle 35

36. CONCEPT OF TQM
(a) Inspection:
 Ascertaining earlier, whether a product
confirms to the specification.
 it uses the measurement of the post
production activity in the business
organisation.
(b)Quality control
 It is post production activity.
It is done to notify whether every
manufacturing activity is performed
according to the predetermined standard and
instructions.
36

37. CONCEPT OF TQM
 it is carried out the structural, for al pack of
information consisting of specification for
- starting material
-the packaging materials
-finished product
(c)Quality assurance:
 it is a III evolutionary phase
 it is a wide ranging concept covering all
matters that individually or collectively
influences the quality of a product.
37

38. CONCEPT OF TQM
 it is a totally of arrangements made that the
object of ensuring that the pharmaceutical
products are of the quality required for their
interest.
 It is an online action having the system of
appraisal(judging the value of the product)
prevention and measurement activity with
management status.
In QA there is auditing by III party
E.g. Government or any other agency
38

39. CONCEPT OF TQM
(d) Quality circle:
• it is a small group of employees
(i) in same working area
(ii) Undergoing similar type of work
• In this on regular basis they directly
involved in the production process to
discuss and make improvements to the
production process.
• it is to improve the quality and
minimising the cost.
39

40. ELEMENTS OF TQM
Total quality is a description of culture,
attitude and organisation of a company that strives
to provide customers product and services that
satisfy their needs.
successful implementing TQM an
organisation must concentrate on 8 key elements
are:
(i) ethics (ii) integrity (iii) trust
(iv) training (v) team work (vi) leadership
(vii) recognitions (viii) communications
40

41. ELEMENTS OF TQM
These elements have been coined to
describe a philosophy that makes quality the driving
faces and leadership design, planning and
improvement initiatives.
BENEFITS OF TQM:
Advantages unique to TQM:
1. it makes company a leader
2. it makes fosters team work
3. it makes the company more sensitive to
customer needs
4. it makes the company adapt more readily to
change. 41

42. BENEFITS OF TQM
BENEFITS FOR THE CUSTOMER:
1.Fewer problems with the product (or)
service.
2. better customer care
3. greater satisfaction.
BENEFITS FOR THE STAFF:
1. Empowerment
2. More training and more skills
3. More recognisation.
42

43. BENEFITS OF TQM
BENEFITS FOR THE COMPANY:
1. Quality improves
2. Staff are more motivated
3. Productivity increases
4. Cost reduced
5. Zero defects
6. Problems resolved faster
43

44. ORGANISATION OF TQM
Organisation is one of the most important
elements of TQM in any field of human activity.
Team working co-operative relationships are of
great importance in TQM.
The main quality functions can be considered
into two distinct groups namely
(a) Quality engineering &
(b) Quality control
44

45. ORGANISATION FOR TQM
QUALITY ENGINEERING:
These compromises of the specialist staff
functions as well as activities connected with
development. Its main work elements are
a). Advice to the management on the quality
policy of the company.
b). Analysis of the customers quality
requirements.
c). The review and evaluation of the product
design.
d). Defining quality standards and preparation of
product specifications.
45

46. ORGANISATION FOR TQM
QUALITY ENGINEERING:
e). Development of quality control techniques
and inspection methods.
f). Conducting process capability
g). Analysis of quality costs
h). Quality audit of the company
QUALITY CONTROL:
It concerned with the interpretation and quality
plants. It comprises of in process and post
production testing. The main work elements are,
46

47. ORGANISATION FOR TQM
a). Assistance in establishing quality control
b). Maintenance and calibration of process
control equipment.
c). Investigation of defects and quality problems
d). Implementation of quality control measures
for incoming materials and stores
e). Arranging final inspection to assess the
quality of the end product
f). Checking the quality of the packaging
products.
g). Feed back to defect data and customer
complaint. 47

48. FUNCTIONS OF MANAGERS IN TQM
1.PLANNING:
Planning involves a rotational and orderly
thinking of ways and means with the help of which
goals are desired to be achieved. In other words it
involves
(a) Diagnosis of the problem
(b) Development of alternatives.
(c) Evaluation of alternatives.
(d) Selection of the best course of action.
48

49. FUNCTIONS OF MANAGERS IN TQM
2. ORGANISATION:
Organisation is a tool for achieving the
objections in a systematic and scientific manner. It
provides an integrated apparatus for attainment of
set goals.
3. DIRECTION:
Direction embraces and includes the
functions of
(i) supervision, (ii) leadership, (iii)
motivation, (iv) communication.
49

50. FUNCTIONS OF MANAGERS IN TQM
4. CONTROL:
Control is a process of evaluation of the
work assigned to individuals and various
departments with a view to achieve the set goals.
5.MOTIVATION:
Management is concerned with the
motivation of people for the realisation of the pre-
determined objectives of the organisation.
Motivation is the process of providing the personnel
an inspiration to get the work done.
50

51. FUNCTIONS OF MANAGERS IN TQM
6. CO-ORDINATION:
Co-ordination is the essence of any
management process. It achieves the commonness
of the purpose.
51

52. 52

53. PROCESS VALIDATION
GENERAL:
 The requirements and principles outlined in this
chapter are applicable to the manufacture of
pharmaceutical dosage forms.
 They cover the initial validation of new processes,
subsequent validation of modified processes and
revalidation.
 Process validation should normally be completed
prior to the distribution and sale of the medicinal
product(prospective validation)
53

54. PROCESS VALIDATION
GENERAL:
 In exceptional circumstances, where this is not
possible it may be necessary to validate processes
during routine production(concurrent validation)
 facilities, systems and equipments to be used
should have been qualified and analytical testing
methods should be validated.
 Facilities, systems, equipments and processes
should be periodically evaluated to verify that they
are still operating in a valid manner.
54

55. PROSPECTIVE VALIDATION
1. Prospective validation should include, but
not be limited to the following:
 Short description of the process
 Summary of the critical processing steps to be
investigated.
 List of the equipments/ facilities to be used
together its calibration status.
 Finished product specification for release
 List of analytical methods as appropriate
 Proposed in process controls with acceptance
criteria. 55

56. PROSPECTIVE VALIDATION
 Additional testing to be carried out, with
acceptance criteria and analytical validation,
as appropriate
 sampling plan
 methods for recording and evaluating results
 functions and responsibilities
 proposed timetable
56

57. PROSPECTIVE VALIDATION
2. Using this designs process a series of
batches of the final product may be produced under
routine conditions.
The number of process runs carried out
and observations made should sufficient to allow
the normal extent of variation and trends to be
established and to provide sufficient data for
evaluation.
57

58. PROSPECTIVE VALIDATION
3. Batches made for process validation should
be the same size as the intended industrial scale
batches
4. If it is intended that validation batches be scald
or supplied. The conditions under which they are
produced should comply fully with the requirements
of good manufacturing practice. Including the
satisfactory outcome of the validation exercise and
marketing authorisation.
58

59. CONCURRENT VALIDATION
In exceptional circumstances it may be
acceptable not to complete a validation programme
before routine production starts.
The decision to carry out concurrent
validation must be justified, document and
approved by authorised personnel.
Documentation requirements for
concurrent are the same as specified for
prospective validation.
59

60. RETROSPECTIVE VALIDATION
Retrospective validation is only acceptable for
well-established processes and will be
inappropriate where there have been recent
changes in the composition of the product.
Operating procedures (or) equipment.
validation of such processes should be
based on historical data. The steps involved require
the preparation of a specific protocol and the
reporting of the results of the data. Review, leading
to a conclusion and a recommendation.
60

61. RETROSPECTIVE VALIDATION
The sources of data for this validation should
include, but not be limited to batch processing and
packaging records, process control charts,
maintenance log books, records of personnel
changes, process capability studies, finished
product data, including trend cards and storage
stability results.
batches selected for retrospective validation
should be representative of all batches made during
the review period, including any batches that failed
to meet specifications, and should be sufficient in
number to demonstrate process consistency.
61

62. RETROSPECTIVE VALIDATION
For retrospective validation, generally
data from ten to thirty consecutive batches should
be examined to assess process consistency but
fewer batches may be examined if justified.
62

63. 63

64. PROCESS
PROCESS VALIDATION:
This section will explaw the implication of validation
in the over all manufacturing process.
PROCESS DECRIPTION FOR DRY PRODUCTION FACILITY
PROCESS
FLOW
CONTROL VARIABLES MEASURED
RESPONCES
Addition of raw
materials active
excipients
Sizing mill/sieve Screen type
Screen size
Granules size
distribution 64

65. PROCESS
PROCESS FLOW CONTROL
VARIABLES
MEASURED
RESPONCES
Action of raw
materials lubricants
disintegrates
Blending
Blender
Load size
Blending time
Blend uniformity
Flow characteristics
Tabulating high-speed
rotary machine
Compression rate
Granules feed rate
Fill-o-matic speed
Weight validation
Friability
Hardness
dissolution
thickness
65

66. PROCESS
PROCESS FLOW, VARIABLES& RESPONCES:
POWDER FOR SUSPENSIONS
PROCESS FLOW CONTROL
VARIABLES
MEASURED
RESPONCES
Addition of raw
materials active
excipients
Sizing
Mill/ sieve
Screen type
Screen size
Granules size
distribution
Blending blender Load size
Blending time
Blend uniformity
Moisture content
Filling automatic
powder filling machine
Filling machine speed
Flow characteristics
Weight variation
66

67. PROCESS
PROCESS FLOW, VARIABLES AND RESPONCES:
SYRUP,SUSPENSIONS AND PRODUCTS
PROCESS FLOW CONTROL
VARIABLES
MEASURED
RESPONSES
Addition of raw
materials active
excipients
Mixing jacketed vessel
with variable speed
mixer
Mixing time
Temperature
Final volume
Clarity
Viscosity
Assay
Filtration filter press/
cartridge filter/ nylon
filter
Mesh size
Filter integrity
Clarity
Filling automatic filling
machine
Filling machine speed volume 67

68. PROCESS FLOW, VARIABLES AND RESPONSES:
CAPSULES
PROCESS FLOW CONTROL
VARIABLES
MEASURED
RESPONCES
Addition of raw
materials active
excipients
Mixing
Mixer
Load size
Mixing time
Mixing uniformity
Addition of raw
materials lubricating
disintegrates
Blending
Blender
Load size
Blending time
Blend uniformity
Flow characteristics
Capsulating high-
speed capsulation
machine
Capsulation speed
Powder speed rate
Weight variation
Disintegration time
Louring 68

69. PROCESS
Process flow, variables and responses: cream,
ointments and suppository products
PROCESS FLOW CONTROL
VARIABLES
MEASURED
RESPONSES
Action of raw materials
active excipients
Mixing jacketed vessel
with variables
Speed mixer
Mixing time
Temperature
Rpm
Amount of stiffening
agent
Final volume
Clarity
Viscosity
Assay
Filling automatic filling
machine
Filling machine
speed
Volume variation
69

70. PROCESS
Process flow, variables and responses: Aseptic fill
products:
70
PROCESS FLOW CONTROL
VARIABLES
MEASURED
RESPONSES
Issurance of flow and
packing material
Addition of raw
material active
Non-active
Medium
Water for injection
Temperature Ph
Conductivity
AMC

71. PROCESS
PROCESS FLOW CONTROL
VARIABLES
MEASURED
RESPONSES
Steam sterilisation
pressure vessel/ filling
and filtration
assembly/ stopper
stand seals/ gowning
Time and temperature
of steam sterilizer
Time & temperature
Printout or graph
Mixing pressure
vessel
Mixing time
RPM
Temperature
Final volume
Ph
clarity
Ampoules/ vials
Washing
Temperature
Pressure
Washing cycle
Ampoules/ vials
Hot air sterilisation
Time& temperature of
dry heat sterilizer
Time & temperature
printout or graph
71

72. PROCESS
PROCESS FLOW CONTROL
VARIABLES
MEASURED
RESPONSES
Filtration
Filtration assembly
and 0.22 micro filter
Pressure Filter integrity test
Aspticing automatic
filling & sealing
machine in line-
filtration casing
Machine speed
Pressure
Flow nature
Filter integrity test
In process check
Environmental
monitoring
Air sampling& gloves
print for microbial
counts
Leak test Temperature
Pressure
Vacuum
Inspection of filled
ampoules or vials
Chemical & micro
biological analysis
In process checks
Labelling/packing
72

73. 73