B. Pharm. Final Year, Sem:- VII, INDUSTRIAL PHARMACY-II, Unit 4 final chapter 5 Quality management systems As per PCI Syllabus

1. PREPARED BY- DHAWAL RAJDEV
M.PHARM (QA)
RK University
1
Unit-IV,
Quality Management System.
Industrial Pharmacy-II
Represented By,
Mr. Audumbar Mali,
Asst. Professor,
Dept:- Pharmaceutics,
Sahyadri College of Pharmacy, Methwade, Tal-
Sangola.

2. Basics of quality
management system
2

3. Quality Management System (QMS) is an important
aspect for the pharmaceutical industry for maintaining the
quality and safety for their products and services. QMS
relies on the regulations and guidelines to maintain the
effective quality in pharmaceutical industries. According
to US FDA, the international harmonized guidance is
intended to assist pharmaceutical manufacturers by
describing a model for an effective quality management
system for the pharmaceutical industry. This guidance is
referred as ICH (International Council for Harmonization)
guideline.
Quality:- Quality can be defined according to US FDA as;
"A measure of a product's or service's ability to satisfy the
customer's stated or implied needs."

4. Basics of quality management
system
4
Quality word oriented from Latin word
‘Qualitus’ it means General excellence OR
distinctive feature.
Quality- a standard of how good something
is as measured against other similar
things.( by OXFORD dictionary)
If we try to analyse definition some
common words like...

5. 1. Standard
2. Measurement
3. Goodness
4. comparison
Most simple definition of quality is ‘fitness
for use’
The customer or user is at focus. if customer or
user is happy and satisfied with our product or
service then product or service is called good
quality.
5

6. It must be remember that the quality
is not the job of only a single person
or single department but, it is
responsibility of whole organization.
Quality of Product and service is
measurable, managerial, technological
and stastical feature of organization.
6

7.  Dimensions of Quality
Performance
Feature
Reliability
Perceived quality
Aesthetics
Durability
Conformance
serviceability
7

8. Quality Assurance (QA):- According to WHO, QA is a
wide-ranging concept covering all matters that
individually or collectively influence the quality of a
product. It is the totality of the arrangements made with
the object of ensuring that pharmaceutical products are
of the quality required for their intended use. Quality
assurance therefore incorporates GMP and other factors.
including those outside the scope of this guide such as
product design and development.
Quality Control (QC):- QC is that part of GMP concerned
with sampling, specification, testing, documentation and
release procedures which ensure that the necessary and
relevant tests are performed and the product is released
for use only after ascertaining its quality.

9. Scope of Pharmaceutical QMS:-
1. Phamaceutical Development:-
#Drug substance development.
#Formulation development (including container/closure
system).
# Manufacture of investigational products.
# Delivery system development (where relevant).
# Manufacturing process development and scale-up.
# Analytical method development.
2. Technology Transfer:
# New product transfers during development through
manufacturing.
# Transfers within or between manufacturing and testing
sites for marketed products.

10. 3. Commercial Manufacturing:-
# Acquisition and control of materials.
# Provision of facilities, utilities and equipment
# Production (including packaging and labeling).
# Quality control and assurance.
ICH Guldellnes:-
ICH guideline is intended for bringing together the
regulatory authorities and pharmaceutical industries
together for the discussion of the scientific and technical
aspects of drug registration.
It is divided into four categories (QSEM):
Q: Quality guidelines:- It includes stability, impurities
testing, GMP.
S: Safety guidelines:- It includes carcinogenicity,
genotoxicity. reprotoxicity.

11. E: Efficacy guidelines:- It includes clinical,
pharmacogenomics.
M: Multidisciplinary guidelines:- It includes medical
dictionary for regulatory activities, electronic
standards, non-clinical safety studies, common
technical document (CTD).
1. Quality Guidelines:-
Harmonization achievements in the quality area
include pivotal milestones such as the conduct of
stability studies defining relevant thresholds for
impurities testing and a more flexible approach to
pharmaceutical quantity based on good
manufacturing practice (GMP) risk management. It
includes the following guidelines:

13. 2. Safety Guidelines:-
ICH has produced a comprehensive set of safety
Guidelines to uncover potential risks like
carcinogenicity, genotoxicity and reprotoxicity.

14. 3. Efficacy Guidelines:-
It is concerned with the design, conduct, safety and
reporting of clinical trials.

15. 4. Multidisciplinary Guidelines: Some
highlights of this guideline are:

16. Sources of Quality Variation:-
1. Materials:
(a) Variations among suppliers of same substances.
(b) Variations among batches from same suppliers.
(c) Variations within a batch.
2. Machines:
(a) Variation of equipment of same process.
(b) Difference in adjustments of equipment.
(c) Aging of machines and improper care.
3. Methods:
(a) Wrong procedure.
(b) Inadequate procedure.
(c) Negligence in procedure by chance.

17. 4. Personnel: (a) Improper working conditions.
(b) Inadequate training and understanding.
(c) Lack of interest and emotional upheavals.
(d) Dishonesty fatigue and carelessness.
Control of Quallty Variatlon:- The mistakes can be
controlled, minimized or eliminated by material
control; packaging control and GMP variations can be
controlled when Quality Control, Quality Function and
Quality Assurance work side by side. Controlling each
and every step of process can control variations.
Control can be divided into:
1. Material control 2. Manufacturing practice control
3. Packaging control
4. Distribution control

18. Total Quality
Management (TQM)
18

19. Introduction:-
19
Total–Made up of the whole (or)
Complete.
Quality –Degree of Excellence a product or
service provides to the customer in present
and future.
Management –Act , art, or manner of
handling , controlling, directing, etc.
TQM is the art of managing the whole to
achieve excellence

20. Definition:- "TQM is a management
approach for an organization, centered on
quality, based on the participation of all its
members and aiming at long-term
success through customer satisfaction,
and benefits to all members of the
organization and to society."
Or
Total Quality Management(TQM) is a
management strategy aimed at
embedding awareness of quality in all
organizational processes. 20

21. TQM requires that the company maintain
this quality standard in all aspects of its
business. This requires ensuring that
things are done right the first time and that
defects and waste are eliminated from
operations.
21
Characteristics :
•Technological strength, hardness,
•Time – oriented, Reliability,
maintainability - availability
•Contractual Guarantee.

22. Goal of TQM
Define
measure
analyseimprove
control
22

23. 23

24. Six basic concepts of TQM:-
24
1. A committed and involved
management to provide long term top
– to – bottom organization support.
2. An unwavering focus on the customer,
both internally and externally.
3. Effective involvement and utilization
of the entire work force.
4. Continuous improvement of the
business and production

25. 5. Treating suppliers of the
business and production
process.
25
6. Establishing the
performance measures

26. Control
Culture
Customer focus
Co-operation
Continuous
improvement
Commitment
26

27.  Total Quality Management and
Continuous Improvement:-
TQM is the management process used
to make continuous improvements to all
functions.
TQM represents an ongoing, continuous
commitment to improvement.
The foundation of total quality is a
management philosophy that supports
meeting customer requirements through
continuous improvement.
27

28. Continuous Improvement versus
Traditional Approach
28
Traditional
Approach
1. Market share
focus
2. Individuals
3. Focus on who
and why
4. Short term focus
5. Product focus
6. Innovation
7. fire fighting
Continuous
Improvement
1. Customer focus
2. Cross functional terms
3. Focus on what and
how
4. Long term focus
5. Process improvement
6. Incremental
improvemen
t

29. Quality
Cost:-
29
Prevention Cost –Planning, Document, Control,
Training.
Appraisal cost- inspection test installation
Calibration, Depreciation, Reports & Rejects.
Internal Failure Cost – Scraps, Repair Rework,
Design Changes, Defect Failure Analysis, Retests &
Re-Inspection, Downgrading, Down Time.
External Failure Cost – Complaints, Goodwill,
& Replacement, Guarantee & Warranty,
Compensation, Recall,
Loss of Sales, Seconds Sales.

30. Benefits of Quality:-
30
Improved quality.
Employee participation.
Less migration of employee
Team work.
Internal external customer
satisfaction.
Productivity with connectivity.
Profibility & increase market share.

31. QUALITY BY DESIGN (QbD):- Introduction:-
Pharmaceutical industries always rely on the
continuous improvement in safety, quality and
efficacy of the products. The pharmaceutical
products are intended for the patient care. So,the
priority is enhanced therapeutic benefits and
absence of impurities. Therefore, the product
should be designed to meet patients needs and the
intended product performance. The product quality
and performance are regulated by finished product
testing, with understanding of the process and
critical process parameters.

32. The US FDA (Food and Drug Administration)
has adopted the principles of QbD in the
development manufacturing and regulation of
pharmaceutical products. ICH guidelines also
focus on the principles of QbD through its
guidelines mentioned as ICH Q8 (R2)
Pharmaceutical Development, ICH Q9 (Quality
Risk Management), ICH Q10 (Pharmaceutical
Quality System) and ICH Q11 (Development
and manufacture of drug substances).

33. Delinition:-
According to US FDA and ICH Q8 (R2) the QbD is a
systematic approach to development which includes the
prior knowledge of product and process understanding
based on the results of studies using design of
experiments, use of quality risk management and use of
knowledge management.
Objectives of QbD:- The main objectives of QbD are as
follows:
1. Increasing manufacturing efficiency.
2. Increasing the efficiency in product development.

34. 3. Enhancement of product quality and
performances to meet patients needs.
4. Increase in process capability.
5. Avoidance of regulatory compliances.
6. Incorporation of risk management.
7. Reduction in production costs and waste.
8. Reduction in product variability, defects and
rejections.

35. The main outcomes of QbD are as follows:
1. Maintenance of product quality to meet expected
clinical performances.
2. Maintenance of product quality by efficient
manufacturing and formulation process.
Elements of QbD:- The following elements can be
included in the study of QbD:
1. QTPP (Quality Target Product Profile): This profile is
related to quality, safety and efficacy.
2. CQA: (Critical Quality Attributes): The study of CQAs
helps in the study and controlling of the product
characteristics that have impact on product quality.

36. 3. Determination of CQAs of drug
substances, excipients, etc. and the
selection of the excipients to attain the
desired drug quality.
4. Suitable manufacturing process
selection.
5. Risk assessment:
# CMAs (Critical Material Attributes)and
# CPPs (Critical Process Parameters)
6. Defining a control strategy.

37. Quality Target Product Profile (QTPP):- It
includes:
1. Dosage forms, route of administration,
delivery systems.
2. Strength of doses.
3. Container closure system.
4. Pharmacokinetic properties.

38. Critical Quality Attributes (CQA) :-
CQA is related with drug substance,
excipients, intermediates (in-process
materials) and drug product. CQA is a
physical, chemical, biological or
microbiological property (should be
within an appropriate limit, range, or
distribution) to ensure the desired
product quality.

39. Risk Assessment: CMAs (Critical Material
Attributes) and CPPs (Critical Process
Parameters) :- Risk assessment, a science-
based method or process, is used in QRM
(Quality Risk Management, mentioned in ICH
Q9). This assessment identifies materials
attributes and process parameters effectively
that have an effect on product CQAs. This
process is utilized in prior pharmaceutical
development process which makes available
more information and

40. knowledge about the development process.
Based on prior knowledge and initial
experimental data, risk assessment method
helps to identify and rank different parameters
like process, equipments and input materials
with potential that have an impact on product
quality.
Control Strategy:-
The pharmaceutical product should be
produced with required quality in consistent
fashion and the control strategy ensures this. It
includes the following elements:

41. 1. Contrel of input material attributes viz, drug
substance, excipients, packaging materials,
considering their utilization and effect on
product quality.
2. Product specifications.
3 Controls of unit operations that have a role to
maintain the product quality. The operations
may Include granulation, drying, degradation,
particle size distribution etc.
4. In-process testing.
5. Finished product testing.
6. Testing of products at every stage at regular
intervals (Monitoring program).

43. 43

44. Six sigma is a business statistical Strategy.
Is to identifying defects and removing them
from the process of products to improve
quality.
A defect is defined as any process
output that does not meet customer
specifications.
Statistical measure to objectively
evaluate processes.
44

45. The Six sigma was founded by Motorola in
the 1970s.
Out of senior executive Art Sundry's
criticism of Motorola’s bad quality.
They founded a connection between
increases in quality and decreases in
costs of production.
Bill Smith, “Father of six sigma” introduce
this quality improvement Methodology to
45

46. • Quality management program
developed by Motorola in the 1980s.
• Management philosophy
focused on business process
improvements to:
Eliminate waste, rework, and
mistakes
Increase customer satisfaction
Increase profitability
and competitiveness
46

47. DMAIC DMADV
• Define
• Measure
• Analyze
• Improve
• Control
47
• Define
• Measure
• Analyze
• Design
• Verify

48. Define : company must identify the customer and
which type of a product and hope from it. These are
analyze by using flow cause/effect diagrams, check
sheets, pareto analysis.
Measure : company will collect the baseline data to
determine where the process stands as compare to
where it needs to be. And also see the critical to
quality characteristics an estimate current process
capability.
Then find out the current sigma level according to
those identified characteristic that are mostly
important to the customer. 48

49. DMAIV cont….
49
Analyze : this shows the amount of improvement
necessary to make the Critical to quality
characteristics the best in the industry. For this
phase company use some descriptive statistical
methods like mean, mode, median…etc.
Improve : Implement the suggested improvements
in this phase And also test possible solutions to
the process problem. Collect data from the all
possible solutions and test them on a small scale
and run a cost/benefit analysis of implementing
the solution. Then choose the best solution and
create a plan for implement the solution.

50. 30
Improvement cycle :
• PDCA cycle
Plan
Do
Check
Act

51. DMAIV cont….
51
Control : measures are implemented to
ensure improvements are maintained.
To monitor the process improvements,
basically use tools like statistically
process control charts. These charts
have three limits, the center line for the
average. Monitor the process to ensure
that the process is in the control limits.

52. This method is also called DFSS (Design For
Six Sigma) and have five phases.
Define design goals that are consistent with
customer demands and the enterprise
strategy. Measure and identify CTQs
(characteristics that are Critical To Quality),
product capabilities, production process
capability, and risks.
Analyze to develop and design alternatives,
create a high-level design and evaluate design 52

53. Design details, optimize the
design, and plan for design
verification. This phase may
require simulations.
Verify the design, set up pilot
runs, implement the production
process and hand it over to the
process owner(s).
53
DMADV cont….

54. Between -1 to 1 standard deviation = 68.3%
(2/3)
Between -2 to 2 standard deviation = 95.5%
Between -3 to3 standard deviation = 99.7%
54

55. •Executive Leadership (CEO and other top
level managers)
•Champions (act as the leaders of black belts.
And also )
•Master Black Belts (chosen by champions,
give their full effort to six sigma. Help to
champions and guide the Black belts and
green belts).
•Black belts (working under Master Black
Belts, they are applying six sigma to specific
projects). 55

56. Implemented Methodologies
Total Quality
Management
Zero
defects
Quality
Control
56

57. 57

58. Focus of Six Sigma
58
• Accelerating fast
breakthrough performance.
• Significant financial results in
4-8 months.
• Ensuring Six Sigma is an
extension of the Corporate
culture, not the program of the
month.

59. • There is nothing new. It only proves defects and
defectives counts offer measurable results.
•It is corrective action system rather than
taking a preventive and proactive approach
to problems.
•It is merely about appraisal system and that
appraisal programs aren’t useful. In appraisals are
great tools for identifying and tracking
improvements, which is critical to any project.
•Critics have suggested that Six Sigma did not bring
quality improvement in all the organizations where
it was implemented. It depends on the tools and 59

60. Management philosophy of quality
Components of Six Sigma are
people power and process power
Define, Measure, Analyze,
Improve, Control
Criticisms
Executive Leader, Champion,
Master Black Belt, Black Belt, and
Green Belt
Statistical target of six sigma or
defects in one million opportunities
Summary
60

61. 61

62. International Organisation for
standardization (ISO)
62
A network of national
standardization bodies from over
160 countries with Nigeria
inclusive.
Based in Geneva Switzerland.
Standard Organisation of Nigeria
(SON) is a Technical Committee
(TC) in ISO, meaning participates

63. ISO management
standardsSelected standards that companies
can be certified for :-
Occupational Health and Safety Assessment Series (OHSAS)
ISO 9001
Quality
ISO 22000
Food safety ISO 22301
Business
continuity
ISO 20000
IT services
ISO 14001
Environment
OHSAS 18001
Health and
Safety
ISO 28000
Supply chain
Security
63
ISO 27001
Information
security

64. ISO 9001:2008 (QMS)basic
principles
64
Principle 1 –
Principle 2 –
Principle 3 –
Principle 4 –
Principle 5 –
Principle 6 –
Principle 7 –
Principle 8 –
Customer focus
Leadership
Involvement of people
Process approach
System approach to management
Continual improvement
Factual approach to decision making
Mutually beneficial supplier
relationships
.

65. Principle 1 - Customer focus
Pragmatically, a quality product centers on meeting
customers current and future requirements in
the needed form, time and place in synchrony with
the company’s policies and objectives.
Customer satisfaction
Employee’s
responsibility
Management
responsibility
Customer requirements
QMS
65

66.  Principle 2 - Leadership
66
Application
Perfect understanding of
the organization short
and long term goals and
objectives.
Setting realistic and
practicable targets.
Make the needs of all
stakeholders a focal
point.
Maintain a trustful work
ambience and not a
fearful environment.
Positive contributions
must be encouraged.
Benefits
More enthusiastic
workers.
Increased employee
loyalty
Effective communication
system is enabled.

67. Principle 3 - Involvement of
the peopleApplications
A sense of belonging
should be created in
people that has direct
and indirect link with the
company.
People should be made
to understand that their
opinion counts.
People openly
discussing problems
and issues.
People identifying
constraints to their
performance.
67
Benefits
Employees shows more
commitment towards
achieving organization
goals and objectives.
Innovation and creativity
within the organization.
People show more
interest in continuous
improvement.

68. Principle 4 - Process
Approach
Input Output
Customers
(and other
interested
parties)
Customers
(and other
interested
parties)
Management
responsibility
Resource
management
Product
realization
Measurement,
analysis and
improvement
Requirement
s Satisfaction
Continual improvement of the quality
management system.
68

69. Principle 5 - System Approach to
Management
System = combinations of entities
(processes)that works dependently and
interrelated with each other and becomes a
culture over a period of time.
Management
responsibility
Measurement,
analysis and
improvement
Product
realization
Resource
management System
51

70. .
70
Principle 6- Factual approach to
decision :-
making
How?
Conducting frequent market
survey and market intelligence.
Customer dissatisfactions be
treated generically, sequel to
extensive market survey to
generate valid information.
Ensuring that data and
information are sufficiently
accurate and reliable
Making data accessible to those
who need it
Analyzing data and information
using valid methods
Making decisions and taking
action based on factual analysis,
balanced with experience and
intuition.
Benefits
Prevents impulsive decision
making that could dissatisfy
majority of the customers.
Only informed decisions will be
made generically.
An increased ability to
demonstrate the effectiveness of
past decisions through reference
to factual records
Increased ability to review,
challenge and change opinions
and decisions.

71. Principle 7 - Mutually
Beneficial Supplier
Relationships
Establishing relationships that
balance short-term gains with
long-term considerations.
Pooling of expertise and
resources with partners.
Identifying and selecting key
suppliers.
Clear and open communication
Sharing information and future
plans
Establishing joint development
and improvement activities
Inspiring, encouraging and
recognizing improvements and
achievements by suppliers.
71
Benefits
Increased ability to create value
for both parties
Flexibility and speed of joint
responses to changing market or
customer needs and expectations
Optimization of costs and
resources.

72. Conclusion
72
All discussed principles are the core
attributes on which ISO 9001:2008 are
based upon, and it is therefore
imperative that to meet up with
International standards, we should strive
to align our operations with these
principles to foster a better competitive
advantage both on local and
international front.

73. 10 Clues
1. Scope
2. Normative references
3. Terms and definition
4. Context of organization
5. Leadership
1. Planning
2. Support
3. Operations
4. Performance Evaluation
5. Improvement
67

74. Management Service Division
ISO 14001:2004 Overview
74

75. To enhance compatibility
with ISO 9001:2000
Revision allows opportunity
to clarify requirements in
the 1996 version and
incorporate needed changes
Why was ISO 14000
revised?
It was due for revision, ISO requires that all
management system standards undergo
periodic revision
75

76. 4.1 General Requirements
The organization shall establish, document,
implement, maintain and continually improve an
environmental management system in accordance
with the requirements of this International Standard
and determine how it will fulfill these
requirements.
The organization shall define and
document the scope of its
environmental management system.
ISO 14001:2004
76

77. Environmental Policy
ISO 14001: 2004
Top management shall define the organization's
environmental policy and ensure that, within the
defined scope of its environmental
management system, it:
a) is appropriate to the nature, scale and
environmental impacts of its activities, products
and services,
b) includes a commitment to continual improvement
and prevention of pollution,
77

78. ISO 14001: 2004
a)includes a commitment to comply
with applicable legal
requirements and with other
requirements to which the
organization subscribes which
relate to its environmental
aspects,
b)provides the framework for
setting and reviewing
78

79. ISO 14001: 2004
a)is documented, implemented and
maintained
b)is communicated to all persons
working for or on behalf of the
organization, and
c)is available to the public.
79

80. ISO 14001: 2004
The organization shall establish,
implement and maintain a
procedure(s)
a)to identify the environmental aspects
of its activities, products and services
within the defined scope of the
environmental management system
that it can control and those that it can
influence taking into account planned
or new developments, or new or
80

81. ISO 14001: 2004
b) to determine those aspects that haveor can
have significant impact(s) on the environment
(i.e. significant environmental aspects).
The organization shall document this
information and keep it up to date.
The organization shall ensure that the
significant environmental aspects are taken
into account in establishing, implementing
and maintaining its environmental
management system.
81

82. Objectives, targets and
programme(s)
The organization shall establish, implement
and maintain documented environmental
objectives and targets, at relevant functions
and levels within the organization.
The objectives and targets shall be
measurable, where practicable, and
consistent with the environmental policy,
including the commitments to prevention
of pollution, to compliance with
applicable legal requirements and with
other requirements to which the
organization subscribes, and to
82

83. When establishing and reviewing its
objectives and targets,
an organization shall take into account the
legal requirements and other
requirements to which the organization
subscribes, and
its significant environmental aspects. It
shall also consider its technological
options, its financial, operational and
business requirements, and the views
of interested parties.
83

84. Resources, roles,
responsibility and authority
Management shall ensure the availability of
resources essential to establish,
implement, maintain and improve the
environmental management system.
Resources include
human resources and specialized skills,
organizational infrastructure, technology
and financial resources.
Roles, responsibilities and authorities shall
be defined, documented and
communicated in order to facilitate
effective environmental management. 84

85. The organization's top management
shall appoint a specific management
representative(s) who, irrespective of
other responsibilities, shall have
defined roles, responsibilities and
authority for
a) ensuring that an environmental
management system is established,
implemented and maintained in
accordance with the requirements of
this International Standard,
85

86. reporting to top
management on the
performance of the
environmental management
system for review, including
recommendations for
improvement.
86

87. Communication
With regard to its environmental aspects and
environmental management system, the
organization shall establish, implement
and maintain a procedure(s) for
a) internal communication among the various
levels and functions of the organization,
b) receiving, documenting and responding to
relevant communication from external
interested parties.
87

88. The organization shall decide
whether to communicate externally
about its significant environmental
aspects, and shall document its
decision.
If the decision is to communicate,
the organization shall establish
and implement a method(s) for
this external communication 88

89. Documentation
The environmental management system documentation shall
include
a) the environmental policy, objectives and targets,
b) description of the scope of the environmental
management system,
c) description of the main elements of the environmental management
system and their interaction, and reference to related documents,
d) documents, including records, required by this
International Standard, and
e) documents, including records, determined by the organization
to be necessary to ensure the effective planning, operation and
control of processes that relate to its significant environmental
aspects.
89

90. Internal audit
Audit programme(s) shall be planned, established,
implemented and maintained by the organization,
taking into consideration the environmental
importance of the operation(s) concerned and the
results of previous audits.
Audit procedure(s) shall be established, implemented
and maintained that address the responsibilities
and requirements for planning and conducting
audits, reporting results and retaining associated
records,
— the determination of audit criteria, scope, frequency
and methods.
Selection of auditors and conduct of audits shall
ensure objectivity and the impartiality of the 90

91. NABL Accreditation
91

92. What is NABL ?
92
NABL specifies the general
requirements for the competence
to carry out tests and
calibrations, including sampling. It
covers testing and calibration
performed using standard
methods, non-standard methods,
and laboratory-developed
methods.

93. National Accreditation Board for Testing and Calibration
Laboratories (NABL) is an autonomous body under Department
of Science & Technology, Government of India, and is registered
under the Societies Act.
NABL has been established with the objective to provide
Government, Industry and Society in general with a scheme for
third- party assessment of
the quality and technical competence of testing and calibration
laboratories.Government of India has authorized NABL as the sole
accreditation body for Testing and Calibration laboratories.
In order to achieve this objective, NABL provides laboratory
accreditation services to laboratories that are performing tests /
calibrations in accordance with NABL criteria based on
internationally accepted standard for laboratory accreditation ISO.
192

94. CONCEP
T
94
The concept of Laboratory Accreditation was developed to provide a
means for third- party certification of the competence of laboratories to
perform specific type(s) of testing and calibration.
Laboratory Accreditation provides formal recognition of competent
laboratories, thus providing a ready means for customers to find
reliable testing and calibration services in order to meet their demands.
Laboratory Accreditation enhances customer confidence in
accepting testing / calibration reports issued by accredited
laboratories.
The globalization of Indian economy and the liberalization policies
initiated by the Government in reducing trade barriers and providing
greater thrust to exports makes it imperative for Accredited

95. Benefits of Accreditation:
95
Potential increase in business due to
enhanced customer confidence and
satisfaction.
Savings in terms of time and money
due to
reduction or elimination of the need for re-
testing .
Better control of laboratory operations and
feedback to laboratories as to whether they
have sound Quality Assurance System and

96. Increase of confidence in Testing /
Calibration data and personnel
performing work.
Customers can search and identify the
laboratories accredited by NABL for
their specific requirements from the
directory of Accredited Laboratories.
Users of accredited laboratories will
enjoy greater access for their
products, in both domestic and
international markets, when tested by
accredited laboratories.
96

97. Types of Laboratory can
seek Accreditation:
97
Laboratories undertaking any sort of
testing or calibration in the specified
fields.
Private or government laboratories.
Small operations to large multi-field
laboratories.
Site facilities, temporary field operations
and
mobile laboratories.

98. TESTING
LABORATORIES
CALIBRATION
LABORATORIES
MEDICAL
LABORATORIES
 Biological
 Chemical
 Electrical
 Electronics
 Fluid-Flow
 Mechanical
 Non-Destructive
Testing
 Photometry
 Radiological
 Thermal
 Forensic
 Electro-Technical
 Mechanical
 Fluid Flow
 Thermal & Optical
 Radiological
 Clinical Biochemistry
 Clinical Pathology
 Haematology &
Immunohaematology
 Microbiology & Serology
 Histopathology
 Cytopathology
 Genetics
 Nuclear Medicine
(in- vitro tests only)
PROFICIENCY TESTING PROVIDERS
REFERENCE
MATERIAL
PRODUCERS
 Testing
 Calibration
 Medical
 Inspection
 Chemical Composition
 Biological &
Clinical Properties
 Physical Properties
 Engineering Properties
 Miscellaneous Properties
198

99. 10 Step Approach To
Accreditation
99
Awareness Training
Quality Policy & Objectives Finalization
Gap Analysis
Documentation / Process Design
Documentation / Process Implementation
Internal Audit
Management Review Meeting
Shadow Audit
Corrective –Preventive Actions
Final Certification Audit

100. Step 1:- Awareness Training
100
Separate training sessions for
top management, middle
management and junior level
management.
Creates a motivating environment
throughout the organization for
ISO 17025 implementation.

101. Step 2:-Quality Policy &
Objectives
101
Work shop with top
management on
development of quality policy.
Work shop with top
management and middle level
functional management on
development of quality
objectives.

102. Step 3:-Gap Analysis
102
Understanding of all the
operations of the organization.
Development of process
map for the activities of the
organization.
Comparing existing operations
with requirements of ISO
17025:2005 standard.

103. Step 4:-Documentation /
Process Design
103
Quality Manual
Functional Procedures
Work Instructions
System Procedures
Formats

104. Step 5:-Documentation /
Process Implementation
104
Work–shop on process /
document implementation
as per ISO 17025
requirements.
Departmental / Individual
assistance in implementing
the new processes /

105. Step 6:-Internal Audit
105
Internal Audit Training & Examination
(Optional).
Successful employees carry out internal
audit of the organization covering all the
departments and operations.
Suggest corrective and preventive
actions for improvements in each of the
audited departments.

106. Step 7:-Management Review
Meeting
106
Quality Policy & Objectives
Results of internal audit
Results of supplier evaluation
Results of customer
complaints
Results of customer feedback
etc.

107. Step 8:-Shadow Audit
107
It is a final certification audit.
Finds degree of compliance
with ISO 17025 standard.
Gives an idea to the employees
about the conduct of the final
certification audit.

108. Step 9:-Corrective –
Preventive Actions
108
On the basis of shadow audit
conducted in the last step, all the
non-conformities will be assigned
corrective and preventive actions.
A check will ensure that all the
points are closed and the
organization is ready for the final
certification audit.

109. Step 10:-Final Certification
Audit
109
Upon completion of
various stages of
accreditation audit, the
audit, your organization
will be awarded
accreditation.

110. Out of Specifications
(OOS):-Introduction:-
When an analytical or test result of any batch or
material is out of prescribed and
predetermined limits or specifications, it is
called as OOS. OOS may be raised in the case of
stability testing, analysis of in-process, test of
raw materials, intermediates and finished
goods (API). Investigation for OOS may be
performed while getting any unacceptable and
questionable results.

111. Identification of OOS: Reports of
Laboratory Investigation:-
This investigation is conducted when OOS is
found in analysis. The main purpose of
obtaining OOS reports is to find out the
source of the results which fall outside the
specifications. In this initial investigation, all
the results should be recorded and well
documented. The data should be conveyed
and forwarded to quality control
department, so that full scale analysis can
be performed.

112. Responsibility of Analyst and Supervisor:-
An analyst has the primary responsibility for the
laboratory testing results. He should have sound
knowledge about the principle, primary requirements
and process of the investigations. The accurate and
precise results are expected, if any wrong results are
found that should be informed to concern superior
department and assessment should be initiated with
immediate effect. The supervisor of the laboratory
should discuss the problems and the malfunctioned
result with the analyst. He should verify the followed
correct procedure and knowledge of the analyst.

113. He should overlook the following points:
1. Raw data of the result.
2. Calculations of the result.
3. Proper functioning of instruments.
4. Procedure performed by the analyst.
5. Quality parameters of soIvents, reagents,
standard solutions.
6. Knowledge of the analyst regarding
investigation.
7. Method validation and evaluation of
performance.
8. Preservation of the results obtained.

114. Identification of OOS: Reports of FuIl-
Scale Investigation: When an initial analysis
does not confirm the errors caused by OOS result from
lab investigations, full scale investigations with proper
design should be performed. The identification of the
source of the errors and the action taken for the
correctness are the main objectives of this
investigation. The following are the important aspects
of OOS results identification with respect to full scale
investigation.
1. Review of manufacturing, production and sampling.
2. Review of lab investigation result.
3. Supplementary laboratory testing procedure.

115. Review of Manufacturing, Production
and Sampling:-
To find out the OOS results, review of
manufacturing, production and sampling
is very important. The errors and
problems should be investigated and
identified. The documents and records of
manufacturing and production should be
reviewed. The investigations should be
reviewed through a well-documented
manner.

116. Review of Lab Investigation ResuIt:-
It contains the following information:
# Cause of the investigation.
# Review and summary of manufacturing
process (which may have identified as
malfunctioned or cause of OOS results).
# Review of previous results to find out the
possible causes of OOS results.
# Review of documented records to analyze the
possible factors of wrong results.
# The actions taken to correct the process.

117. Supplementary Laboratory Testing Procedure:
To investigate OOS results in full scale, additional
laboratory testing may be performed. This includes
Re-testing and Re-sampling.
In Re-testing, a portion of original samples are tested
again according to the standard procedures. The
results are kept in a well documented manner. This
process helps to find out the problems encountered
due to error in instruments, process, dilution or
sample handling.
In Re-sampling, a specimen is collected from any
additional units from original sample or a new sample
is prepared from the same batch and analyzed further.

118. Analysis of Investigated
Results:-
The reported results should be
analyzed and interpreted to find
out the possible, probable and
actual causes of OOS results.
Some possibilities are discussed
below:

120. Change Control:-
Introduction:-
In pharmaceutical industry change control
is an important part of quality assurance.
The changes proposed and made in any
procedure or process should be reviewed,
established, documented and approved by
the concerned authorities. Change control
is the system to implement this approved
change to confirm the regulatory
requirements.

121. Defination:- Change control can be defined as a formal
system by which qualified representatives of
appropriate disciplines review proposed or actuaI
changes that might affect the validated status of
facilities, systems, equipment or processes. The intent
is to determine the need for action that would ensure
and document that the system is maintained in a
validated state.
Function: Any change in manufacturing process.
equipment, materials used that may cause alteration in
product quality should be validated.
The main functions of change control are:
1. Identification of the changes made.
2. Review of the change.
3. Approval of the change.

122. 4. Validating the changes which can alter the
product quality, regulatory or GMP requirements.
5. Analysis of the change and monitoring of the
impact of change.
Area of Change:
1. Manufacture: Following changes are
concerned:
# Raw materials,
# Equipments,
# Process/parameters,
# Testing/validation procedures,
# Packaging materials,
# Cleaning process.

123. 2. Quality control and quality assurance:
Following changes are considered: # Quality testing
parameters,
# Sampling size,
# Validation process,
# Specifications of raw materials, intermediates and
final product,
# Documentation,
# Standard operating procedures (SOPs).
Research and development: It includes the
change in:-
# Manufacturing process (any addition of elimination of
steps),
# Raw materials (any addition of omission of the

124. # Specifications of raw materials, intermediates and
final product,
# Quantitative aspects of raw materials and finished
products,
# Manufacturing conditions and storage conditions,
# Testing/validation procedures.
4. Engineering: # Equipment used,
# Validation of the equipment,
# Parts of equipment,
# Working and design layout,
# Software/ Hardware or Change in any program.
5. Marketing.

125. Written Procedures & Documentation:
Procedures in writing should be kept at the proper
place to describe the changes made related to the
materials, equipment and method of manufacturing or
testing conditions or any other change that can affect
the quality of the product. Standard operating
procedure (SOP) and records of change control
documents are required for the documentation. The
Change Control Form (CCF) is an important
documentation part of change control. It contains the
form related to initiate department for the proposed
change, proposed change details, comments from QA
Head, category of the changes, supportive documents,
management review form and assessment of CCF.

127. GLP (Good Laboratory Practice):-
Introduction:- GLP was introduced for the non-clinical
safety studies in 1976. In late 90's this practice along with
OECD (Organization for Economic Co-operation and
Development) was accepted as industry standards. GLP has
been introduced due to the poor and dishonest practice in
laboratory in the early 70's. The poor lab practices include
wrong caIibration of equipments, inaccurate test systems and
accounts. In 1983, Industrial Bio Test Laboratory (1952-1978)
of New York was found guilty as it provided wrong and
inaccurate research data to the Government. The company
provided fake, fabricated and concealed data of the tests on
rodents involving Trichlorobanilide (deodorant soap
additives), Naprosyn (arthritis drug), Sencor (Herbicide) and
Nemacur (Pesticide).

128. Definition:- According to Valcarcel M., GLP is a set of
rules, operating procedures and practices
established by an organization to ensure the quality
and accurate results in a laboratory practice. In this
practice, the given organization sets the principles
and the |aboratory works are planned, operated,
overlooked and reported.
Fundamentals of GLP: A. Resources:
It includes the following:
1. Organization and Management: Management
has the overall responsibility for the implementation
of both good science and good organization within
their institutions.

129. Good science includes proper definition of experimenta|
design, knowIedge of scientific principles, documentation
of experimental and environmental variables, complete
evaluation of the results and reporting of results.
Whereas, good organization should provide proper
planning of studies, qualified skilled personnel, adequate
facilities, infrastructures, proper conduction of studies and
veriflcation process for the study results.
2. Personnel: The detailed records should be
maintained for every individual staff of the institution. The
records include the detail curriculum vitae, training
records and their job descriptions. These records should
meet the GLP requirements and these

130. are maintained to establish that every staff has the
competence, education, experience and training to
perform the tests.
3. Avallability of Facilities: Adequate facilities with
state-of-the-art infrastructure should be provided by
the institution and management to ensure the
validation of the studies. The cleaning, maintenance
and documents of the site plan should satisfy the
guidelines.
4. Availability of Equipments: Adequate
equipments must be available for the study in the
organization. The suitability of the equipment and
calibrated instruments should be provided by the
management.

131. C. Characterization:-
It includes:
1. Test Items: It may be an active ingredient for a
medicine, a pesticide, a food additive, a vaccine, an
industrially used chemical, a biomass or an extraction from
plants. These items are characterized by analytical profile
like chemical identification test, solubility, stability etc. The
test items should be stored properly to avoid the
contamination.
2. Test Systems: The test systems could be the animals,
bacteria, cells, organs and plants. Sometimes they may be
analytical equipments also. The test systems shou|d be
handled in such a way that it must comply with the GLP
guidelines and with the national animal welfare law.

132. C. Rules:-
1. Study Protocols: The study plan or protocol
describes how the study is designed and how it is to
be conducted. The plan should include the expected
time frame of the study.
2. Written Procedures: Written procedures are
often known as SOPs (Standard Operating
Procedures). SOPs provide the instructions how each
technical procedure should be performed, how to
ensure the sound organization of the study,
environmental variables and data.

133. D. Results:-
It includes raw data, final reports and data archiving.
1. Raw Data: The original record and the data needed
for the reconstruction should be recorded. The raw data
should include 'what‘ was done, 'how' it was done,
'when’ the work was done and ’who’ performed the
work. The recorded data should clarify the process by
which it is generated and should confirm the process has
been performed as per the guidelines and SOPs.
2. Final Results: Final results are the responsibility of
the study director. These results should describe the
study accurately and the scientific interpretation. The
results

134. should reflect accurately the raw data. The
review and audit of these reports should be
done. All accepted changes in the results
approved by the reviewer should be
incorporated before the finalization of the
results.
3 Archives: Archiving is a safe depositing of
all information. It is considered to be a center
for the compilation and distribution of summary
documents. The archiving of document helps
the reconstruction of studies performed earlier.

135. E. Quallty Assurance:-
The requirement of the quality assurance is to
validate the experimental results. Quality
assurance unit (QAU) or simply QA must
review all phases of preclinical research,
organization framework, staff documents,
study procedures and SOPs. The internal audits
and inspections should be performed by the
QA officers. The QA performs the study-based
audit, facility and systems-based inspection
and process-based inspections.

136. GLP Principles:-
GLP principles are set of organizational
requirements. GLP is a regulation covering the
quality management of non-clinical safety studies.
The aim of the regulation is to encourage scientists
to organize and perform their studies in a way
which promotes the quality and validity of the test
data. GLP deals with the following issues:
# The facility provided by the organization.
# Efficient and trained personnel.
# Quality of validated equipment and reagents.
# Predetermined study design.

137. # SOPs, process validation and test procedures.
# Correctness of the results.
# Quality assurance laboratory (QAL) and Quality
assurance program (QAP).
# Recorded and documented results and their storage.
The organizations should fulfill all the criteria
to provide all the facilities for the good practice in
laboratory. The personnel should have enough
knowledge about the principles and working of the
practices. In the elements of GLP, SOP is an important
part with respect to quality assurance. To maintain the
productivity of the result, a well documented SOP is
required; moreover, the personnel should have complete
information mentioned in SOPs.

138. SOPs define the complete process flow and work
steps which help to achieve the accurate and precised
results. Validated modern equipments and adequate
facilities should be provided by the organization to
maintain the good practice in laboratory. The
complete specifications and storage of reagents and
materials should be provided. QA laboratory should
have the proper test procedures (physical, chemical
and biological) and characterized data for both the
test and reference materials. Quality assurance unit
(QAU) bears the responsibility to assure the GLP and
this unit is attached with QAL and QAP. The audit of
the

139. laboratory and verification of the quality parameters
are the major responsibilities of the QAU. The
reported study results should be stored and retained
with well documented manner.
Aim of GLP:-
1. GLP helps to reduce the number of false negatives
arising from the studies. False negative result for a
toxicity study falsely intimated that the test item is
not toxic, but in real the item is toxic.
2. GLP also helps to reduce the chance of false
positives. In the case of a non-clinical safety study,
the results wrongly predict that the test item is toxic,
when really it is not.

140. 3. GLP promotes international
recognition of study data. When studies
are performed according to OECD GLP
principles, then the acceptability and
reliability of the data are recognized in
the international level by the OECD
member states.
*******

141. References:-
1. A Textbook of Industrial Pharmacy-II,
By, Dr. K. P. Sampath Kumar,
Dr. Debjit Bhowmik, Rishab Bhanot, Shambaditya
Goswami, Nirali Prakashan,
Page No. 4.1 to 4.28.
2. A Textbook of Industrial Pharmacy-II,
By, Dr. Ashok A. Hajare, Nirali Prakashan,
Page No.5.1 to 5.50.
3. Pharmaceutical Quality Management System,
By, Mr. Dhawal Rajdev, R K University.
4. www.google.com.

142. Thank you