The document discusses quality management systems in the pharmaceutical industry. It states that quality management systems (QMS) rely on regulations and guidelines to ensure effective quality control in pharmaceutical companies. The International Council for Harmonization (ICH) guideline provides a model for an effective QMS and is intended to assist manufacturers in maintaining quality and safety of their products and services. QMS is an important aspect of the pharmaceutical industry for regulating quality and safety.

1. Quality Management
System

2. 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

3. Basics of quality management system
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 analyze definition some common words like...
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.

4. 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.
Dimensions of Quality
 Performance
 Feature
 Reliability
 Perceived
 quality
 Aesthetics
 Durability
 Conformance
 serviceability

5. 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.

6. Scope of Pharmaceutical QMS:
1.Pharmaceutical 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.

7. 3. Commercial Manufacturing:
 Acquisition and control of materials.
 Provision of facilities, utilities and equipment
 Production (including packaging and labeling).
 Quality control and assurance.
ICH Guidelines: 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.
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).

8. QSEM

9. 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:

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

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

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

13. 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.
4. Personnel:
(a) Improper working conditions.
(b) Inadequate training and understanding.
(c) Lack of interest and emotional upheavals.
(d) Dishonesty fatigue and carelessness.

14. Control of Quality Variation: 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

15. Total Quality Management
(TQM)

16. Total Quality Management (TQM)
Introduction:
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
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.

17. 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.
Characteristics :
 Technological strength, hardness,
 Time – oriented, Reliability, maintainability – availability
 Contractual Guarantee.

18. Define
Measure
Analyse
Improve
Control
GOAL OF TQM

19. Kano Model

20. Six basic concepts of TQM:
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
5. Treating suppliers of the business and production process.
6. Establishing the performance measures

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

22. 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

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

24. Quality Cost:
 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.

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

26. 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

27. 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).
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.

28. Objectives of QbD: The main objectives of QbD are as
follows:
1. Increasing manufacturing efficiency.
2. Increasing the efficiency in product development.
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.

29. 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.
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.

30. 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.
5.Drug product quality criteria.
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.

31. 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
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, equipment's and input materials with potential that
have an impact on product quality.

32. 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:
1.Control 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).

33. Quality by Design ( QbD )

34. SIX SIGMA

36. Six sigma
 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.
History:
 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 Motorola

37. Definition :
 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

38. • Define
• Measure
• Analyze
• Improve
• Control
• Define
• Measure
• Analyze
• Design
• Verify

39. DMAIV Explanation
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, pare to 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.

40. 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.
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.

41. Plan
DO
Check
Act
Improvement cycle – PDCA cycle

42. DMADV Explanation
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
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).

43. Statistical view of Six Sigma

44. Implementing Roles
 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).

45. Implementing Methodologies

46. Six Sigma Companies

47. Focus of Six Sigma
 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.
Criticisms
 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

49. ISO 9001:2008 CERTIFICATION

50. International Organization for standardization (ISO)
A network of national standardization bodies from over 160 countries with
Nigeria inclusive.
Based in Geneva Switzerland. Standard Organization of Nigeria (SON) is a
Technical Committee (TC) in ISO, meaning participates fully developing ISO
standards.
ISO management standards
Selected 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 & Safety
ISO 28000 Supply chain Security
ISO 27001 Information security

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

52. 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.

53. Principle 2 – Leadership
Applications Benefits
 Perfect understanding of the More enthusiastic workers.
organization short and Increased employee loyalty
long term goals and objectives. Effective communication system
 Setting realistic and is enabled
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

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

55. 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.
In put Out put
Requirements Satisfaction

56. 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.

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

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

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

60. Management Service Division
ISO 14001:2004 Overview

61. Why was ISO 14000 revised?
 It was due for revision, ISO requires that all management system
standards undergo periodic revision.
 To enhance compatibility with ISO 9001:2000
 Revision allows opportunity to clarify requirements in the 1996
version and incorporate needed changes.
ISO 14001:2004
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.
Scope The organization shall define and document the scope of its
environmental management system.

62. 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,

63. 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
environmental objectives
ISO 14001: 2004
a)is documented, implemented and maintained
b)is communicated to all persons working for or on behalf
of the organization.
c)is available to the public

64. 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 modified activities
products
b) to determine those aspects that have or 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.

65. 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 continual improvement.
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

66. 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.
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,
reporting to top management on the performance of the environmental
management system for review, including recommendations for
improvement.

67. 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.
c) The organization shall decide whether to communicate externally
about its significant environmental aspects, and shall document its
decision.
d) If the decision is to communicate, the organization shall establish
and implement a method(s) for this external communication.

68. 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.

69. 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

70. NABL Accreditation
NATIONAL ACCREDATION BOARD FOR
TESTING AND CALIBRATION
LABORATORIES (NABL)

71. What is NABL ? 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.
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.

72. CONCEPT: 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.

73. Benefits of Accreditation:
 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
 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.

74. Types of Laboratory can seek Accreditation:
 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.

75. CALIBRATION
LABORATORIES
MEDICAL
LABORATORIES
PROFICIENCY
TESTING
PROVIDERS
REFERENCE
MATERIAL
PRODUCERS
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
Hematology &
Immunohematology
Microbiology &
Serology
Histopathology
Cytopathology
Genetics
Nuclear Medicine (in-
vitro tests only)
Testing
Calibration
Medical
Inspection
Chemical Composition
Biological & Clinical
Properties
Physical Properties
Engineering Properties
Miscellaneous
Properties
TESTING
LABORATORIES

76. 10 Step Approach To Accreditation
 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
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.

77. Step 2: Quality Policy & Objectives
 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
Step 3: Gap Analysis
 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.
Step 4: Documentation / Process Design
 Quality Manual
 Functional Procedures
 Work Instructions
 System Procedures
 Formats

78. Step 5: Documentation / Process Implementation
 Work–shop on process / document implementation as per ISO 17025 requirements.
 Departmental / Individual assistance in implementing the new processes / documents.
Step 6: Internal Audit
 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.
Step 7: Management Review Meeting
 Quality Policy & Objectives
 Results of internal audit
 Results of supplier evaluation
 Results of customer complaints
 Results of customer feedback etc.

79. Step 8: Shadow Audit
 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.
Step 9: Corrective – Preventive Actions
 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.
Step 10: Final Certification Audit
 Upon completion of various stages of accreditation audit, the audit, your
organization will be awarded accreditation.


80. 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.

81. 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.

82. 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.

83. 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 solvent's, reagents, standard
solutions.
6. Knowledge of the analyst regarding investigation.
7. Method validation and evaluation of performance.
8. Preservation of the results obtained.

84. 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.

85. 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.

86. Review of Lab Investigation Results:-
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.

87. 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.

88. 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:
Analysis of Investigated Results

89. Analysis of Investigated Results

90. 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.
Definition:- Change control can be defined as a formal system
by which qualified representatives of appropriate disciplines
review proposed or actual 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.

91. 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.
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

92. Area of Change:
1. Manufacture: Following changes are concerned:
 Raw materials,
 Equipment's,
 Process/parameters,
 Testing/validation procedures,
 Packaging materials,
 Cleaning process
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).

93. 3. Research and development: It includes the change in:-
 Manufacturing process (any addition of elimination of steps),
 Raw materials (any addition of omission of the product )
 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.

94. 5.Marketing: 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.

96. 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
calibration 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).

97. 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
laboratory works are planned, operated, overlooked and reported.
Fundamentals of GLP:
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. Good science includes proper
definition of experimental design, knowledge 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 verification process
for the study results

98. 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 are maintained to establish that every
staff has the competence, education, experience and training
to perform the tests.
3. Availability 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.

99. 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 should be
handled in such a way that it must comply with the GLP
guidelines and with the national animal welfare law.

100. 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.

101. 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 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.

102. 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.
E. Quality 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.

103. 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.
 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.

104. 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 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.

105. 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.
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.

106. Thank you