The document provides a comprehensive overview of quality management systems (QMS) particularly in the pharmaceutical and biotech industries, emphasizing the importance of maintaining product quality, regulatory compliance, and customer satisfaction. It discusses key concepts such as the ISO 9000 series, total quality management (TQM), good manufacturing practices (GMP), and risk management frameworks. The article also outlines the roles and objectives of QMS, including procedures for corrective and preventive actions, change control, and the integration of various quality practices to enhance operational efficiency.

1. Quality Management
Systems: An Overview
SK
Dr. Smita Kumbhar
DR. SMITA KUMBHAR (M. Pharm. PhD)
Associate Professor,
HOD, Pharmaceutical Regulatory Affairs Department,
Sanjivani College of Pharmaceutical Education and
Research (Autonomous), Kopargaon, Maharashtra, India

2. Concept of Quality
 Definition of Quality: Degree of Excellence
 The degree to which a product or service meets
specified requirements and customer expectations.
 Pharmaceutical products must meet the identity,
strength, safety, purity, and efficacy.
 Key Elements: Accuracy, reliability, durability,
compliance with standards, and customer satisfaction.
 Importance: High-quality standards prevent errors,
ensure safety and efficacy of products, and maintain
regulatory compliance.
SK
Dr. Smita Kumbha
SK
Dr. Smita Kumbhar

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Dr. Smita Kumbhar
Dimension Meaning and Example
Performance Primary product characteristics, such as
brightness of the picture
Features Secondary product characteristics and added
features, such as remote control
Conformance Meeting specifications or industry standards,
workmanship
Reliability
Consistency of performance over time, average
time for the unit to fail
Durability Useful life, includes repair
Service Resolution of problems and complaints, ease of
repair
Aesthetics Sensory characteristics, such as exterior finish
Reputation Past performance and other intangibles, such as
being ranked first
Dimensions of Quality

4.  Implementation of quality policies, as per WHO, it is
aspect of management function that determines
and implements the ‘Quality Policy’.
 Quality management systems (QMS) are a critical
aspect of ensuring product quality and customer
satisfaction. They establish a framework for
consistent processes, documented procedures, and
ongoing monitoring to ensure that products or
services meet predefined standards.
 QMS are designed to achieve a balance between
meeting customer expectations, regulatory
requirements, and organizational goals, ultimately
leading to improved efficiency and profitability.
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Dr. Smita Kumbhar
Concepts and Practices in Pharmaceutical and Biotech Industries

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Dr. Smita Kumbhar
PDCA
Plan-Do-Check-Act (PDCA)9
applies to all processes. Each ISO
9001 main clause starts with a
‘planning’ activity, has a ‘doing’
activity, has a ‘checking’ activity
(measurement may be implied)
and has an ‘acting’ activity
(improvement may be applied).
QMS
Building a quality management system
(QMS) from scratch can be challenging,
especially when the appropriate regulatory
standards or compliance guidelines are not
followed. Management system standards
make best practices available to
organizations of all sizes, in all sectors. Any
organization can implement a system to
improve efficiency and effectiveness and
manage its way of doing things by:
• ensuring nothing important is omitted
• clearly defining who is responsible
• describing what to do, why, when, how and
where
• ensuring people are not just “doing their
own thing”
• ensuring the organization goes about its
ISO 9000 series
The ISO 9000 series, originally
published in 1987, was based on
the British Standards Institution’s
(BSI) BS 5750 series of standards.
ISO 9001 covers both product
quality assurance (providing
confidence that quality
requirements will be fulfilled)
and enhanced customer
satisfaction.
ISO 9001 is based on the eight-
quality management principles:
1. process approach
2. system approach to
management
3. continual improvement
4. factual approach to decision
making
5. mutually beneficial supplier
relationship
6. customer focus

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QMS
TQM GMP
cGMP
GDP
GALP
GLP

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Relationships and Integration
 QMS: The central framework encompassing all practices.
 QMS serves as the overarching framework within which TQM, GMP, cGMP, GLP,
GDP, and GALP operate. A well-implemented QMS ensures that all these
practices work together seamlessly.
 TQM: The cultural and philosophical approach integrated within QMS.
 TQM can be seen as a philosophy that emphasizes continuous improvement
and customer satisfaction, often forming the cultural foundation of an
organization's QMS.

11.  GMP, GLP, GDP, GALP: Specific good practices that fall under the umbrella of QMS.
 cGMP: An updated version of GMP emphasizing the current best practices.
 GMP and cGMP are subsets of QMS that focus specifically on manufacturing practices to
ensure product quality and safety.
 GLP is a subset of QMS focused on laboratory practices, ensuring the reliability and
integrity of non-clinical study data.
 GDP is a subset of QMS concerned with maintaining product quality throughout the supply
chain.
 GALP integrates with GLP and QMS to ensure the accuracy and reliability of data produced
by automated laboratory systems.
Relationships and Integration
SK
Dr. Smita Kumbhar

12. Quality Management Systems (QMS):
 Definition of Quality Management Systems
(QMS): A set of policies, processes, and
procedures required for planning and execution
in the core business area of an organization.
 Importance of QMS: Ensures consistent quality,
compliance with regulations, reduces waste,
increases efficiency, and improves customer
satisfaction in the pharmaceutical and biotech
industries. SK
Dr. Smita Kumbha
SK
Dr. Smita Kumbhar

13. Quality Management Systems (QMS)
 QMS is a formalized system that documents processes, procedures, and
responsibilities for achieving quality policies and objectives. It helps coordinate and
direct an organization’s activities to meet customer and regulatory requirements
and improve its effectiveness and efficiency on a continuous basis.
 QMS can incorporate elements of TQM but is often more structured and
formalized.
SK
Dr. Smita Kumbhar

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Objectives of Quality Management System (QMS)
Objective Description
Ensure Product Quality Maintain the quality, safety, and efficacy of products.
Regulatory Compliance Adhere to regulatory standards like FDA, EMA, and WHO.
Customer Satisfaction Deliver reliable products to meet customer expectations.
Process Efficiency Streamline operations for consistent performance.
Risk Management Identify and mitigate risks in production and distribution.
Document Control Maintain accurate and organized records.
Training and Competence Ensure staff are well-trained and skilled.
Continuous Improvement Regularly enhance processes and systems.
Product Traceability Track and trace products throughout the supply chain.
Complaint Handling and CAPA Address complaints and implement corrective actions effectively.
Audit Readiness Stay prepared for audits and inspections.
Sustainability Support eco-friendly manufacturing and distribution practices.

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Dr. Smita Kumbhar
Principle Description
Customer Focus Meeting customer requirements and striving to
exceed their expectations.
Leadership Establishing unity of purpose and direction to
create a conducive environment for quality.
Engagement of
People
Ensuring that all employees are competent,
empowered, and engaged in delivering quality.
Process
Approach
Managing activities as processes to achieve
consistent and predictable results.
Improvement Focusing on continuous enhancement of products,
processes, and systems.
Evidence-Based
Decision Making
Making decisions based on the analysis of data and
information.
Relationship
Management
Maintaining mutually beneficial relationships with
stakeholders for sustained success.
Key Principles of a Quality Management System (QMS)

16. Total Quality Management (TQM)
 Definition: TQM is the ‘ART of Managing the whole to
achieve excellence’.
 “TQM is defined as both a philosophy and a set of
guiding principles that represent the foundation of a
continuously improving organization. It is the
application of quantitative methods and human
resources to improve all the processes within an
organization and exceed customer needs now and in
the future.”
 Principles: Customer focus, continuous improvement,
employee involvement, process approach, and data-
driven decision making.
 Benefits: Enhanced product quality, improved SK
Dr. Smita Kumbha

17. Total Quality Management (TQM)
Customer Focus
TQM prioritizes understanding and meeting
customer needs and expectations. It involves
actively seeking feedback and incorporating it into
product development and service delivery.
Employee Empowerment
TQM empowers employees at all levels to
contribute to quality improvement. It fosters
a culture of ownership and responsibility,
encouraging teamwork and collaboration.
Process Improvement
TQM emphasizes continuous process
improvement through data analysis, problem-
solving, and implementation of corrective actions.
It seeks to eliminate waste, optimize efficiency,
and enhance performance.
Leadership Commitment
TQM requires strong leadership commitment to
drive quality initiatives. Leaders must champion
the principles of TQM, provide resources, and
create a supportive environment for quality
excellence.
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Dr. Smita Kumbhar

18. Origin of Total Quality Management
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19. The Total Quality Management Framework
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Quality Guru Key Years Main Contributions
Walter A. Shewhart 1920s Developed statistical process control (SPC) and control charts to monitor process
variability.
W. Edwards Deming 1950s Introduced the "Plan-Do-Check-Act" (PDCA) cycle; emphasized management's role in
quality improvement.
Joseph M. Juran 1950s
Defined quality as "fitness for use"; introduced the Juran Trilogy: quality planning,
control, and improvement.
Armand V. Feigenbaum 1951
Introduced the concept of Total Quality Control, emphasizing organization-wide quality
responsibility.
Philip B. Crosby 1979
Advocated for "zero defects" and defined quality as conformance to requirements;
authored "Quality is Free."
Kaoru Ishikawa 1960s Developed the cause-and-effect diagram (Ishikawa or fishbone diagram); promoted
quality circles for worker involvement.
Genichi Taguchi 1950s Developed Taguchi methods focusing on robust design and the Taguchi loss function to
improve quality.
Shigeo Shingo 1960s Introduced poka-yoke (mistake-proofing) and the Single-Minute Exchange of Die
(SMED) system to reduce setup times.
Taiichi Ohno 1970s Developed the Toyota Production System, which became the foundation for lean
manufacturing principles.
Quality Gurus, Their Contributions

21. Total Quality Management (TQM)
 TQM is a comprehensive management approach that focuses on long-term
success through customer satisfaction. It involves the participation of all
members of an organization in improving processes, products, services, and
the culture in which they work.
SK
Dr. Smita Kumbhar

23. Elements of Total Quality Management
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Dr. Smita Kumbhar

24. Good Manufacturing Practice (GMP)
 GMP refers to the practices required to conform to the guidelines recommended by agencies that
control the authorization and licensing of the manufacture and sale of food and beverages,
cosmetics, pharmaceutical products, dietary supplements, and medical devices.
 GMP guidelines provide minimum requirements that a manufacturer must meet to ensure that
their products are consistently high in quality, from batch to batch, for their intended use.
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Dr. Smita Kumbhar

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Good Manufacturing
Practice
ICH: Q7
US FDA: 21 CFR Part 210 –
cGMP General
211- cGMP for Finished
Pharmaceuticals
WHO- Technical Report
Series-937
PIC/S- Recommendations
PE-009
EU-Part1, Annex5
EU-Part11, Chapter 13

27. Current Good Manufacturing Practice (cGMP)
 cGMP emphasizes that manufacturing practices must be up-to-date and use the
latest technologies and systems to ensure product quality. The "current" part
implies that companies must stay abreast of current standards.
 cGMP is a dynamic version of GMP that requires manufacturers to use the latest
and most effective quality management systems.
SK
Dr. Smita Kumbhar
CGMP Attributes: (SISPQ)
S – Safety
I – Identity
S – Strength
P – Purity
Q – Quality

28. Good Laboratory Practice (GLP)
 GLP ensures the quality and integrity of non-clinical laboratory studies
such as the testing of chemicals and biological products. It is a set of
principles intended to assure the quality and integrity of non-clinical
laboratory studies.
 GLP covers aspects like study planning, execution, monitoring, recording,
and reporting.
SK
Dr. Smita Kumbhar

29. Good Distribution Practice (GDP)
 GDP ensures that the quality of pharmaceutical products is maintained
throughout the distribution process. It covers the procurement, purchasing,
storage, distribution, transportation, and handling of medicinal products.
 GDP ensures that products are consistently stored, transported, and
handled under suitable conditions as required by the marketing
authorization or product specification.
SK
Dr. Smita Kumbhar

30. Good Automated Laboratory Practice (GALP)
 GALP applies to automated laboratory systems and ensures the accuracy,
reliability, and consistent intended performance of laboratory data produced by
automated systems.
 GALP encompasses principles and procedures for managing laboratory systems
to assure the quality and integrity of electronic data.
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Dr. Smita Kumbhar

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Dr. Smita Kumbhar

32. Quality by Design (QbD)
1
Define Target Product Profile
QbD begins with a clear understanding of the target product profile,
encompassing its intended use, critical quality attributes, and desired
performance characteristics.
2 Identify Critical Quality Attributes (CQAs)
CQAs are the key quality characteristics that must be controlled to
ensure product quality and efficacy. They are identified through a
thorough understanding of the product's mechanism of action,
formulation, and manufacturing processes.
3 Design Control Strategies
QbD involves designing control strategies to ensure that CQAs are
consistently met throughout the product lifecycle. This includes
establishing specifications, setting limits, and implementing monitoring
procedures.
4 Risk Management
QbD incorporates a risk-based approach to quality management,
identifying potential risks and implementing appropriate mitigation
strategies to minimize the probability of product failure or deviations
from quality standards.
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Dr. Smita Kumbhar

33. Quality by Design (QbD)
 Introduction: QbD is a systematic approach to
pharmaceutical development that emphasizes
designing quality into products from the
beginning.
 Objectives: To build quality into products and
processes, ensure consistent delivery of high-
quality products, and reduce risks.
 Steps: Define objectives, identify critical
quality attributes (CQAs), determine critical
process parameters (CPPs), and control
strategies. SK
Dr. Smita Kumbhar

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Aspect Risk Management Risk Assessment
Definition
Systematic process of identifying, evaluating, and
mitigating risks to ensure quality objectives are met.
Evaluation of specific risks within processes,
products, or compliance to determine impact and
likelihood.
Scope Broad, covering overall quality systems, processes,
and strategic objectives.
Focused, assessing specific risks within defined areas
or processes.
Steps
1. Risk Identification
2. Risk Analysis
3. Risk Evaluation
4. Risk Mitigation
5. Risk Monitoring and Review
1. Define Scope
2. Identify Hazards
3. Analyze Risks
4. Evaluate Risks
5. Develop Controls
6. Document and Review
Outcome Comprehensive risk management strategy integrated
into QMS.
Identification and prioritization of risks with
actionable controls.
Approach Proactive and preventive across the system. Analytical and focused on specific scenarios.
Examples Risk-based decision-making in ISO 9001 or ISO 13485
compliance.
Tools like FMEA, HACCP, or risk matrices for specific
assessments.
Frequency Ongoing and integrated into daily operations. Conducted periodically or when changes occur.
Purpose Minimize risks to processes, products, and services to
ensure quality and compliance.
Assess and control specific risks to maintain process
or product integrity.
Risk Management and Risk Assessment

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35
Process
Development
Control Strategy
Development
Continual
Improvement
Quality Risk Management Process (Q9)

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Role of Quality Risk Management in
Development & Manufacturing

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CAPA (Corrective and Preventive Action) is a systematic approach used in
quality management systems to address issues and prevent their recurrence
or occurrence.
1.Corrective Action:
1. Identifies the root cause of a problem or non-conformance.
2. Implements actions to eliminate the root cause and prevent recurrence.
2.Preventive Action:
1. Identifies potential issues or risks before they occur.
2. Implements actions to eliminate the root cause and prevent occurrence.
Steps in CAPA:
• Identify the problem or potential risk.
• Analyze the root cause using tools like RCA or 5 Whys.
• Develop and implement corrective and preventive measures.
• Monitor and verify the effectiveness of the actions taken.
CAPA (Corrective and Preventive Action)

38. Six Sigma Concept
DMAIC
Six Sigma employs a
structured problem-solving
methodology known as
DMAIC, which stands for
Define, Measure, Analyze,
Improve, and Control. This
process is used to identify,
analyze, and eliminate
defects in processes,
leading to significant
quality improvements.
Statistical Tools
Six Sigma relies heavily on
statistical tools and
techniques to analyze data,
identify root causes of
variation, and evaluate the
effectiveness of
improvement initiatives.
These tools help quantify
process performance and
measure the impact of
changes.
Lean Principles
Six Sigma incorporates
lean principles to eliminate
waste and optimize
processes. This includes
identifying and eliminating
non-value-added activities,
streamlining workflows,
and reducing cycle times.
SK
Dr. Smita Kumbhar

39. Six Sigma Concept
 Overview: Six Sigma is a data-driven methodology
aimed at reducing defects and variability in
processes.
 DMAIC: Define, Measure, Analyze, Improve, Control
– a systematic approach for process improvement.
 Application: Used to enhance quality, reduce
variability, and improve efficiency in pharmaceutical
manufacturing.
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Dr. Smita Kumbhar

40. Out of Specifications (OOS) and
Change Control
OOS Investigations
When an OOS result is obtained, a thorough investigation is conducted to
determine the root cause of the deviation. This typically involves reviewing
manufacturing records, laboratory data, and equipment logs to identify
potential sources of error.
Change Control
Change control procedures are established to manage modifications to
processes, formulations, or equipment. These procedures aim to ensure
that any changes are thoroughly evaluated, documented, and
implemented in a controlled manner to minimize the risk of impacting
product quality.
Corrective Actions
Corrective actions are implemented to address the root cause of the OOS
result and prevent recurrence. These actions may involve process
adjustments, equipment calibration, or training of personnel.
Documentation and Reporting
All aspects of OOS investigations, change control procedures, and
corrective actions are meticulously documented and reported. This
documentation provides a historical record of events and facilitates
continuous improvement initiatives. SK
Dr. Smita Kumbhar

41. Out of Specifications (OOS)
 Definition: OOS results occur when test results fall outside the specifications
or acceptance criteria established in drug applications or official compendia.
 Causes: Human error, instrument malfunction, method inadequacy,
environmental factors, and raw material variability.
 Guidelines: Regulatory procedures for investigating, documenting, and
resolving OOS results to ensure product quality and compliance.
SK
Dr. Smita Kumbhar

42. Change Control
 Definition: Change control is a formal
process to manage changes
systematically, ensuring no unintended
impact on product quality.
 Importance: Maintains product
consistency, ensures regulatory
compliance, and prevents disruptions
in production.
 Process: Change proposal, evaluation,
approval, implementation, and
documentation.
SK
Dr. Smita Kumbhar
Not requiring
control
Minor change Major change
No relevance to
GMP or
authorization
Influences a unit
requiring control
Influences product
quality or process
reliability
Significanc
e of change
•No relevance to
GMP or
authorization
•Amendment
•Review
•documentation
•Official license
•New approval
•revalidation
Possible
measures
(selection)
•Change to
working times
•Installation of
air conditioner
in
administrative
area
•Change in
purchase
procedure
•Replacement of
apparatus part of
the same design
•Change of cleaning
agent for floors
•Change of laundry
for work clothes
(non-sterile or
antibiotics area)
•Change of
manufacturer: other
synthesis route of a
starting material
(other impurities)
•Removal of
processes to another
site
•Change in the
product composition
•Change to the
process parameters
examples

43. Validation: Types, Qualification, and Validation Master Plan (VMP)
Type of Validation Description
Process Validation Demonstrates that a manufacturing process consistently
produces a product that meets predefined quality attributes.
Cleaning Validation Confirms that cleaning procedures effectively remove
residues and contaminants from equipment, preventing
cross-contamination.
Analytical Method Validation
Establishes the accuracy, precision, linearity, and other
performance characteristics of analytical methods used for
quality control.
Computer System ValidationVerifies that computer systems used in manufacturing or data
management meet quality standards and operate reliably.
SK
Dr. Smita Kumbhar

44. Validation
 Definition: Validation is the
documented process of
demonstrating that a
procedure, process, or activity
consistently leads to the
expected results.
 Purpose: Ensures product
quality, efficacy, and safety by
proving that systems and
processes work as intended.
SK
Dr. Smita Kumbhar

45. Types of Validation
 Process Validation: Ensures that manufacturing processes consistently produce products
meeting predetermined specifications.
 Cleaning Validation: Confirms that cleaning procedures remove residues to
predetermined levels of acceptability.
 Analytical Method Validation: Ensures that analytical methods are accurate, precise,
specific, and robust.
 Computer System Validation: Verifies that computer systems used in production and
quality control perform correctly.
 Equipment Validation: Confirms that equipment operates correctly and produces results
meeting specifications. SK
Dr. Smita Kumbhar

46. Types of Qualification
 Design Qualification (DQ): Documents that design specifications match user
requirements.
 Installation Qualification (IQ): Verifies that equipment is installed correctly.
 Operational Qualification (OQ): Ensures that equipment operates according to defined
specifications under various conditions.
 Performance Qualification (PQ): Confirms that the system consistently performs as
intended in the production environment.
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48. Validation Master Plan (VMP)
 Definition: A comprehensive document outlining
the approach and process for validation activities.
 Components: Includes validation strategy,
responsibilities, resources, and schedules for
validation activities.
 Importance: Provides a clear roadmap for
validation, ensuring systematic and compliant
validation processes. SK
Dr. Smita Kumbhar

49. Analytical Method Validation
 Definition: The process of proving that an analytical method is acceptable for its
intended purpose.
 Key Parameters: Accuracy, precision, specificity, linearity, range, robustness.
 Guidelines: Follow regulatory guidelines for method validation, including ICH
Q2(R1) for pharmaceuticals.
SK
Dr. Smita Kumbhar

50. Analytical Method Validation
Accuracy
Measures the closeness of the measured
value to the true value.
Precision
Reflects the reproducibility of
measurements when performed
multiple times under the same
conditions.
Linearity
Assesses the method's ability to produce
results that are proportional to the
concentration of the analyte over a
specified range.
Range
Defines the concentration range over
which the method provides reliable and
accurate results.
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Dr. Smita Kumbhar

51. Terms Used in Analytical Method Validation
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 Accuracy: Closeness of the test results to the true value.
 Precision: The degree of agreement between replicate measurements.
 Repeatability: Precision under the same operating conditions over a short time period.
 Intermediate Precision: Precision within a laboratory across different days, analysts, and equipment.
 Reproducibility: Precision between different laboratories.
 Specificity: Ability of the method to measure the analyte without interference from other components.
 Linearity: The ability to obtain test results that are directly proportional to the concentration of analyte.
 Range: The interval between the upper and lower levels that have been demonstrated to provide accurate
results.
 Limit of Detection (LOD): The lowest amount of analyte that can be detected but not necessarily quantified.
 Limit of Quantitation (LOQ): The lowest amount of analyte that can be quantitatively measured with suitable
precision and accuracy.
 Robustness: The method’s capacity to remain unaffected by small, deliberate variations in method
parameters.
 Ruggedness: The degree of reproducibility of test results under variable conditions, such as different
laboratories or analysts.

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 Calibration Curve: A plot used to establish the relationship between the concentration of the analyte and the detector
response.
 System Suitability Test (SST): Verifies that the analytical system is functioning properly before analysis begins.
 Bias: The difference between the average value obtained and the true value.
 Analyte: The substance being measured or analyzed.
 Matrix: The components of a sample other than the analyte.
 Signal-to-Noise Ratio: A measure used to determine the detectability of an analyte.
 Standard Deviation: A measure of the dispersion of data points around the mean.
 Coefficient of Variation (CV): The ratio of the standard deviation to the mean, expressed as a percentage.
 Selectivity: The extent to which a method can determine particular analytes in complex mixtures.
 Validation Protocol: A documented plan for conducting the validation process.
 Validation Report: A summary document that describes the validation process and its results.
 Cross-validation: Comparing the results of different analytical methods to check consistency.
 Forced Degradation Study: Tests the stability of an analyte under stressed conditions to validate the method’s stability-
indicating properties.
 Reference Standard: A well-characterized substance used to calibrate the system or evaluate the analyte’s
performance.

53. Validation of Utilities
 Importance: Validating utilities like compressed air, steam, water systems, and HVAC
ensures they meet quality and regulatory requirements.
 Compressed Air: Validation ensures air quality meets standards for production use.
 Steam: Validation confirms steam purity and quality for sterilization.
 Water Systems: Validating purity and quality of water used in production processes.
 HVAC: Ensures environmental control systems meet required specifications for
cleanrooms and production areas.
SK
Dr. Smita Kumbha

54. Validation of Utilities
(Compressed Air, Steam, Water,
HVAC)
1 Compressed Air
Validation of compressed air
systems focuses on ensuring
the purity, pressure, and flow
rate meet established
specifications, minimizing
contamination risks.
2 Steam
Validation of steam systems
involves verifying the purity,
pressure, and temperature
meet requirements, ensuring
the quality of steam used in
manufacturing processes.
3 Water Systems
Validation of water systems
encompasses verifying the
purity, microbial content, and
physical properties of water,
ensuring its suitability for
various applications.
4 HVAC
Validation of HVAC systems
involves confirming the
temperature, humidity, and
airflow meet specific
parameters, maintaining a
controlled environment for
manufacturing and storage.
SK
Dr. Smita Kumbhar

55. Cleaning Validation
 Definition: The process of proving the effectiveness and consistency of cleaning
procedures for equipment.
 Objectives: Ensure no cross-contamination, residues are within acceptable limits, and
cleaning procedures are reproducible.
 Steps: Develop a cleaning validation plan, conduct cleaning studies, analyze results, and
document findings.
 Acceptance Criteria: Establish limits for residues and contaminants, based on safety and
product quality.
SK
Dr. Smita Kumbhar

56. Cleaning Validation
1
Establish Cleaning Limits
Cleaning limits are defined based on acceptable levels of residues that do
not compromise product quality or safety. They are set according to
regulatory guidelines and product specifications.
2
Develop Cleaning Procedures
Detailed cleaning procedures are established, outlining the steps,
cleaning agents, and equipment used for effective residue removal.
These procedures are validated to ensure their effectiveness.
3 Conduct Cleaning Validation Studies
Validation studies are conducted to demonstrate that cleaning
procedures achieve the established cleaning limits. This involves
simulating worst-case scenarios and analyzing samples for residual
levels.
4 Document and Review
All aspects of cleaning validation, including procedures, studies, and results,
are meticulously documented and reviewed. This documentation provides a
historical record and supports ongoing improvement initiatives. SK
Dr. Smita Kumbha

57. The International Conference on
Harmonization (ICH) Process
 Overview: ICH brings together regulatory
authorities and industry to discuss scientific
and technical aspects of drug registration.
 Importance: Harmonizes regulatory
requirements to ensure safe, effective, and
high-quality medicines.
 Key ICH Guidelines: Provide comprehensive
guidance on quality, safety, efficacy, and
multidisciplinary topics. SK
Dr. Smita Kumbha

58. ICH Guidelines
 Quality Guidelines (Q-series): Focus on quality aspects like
stability testing, impurity testing, and Good Manufacturing
Practices (GMP).
 Safety Guidelines (S-series): Address safety concerns,
including carcinogenicity, genotoxicity, and reprotoxicity.
 Efficacy Guidelines (E-series): Cover clinical studies,
pharmacovigilance, and clinical safety data management.
 Multidisciplinary Guidelines (M-series): Include medical
terminology and electronic standards for the transfer of
regulatory information.
SK
Dr. Smita Kumbhar
ICH Q: Quality
Q1 Stability
Q2 Analytical Validation
Q3 Impurities
Q4 Pharmacopeias
Q5 Quality of Biotechnological
Products
Q6 Specifications
Q7 Good Manufacturing Practice
Q8 Pharmaceutical Development
Q9 Quality Risk Management
Q10 Pharmaceutical Quality Systems
Q11 Development and Manufacture
of Drug Substance
Q12 Life Cycle Management
Q13 Continuous Manufacturing of
Drug Substances and Drug Products

59. ISO 13485
 ISO 13485:2016 was published on 26 February 2016.
 Overview: ISO 13485 specifies requirements for a quality
management system for the design and manufacture of
medical devices.
 Key Elements: Risk management, process validation,
documentation, and regulatory compliance.
 Benefits: Ensures the safety and effectiveness of
medical devices, improves product quality, and
enhances customer satisfaction.
SK
Dr. Smita Kumbha
SK
Dr. Smita Kumbhar

60. ISO 13485
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Dr. Smita Kumbhar

61. Schedule MIII and Other CDSCO Regulatory Guidance
 Schedule MIII: Indian regulatory
requirements for the manufacture,
distribution, and sale of medical devices.
 CDSCO Guidance: Central Drugs Standard
Control Organization provides guidelines for
drug and medical device approval, ensuring
safety, efficacy, and quality.
 Importance: Compliance with Schedule MIII
and CDSCO guidelines ensures regulatory
approval and market access in India.
SK
Dr. Smita Kumbhar

62. SK
Dr. Smita Kumbhar
Quality Management System
(QMS)
- ISO 9001: Global standard for Quality Management
Systems.
- ISO 13485: Quality management systems for medical
devices.
- FDA 21 CFR Part 820: Quality system regulations for
medical devices.
- ICH Q10: Pharmaceutical Quality System.
- Schedule M: GMP requirements for pharmaceutical
manufacturing in India.
QMS encompasses the processes,
resources, and activities required to
meet quality objectives, ensuring that
products meet the necessary
standards of safety and quality.
Total Quality Management
(TQM)
- ISO 9000: International standards for QMS that
include TQM principles.
- ISO 13485: Quality management for medical devices
includes TQM concepts.
- FDA QSR 21 CFR Part 820: Implements TQM through
quality systems for devices.
- EPA: Encourages TQM practices for environmental
compliance and safety standards in manufacturing.
TQM focuses on continuous
improvement, customer satisfaction,
and employee involvement in all
aspects of quality control and
assurance within an organization.
Key Regulatory Guidelines
Category/Concept Key Regulatory Guidelines Description

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Dr. Smita Kumbhar
Six Sigma
- ISO 9001: General framework for quality management
including Six Sigma principles.
- FDA 21 CFR Part 820: Encourages Six Sigma tools in process
improvement.
- Six Sigma in Medical Device Industry (FDA Guidance):
Supports Six Sigma practices in the medical device industry.
- ICH Q9: Quality Risk Management, supports Six Sigma as a
risk management tool.
Six Sigma is a methodology that
uses statistical tools and data
analysis to eliminate defects and
variations in processes, aiming for
near-perfect quality (less than 3.4
defects per million).
Quality by Design (QbD)
- ICH Q8(R2): Pharmaceutical Development, emphasizes QbD in
drug development.
- ICH Q9: Quality Risk Management, promotes risk
management in design.
- FDA QbD: Encourages the use of QbD for new drug
applications.
- ICH Q10: Pharmaceutical Quality System, emphasizes QbD
principles in manufacturing.
QbD integrates quality into the
product development process from
the beginning, focusing on
designing products with built-in
quality to ensure consistency and
efficacy.
Key Regulatory Guidelines

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Dr. Smita Kumbhar
Out of
Specifications
(OOS)
- FDA 21 CFR Part 211: GMP regulations for OOS investigations
in pharmaceutical manufacturing.
- USP <1058>: Analytical procedures and OOS results in
pharmaceutical manufacturing.
- ICH Q2(R1): Validation of analytical methods, addressing OOS
scenarios.
- Schedule M: GMP regulations that deal with OOS in the
pharmaceutical industry.
OOS refers to results that fall outside
predefined limits or specifications,
which require thorough investigation
to identify root causes and prevent
recurrence.
Change Control
- FDA 21 CFR Part 820.70: Change control regulations for
medical devices.
- ISO 13485: Change control requirements for medical devices.
- ICH Q10: Pharmaceutical Quality System, change control is a
key principle.
- Schedule M (India): GMP guidelines for change control in
pharmaceutical manufacturing.
Change control ensures that any
modifications to systems, processes, or
products are documented, assessed,
and validated to avoid unintended
consequences and maintain compliance.
Key Regulatory Guidelines

65. SK
Dr. Smita Kumbhar
Key Regulatory Guidelines
Good
Manufacturing
Practice (GMP)
- FDA 21 CFR Part 211: GMP regulations for pharmaceutical
products.
- ICH Q7: Good Manufacturing Practice for Active
Pharmaceutical Ingredients.
- ISO 13485: GMP for medical devices.
- Schedule M (India): GMP requirements for pharmaceutical
manufacturing.
- WHO GMP Guidelines: Global GMP standards for
pharmaceutical manufacturing.
GMP refers to the practices and
guidelines required to ensure that
pharmaceutical products are
consistently produced and controlled
according to quality standards.
Current Good
Manufacturing
Practice (CGMP)
- FDA 21 CFR Parts 210 and 211: CGMP regulations for
pharmaceutical products.
- ICH Q7: CGMP guidelines for Active Pharmaceutical
Ingredients.
- ISO 13485: CGMP for medical devices.
- WHO CGMP Guidelines: Global CGMP standards for
pharmaceutical manufacturing.
CGMP refers to the minimum standards
for manufacturing processes, ensuring
that drugs and medical devices are
produced consistently and meet quality
standards.

66. SK
Dr. Smita Kumbhar
Key Regulatory Guidelines
Risk Management
- ISO 31000: Risk management guidelines for
organizations.
- ICH Q9: Quality Risk Management in pharmaceutical
industry.
- FDA 21 CFR Part 820: Risk management and controls
for medical devices.
- ISO 14971: Risk management for medical devices.
- Schedule M: Risk management for pharmaceutical
production.
Risk management in the
pharmaceutical industry involves
identifying, assessing, and controlling
risks to ensure safety, efficacy, and
compliance in drug production and
distribution.
Corrective and Preventive
Action (CAPA)
- FDA 21 CFR Part 820.100: Quality System Regulation
(QSR) on CAPA for medical devices.
- ISO 13485: Includes CAPA requirements for medical
devices.
- ICH Q10: Pharmaceutical Quality System, includes CAPA
guidelines.
- Schedule M (India): Provides CAPA guidelines for
pharmaceutical manufacturing.
CAPA is the process of identifying and
addressing non-conformances and
preventing their recurrence, ensuring
continuous improvement in manufacturing
and quality management systems.

67. SK
Dr. Smita Kumbhar
Key Regulatory Guidelines
Process Validation
- FDA 21 CFR Part 211.110: Process validation
requirements for pharmaceutical manufacturing.
- ICH Q7: GMP for active pharmaceutical ingredients,
includes process validation guidelines.
- ICH Q10: Pharmaceutical Quality System, process
validation recommendations.
- Schedule M: Process validation standards for drug
products in India.
Process validation is the documented
evidence that a manufacturing process
operates consistently within specified
limits and produces products of the
required quality.
Cleaning Validation
- FDA 21 CFR Part 211.67: Cleaning and sanitation
requirements in GMP regulations.
- USP <1072>: Cleaning validation in pharmaceutical
manufacturing.
- ICH Q10: Pharmaceutical Quality System, includes
cleaning validation requirements.
- Schedule M: Cleaning validation practices for
pharmaceutical manufacturing in India.
Cleaning validation ensures that
cleaning procedures are effective and
that residues of previous products do
not affect the quality of the next
product manufactured.

68. SK
Dr. Smita Kumbhar
Key Regulatory Guidelines
Good Laboratory Practice
(GLP)
- OECD GLP Principles: Guidelines for Good
Laboratory Practice in non-clinical safety studies.
- FDA GLP: Regulations for Good Laboratory
Practices in the United States.
- ICH GLP: International guidelines for GLP.
- Schedule L (India): GLP guidelines for
laboratories involved in testing and research.
GLP refers to a set of principles
intended to assure the quality and
integrity of non-clinical safety data,
particularly in the pharmaceutical and
chemical industries.
Good Automated Laboratory
Practice (GALP)
- OECD GALP: Guidelines for automated laboratory
systems and data integrity.
- FDA GALP: FDA regulations for automated laboratory
systems.
- Schedule L (India): Guidelines for automated laboratory
practice in pharmaceutical testing.
GALP involves the use of automated
laboratory systems that meet the
required standards of performance, data
integrity, and traceability in regulated
environments.

69. SK
Dr. Smita Kumbhar
Key Regulatory Guidelines
Good Distribution Practice (GDP)
- EU GDP Guidelines: Guidelines for the distribution
of medicinal products for human use.
- WHO GDP Guidelines: World Health Organization
guidelines for pharmaceutical distribution.
- FDA Drug Distribution Guidelines: Guidelines for
distribution, focusing on storage, transportation,
and handling.
- Schedule M: Indian GMP guidelines related to
distribution practices.
GDP ensures that medicinal products are
consistently stored, transported, and
handled to maintain their quality
throughout the distribution process.
Data Integrity
- FDA 21 CFR Part 11: Electronic records and
signatures, emphasizing data integrity.
- ICH E6: Good Clinical Practice (GCP), addresses
data integrity in clinical trials.
- ISO 9001: Addresses documentation and record
keeping for maintaining data integrity.
- Schedule M: Data integrity requirements for GMP-
compliant pharmaceutical manufacturing.
Data integrity ensures that data is accurate,
complete, and reliable throughout its
lifecycle, crucial for compliance, validation,
and regulatory purposes.

70. Conclusion
 Summary: Quality Management Systems (QMS) ensure consistent product
quality, regulatory compliance, and customer satisfaction.
 Key Takeaways: Importance of Total Quality Management (TQM), Quality by
Design (QbD), Six Sigma, validation processes, and regulatory guidelines.
 Future Outlook: Continuous improvement and adherence to regulatory
standards will drive innovation and quality in the pharmaceutical and biotech
industries. SK
Dr. Smita Kumbhar

71.  U.S. Food and Drug Administration (FDA)
 FDA Guidance for Industry: Process Validation: General Principles and Practices
 FDA Guidance for Industry: Q7 Good Manufacturing Practice Guidance for Active
Pharmaceutical Ingredients
 Central Drugs Standard Control Organization (CDSCO)
 Schedule MIII - Requirements for the Manufacture of Medical Devices and In Vitro
Diagnostic Kits
 Books and Articles
 "Total Quality Management: Key Concepts and Case Studies" by D.R. Kiran
 "Pharmaceutical Quality by Design: A Practical Approach" edited by Walkiria S. Schlindwein
and Mark Gibson
 "Six Sigma for Medical Device Design" by Jose Justiniano and Venky Gopalas
References
SK
Dr. Smita Kumbhar

72. References
 International Organization for Standardization (ISO)
 ISO 9001:2015 - Quality Management Systems
 ISO 13485:2016 - Medical Devices – Quality Management Systems – Requirements for
Regulatory Purposes
 International Conference on Harmonisation (ICH)
 ICH Q8 (R2): Pharmaceutical Development
 ICH Q9: Quality Risk Management
 ICH Q10: Pharmaceutical Quality System
 ICH Q11: Development and Manufacture of Drug Substances (Chemical Entities and
Biotechnological/Biological Entities)
 ICH Q2 (R1): Validation of Analytical Procedures: Text and Methodology
SK
Dr. Smita Kumbhar