The document discusses the validation of water supply systems for pharmaceutical use. It outlines the need to validate water systems due to water being the most commonly used raw material. The validation process includes design qualification, installation qualification, operation qualification and performance qualification to ensure appropriate design, installation, and operation of the system. Regular monitoring and maintenance is also required to guarantee continued production of water meeting quality specifications.
Aseptic / sterile- “ A state of control attained by using an aseptic work area and performing activities in a manner that precludes microbiological contamination of the exposed sterile product”
Aseptic / sterile- “ A state of control attained by using an aseptic work area and performing activities in a manner that precludes microbiological contamination of the exposed sterile product”
A brief summary of Water System in pharmaceuticals including its production and distribution with regulatory and qualification requirements. This presentation gives a basic layout to non-engineering people a basic understanding of Water System in Pharmaceutical.
WHO has recently issued draft document titled "Guidelines on Validation". These guidelines (i.e., the main text included in this working document) cover the general principles of validation and qualification.
These guidelines focus mainly on the overall concept of validation and are not intended to be prescriptive in specific validation requirements. This document serves as general guidance only and the principles may be considered useful in its application in the manufacture and control of starting materials and finished pharmaceutical products (FPPs), as well as other areas. Validation of specific processes and systems, for example, in sterile product manufacture, requires much more consideration and a detailed approach that is beyond the scope of this document. The general text in this document may be applicable to validation and qualification of premises, equipment, utilities, systems, processes, and procedures.
The draft on the specific topics, the appendices to this main text, will follow. The following is an overview on the appendices that are intended to complement the text of this working document:
Appendix 1: Validation of heating, ventilation and air-conditioning systems - will be replaced by cross reference to WHO Guidelines on GMP for HVAC systems for considerations in qualification of HVAC systems (update - working document QAS/15.639/Rev. 1)
Appendix 2: Validation of water systems for pharmaceutical use - will be replaced by cross-reference to WHO Guidelines on water for pharmaceutical use for consideration in qualification of water purification systems
Appendix 3: Cleaning validation - consensus to retain
Appendix 4: Analytical method validation - update in process
Appendix 5: Validation of computerized systems - update in process
Appendix 6: Qualification of systems and equipment - update in process
Appendix 7: Non-sterile process validation - update already published as Annex 3, WHO Technical Report Series, No. 992, 2015
Comments on this draft document are due by July 12, 2016.
A presentation on this guidance is given below:
Presentation on New WHO Guidance on Validations
Master batch record,batch production record ,Quality Audit Type and plan &Rec...KarishmaFuse
Standard Operating procedure(SOP), Preparation review ,Approval Issuance of master batch Record MBR and Batch Production Record (BPR) and Quality Audit Type, plan and Objectives.
In this slide contains details about Pharmaceutical validation of water system
Presented by: K VENKATSAI PRASAD (Department of pharmaceutical analysis and quality assurance).RIPER, anantapur
A brief summary of Water System in pharmaceuticals including its production and distribution with regulatory and qualification requirements. This presentation gives a basic layout to non-engineering people a basic understanding of Water System in Pharmaceutical.
WHO has recently issued draft document titled "Guidelines on Validation". These guidelines (i.e., the main text included in this working document) cover the general principles of validation and qualification.
These guidelines focus mainly on the overall concept of validation and are not intended to be prescriptive in specific validation requirements. This document serves as general guidance only and the principles may be considered useful in its application in the manufacture and control of starting materials and finished pharmaceutical products (FPPs), as well as other areas. Validation of specific processes and systems, for example, in sterile product manufacture, requires much more consideration and a detailed approach that is beyond the scope of this document. The general text in this document may be applicable to validation and qualification of premises, equipment, utilities, systems, processes, and procedures.
The draft on the specific topics, the appendices to this main text, will follow. The following is an overview on the appendices that are intended to complement the text of this working document:
Appendix 1: Validation of heating, ventilation and air-conditioning systems - will be replaced by cross reference to WHO Guidelines on GMP for HVAC systems for considerations in qualification of HVAC systems (update - working document QAS/15.639/Rev. 1)
Appendix 2: Validation of water systems for pharmaceutical use - will be replaced by cross-reference to WHO Guidelines on water for pharmaceutical use for consideration in qualification of water purification systems
Appendix 3: Cleaning validation - consensus to retain
Appendix 4: Analytical method validation - update in process
Appendix 5: Validation of computerized systems - update in process
Appendix 6: Qualification of systems and equipment - update in process
Appendix 7: Non-sterile process validation - update already published as Annex 3, WHO Technical Report Series, No. 992, 2015
Comments on this draft document are due by July 12, 2016.
A presentation on this guidance is given below:
Presentation on New WHO Guidance on Validations
Master batch record,batch production record ,Quality Audit Type and plan &Rec...KarishmaFuse
Standard Operating procedure(SOP), Preparation review ,Approval Issuance of master batch Record MBR and Batch Production Record (BPR) and Quality Audit Type, plan and Objectives.
In this slide contains details about Pharmaceutical validation of water system
Presented by: K VENKATSAI PRASAD (Department of pharmaceutical analysis and quality assurance).RIPER, anantapur
validation is a technique of validating the final product either starting from the raw material or within the process, its all types cover the methods of validation and sequence in the product development.
Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
- ARTIFICIAL INTELLIGENCE AND ETHICS
- GENE THERAPY
- BEYOND BORDERS: GLOBAL INITIATIVES FOR DEMOCRATIZING LIFE SCIENCE TECHNOLOGIES AND PROMOTING ACCESS TO HEALTHCARE
- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
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Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
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Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...VarunMahajani
Disruption of blood supply to lung alveoli due to blockage of one or more pulmonary blood vessels is called as Pulmonary thromboembolism. In this presentation we will discuss its causes, types and its management in depth.
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
3. OBJECTIVE
3
To understand:
1. The need for water quality manual
2. reason for usage of pharmaceutical water
supply systems.
3. The technical requirements for water supply
systems.
4. Different types of water supply systems.
5. Validation requirements.
6. Qualification & inspection requirement
4. INTRODUCTION
4
High-quality water is essential for the manufacturing of
pharmaceuticals. Water is the most commonly used raw
material in pharmaceutical manufacturing.
water is directly or indirectly used in the pharmaceutical
manufacturing such as a major component in injectable
products and in cleaning of manufacturing equipment.
It is one of the raw material that is usually processed by the
pharmaceutical manufacturer prior to use because it cannot be
supplied by the vendor.
Water is thus an important raw material in GMP and in
validating the manufacturing process.
5. INTRODUCTION
5
Why purification?
o Although tap water is reasonably pure, it is
always variable due to seasonal variations,
regional variation in quality.
o One must remove impurities and control microbes
to avoid contamination of products.
o Pretreatment depends on quality of feed water.
6. INTRODUCTION
6
Quality of water should be specific for product
quality.
Water contains,
Organic and inorganic impurities
Microbial contamination
Endotoxin
Particulate contamination
Low quality of water can lead to
product degradation
product contamination
loss of product and profit
7. TYPES OF WATER
7
Different grades of Water for Pharmaceutical
Purposes-each
type has its on characteristic for all parameters.
Potable water
Purified water
Water for injection(WFI)
Sterile water for injection, inhalation, irrigation
Sterile bacteriostatic water for injection
10. DIFFERENT TECHNIQUES USED FOR
WATER TREATMENT
10
De-chlorination (Sodium Bisulphite,
Carbon Filter)
Filtration
Ultra Filtration
Softening
Demineralization
Reverse Osmosis
UV Treatment
Deionization
Ozonization
11. DIFFERENT EQUIPMENTS AND
COMPONENTS FOR WATER SYSTEM
11
Piping
Valves
Pumps
Pressure gauges
Heat exchangers
Distillation unit
Filters
Deionizers
Sensors
Auxiliary equipment
12. WATER STORAGE AND
DISTRIBUTION – CONSIDERATIONS
12
Materials of Construction (Chemical and Heat
Compatibility)
Stainless Steel (316 or 316L)
Teflon, Silicone, Viton (gaskets, diaphragms)
Minimize Dead Legs (<= 2 pipe diameters)
Smooth Surfaces (Mechanical Polish , Electropolish)
Clean joints (sanitary Tri®Clamp, automatic orbital
welding)
Passivate interior surfaces to form barrier between
water and free iron (0.5 to 1% alkali at 160ºF for 30
minutes followed by 1% Phosphoric Acid or Nitric Acid
at 150ºF to 180º F for 10 minutes.)
13. Conti….
13
Design of the following should be appropriate to
prevent recontamination after treatment-
Vent filter
Sanitary overflow
Tank UV light
Conical Bottom
Steam sterilization
Combination of on-line (TOC, Conductivity meter etc.)
and off-line monitoring (lab testing by proper sampling)
to ensure compliance with water specification
14. VALIDATION CONCEPT
14
To prove the performance of processes or systems under
all conditions expected to be encountered during future
operations.
To prove the performance, one must demonstrate
(document) that the processes or systems consistently
produce the specified qquuaannttiittyy aanndd qquuaalliittyy of water when
operated and maintained according to specific written
operating and maintenance procedures.
validation involves proving-
1. Engineering design
2.Operating procedures and acceptable ranges for control
parameters
3. Maintenance procedures to accomplish it
15. Conti..
15
the system must be carefully,
-designed
-installed
-tested during processing, after construction, and
under all operating conditions.
Variations in daily, weekly and annual system
usage patterns must be validated.
16. WHY VALIDATION OF WATER
SYSTEM?
16
Most widely used and sometimes most expensive
ingredient
Drug component even if not in product
Generally reviewed in depth by Regulators
Many recalls water related
Always considered direct impact system
To ensure reliable, consistent production of water of
required quality
To operate system within design capacity
To prevent unacceptable microbial, chemical and
physical contamination during production, storage
and distribution
To monitor system performance, storage and
distribution systems
17. VALIDATION CYCLE:
17
It includes four major steps-
Determination of Quality Attributes
The Validation Protocol
Steps of Validation
Control during routine operation
18. DETERMINATION OF QUALITY ATTRIBUTES
18
The quality attributes, is gaining a clear
understanding of the required quality of water and
its intended use
Should be determined before starting the
validation.
Without defining required quality attributes, we
cannot establish validation protocols.
19. THE VALIDATION PROTOCOL
19
A written plan stating how validation will be
ccoonndduucctteedd and defining aacccceeppttaannccee ccrriitteerriiaa for
quality.
For example, the protocol for a manufacturing
process-it
identifies -process equipment
-critical process parameters
-product characteristics,
-sampling,
-test data to be collected,
-number of validation runs
-acceptable test results
20. STEPS OF VALIDATION
20
Establishing standards for quality attributes
Defining system and subsystem
Designing equipment, control, & monitoring
technologies
Establishing standards for operating parameters
Developing an IQ stage & OQ stage
Establishing alert and action levels
Developing a prospective PQ stage
Completing protocols and documenting each
steps
22. ALERT AND ACTION LEVELS:
22
Alert and action levels are distinct from process
parameters and product specifications.
They are used for monitoring and control rather than
accept or reject decisions.
The levels should be determined based on the statistical
analysis of the data obtained by monitoring at the PQ
step.
Alert levels are levels or ranges that when exceeded
indicate that a process may have drifted from its normal
operation condition.
Alert levels indicate a warning and do not necessarily
require a corrective action. Exceeding an action level
indicates that corrective action should be taken to bring
the process back into its normal operating range.
23. SYSTEM QUALIFICATION
23
Validation Master Plan
User Requirement Specification
Design Qualification
Installation Qualification
Operation Qualification
Performance Qualification
Re- Qualification.
24. DESIGN QUALIFICATION OF WATER SYSTEM
24
Based on the URS, supplier designs the equipment.
This is 1st step in the qualification of new water supply
systems.
Define process schematically by use of PFD and P&IDs.
It is documented the design of the system & will include :
-Functional Specification.(Storage, purification, etc)
-Technical/Performance specification for equipment.
(requirements of water volume and flow, define pumps and
pipe sizes )
-Detailed layout of the system.
Design must be in compliance with GMPs and other regulatory
requirements.
25. INSTALLATION QUALIFICATION
25
IQ is in the form of checklist and it should include-
Instrumentation checked against current engineering
drawings and specifications
Review of P&ID
Verification of materials of construction
Installation of equipment with piping
Calibration of measuring instruments
Collection and collation of supplier operating and
working instructions and maintenance requirements
26. Conti…
26
Installation of system as per Design requirements.
Installation Verification-
Systematic range of adjustments, measurements
and tests should be carried out to ensure proper
installation.
Documentation include details of completed
installation.
27. 27
Conti…
• IQ Document should contain,
Instrument name, model, I.D. No., Personnel
responsible for activities and Date.
A fully verified installation that complies with the
documented design. (all deviations will have been
recorded and assessed.)
All equipment documentation and maintenance
requirements would be documented.
Completed calibration of measuring
instruments.
Verification of Materials of construction.
28. OPERATION QUALIFICATION
28
Definition : The purpose of OQ is to establish, through
documented testing, that all critical components are
capable of operating within established limits and
tolerances.
it is the functional testing of system components
mainly the critical components.
The purpose of OQ is also to verify and document that
the water supply system provides acceptable operational
control under “at-rest” conditions.
29. 29
Conti…
Operation Qualification Checks-
Ability to provide water of sufficient quality and
quantity to ensure achievement of specifications.
Ability to maintain general parameters like
temperature, pressure, flow at set points.
Ability to maintain any critical parameters(pH,
TOC, endotoxin, microbial level, conductivity etc ).
30. 30
Conti…
Includes the tests that have been developed from
knowledge of processes, systems and equipment.
Tests include a condition or a set of conditions with
upper and lower operating limits, sometimes referred
to as ‘worst case’ conditions.
31. 31
PERFORMANCE QUALIFICATION
The purpose of PQ is to verify and document that
water supply system provides acceptable control
under ‘ Full Operational ‘ conditions.
PQ should follow successful completion of IQ
and OQ.
PQ verifies that over time, the critical
parameters, as defined in the DQ are being
achieved.
32. 32
Conti…
According to the FDA’s advice:
“The observed variability of the equipment
between and within runs can be used as a basis
for determining the total number of trials
selected for the subsequent PQ studies of the
process.”
33. 33
Conti…
PQ is used to demonstrate consistent achievement of
critical parameters over time.
(such as pH, TOC, conductivity)
PQ and OQ tests are sometimes performed in
conjunction with one another.
34. QUALIFICATION PHASES
34
Three phase approach recommended according to
WHO Technical Report Series 929 to prove
reliability and robustness.
Phase 1 (investigational phase):
A test period of 2-4 weeks – monitor the system
System to operate continuously without failure or
performance deviation
Chemical and microbiological testing should
include in accordance with a defined plan
35. Conti…
35
Sample daily from-
incoming feed-water
after each step in the purification process
each point of use and at other defined sample
points
Develop:
appropriate operating ranges
and finalize operating, cleaning, sanitizing
and maintenance procedures
36. Conti…
36
Demonstrate production and delivery of water of
the required quality and quantity
Use and define the standard operating procedures
(SOPs) for operation, maintenance, sanitization
and troubleshooting
Verify provisional alert and action levels
Develop and define test-failure procedure
37. 37
Phase 2(verification step)
A further test period of 2-4 weeks – further intensive
monitoring of the system
Utilization of all the SOPs after the satisfactory
completion of phase 1
Sampling scheme generally the same as in phase 1
Water can be used for manufacturing purposes during
this phase
38. Conti..
38
Phase-2 demonstrates:
Consistent operation within established ranges. so
it demostrate that the system is in control.
Consistent production and delivery of water of the
required quantity and quality when the system is
operated in accordance with the SOPs.
39. 39
Phase 3
Over 1 year after the satisfactory completion of
phase 2
Water can be used for manufacturing purposes
during this phase
Demonstrate:
extended reliable performance
that seasonal variations are evaluated
Sample locations, sampling frequencies and tests
should be reduced to the normal routine pattern
based on established procedures proven during
phases 1 and 2
40. MONITORING
40
Monitoring and feed back data are important in maintaining
the performance systems. Monitoring parameters include:
Flow, pressure, temperature, conductivity, TOC
Samples taken:
From points of use, and specific sample points
In a similar way how water is used in service
Tests should include physical, chemical and microbial
attributes
For example, stable state can be achieved by applying
automatic continuous monitoring of TOC and conductivity of
the water system. They are the major quality attributes of
water by which organic and inorganic impurities can be
determined.
41. MAINTENANCE
41
A controlled, documented maintenance covering :
Defined frequency with plan and instructions
Calibration programme
SOPs for tasks
Control of approved spares
Record and review of problems and faults during
maintenance
42. MAINTENANCE
System sanitization and bioburden control
Systems in place to control proliferation of microbes
Techniques for sanitizing or sterilization
Consideration already during design stage – then
validated
Special precautions if water not kept in the range of
70 to 80 degrees Celsius
43. REVALIDATION & CHANGE CONTROL
43
Once the validation is completed, the standard operating
procedures (SOPs) are formalized.
Routine operation should be performed according to the
established SOP.
If any deviation from SOP observed, determine the change
and their impact on whole system
Revalidation and evaluation should be performed
depending upon the impact of the change on system.
44. VALIDATION REPORT
44
Written at the conclusion of the equipment IQ, OQ
and at completion of process validation.
Will serve as primary documentation for FDA
regulatory inspection
Will serve as reference document when changes to
the system are occurred and revalidation is needed.
45. VALIDATION REPORT
45
STANDARD FORMAT
1. Executive summary
2. Discussion
3. Conclusions & recommendation
4. List of attachment
Topic should be presented in the order in which they
appear in the protocol.
Protocol deviation are fully explained & justified.
The report is signed & dated by designated representatives
of each unit involved in water system validation.
46. 46
Complete Documentation
Verification of design documentation, including
◦ Description of installation and functions
◦ Specification of the requirements
Instructions for performance control
Operating procedures
Maintenance instructions
Maintenance records
Training of personnel (program and records)
Environmental records
Inspection of plant
Finally certification (Sign Off) by Engineering,
User (Production) and QA Heads.
47. SUMMARY
47
Water supply systems,
Play a major role in the quality of
pharmaceuticals.
Must be designed properly by professionals.
Must be validated as a critical system.
48. REFERENCES
48
“Validation in pharmaceutical industry” ; edited by P.P.
sharma ;first edition 2007 ; 193-220
“Pharmaceutical Process Validation”; An international 3rd
edition; edited by R. A. Nash and A. H. Wachter; 401-442
“Validation of Pharmaceutical Processes”; by Agalloco
James, Carleton J.Fredrick; 3rd edition; 59-92.
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