This document provides guidance on validation and qualification principles from the World Health Organization (WHO). It discusses the need for validation and qualification activities to ensure product quality, safety, and efficacy throughout the product lifecycle. Key aspects covered include definitions of validation terms, approaches to validation planning, and documentation requirements such as a validation master plan and protocols.
Validation: Validation is a documented program that provides high degree of assurance that a specific process, method or system consistently produces a result meeting pre-determined acceptance criteria.
Fluidized Bed Dryer
Principle of FBD
Construction of FBD
Working of FBD
Steps of Fluidization
Qualification of FBD
Design Qualification
Installation Qualification
Operational Qualification
Performance Qualification
References
PIC/S is a combine term used for the execution of activities of Pharmaceutical Inspection Convention and Pharmaceutical Inspection Co-operation Scheme
harmonize, educate, and update aspects relating to Good Manufacturing Practice among member countries
harmonized relation among regulatory authorities and governments
members
history
role
objective and function
guidlines
Manufacturing Control Systems. J R Controls provides control systems for the manufacturing industry. A typical control system will monitor the progress of parts through the manufacturing and finishing process.
Validation: Validation is a documented program that provides high degree of assurance that a specific process, method or system consistently produces a result meeting pre-determined acceptance criteria.
Fluidized Bed Dryer
Principle of FBD
Construction of FBD
Working of FBD
Steps of Fluidization
Qualification of FBD
Design Qualification
Installation Qualification
Operational Qualification
Performance Qualification
References
PIC/S is a combine term used for the execution of activities of Pharmaceutical Inspection Convention and Pharmaceutical Inspection Co-operation Scheme
harmonize, educate, and update aspects relating to Good Manufacturing Practice among member countries
harmonized relation among regulatory authorities and governments
members
history
role
objective and function
guidlines
Manufacturing Control Systems. J R Controls provides control systems for the manufacturing industry. A typical control system will monitor the progress of parts through the manufacturing and finishing process.
In the last year or so the FDA and the EMA have issued new guidance/ draft guidance on "Process Validation".These align process validation activities with a product lifecycle concept and the International Conference on Harmonisation (ICH) guidances for industry, Q8(R2) Pharmaceutical Development, Q9 Quality Risk Management, and Q10 Pharmaceutical Quality System. The earlier guidelines were developed before the elaboration of the new ICH guidelines.With these new guidelines, additional opportunities are available to verify the control of the process by alternative means to the manufacture of traditional process validation batches. The main objective of process validation remains that a process design yields a product meeting its pre-defined quality criteria. ICH Q8, Q9 and Q10 provide a structured way to define product critical quality attributes, design space, the manufacturing process and the control strategy. ICH Q8 refers to an ‘enhanced’ approach to pharmaceutical development which includes an alternative to the traditional process validation.
Continuous process verification [see definition in ICH Q8(R2) glossary] can be utilised in process validation protocols for the initial commercial production and for manufacturing process changes for the continual improvement throughout the remainder of the product lifecycle.
There is now a new paradigm in process validation. This presentation has been prepared from material available from FDA , EMA and ICH for beginners to have an overview of the new paradigm.
Qualification of Dissolution Test Apparatus and Validation of Utility System this presentation will help to enhance your knowledge in validation and qualification area.
The presentation was an overview of the GMP regulations specific to cleaning validation for medicine manufacturers. New guidelines for Health Based Exposure Limits were discussed along with common GMP deficiencies observed during TGA inspections.
Qualification and Validation have big Weightage in the Regulatory Compliance and GMP. Qualification and Validation only can guarantee about the Product Safety, Integrity, Strength, Purity and Quality assurance.
It is process of “Establishing documentary evidence that provide a high degree of assurance that a specific process will consistently produce a product meeting its predetermined specifications and quality attributes”.
In the pharmaceutical industry, it is very important that in addition to final testing and compliance of products, it is also assured that the process will consistently produce the expected results.
Validation is action of proving in accordance with the principles of good manufacturing practices, that any procedure, process, equipment, material, activity or system actually leads to expected results.
Cleaning validation is documented evidence with a high degree assurance that one can consistently clean a system or a piece of equipment to predetermined and acceptable limits.
The primary regulatory concern driving the need for cleaning validation is cross contamination of the desired drug substance either by other API from previous batch runs or by residues from the cleaning agents used.
The prime purpose of validating a cleaning process is to ensure compliance with federal and other standard regulations
1. Cross contamination with active ingredients
Contamination of one batch of product with significant levels of residual active ingredients from previous batch cannot be tolerated.
In addition to the obvious problems posed by subjecting consumers or patients to unintended contaminants, potential clinically significant synergistic interactions between pharmacologically active chemicals are a real concern.
2. Contamination with unintended materials or compounds
While inert ingredients used in drug products are generally recognized as safe for human consumption, the routine use, maintenance and cleaning of equipment's provide the potential contamination with such items as equipment parts, lubricants and chemical cleaning agents3. Microbiological contamination
Maintenance , cleaning and storage conditions may provide adventitious microorganisms with the opportunity to proliferate within the processing equipment.
PIC/S Guide to GMP PE009-13 - Key changes to Annex 15 - Qualification and val...TGA Australia
The TGA has now legislated version 13 of the PIC/S guide to GMP for medicinal products with a transition period for implementation ending at the end of 2018. Some of the biggest changes in this version were in Annex 15 – Qualification and Validation. This has an impact across all areas in including small to medium sized manufacturers as well as sponsors who need to understand the impact in their supply chain including contract manufacturing and storage and transportation.
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”
Equipment used in pharmaceuticals dosage form manufacturing need to observe continuous qualification to monitor its performance and Concept of URS ,DQ, IQ,OQ,PQ,MQ...
Effective process validation contributes significantly to assuring drug quality. The basic
principle of quality assurance is that a drug should be produced that is fit for its intended use.
This principle incorporates the understanding that the following conditions exist:
• Quality, safety, and efficacy are designed or built into the product.
• Quality cannot be adequately assured merely by in-process and finished-product
inspection or testing
In the last year or so the FDA and the EMA have issued new guidance/ draft guidance on "Process Validation".These align process validation activities with a product lifecycle concept and the International Conference on Harmonisation (ICH) guidances for industry, Q8(R2) Pharmaceutical Development, Q9 Quality Risk Management, and Q10 Pharmaceutical Quality System. The earlier guidelines were developed before the elaboration of the new ICH guidelines.With these new guidelines, additional opportunities are available to verify the control of the process by alternative means to the manufacture of traditional process validation batches. The main objective of process validation remains that a process design yields a product meeting its pre-defined quality criteria. ICH Q8, Q9 and Q10 provide a structured way to define product critical quality attributes, design space, the manufacturing process and the control strategy. ICH Q8 refers to an ‘enhanced’ approach to pharmaceutical development which includes an alternative to the traditional process validation.
Continuous process verification [see definition in ICH Q8(R2) glossary] can be utilised in process validation protocols for the initial commercial production and for manufacturing process changes for the continual improvement throughout the remainder of the product lifecycle.
There is now a new paradigm in process validation. This presentation has been prepared from material available from FDA , EMA and ICH for beginners to have an overview of the new paradigm.
Qualification of Dissolution Test Apparatus and Validation of Utility System this presentation will help to enhance your knowledge in validation and qualification area.
The presentation was an overview of the GMP regulations specific to cleaning validation for medicine manufacturers. New guidelines for Health Based Exposure Limits were discussed along with common GMP deficiencies observed during TGA inspections.
Qualification and Validation have big Weightage in the Regulatory Compliance and GMP. Qualification and Validation only can guarantee about the Product Safety, Integrity, Strength, Purity and Quality assurance.
It is process of “Establishing documentary evidence that provide a high degree of assurance that a specific process will consistently produce a product meeting its predetermined specifications and quality attributes”.
In the pharmaceutical industry, it is very important that in addition to final testing and compliance of products, it is also assured that the process will consistently produce the expected results.
Validation is action of proving in accordance with the principles of good manufacturing practices, that any procedure, process, equipment, material, activity or system actually leads to expected results.
Cleaning validation is documented evidence with a high degree assurance that one can consistently clean a system or a piece of equipment to predetermined and acceptable limits.
The primary regulatory concern driving the need for cleaning validation is cross contamination of the desired drug substance either by other API from previous batch runs or by residues from the cleaning agents used.
The prime purpose of validating a cleaning process is to ensure compliance with federal and other standard regulations
1. Cross contamination with active ingredients
Contamination of one batch of product with significant levels of residual active ingredients from previous batch cannot be tolerated.
In addition to the obvious problems posed by subjecting consumers or patients to unintended contaminants, potential clinically significant synergistic interactions between pharmacologically active chemicals are a real concern.
2. Contamination with unintended materials or compounds
While inert ingredients used in drug products are generally recognized as safe for human consumption, the routine use, maintenance and cleaning of equipment's provide the potential contamination with such items as equipment parts, lubricants and chemical cleaning agents3. Microbiological contamination
Maintenance , cleaning and storage conditions may provide adventitious microorganisms with the opportunity to proliferate within the processing equipment.
PIC/S Guide to GMP PE009-13 - Key changes to Annex 15 - Qualification and val...TGA Australia
The TGA has now legislated version 13 of the PIC/S guide to GMP for medicinal products with a transition period for implementation ending at the end of 2018. Some of the biggest changes in this version were in Annex 15 – Qualification and Validation. This has an impact across all areas in including small to medium sized manufacturers as well as sponsors who need to understand the impact in their supply chain including contract manufacturing and storage and transportation.
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”
Equipment used in pharmaceuticals dosage form manufacturing need to observe continuous qualification to monitor its performance and Concept of URS ,DQ, IQ,OQ,PQ,MQ...
Effective process validation contributes significantly to assuring drug quality. The basic
principle of quality assurance is that a drug should be produced that is fit for its intended use.
This principle incorporates the understanding that the following conditions exist:
• Quality, safety, and efficacy are designed or built into the product.
• Quality cannot be adequately assured merely by in-process and finished-product
inspection or testing
FDA Process Validation Guidance (Guidance for Industry: Process Validation- General Principles and Practices, Jan. 2011) outlines process validation activities in three stages - Stage 1: Process Design, Stage 2: Process Qualification and Stage 3: Continued Process Verification. Completion of Stage 2 subsequent to Stage 1 is a major milestone in the Process Validation Lifecycle as it confirms the process design and demonstrates the expected consistent performance of the manufacturing process. Knowledge and information gained from the design stage through the process qualification stage is used to complete this assessment. Stage 2 demonstrates suitability for successful commercial distribution where the data indicates that the process meets the conditions established in the protocol. Continued Process Verification is initiated for the subsequent commercial batches. Stage 3 assures that the process remains in a state of control during commercial manufacture.
This presentation gives a practical approach to implement the stage 3 of the FDA Process Validation Guide.
This presentation describes the principles of qualification and validation which are applicable to the facilities, equipment, utilities and processes used for the manufacture of medicinal products. It is a GMP requirement that manufacturer’s control the critical aspects of their particular operations through qualification and validation over the life cycle of the product and process. Any planned changes to the facilities, equipment, utilities and processes, which may affect the quality of the product, should be formally documented and the impact on the validated status or control strategy assessed.
This presentation describes approaches for software validation used to automate laboratory research procedures, consolidate data collection and analysis and/or run sophisticated QC or manufacturing operations.
Several approaches to software validation exist and may be appropriate for a specific project.
The scope of any validation effort depends upon a number of factors
Size and complexity of the software,
Origin of the software (custom vs. off-the-shelf) and
Whether the functions are critical or non-critical in nature.
By effectively planning the process, validation time and resources can be reduced while meeting regulatory requirements.
A primary mission of the Food and Drug Administration is to conduct comprehensive regulatory coverage of all aspects of production and distribution of drugs and drug products to assure that such products meet the 501(a)(2)(B) requirements of the Act. FDA has developed two basic strategies:
. 1) evaluating through factory inspections, including the collection and analysis of associated samples, the conditions and practices under which drugs and drug products are manufactured, packed, tested and held, and
. 2) monitoring the quality of drugs and drug products through surveillance activities such as sampling and analyzing products in distribution.
FDA compliance program “ Drug Manufacturing Inpsections” (7356.002) is designed to provide guidance for implementing the first strategy. Products from production and distribution facilities covered under this program are consistently of acceptable quality if the firm is operating in a state of control.
The inspectional guidance in this program is structured to provide for efficient use of resources devoted to routine surveillance coverage, recognizing that in-depth coverage of all systems and all processes is not feasible for all firms on a biennial basis. It also provides for follow-up compliance coverage as needed.
“Drug Regulations” has prepared a summary from the compliance programme and is given below in the presentation.
Global Regulatory Outlook: 2017 and Beyond - OMTEC 2017April Bright
Keeping a finger on the pulse of regulatory changes taking place worldwide is hard to do, but nonetheless imperative. This presentation will provide a high-level overview of the more significant global regulatory changes that will impact orthopaedic manufacturers in the next two years. These include European Medical Device Regulation, ISO 13485:2016, MDSAP and U.S. FDA changes, as well as other global topics of interest. Ms. Loh, who leads the regulatory team at EMERGO, returned to OMTEC to provide perspective on strategies and risks to consider with these wide-ranging and sometimes overlapping matters.
This presentation will highlight the actions you should take now in order to successfully transition to the updated standard.
A proper technology transfer (TT) is both essential and important to drug discovery and development for new medicinal products. It is also required to upgrade drug quality planned during research development and to final product during manufacturing as well as to guarantee that stable quality is transferred
Provide recommendations and background information concerning computerised systems
Information will be of assistance to inspectors for training purposes and during the inspection
Where automated systems and electronic records are used in warehouses and similar establishments where GDP requirements are applicable, controls and disciplines outlined in this document, or a best practice alternatives are expected to be in place.
Vertically integrated companies (R&D, manufacturing and distribution) will already apply such controls and compliance measures.
International regulatory agencies have collaborated to produce this guidance.
Intended as a reference for regulated users, including their suppliers, in addition to regulatory inspectors and investigators.
Provides a logical explanation of the basic requirements for the implementation, validation and operation of computerised systems.
May be adapted to identify the criteria for a regulated user, or a regulatory agency, in an inspection of GxP computer systems.
National legislation should to be referred to when determining the extent to which the provisions laid down in this document may be applicable.
This presentation gives a summary of this guidance.
Clinical evaluation and the latest 2016 guidelineGRCTS
This “General Guidance” document promotes a common approach to clinical evaluation for "medical devices regulated by directives 90/385/EEC and 93/42/EEC. It does not concern in vitro diagnostic devices. The depth and extent of clinical evaluations should be flexible and appropriate to the nature, intended purpose, and risks of the device in question.
In March 2011, the EMA and FDA launched a pilot program that aims at a parallel assessment by both agencies of certain quality/CMC sections which are relevant to Quality by Design (QbD). This voluntary pilot program is open. This presentation gives a summary of the FDA and EMA expectation for QbD submissions based on the pilot programme.
This presentation highlights the reasons which lead to the withdrawal of the 2002 Guidance of the FDA and the current issue with Blend Uniformity and Content Uniformity Determinations.
Environmental Monitoring describes the microbiological testing under- taken in order to detect changing trends of microbial counts and micro- flora growth within cleanroom or controlled environments. The results obtained provide information about the physical construction of the room, the performance of the Heating, Ventilation, and Air-Conditioning (HVAC) system, personnel cleanliness, gowning practices, the equipment, and cleaning operations.
Over the past decade, environmental monitoring has become more sophisticated in moving from random sampling, using an imaginary grid over the room and testing in each grid, to the current focus on risk assessment and the use of risk assessment tools to determine the most appropriate methods for environmental monitoring.
This presentation gives current trends in the application of risk assessment to the practice of environmental monitoring.
This presentation is compiled from freely available resources like the websites of FDA, EMA ,WHO and research papers published by experts in this field like Sandle, T Reinmüller, B , Hyde, W,, Costello, E.K., Lauber, C. L., Hamady, M., Fierer, N., Gordon, J.I., Knight, R.
Paper published by T. Sandle on clean room contamination was referred extensively for this presentation. “Drug Regulations” is a non profit organization which provides free online resource to the Pharmaceutical Professional.
Visit http://www.drugregulations.org for latest information from the world of Pharmaceuticals.
This presentation gives an overview of : Validation of microbiological methods , Considering some of the limitations and
Key criteria that may be applicable for assessment.
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
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
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.
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.
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Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
1. This presentation is compiled by “ Drug Regulations”
a non profit organization which provides free online
resource to the Pharmaceutical Professional.
Visit http://www.drugregulations.org for latest
information from the world of Pharmaceuticals.
7/5/2016 1
2. This presentation is compiled from freely available
resource like the website of WHO, specifically the
WHO Draft Guidance on Process Validations.
“Drug Regulations” is a non profit organization
which provides free online resource to the
Pharmaceutical Professional.
Visit http://www.drugregulations.org for latest
information from the world of Pharmaceuticals.
7/5/2016 2
Drug Regulations : Online
Resource for Latest Information
3. This presentation is based on
WHO Working document
◦ QAS/16.666 May 2016
◦ titled “ Guidelines on Validation”
7/5/2016 3Drug Regulations : Online Resource for Latest Information
4. WHO published guidance on Validations in TRS No. 937 Annex 4, 2006
titled Supplementary guidelines on good manufacturing practices:
validation
Prequalification of Medicines Programme had identified the need for
revision of this guidance
A draft document was circulated for comment in early 2013.
The focus of the revision was the Appendix on non-sterile process
validation (Appendix 7),
This had been revised and was adopted by the Committee at its forty-
ninth meeting in October 2014.
7/5/2016 4Drug Regulations : Online Resource for Latest Information
5. The main text included in this working document
constitutes the general principles of the new
guidance on validation.
The draft on the specific topics, the appendices to
this main text, will follow.
Overview on the appendices that are intended to
complement this general guidance is given in
subsequent slides.
7/5/2016 5Drug Regulations : Online Resource for Latest Information
6. 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
7/5/2016 6Drug Regulations : Online Resource for Latest Information
7. Appendix 3
◦ Cleaning validation – consensus to retain
Appendix 4
◦ Analytical method validation – update in process
Appendix 5
◦ Validation of computerized systems – update in progress
7/5/2016 7Drug Regulations : Online Resource for Latest Information
8. 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
7/5/2016 8Drug Regulations : Online Resource for Latest Information
9. Validation is an essential part of good practices
This includes good manufacturing practices (GMP) and good
clinical practices (GCP).
It is therefore an element of the pharmaceutical quality system.
Validation, as concept, incorporates qualification
It should be applied over the life cycle ,
◦ e.g. the applicable product, process, system, equipment or utility.
These guidelines cover the general principles of validation and
qualification.
7/5/2016 9Drug Regulations : Online Resource for Latest Information
10. In addition to the main part, appendices on validation and
qualification following validations are included in appendix.
◦ Cleaning
◦ Computer and computerized systems
◦ Equipment
◦ Utilities and systems
◦ Analytical methods
7/5/2016 10Drug Regulations : Online Resource for Latest Information
11. Following principles apply:
◦ The execution of validation should be in compliance with regulatory
expectations;
◦ Quality, safety and efficacy must be designed and built into the product;
◦ Quality cannot be inspected or tested into the product;
◦ Quality risk management principles should be applied in determining the
need, scope and extent of validation;
◦ Ongoing review should take place to ensure that the validated state is
maintained and opportunities for continuing improvement are identified.
7/5/2016 11Drug Regulations : Online Resource for Latest Information
12. The implementation of validation work requires considerable
resources such as:
◦ Time: generally validation work is subject to rigorous time schedules;
◦ Financial: validation often requires the time of specialized personnel and
expensive technology.
◦ Human: validation requires the collaboration of experts from various
disciplines
(e.g. a multidisciplinary team, comprising quality assurance, engineering,
information technology, manufacturing and other disciplines, as appropriate.).
7/5/2016 12Drug Regulations : Online Resource for Latest Information
13. These guidelines focus mainly on the overall concept of
validation
They are not intended to be prescriptive in specific validation
requirements.
This document serves as general guidance only
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.
7/5/2016 13Drug Regulations : Online Resource for Latest Information
14. Validation of specific processes and systems
requires much more consideration
A detailed approach that is beyond the scope of
this document.
◦ For example, in sterile product manufacture,
7/5/2016 14Drug Regulations : Online Resource for Latest Information
15. There are many factors affecting different types of validation
This document is not intended to define and address all
aspects related to one particular type of validation.
The general text in the main part of these guidelines may be
applicable to validation and qualification of
◦ Premises
◦ Equipment
◦ Utilities
◦ Systems
◦ Processes and procedures.
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16. The definitions given below apply to the terms
used in these guidelines. They may have different
meanings in other contexts.
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17. Calibration.
◦ The set of operations that establish, under specified conditions,
the relationship between values indicated by an instrument or
system for measuring (for example, weight, temperature and pH),
recording, and controlling, or the values represented by a material
measure, and the corresponding known values of a reference
standard. Limits for acceptance of the results of measuring should
be established.
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18. Change control (including change
management).
◦ A formal system by which qualified representatives of
appropriate disciplines review proposed or actual changes that
might affect a validated status.
◦ The intent is to determine the need for action that would
ensure that the system is maintained in a validated state
(reference working document
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19. Cleaning validation.
◦ Documented evidence to establish that cleaning
procedures are removing residues to
predetermined levels of acceptability, taking into
consideration factors such as batch size, dosing,
toxicology and equipment size.
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20. Commissioning.
◦ The setting up, adjustment and testing of equipment or a
system to ensure that it meets all the requirements, as
specified in the user requirement specification, and
capacities as specified by the designer or developer.
◦ Commissioning is carried out before qualification and
validation.
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21. Computer validation (including
computerized system validation).
◦ Confirmation by examination and provision of
objective documented evidence that
computerized system specifications conform to
user needs and intended uses, and that all
requirements can be consistently fulfilled.
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22. Concurrent validation.
◦ Validation carried out during routine production
of products intended for sale.
Design qualification.
◦ Documented verification that the proposed
design of facilities, systems and equipment is
suitable for the intended purpose.
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23. Good engineering practices.
◦ Established engineering methods and standards
that are applied throughout the project life-cycle
to deliver appropriate, cost-effective solutions.
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24. Installation qualification.
◦ Documented verification that the installations
(such as machines, computer system
components, measuring devices, utilities and
manufacturing areas) used in a processor system
are appropriately selected and correctly installed
in accordance with established specifications.
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25. Operational qualification.
◦ Documented verification that the system or
subsystem operates as intended over all
anticipated operating ranges.
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26. Performance qualification.
◦ Documented verification that the equipment or
system performs consistently and reproducibly
within defined specifications and parameters in
its normal operating environment
(i.e. in the production environment). (In the context
of systems, the term “process validation” may also
be used.)
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27. Process validation.
◦ The collection and evaluation of data, throughout
the product life cycle, which provides
documented scientific evidence that a process is
capable of consistently delivering quality
products.
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28. Prospective validation.
◦ Validation carried out during the development stage
on the basis of a risk analysis of the production
process, which is broken down into individual steps;
◦ these are then evaluated on the basis of past
experience to determine whether they may lead to
critical situations.
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29. Qualification.
◦ Documented evidence that premises, systems or
equipment are able to achieve the predetermined
specifications properly installed, and/or work
correctly and lead to the expected results.
Qualification is often a part (the initial stage) of
validation, but the individual qualification steps
alone do not constitute process validation.
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30. Revalidation.
◦ Repeated validation of a previously validated
system (or a part thereof) to ensure continued
compliance with established requirements.
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31. Standard operating procedure.
◦ An authorized written procedure giving instructions for
performing operations not necessarily specific to a given product
or material but of a more general nature (e.g. equipment
operation, maintenance and cleaning; validation; cleaning of
premises and environmental control; sampling and inspection).
◦ Certain standard operating procedures may be used to
supplement product-specific master batch production
documentation.
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32. Validation.
◦ Action of proving and documenting that any
process, procedure or method actually and consistently
leads to the expected results.
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33. Validation master plan.
◦ The validation master plan is a
high-level document that establishes an umbrella validation plan for the
entire project and
summarizes the manufacturer’s overall philosophy and approach, to be
used for establishing performance adequacy.
◦ It provides information on the manufacturer’s validation work programme
◦ It defines details of and timescales for the validation work to be
performed, including a statement of the responsibilities of those
implementing the plan.
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34. Validation protocol.
◦ A document describing the activities to be performed during a
validation, including the acceptance criteria for the approval of
a process or system – or a part thereof – for intended use.
Validation report.
◦ A document in which the records, results and evaluation of
validation are assembled and summarized. It may also contain
proposals for the improvement of processes and/or systems
and/or equipment.
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35. Verification.
◦ The application of methods, procedures, tests and other evaluations, in
addition to monitoring, to determine compliance with established
requirements and specifications.
Worst case.
◦ A condition or set of conditions encompassing the upper and lower
processing limits for operating parameters and circumstances, within
SOPs, which pose the greatest chance of product or process failure when
compared to ideal conditions. Such conditions do not necessarily include
product or process failure.
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36. Qualification and validation are essentially the same.
The term qualification is normally used for equipment
and utilities, and validation for systems and processes.
In this sense, qualification can be seen as part of
validation.
Where the term “validation” is used in the presentation,
the same principles may be applicable for “qualification”
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37. Approaches to validation
◦ Manufacturers should organize and plan
validation in a manner that will ensure product
quality, safety and efficacy throughout its life
cycle.
◦ The scope and extent of qualification and
validation should be based on risk management
principles.
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38. Statistical calculations should be applied,
Scientific evidence should be provided that the
process, system or other related aspect is
appropriately validated.
Qualification and validation should be done in
accordance with predetermined protocols,
The results appropriately documented, e.g. in
reports.
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39. There should be an appropriate and effective quality
system
This should ensure the organization and management of
validation.
Senior management should ensure that there are sufficient
resources to perform validation in a timely manner.
Management and persons responsible for quality
assurance should be actively involved in the process and
authorization of protocols and reports.
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40. Personnel with appropriate qualification and experience
should be responsible for performing validation.
There should be a specific programme or schedule to
support planning and execution of validation activities.
Validation should be performed in a structured way
according to the documented protocols and
procedures.
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41. The scope and extent of validation should be based
on
◦ Knowledge and experience, and
◦ Outcome of quality risk management principles
as described in the World Health Organization (WHO) guidelines on
quality risk management.
◦ Where necessary worst-case situations or specific challenge tests
should be considered for inclusion in the validation,
for example, stress load and volume verification in computer system
validation.
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42. Qualification and validation should be done
according to written procedures.
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43. Documents associated with qualification and validation
include:
◦ Specifications;
◦ Protocols and reports;
◦ Validation master plan (VMP);
◦ Standard operating procedures (SOPs);
◦ Risk assessment outcomes;
◦ Process flow charts;
◦ Operator manuals;
◦ Training records;
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44. Documents associated with qualification and validation
include:
◦ Calibration procedures and records;
◦ Sampling plans;
◦ Testing plans and methods;
◦ Statistical methods and results;
◦ History of qualification or validation;
◦ Plan for ensuring review of validation status;
◦ Plan for ensuring maintaining a validated state
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45. A manufacturer should have a VMP which reflects the key elements of
validation.
It should be concise and clear and contain at least the following:
◦ Title page and authorization (approval signatures and dates);
◦ Table of contents;
◦ Abbreviations and glossary;
◦ Validation policy; philosophy, intention and approach to validation;
◦ Roles and responsibilities of relevant personnel;
◦ Resources to ensure validation is done;
◦ Outsourced services (selection, qualification, management through life cycle);
◦ Deviation management in validation;
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46. A manufacturer should have a VMP which reflects the key elements of
validation.
It should be concise and clear and contain at least the following:
◦ Change control in validation;
◦ Risk management principles in validation;
◦ Training;
◦ Scope of validation;
◦ Documentation required in qualification and validation such as procedures,
certificates, protocols and reports;
◦ Premises qualification;
◦ Utilities qualification;
◦ Equipment qualification;
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47. A manufacturer should have a VMP which reflects the key elements of validation.
It should be concise and clear and contain at least the following:
◦ Process validation;
◦ Cleaning validation;
◦ Personnel qualification such as analyst qualification;
◦ Analytical method validation;
◦ Computerized system validation;
◦ Establishing acceptance criteria;
◦ Life-cycle management including retirement policy;
◦ Requalification and revalidation;
◦ Relationship with other quality management elements; validation matrix;
◦ References.
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48. The VMP should be reviewed at regular intervals and kept up
to date according to current GMP.
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49. There should be qualification and validation
protocols describing the qualification and
validation to be performed.
As a minimum the protocols should include the
following significant background information:
◦ See subsequent slides
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50. The objectives;
The site;
The responsible personnel
Description of the standard operating procedures (SOPs)
to be followed;
Equipment or instruments to be used;
Standards and criteria as appropriate;
The stage of validation or qualification;
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51. The processes and/or parameters;
Sampling, testing and monitoring requirements;
Stress testing where appropriate;
Calibration requirements;
Predetermined acceptance criteria for drawing
conclusions; review and interpretation of results;
Change control, deviations;
Archiving and retention.
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52. There should be a description of the way in which
the results will be analyzed
This should include statistical analysis where
appropriate
The protocol should be approved prior to use.
Any changes to a protocol should be approved
prior to implementation of the change.
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53. There should be written reports on the qualification and
validation performed.
Reports should reflect the protocols and procedures followed
They should
◦ Include at least the title and objective of the study;
◦ Make reference to the protocol;
◦ Reference to the appropriate risk assessment;
◦ Details of materials, equipment, programmes and cycles used;
procedures and test methods with appropriate traceability.
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54. Results should be recorded
They should be in compliance with good data and record
management practices.
Results should be
Reviewed, analyzed and compared against the justified
predetermined acceptance criteria,
Interpreted and statistically analysed where appropriate.
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55. Results should meet the acceptance criteria.
Deviations, out-of specification and out-of-limit results
should be documented.
They should be investigated according to appropriate
procedures.
If these deviations are accepted, this should be justified.
Where necessary, further studies should be performed.
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56. The conclusion of the report should state whether or not
the outcome of the qualification and/or validation was
considered successful,
They should make recommendations for future monitoring
and setting of alert and action limits where applicable.
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57. The departments responsible for the qualification
and validation work should approve the completed
report.
The quality assurance department should approve
the report after the final review.
The criteria for approval should be in accordance
with the company’s quality assurance system.
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58. Any deviations found during the validation process
should be managed and documented.
Corrective actions should be considered.
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59. There are different approaches in qualification and
validation.
The manufacturer should select an appropriate
approach for the conduct thereof.
Figure 1 gives the V-model as an example of an
approach to qualification and validation.
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61. All relevant SOPs for operation, maintenance and
calibration should be prepared during qualification.
Training should be provided to operators and
training records should be maintained.
Normally, qualification should be completed before
process validation is performed
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62. The process of qualification
◦ Should be a logical, systematic process and
◦ Should follow a logical flow from the premises,
◦ Followed by utilities, equipment, to procedures and
processes.
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63. Stages of qualification
Should normally start with the preparation of user requirement
specifications (URS).
Depending on the function and operation of the utility, equipment or
system,
This is followed by different stages in qualification
◦ Factory acceptance test (FAT)
◦ Site acceptance test (SAT)
◦ Design qualification (DQ)
◦ Installation qualification (IQ)
◦ Operational qualification (OQ)
◦ Performance qualification (PQ)
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64. One stage of qualification should be successfully completed
before the next stage is initiated, e.g. from IQ to OQ.
In some cases, only IQ and OQ may be required,
◦ In such instances the correct operation of the equipment, utility or system
could be considered to be a sufficient indicator of its performance.
Major equipment and critical utilities and systems, however,
may require URS, DQ, IQ, OQ and PQ.
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65. Computerized systems, including equipment with software
component(s), require
User and functional requirements specifications
Design and configuration specifications
Development of SOPs
Training programmes for system use and administration
An appropriate level of IQ, OQ and PQ verification testing.
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66. This includes tests such as
Stress
Load
Volume and other performance verification tests that mimic
the live production environment.
It also includes
◦ User acceptance testing according to draft SOPs
◦ Training as well as end-to-end business processes for intended use.
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67. User requirement specifications
◦ Manufacturers should prepare a document that describes the
utility or equipment to be sourced.
◦ The requirements and specifications for the utility or equipment
should be defined by the user and documented in the URS.
◦ The URS should be used
When selecting the required utility or equipment from an approved
supplier,
To verify suitability throughout the subsequent stages of qualification.
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68. Factory acceptance test and site acceptance
test
◦ Where appropriate, FAT and SAT should be performed to
verify the suitability of the system at site, prior to the
subsequent stages of qualification.
◦ This should be appropriately documented.
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69. Design qualification
◦ DQ should provide documented evidence that the design
specifications were met and are in accordance with the URS.
Installation qualification
◦ IQ should provide documented evidence that the
installation was complete and satisfactory.
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70. The design specifications, including purchase specifications,
drawings, manuals, spare parts lists and vendor details should be
verified during IQ
Similarly the configuration specifications for the intended
operational environment should be verified.
Components installed should be verified
There should be documented evidence to demonstrate that
components meet specifications, are traceable and are of the
appropriate material of construction
Control and measuring devices should be calibrated.
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71. Operational qualification
◦ OQ should provide documented evidence that utilities, systems or
equipment and all its components operate in accordance with operational
specifications
◦ Tests should be designed to demonstrate satisfactory operation over the
normal operating range as well as at the limits of its operating conditions
(including worst-case conditions).
◦ Operation controls, alarms, switches, displays and other operational
components should be tested.
◦ Measurements made in accordance with a statistical approach should be
fully described.
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72. Performance qualification
◦ P Q should be conducted prior to release of the utilities, systems
or equipment
Under conditions simulating conditions of intended use
To provide documented evidence that utilities, systems or equipment
and all its components can consistently perform in accordance with the
specifications under routine use.
Test results should also be collected over a suitable period of time
This should be during continuous process verification and/or periodic
review and monitoring of the utilities, systems and equipment to prove
consistency.
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73. Requalification
Utilities, systems and equipment should be maintained in a validated state.
Any changes made to these should be managed through the change control
procedure.
The extent of validation or qualification as a result of such a change should be
determined based on risk management principles.
Requalification should be done based on the identified need.
The requalification should be considered based on risk management principles.
Factors such as the frequency of use, breakdowns, results of operation, criticality,
preventive maintenance, repairs, calibration, verification may be considered.
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74. Requalification
Changes of equipment which involve the replacement of
equipment on a “like-for-like” basis will require requalification.
Replacement of parts may not require full requalification.
Where a system, utility or equipment has not been used for an
extended period of time, requalification may have to be
considered.
Where appropriate, periodic requalification may be performed.
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75. Revalidation
◦ Systems should be in place to ensure that procedures remain in a
validated state,
◦ e.g. such as through verification in cleaning validation and analytical
method validation.
◦ Revalidation should be done when the need is identified.
◦ Where periodic revalidation is done, this should be done in accordance
with a defined schedule to ensure that the validated state is maintained.
◦ Periodic revalidation should be considered as some process changes may
occur gradually over a period of time, or because of wear of equipment.
◦ The frequency and extent of revalidation should be determined using a
risk-based approach together with a review of historical data.
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76. Process validation
“New approach”
◦ It is recommended that manufacturers implement the new approach in
process validation. See Guidelines on process validation.
“Traditional approach”
◦ Where the “traditional approach” in process validation is followed, the
need for validation should be considered, e.g. through product quality
review.
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77. Changes should be controlled in accordance with an SOP
as changes may have an impact on a qualified utility or piece of
equipment, and a validated process, system and/or procedure.
When a change is initiated, consideration should be given
to previous changes and whether requalification and/or
revalidation is needed as a result of the cumulative effect of the
changes.
The procedure should describe the actions to be taken, including
the need for and extent of qualification or validation to be done.
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78. Deviations during validation and qualification should
be documented and investigated, through the deviation
management procedure
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79. Calibration and verification of equipment, instruments and other
devices, as applicable, should be initiated during installation
qualification
It should be ensured that the system operates according to the
described specifications
This is because the calibration status could have been affected
during transport and installation.
Thereafter, it should be performed at regular intervals in
accordance with a calibration programme and SOPs.
Personnel who carry out calibration and preventive maintenance
should have an appropriate qualification and training.
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80. A calibration programme should be available and should
provide information such as calibration standards and limits,
responsible persons, calibration intervals, records and actions
to be taken when problems are identified.
There should be traceability to standards (e.g. national,
regional or international standards) used in the calibration.
A valid certificate of calibration should be maintained which is
dated and includes reference to and traceability to,
◦ e.g. standards used, acceptance limits, uncertainty where applicable,
range, calibration due date.
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81. Calibrated equipment, instruments and other devices should
be labelled, coded or otherwise identified to indicate the
status of calibration
It should also have the date on which recalibration is due.
When the equipment, instruments and other devices have not
been used for a certain period of time, their function and
calibration status should be verified and shown to be
satisfactory before use.
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82. Equipment, instruments and other devices should be
calibrated before or on the due date for calibration to ensure
that they remain in a calibrated state.
Where instruments and devices are identified as critical or
non- critical, or impacting and non-impacting for the
purpose of calibration, documented evidence of the decision
making process should be available.
This should include impact and or risk assessment.
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83. This presentation is compiled from freely available
resource like the website of WHO, specifically the
WHO Draft Guidance on Process Validations.
“Drug Regulations” is a non profit organization
which provides free online resource to the
Pharmaceutical Professional.
Visit http://www.drugregulations.org for latest
information from the world of Pharmaceuticals.
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