In the last year or so the FDA and the EMA have issued new guidance/ draft guidance on "Process Validation".These align process validation activities with a product lifecycle concept and the International Conference on Harmonisation (ICH)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.
In the last year or so the FDA and the EMA have issued new guidance/ draft guidance on "Process Validation".These align process validation activities with a product lifecycle concept and the International Conference on Harmonisation (ICH)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.
The Validation Master Plan is a a valuable opportunity to provide an overview of your company’s validation process, including organization structure, content, and planning.
Pharmaceutical Validation, its scope and types. Validation Team. validation Master plan. Validation protocols. Elements of Validation. Approaches of Validation. Dosage form Validation along with example of Validation of Tablet Dosage form.
Process validation is a requirement of the current Good Manufacturing Practices (cGMP) Regulations for Finished Pharmaceuticals. Validation is defined as a documented program that provides a high degree of assurance that a specific process, method, or system will consistently produce a result meeting pre-determined acceptance criteria.
This workshop examines the approach to Continued Process Verification and demonstrating that your product and process are operating in a state of control and continue to do so over the life of the product. Without any prior coordination, the theme was elaborated by the afternoon speakers once the conference itself was underway. The concept of “step up step down” for adjusting the level of product scrutiny both for process parameters monitoring and for sampling and testing quality attributes was explored and developed.
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.
Regulatory aspect of pharmaceutical change control systemDeveshDRA
CHANGE CONTROL,BENEFITS OF CHANGE CONTROL SYSTEM,MANAGEMENT OF CHANGE AND CONTINUOUS IMPROVEMENT(Prepare a Change Proposal,Classify & Approve Proposed Changes,Develop an Implementation Plan, Install the Change,Verify Installation,Close out the change
) FLOW CHART OF CHANGE MANAGEMENT,HANDLING AND CONTROLLING CHANGES,SOP ON CHANGE CONTROL SYSTEM,
CATEGORY OF CHANGES(Major Changes,Moderate changes,Minor changes),ENSURING TRAINING & PROCEDURES IN A MANAGEMENT OF CHANGE PROGRAM,LEVEL OF APPROVAL,REGULATOR PROSPECTIVE OF CHANGE CONTROL(21 CFR Part 211: Sec. 211.100,21 CFR Part 211.194 (Laboratory Records),ICH Q7A,USFDA Guidance for Industry: Change to an approved NDA or ANDA ( April 2004- Revison-1)),CONCLUSION
,
Process Validation is Key important factor for the Pharmaceutical Industry to maintain Consistent Quality in product which claimed by the manufacturer.
The Validation Master Plan is a a valuable opportunity to provide an overview of your company’s validation process, including organization structure, content, and planning.
Pharmaceutical Validation, its scope and types. Validation Team. validation Master plan. Validation protocols. Elements of Validation. Approaches of Validation. Dosage form Validation along with example of Validation of Tablet Dosage form.
Process validation is a requirement of the current Good Manufacturing Practices (cGMP) Regulations for Finished Pharmaceuticals. Validation is defined as a documented program that provides a high degree of assurance that a specific process, method, or system will consistently produce a result meeting pre-determined acceptance criteria.
This workshop examines the approach to Continued Process Verification and demonstrating that your product and process are operating in a state of control and continue to do so over the life of the product. Without any prior coordination, the theme was elaborated by the afternoon speakers once the conference itself was underway. The concept of “step up step down” for adjusting the level of product scrutiny both for process parameters monitoring and for sampling and testing quality attributes was explored and developed.
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.
Regulatory aspect of pharmaceutical change control systemDeveshDRA
CHANGE CONTROL,BENEFITS OF CHANGE CONTROL SYSTEM,MANAGEMENT OF CHANGE AND CONTINUOUS IMPROVEMENT(Prepare a Change Proposal,Classify & Approve Proposed Changes,Develop an Implementation Plan, Install the Change,Verify Installation,Close out the change
) FLOW CHART OF CHANGE MANAGEMENT,HANDLING AND CONTROLLING CHANGES,SOP ON CHANGE CONTROL SYSTEM,
CATEGORY OF CHANGES(Major Changes,Moderate changes,Minor changes),ENSURING TRAINING & PROCEDURES IN A MANAGEMENT OF CHANGE PROGRAM,LEVEL OF APPROVAL,REGULATOR PROSPECTIVE OF CHANGE CONTROL(21 CFR Part 211: Sec. 211.100,21 CFR Part 211.194 (Laboratory Records),ICH Q7A,USFDA Guidance for Industry: Change to an approved NDA or ANDA ( April 2004- Revison-1)),CONCLUSION
,
Process Validation is Key important factor for the Pharmaceutical Industry to maintain Consistent Quality in product which claimed by the manufacturer.
Controlled Release Oral Drug Delivery System
Controlled drug delivery is one which delivers the drug at a predetermined rate, for locally or systemically, for a specified period of time.
Computerized System Validation Business Intelligence SolutionsDigital-360
Executive Summary
Regulated pharmaceutical, biotech and medical device companies are challenged to develop manufacturing capabilities quickly and cost-effectively while at the same time safeguarding product quality and patient safety.
Validation has been an essential part of regulated industries for over 20 years, yet as the field has evolved, little has changed in the business, or manual, approach to validation.
ICH guidelines for validation Of Equipments by Nikita Sahu[1].pptxNikitaSahu39
VALIDATION- As per WHO,
Validation means providing documented evidence that any procedure, process, activity or system actually leads to the expected results.
As per FDA , Validation is establishing documented evidence, which provides a high degree of assurance that a specific process will produce a product meeting its pre determined specification & quality attributes.
In this presentation from, Janeen Santorosa discusses the best practices for harmonization of GMP auditing, domestic and international regulations for supplier auditing, integration of risk-based practices, and supplier audit practice tools.
In this presentation from IVT's 4th Annual Validation Week EU, Paul Pluta, discussed the differences between the traditional approach to cleaning validation and the lifecycle approach, applicable regulatory guidance, current industry trends, the necessary phases of the lifecycle approach (design and definition, cycle development, validation, and implementation), how to continously monitor the process, change control, and common obstacles to compliance.
This session from the Institute of Validation Technology's 14th Annual CSV Conference looks at B. Braun’s journey in moving from an in-house validated training tracking system to learning management in the cloud.
In this session from the Institute of Validation Technology's Validation Week Europe, Kurtis Epp and John Kandl discuss how to implement QbD to all three stages of process validation.
This presentation from the Institute of Validation Technology's first annual Validation and cGMP Compliance Week Singapore discusses the obstacles to quality such, the key components to improve quality, and the tools for strategic teamwork.
This session from the Institute of Validation Technology's Contamination and Control Week discusses regulatory expectations and industry drivers for aseptic cleaning and environmental monitoring, regulatory expectations for cleanrooms, and current FDA and EU expectations during inspection of sterile and aseptic operations.
In this presentation from the Institute of Validation Technology's Life Sciences Aseptic Processing, Kim Van Antwerpen discusses collecting environmental data, methods for trending, and interpreting and sharing environmental monitoring data.
Regulatory inspections have had a significant impact on the number of drug shortages and companies facing adverse regulatory actions.
Review of the inspection trends can be useful in assessing the regulatory status of your own company and help aid in the preparation for upcoming inspections. This session from IVT's Contamination and Control Week provides an in-depth, practical look at some of the recent Warning Letters and discusses current trends.
Regulatory guidelines on stability testing are mainly designed to address studies that will be applied to support NDAs. However, in any pharmaceutical development program, a number of other stability studies are also required, for example, to help select appropriate formulations and to support regulatory applications for clinical programs. This session from the Institute of Validation Technology's Stability Programs Forum outlines a number of examples of early development stability studies.
This presentation from IVT's 4th Annual reviews what to do when you have an exception, critical vs. non-critical exceptions, and learning how to prevent exceptions.
This presentation from IVT's 4th Annual Validation Week Europe provided a thorough explanation of developing a gap analysis, areas in validation that are issues of concern, and FDA expectations of a manufacturer's gap analysis.
In this presentation from Validation Week Europe, Karen Ginsbury discusses the rigors, preparations, strategies, and the do's and the don't of the FDA Inspection process.
In this presentation from IVT's GMP Week, Journal of Validation Technology Editor-in-Chief, Paul Pluta, Ph.D., asks "can compliance be improved by using quality by design [QbD] concepts?" Pluta discussed the QbD application, development of validation master plans, and the lifecycle approach to process validation. Furthermore, he discusses how to incorporate these essential parts of the validation process to implement effective, and efficient, compliance by design into the quality system.
This presentation from IVT's 2nd Annual Validation Week Canada covers the 2011 FDA Process validation and the subsequent statistical processes. Statistics in process validation is introduced as well as the integration with six sigma and solutions to common mistakes.
A comprehensive presentation on GMP systems and integration. This includes validations, vendor qualification, preventative maintenance, audits, CAPA, and utilization of system results.
This presentation from IVT Network's Method Validation Conference covers required and suggested regulations and guidances for biological process specifications. It also covers dosage form considerations and specifications for other components.
This presentation from the Institute of Validation Technology's 7th Annual Method Validation covers regulatory expectations for deviations and out-of-specification results and protocol exceptions, change control, handing investigations and CAPAs, and avoiding common pitfalls.
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
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.
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.
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.
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
- 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
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
Hemodialysis: Chapter 3, Dialysis Water Unit - Dr.Gawad
Implement Process Validation
1. Institute of Validation Technology
Validation Week- Philadelphia
Session 4: Best Practice to Implement Process
Validation in Device Manufacturing Enterprise-
wide
Tanya Fletcher-Scott
Validation Manager- Greenville SC Solutions Facility
Tanya.Fletcher-Scott@Bausch.com
October 24, 2012
CONFIDENTIAL [1]
2. Agenda
£ Getting Started-Overview
£ Process Validation
£ Enterprise wide Roll Out of Process Validation
£ Interactive Exercise
Look out for
the
Best
Practice
[2]
3. Getting Started-Overview
o The Rules- Review of Standards and Guidances for
Process Validation of Devices
o Tools- Risk Assessments and Statistics
o The Team- Don’t go it alone!
o The Docs- Documenting the process validation
activities
[3]
4. Getting Started-Overview
The Rules- Review of Standards and Guidances for Process
Validation of Devices:
• 21 CFR 820 Quality System Regulators
• ISO, EN ISO 13485 Medical devices- Quality management
systems- Requirements for regulatory purposes
• ISO, EN ISO 14971 Medical devices-Application of risk
management to medical devices
Best Practice:
• ISO, EN ISO 9001 Quality management systems —Requirements your
Know
regs and
guidances
[4]
5. Getting Started-Overview
The Rules- Review of Standards and Guidances for Process
Validation of Devices:
• GHTF, Global Harmonization Task Force- Quality management
Systems-Process Validation Guidance*
• SOR/98-282 Canadian Medical Regulators
Best Practice:
Know your
• 93/42/EEC Medical Device Directive
regs and
guidances
*Copy provided as bonus material
[5]
6. Getting Started-Overview
The Rules- Review of standards and guidances for Process
Validation of Devices:
21 CFR 820 Quality System Regulators
Sec. 820.70 Production and process controls.
b-Production and process changes. Each manufacturer shall
establish and maintain procedures for changes to a specification,
method, process, or procedure. Such changes shall be verified or
where appropriate validated according to 820.75 (Process
Validation), before implementation and these activities shall be
documented. Changes shall be approved in accordance with 820.40
(Document controls).
[6]
7. Getting Started-Overview
The Rules- Review of standards and guidances for Process
Validation of Devices:
Sec. 820.75 Process Validation.
a- Where the results of a process cannot be fully verified by
subsequent inspection and test, the process shall be validated with
a high degree of assurance and approved according to established
procedures. The validation activities and results, including the date
and signature of the individual(s) approving the validation and
where appropriate the major equipment validated, shall be
documented.
b- Each manufacturer shall establish and maintain procedures for
monitoring and control of process parameters for validated
process to ensure that the specified requirements continues to
be met.
[7]
8. Getting Started-Overview
The Rules- Review of standards and guidances for Process
Validation of Devices:
ISO, EN ISO 13485 Medical devices- Quality management systems-
Requirements for regulatory purposes
7 Product realization, 7.1 Planning of product realization
The organization shall plan and develop the processes needed for product
realization. Planning of product realization shall be consistent with the
requirements of the other processes of the quality management system. In
planning product realization, the organization shall determine the following, as
appropriate:
a) quality objectives and requirements for the product;
b) the need to establish processes, documents, and provide resources specific to
the product;
c) required verification, validation, monitoring, inspection and test activities
specific to the product and the criteria for product acceptance;
d) records needed to provide evidence that the realization processes and
resulting product meet requirements
[8]
9. Getting Started-Overview
The Rules- Review of standards and guidances for Process
Validation of Devices:
ISO, EN ISO 13485 Medical devices- Quality management systems-
Requirements for regulatory purposes
7.5.2 Validation of processes for production and service provision
The organization shall validate any processes for production and service
provision where the resulting output cannot be verified by subsequent monitoring
or measurement. This includes any processes where deficiencies become
apparent only after the product is in use or the service has been delivered.
Validation shall demonstrate the ability of these processes to achieve planned
results. The organization shall establish arrangements for these processes
including, as applicable
a) defined criteria for review and approval of the processes,
b) approval of equipment and qualification of personnel,
c) use of specific methods and procedures,
d) requirements for records and
e) revalidation.
[9]
10. Getting Started-Overview
Tools- Risk Assessments and Statistics Best
Practice:
Use your
statisticians
Statistics
Sec. 820.250 Statistical techniques.
(a) Where appropriate, each manufacturer shall establish and maintain
procedures for identifying valid statistical techniques required for
establishing, controlling, and verifying the acceptability of process
capability and product characteristics.
(b) Sampling plans, when used, shall be written and based on a valid
statistical rationale. Each manufacturer shall establish and maintain
procedures to ensure that sampling methods are adequate for their
intended use and to ensure that when changes occur the sampling
plans are reviewed. These activities shall be documented.
[ 10 ]
11. Getting Started-Overview
Tools- Risk Assessments and Statistics
ISO 13485
8 Measurement, analysis and improvement, 8.1 General
The organization shall plan and implement the monitoring, measurement,
analysis and improvement processes needed
a) to demonstrate conformity of the product,
b) to ensure conformity of the quality management system, and
c)to maintain the effectiveness of the quality management system.
This shall include determination of applicable methods, including statistical
techniques, and the extent of their use.
[ 11 ]
12. Getting Started-Overview
Risk Analysis
Tools- Risk Assessments and Statistics
Risk Assessments
ISO 14971 Medical devices —
Application of risk management Risk Evaluation
to medical devices
Risk Control
The ISO Standard defines risk as
combination of the probability of
occurrence of harm and the
severity of that harm
Evaluation of overall
residual risk acceptability
Risk Management Report
Production and post-
production information
[ 12 ]
13. Getting Started-Overview
Tools- Risk Assessments and Statistics
Risk Management Tools
• Preliminary Hazard Analysis (PHA) is a technique that
can be used early in the development process to
identify the hazards, hazardous situations, and events
that can cause harm when few of the details of the
medial device design are known.
• Fault Tree Analysis (FTA) is especially useful in safety
engineering, early in the development stages, for the
identification and prioritization of hazards and
hazardous situations as well as for analyzing adverse
events.
[ 13 ]
14. Getting Started-Overview
Tools- Risk Assessments and Statistics
Risk Management Tools
• Failure Mode and Effects Analysis (FMEA) and Failure
Mode, Effects and Criticality Analysis (FMECA) are
techniques by which an effect or consequences of
individual components are systematically identified and is
more appropriate as the design matures.
• Hazard and Operability Study (HAZOP) and Hazard
Analysis and Critical Control Point (HACCP) are typically
used in the latter stages of the development phase to
verify and then optimize design concepts or changes.
[ 14 ]
15. Getting Started-Overview
The Team- Don’t go it alone!
The types of products manufactured in the
Greenville facility are lens care solutions.
When we are conducting a process validation
to support a product transfer or significant
formulation change, we need the support of a
cross functional group inclusive of corporate
and site wide subject matter experts.
[ 15 ]
16. Getting Started-Overview
The Team- Don’t go it alone!
The Global Harmonization Task Force- Quality Management Systems –
Process Validation Guidance suggests the following subject matter team
members:
• Quality Assurance*
Best
• Engineering* Practice:
• Manufacturing* Project Managers
are key to any
• Laboratory (Chemistry and Microbiology)* success tech
• Technical Services transfer
• Research & Development*
• Regulatory Affairs*
• Clinical Engineering
• Purchasing/Planning
• Process Excellence / Statistician*
• Project Manager*
*B+L’s typical team core members for major process validation projects
[ 16 ]
17. Getting Started-Overview
The Docs- Documenting the process validation activities
Sec. 820.75 Process Validation.
a- Where the results of a process cannot be fully verified
by subsequent inspection and test, the process shall be
validated with a high degree of assurance and approved
according to established procedures. The validation
activities and results, including the date and signature of
the individual(s) approving the validation and where
appropriate the major equipment validated, shall be
documented.
[ 17 ]
18. Getting Started-Overview
The Docs- Documenting the process validation activities
The Global Harmonization Task Force- Quality Management Systems –
Process Validation Guidance suggests the following elements in your
process validation protocols:
Elements Validation IQ OQ PQ PV
Strategy
Identification of the process to be validated X X X X X
Identification of device(s) to be manufactured X X X X X
using this process
Objective and measurable criteria for a X X X X X
successful validation
Identification of operators and required operator X X
Best
qualification Practice:
Validation
Strategies are a
great tool for ‘big
scope’ projects
[ 18 ]
19. Getting Started-Overview
The Docs- Documenting the process validation activities
The Global Harmonization Task Force- Quality Management Systems –
Process Validation Guidance suggests the following elements in your
process validation protocols:
Elements Validation IQ OQ PQ PV
Strategy
X
Length and duration of the validation
X X
Shifts, operators, equipment to be used in the
process
X X X X
Any subjective criteria used to evaluate the
product
X X
Identification of utilities for the process
equipment and quality of the utilities
X X X X X
Complete description of the process
[ 19 ]
20. Getting Started-Overview
The Docs- Documenting the process validation activities
The Global Harmonization Task Force- Quality Management Systems –
Process Validation Guidance suggests the following elements in your
process validation protocols:
Elements Validation IQ OQ PQ PV
Strategy
X X X X
Relevant specifications that relate to the
product, components, manufacturing
materials, etc
X X
Process parameters to be monitored, and
methods for controlling and monitoring*
X X
Product characteristics to be monitored and
method for monitoring*
X X
Any subjective criteria used to evaluate the
product
*Use of a Control Plan is a great tool and best practice. Example included in bonus material
[ 20 ]
21. Getting Started-Overview
The Docs- Documenting the process validation activities
The Global Harmonization Task Force- Quality Management Systems –
Process Validation Guidance suggests the following elements in your
process validation protocols:
Elements Validation IQ OQ PQ PV
Strategy
X X X X X
Definition of what constitutes non-
conformance for both measurable and
subjective criteria
X X X X
Statistical methods for data collection and
analysis
X
Consideration of maintenance and
repairs of manufacturing equipment
X
Criteria for revalidation
When it’s all done, generate the final report summarizing all
requirements, results, issues and conclusions
[ 21 ]
22. Agenda
£ Getting Started-Overview
£ Process Validation
£ Enterprise wide Roll Out of Process Validation
£ Interactive Exercise
[ 22 ]
23. Process Validation
o Creating a strategy/validation plan
o Strategies for new and existing products
o Runs and samples
o When are you done?
[ 23 ]
24. Process Validation
Creating a strategy/validation plan
A Validation plan which defines what needs to be validated (i.e.
equipment, systems and processes) and how validation needs will be
met for a given project.
The strategy also provides a roadmap to follow ensuring the
requirements are defined and agreed upon up-front and that all
requirements are met prior to implementation or launch
Best
Practice:
Wait until you
have created or
updated your risk
assessment
before generating
a strategy.
[ 24 ]
25. Process Validation
Creating a strategy/validation plan
B+L’s validation systems does not require validation strategies for smaller, less
complex validation projects whose strategy can be fully detailed within a protocol.
The strategy is useful to communicate completion of validation strategy activities
and results of the testing performed to support product Launch or Design Change
Implementation
<Let’s review the sample validation strategy in your bonus material>
[ 25 ]
26. Process Validation
Strategies for new and existing products
New Products
Per ISO 9001, all new products must under Design and development
which includes:
• Planning
• Design and development inputs
• Design and development outputs
• Design and development review
• Design and development verification
• Design and development validation*
• Control of design and development changes*
*At the completion of the design and development validation and
before the control of design changes, product transfer and process
validation occurs.
[ 26 ]
27. Process Validation
Strategies for new and existing products
New Products
During the product transfer process, the product is being evaluated
at the manufacturing site for scale up.
It is at this stage that the use of statistician can help evaluate
process capability and readiness for process validation. Also
helpful with defining acceptance criteria, number of Best
samples, etc. Practice:
During the product
transfer stage there
Risk analysis can be a great tool in defining worse needs to be high
case conditions a process can potential see in routine engagement with site
validation
manufacturing. These failure modes can be tested
in product evaluation and/or validation trials.
(reference validation strategy risk mitigation table)
[ 27 ]
28. Process Validation
Strategies for new and existing products
New Products
Process Validation Readiness should include the following:
• Design review confirms process is capable
• All prerequisite validations are complete (e.g. equipment,
facility, software, etc.)
• Process control plan has been created or updated*
• Risk analysis has been updated
*<Let’s review the sample control plan in your bonus material>
[ 28 ]
30. Process Validation
Strategies for new and existing products
New Products
Process Validation Readiness should include the following:
• All procedures, batch records, inspection plans,
specifications, drawings are updated and approved.
• All impacted personnel are trained on procedure, batch
records, inspection plans, etc.
• All raw materials are procured and in approved status
• All new suppliers are in approved status
<Let’s review the sample readiness form in your bonus material>
[ 30 ]
32. Process Validation
Strategies for new and existing products
Existing Products
Existing products are defined as validated products that have
been transferred to the manufacturing site for routine
manufacture. For validations involving any existing product,
B+L follows a global change management process.
Sec. 820.70 Production and process controls.
b-Production and process changes. Each manufacturer shall establish
and maintain procedures for changes to a specification, method,
process, or procedure. Such changes shall be verified or where
appropriate validated according to 820.75 (Process Validation), before
implementation and these activities shall be documented. Changes shall
be approved in accordance with 820.40 (Document controls).
[ 32 ]
33. Process Validation
Strategies for new and existing products
Existing Products
B+L’s global change management software tracks all changes for
existing products.
Depending on the scope of the change; a limited, extensive or full
revalidation may need to be conducted. A key element of change control
is the impact analysis. The impact analysis considers the impact of the
change to the risk management file. Best
Practice:
A Validation
representative
needs to evaluate
changes impacting
validated state.
[ 33 ]
34. Process Validation
Strategies for new and existing products
Existing Products
A useful tip is to work with your Research and Development group
or Technical Services group to evaluate the capability of the
product device after proposed change.
Pros:
• Better process understanding
• Greater confidence in the process to pass when you go into live
validation.
Cons:
• May require additional equipment, line time, resources, lab support to
generate data
• Cost of material/product that may need to be scrapped
It’s a Risk decision
[ 34 ]
36. Process Validation
Runs and Samples
How many runs do we need???
How many samples do we need to take???
[ 36 ]
37. Process Validation
Runs and Samples
How many runs do we need???
How many samples do we need to take???
Can we runs this concurrent with production???
[ 37 ]
38. Process Validation
Runs and Samples
How many runs do we need???
How many samples do we need to take???
Can we runs this concurrent with production???
It depends on the scope, level of risk and confidence we have in the
process. It’s a question of risk!
[ 38 ]
39. Process Validation
Runs and Samples
For the number of runs, we use 3 as a starting point. We let our risk
assessment drive the number of runs needed. Example:
There is a process change that will impact the manufacturing of a
formulation in 2 different tanks. Our engineering data indicates that although
the 2 tanks are the same size they are both designed differently and have
different heating and agitation profiles. A risk analysis indicates that heating
and agitation may have significant impact on product acceptance. For this
process validation a minimum of 6 runs (3 runs/tank) may be recommended
in addition to engineering trials to confirm capability of the formulation.
[ 39 ]
40. Process Validation
Runs and Samples
In sampling, we target confidence level of at least 90%. We also let our
risk analysis drive the number and type of samples needed. There
needs to be an understanding of what’s important to your process.
Let’s illustrate this point with the validation of Product XYZ
[ 40 ]
41. Process Validation
Runs and Samples
Overview of product and manufacturing process for Product XYZ
£ Raw Materials: Best
Practice:
• Sterile Water A key to the
• NaCL sampling rationale
is found in the
• Raw Material A CQA’s. They
define what’s
• Raw Material B (new) important
• Excipients
£ Critical Quality Attributes (CQAs).
• Solution is safe and effective for intended purpose (attribute or go/no-go)
• Batch is homogeneous (variable data)
• Raw Materials A and B must meet label claim (attribute or go/no-go)
[ 41 ]
42. Process Validation
Runs and Samples
Product XYZ
Bulk Sterile Packaging
Compounding Filling
Step 1
• Purified Water
Step 3
• Add Excipents
• Mix and Sterile filter Raw
• Heat sterilize mixture
Materials A and B
CPPs=batch temp,
agitation speed 19,000 L CPP=batch temp, mix time
Tank
Step 4
Step 2 • Mix dissolve and Sterile
filter NaCL and excipients
• Mix, dissolve and Sterile
filter excipents CPP=batch temp, mix
time
CPP=batch temp, mix time
CPP=Critical Process Parameter
[ 42 ]
43. Process Validation
Runs and Samples
Product XYZ
Bulk Sterile Packaging
Compounding Filling
CPP= Line length,
product conditioning
19,000 L volume, filling speed, etc.
Tank
[ 43 ]
44. Case Study- Process Validation for Product XYZ
Runs and Samples
Bulk Sterile Packaging
Compounding Filling
• Our product and process risk assessment identified both the bulk compounding
and sterile filling process steps as having the highest potential risk. Critical Quality
Attributes (CQAs).
• Solution is safe and effective for intended purpose (most likely impacted in bulk
compounding and sterile filling process)
• Batch is homogeneous (most likely impacted in bulk compounding)
• Raw Materials A and B must meet label claim (most likely impacted in bulk
compounding)
• We focused more effort (sampling and runs) on these high risk process steps
during scale up and process validation
[ 44 ]
45. Process Validation
Runs and Samples
Bulk Sterile Packaging
Compounding Filling
• Based on historical data and information from our risk assessments, the heaviest
use of statistics (sampling) was focused on the bulk compounding and sterile filling
processes as we needed to demonstrate a high level of assurance at these stages.
• We used process capability data from similar products and development work to
establish standard deviations for Raw Materials A and B.
• Our sample size was based on the use of standard deviations from engineering
trials, 90% Confidence
• For batch and bottle homogeneity we demonstrated with 90%Confidence that
batch and bottle sample sets were homogeneous.*
[ 45 ]
46. Process Validation
When are you done?
Now that the execution is complete with your
Process Validation and Final Report has been
written and approved,
Are You Done?
[ 46 ]
47. Process Validation
When are you done?
According to GHTF - Quality Management Systems Process
Validation Guidance, you should maintain a state of
validation:
• Monitor and control
• Changes in processes and/or product
• Continued state of control
[ 47 ]
48. Process Validation
When are you done?
Most companies including B+L are using the product quality review
process to confirm medical device products are maintained in a state of
control. Key attributes include:
• In process and final product manufacturing trend data
• Complaints
• Non-conformances
• Corrective Preventive Actions
• Stability
• Changes and subsequent validations
[ 48 ]
49. Agenda
£ Getting Started-Overview
£ Process Validation
£ Enterprise wide Roll Out of Process Validation
£ Interactive Exercise
[ 49 ]
50. Enterprise wide Roll Out of Process Validation
o Enterprise-wide policies and procedures
o Quality System standardization, design management, change
management and validation
o Train personnel
[ 50 ]
51. Enterprise wide Roll Out of Process Validation
Enterprise-wide policies and procedures
The CFR requires established procedures to conduct process validation and
support monitoring and control of process parameters.
Sec. 820.75 Process Validation.
a- Where the results of a process cannot be fully verified by subsequent
inspection and test, the process shall be validated with a high degree of
assurance and approved according to established procedures. The
validation activities and results, including the date and signature of the
individual(s) approving the validation and where appropriate the major
equipment validated, shall be documented.
b- Each manufacturer shall establish and maintain procedures for
monitoring and control of process parameters for validated process to
ensure that the specified requirements continues to be met.
[ 51 ]
52. Enterprise wide Roll Out of Process Validation
Enterprise-wide policies and procedures
Best practices for a multi-site / global company to deploy process validation
procedures is Enterprise-wide policies and procedures:
Pros:
• Provides clear instruction for ‘how things are done’.
• Offers consistent approach to validation to train to and follow regardless of site
location, manufacturing platform, products manufactured
• Presents to regulators the company’s position on process validation
• Capitalize on best practices at each site. Best
• Ensures alignment to guidances, standards and industry best Practice:
practices In addition to policies
and procedures,
templates provide
consistency
[ 52 ]
53. Enterprise wide Roll Out of Process Validation
Enterprise-wide policies and procedures
Cons:
• Difficult to gain consensus with multiple sites who have always ‘done it
their way’.
• Procedures and templates may not be flexible to meet needs of different
products, manufacturing platforms
• Learning curve and time to implement
Tips for Enterprise-Wide roll out are:
• Getting engagement and feedback from stakeholders at the
manufacturing site. Feedback should be from each type of
manufacturing site.
• Deploy procedures and templates on a trial basis to ‘validate’ its use.
• Allow extended phase in period (60-90 days) for training
[ 53 ]
54. Enterprise wide Roll Out of Process Validation
Quality System standardization, design management, change
management and validation
The success of any Validation Program is contingent on a
healthy Quality System.
ISO 9001 identifies the some of the Quality Systems evaluated during
management review:
5.6.2 Review input- The input to management review shall include information
on:
a) results of audits, (Internal and External Audits)
b) customer feedback, (Complaints)
c) process performance and product conformity, (NonConformance Management)
d) status of preventive and corrective actions, (NonConformance Management)
e) follow-up actions from previous management reviews,
f) changes that could affect the quality management system, and (Change Mgmt)
g) recommendations for improvement. (Continuous Improvement)
[ 54 ]
55. Enterprise wide Roll Out of Process Validation
Quality System standardization, design management, change
management and validation
ISO 9001 state the following responsibilities of Management Review:
5.6.3 Review output- The output from the management review shall include any
decisions and actions related to:
a) improvement of the effectiveness of the quality management system and its
processes,
b) improvement of product related to customer requirements, and
c) resource needs.
[ 55 ]
56. Enterprise wide Roll Out of Process Validation
Quality System standardization, design management, change
management and validation
Standardization of key quality systems like design management, change
management and validation ensures:
• Provides clear instruction for ‘how things are done’.
• Offers consistent approach to train and follow regardless of site location,
manufacturing platform, products manufactured
• Presents to regulators the company’s position on key quality systems
• Ensures alignment to guidances and standards
<Reference a sample global final report template in bonus material>
[ 56 ]
57. Agenda
£ Getting Started-Overview
£ Process Validation
£ Enterprise wide Roll Out of Process Validation
£ Interactive Exercise
[ 57 ]
58. Interactive Exercise
Firm is rebranding a legacy medical device product in a
new bottle.
Product is a sterile liquid. Bottle is being sourced from a
new supplier. Bottle requires a different sterilization
method. New equipment will be needed to run this bottle.
Validation needs to be conducted to launch to ‘new
product’.
What will the validation strategy be?
[ 58 ]
59. Interactive Exercise
• Product ABC is currently filled in an oval and opaque HDPE. New
bottle is round, transparent (without colorant) HDPE
• Sterilization Method for current bottle is Ethylene Oxide. New bottle
will require gamma irradiation
• Bottle will be filled in Fill Room C. Fill Room C only has change
parts for oval bottles.
• Instead of using the checkweighing system, the firm would like to
use fill volume sensors that were always integrated on Fill Room C
but never used because firm uses opaque bottles.
• Original validation for Product ABC was conducted 15 ago.
[ 59 ]
60. Interactive Exercise
Each team, take 5-10 minutes to develop a validation strategy.
Demonstrate the use of the following:
• Success criteria
• Team Members
• Any necessary pre-work (engineering, develop studies, etc.)
• Training
• Proposed risk analysis
• Proposed statistics
• Process steps to focus validation effort
[ 60 ]