The document discusses pharmaceutical process validation. It defines validation as proving a process consistently produces quality products. There are three main types of validation: prospective validation done before use, retrospective using historical data, and concurrent during routine production. Validation ensures quality, reduces costs, and meets regulations. It involves qualification of facilities and equipment, then protocols to test processes over multiple batches and demonstrate control. Periodic revalidation is also required when changes are made.
Process Validation is Key important factor for the Pharmaceutical Industry to maintain Consistent Quality in product which claimed by the manufacturer.
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.
QUALIFICATION & VALIDATION.Validation is an essential part of GMP, and an element of QA.Critical steps in the process need to be validated.Need for confidence that the product will consistently meet predetermined specifications and attributes.
QUALIFICATION OF UV-VISIBLE SPECTROPHOTOMETER, FTIR, DSC, HPLCAnupriyaNR
Analytical method qualification consists of a simplified evaluation of a subset of validation characteristics with a goal to demonstrate that an analytical method is scientifically sound and suitable for its intended use. In contrast to validation, analytical method qualification is performed without predefined acceptability criteria. Qualification may be performed as a prerequisite to method validation, or when an assay for product knowledge has not yet been established as a test for a critical product quality attribute. Qualification of equipment is pre-requisite for validation of the process in which the equipment is being used. Many types of equipment have measuring devices on them. Calibration of measuring devices is a part of qualification. Calibration of measuring devices is important, as the data is often collected through them. If the data collected is not from measuring devices that have been calibrated, the data cannot be relied upon. Thus the whole validation exercise can be questioned.
Introduction, Regulatory requirements for validation, Role of FDA, Code of Federal regulation, Validation life cycle, Significance of validation, Types of validation, Process valiadation, Phases of process validation, Process capability design, Process Qualification, Validation maintainance phase
Types of Process validation, Examples
Process Validation is Key important factor for the Pharmaceutical Industry to maintain Consistent Quality in product which claimed by the manufacturer.
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.
QUALIFICATION & VALIDATION.Validation is an essential part of GMP, and an element of QA.Critical steps in the process need to be validated.Need for confidence that the product will consistently meet predetermined specifications and attributes.
QUALIFICATION OF UV-VISIBLE SPECTROPHOTOMETER, FTIR, DSC, HPLCAnupriyaNR
Analytical method qualification consists of a simplified evaluation of a subset of validation characteristics with a goal to demonstrate that an analytical method is scientifically sound and suitable for its intended use. In contrast to validation, analytical method qualification is performed without predefined acceptability criteria. Qualification may be performed as a prerequisite to method validation, or when an assay for product knowledge has not yet been established as a test for a critical product quality attribute. Qualification of equipment is pre-requisite for validation of the process in which the equipment is being used. Many types of equipment have measuring devices on them. Calibration of measuring devices is a part of qualification. Calibration of measuring devices is important, as the data is often collected through them. If the data collected is not from measuring devices that have been calibrated, the data cannot be relied upon. Thus the whole validation exercise can be questioned.
Introduction, Regulatory requirements for validation, Role of FDA, Code of Federal regulation, Validation life cycle, Significance of validation, Types of validation, Process valiadation, Phases of process validation, Process capability design, Process Qualification, Validation maintainance phase
Types of Process validation, Examples
Documentation is an integral part of good manufacturing practices. It defines a system of information and control so that risks so inherent in misinterpretation and/or error in oral communication are minimized.
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.
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.
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
Definition
Scope of calibration
Scope of validation
Frequency of calibration
Importance/ purpose of calibration
Importance/ advantages of validation
Difference between calibration & validation
IPQC cover the entire chain of operations from the receipt of raw material in the warehouse to the release of finished products from the warehouse for distribution and or sale. IPQC is a process where quality of a product is ensured that it meets the standard according to regulatory authority guidline.
QUALIFICATION OF MANUFACTURING EQUIPMENTSANKUSH JADHAV
it gives the information about qualification of various manufacturing equipment which is used into the pharmaceutical labs. (only for information purpose)
Process validation incorporates a lifecycle approach linking product and process development, validation of the commercial manufacturing process and maintenance of the process in a state of control during routine commercial production.
Documentation is an integral part of good manufacturing practices. It defines a system of information and control so that risks so inherent in misinterpretation and/or error in oral communication are minimized.
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.
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.
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
Definition
Scope of calibration
Scope of validation
Frequency of calibration
Importance/ purpose of calibration
Importance/ advantages of validation
Difference between calibration & validation
IPQC cover the entire chain of operations from the receipt of raw material in the warehouse to the release of finished products from the warehouse for distribution and or sale. IPQC is a process where quality of a product is ensured that it meets the standard according to regulatory authority guidline.
QUALIFICATION OF MANUFACTURING EQUIPMENTSANKUSH JADHAV
it gives the information about qualification of various manufacturing equipment which is used into the pharmaceutical labs. (only for information purpose)
Process validation incorporates a lifecycle approach linking product and process development, validation of the commercial manufacturing process and maintenance of the process in a state of control during routine commercial production.
On FDA’s Guidance on Pharmaceutical Process Validation (2011)lAjaz Hussain
Connectors between Culture – Metrics – Continued Process Verification in Process Validation?
Confidence is a critical quality attribute. CGMP violations erode confidence and increase nocebo effects. Currently – “breaches in assurance of data integrity” is a global concern. Have exposed the prevailing ‘regulator heterogeneity’. Re-building ‘epistemic trust” is difficult generally; more so with US FDA. Some thoughts on how to ....
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.
According to U.S.Food and Drug Administration
Process validation is establishing documented evidence which provides a high degree of assurance that a specific process will consistently produce a product meeting its predetermined specifications and quality characteristics.
complete and detail study on the topic of validation used in pharmaceuticals industry and also in the learning purpose for the students in the classrooms. this ppt help a lot to the students as well as teachers to learn more on the validation topics.
Introduction to Pharmaceutical Validation, Scope & Merits of Validation, Validation and calibration of Master plan, Hrs ICH & WHO guidelines for calibration and validation of
equipment's, Validation of specific dosage form, Types of validation. Government regulation, Manufacturing Process Model, URS, DQ, IQ, OQ & P.Q. of facilities.
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.
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
Anti ulcer drugs and their Advance pharmacology ||
Anti-ulcer drugs are medications used to prevent and treat ulcers in the stomach and upper part of the small intestine (duodenal ulcers). These ulcers are often caused by an imbalance between stomach acid and the mucosal lining, which protects the stomach lining.
||Scope: Overview of various classes of anti-ulcer drugs, their mechanisms of action, indications, side effects, and clinical considerations.
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
These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
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.
MANAGEMENT OF ATRIOVENTRICULAR CONDUCTION BLOCK.pdfJim Jacob Roy
Cardiac conduction defects can occur due to various causes.
Atrioventricular conduction blocks ( AV blocks ) are classified into 3 types.
This document describes the acute management of AV block.
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.
2. Validation
Definition:
• Validation is the action of
proving that any procedure,
process, equipment,, method,
material or activities actually
leads to the expected results
and produce a quality
products.
3. Why Validation?
Need of Validation:
• To obtain consistent, reliable
and accurate data
• Act as a proof in decision
making
• To get assurance of Quality
product
4.
5. Validation is the scientific study of a process:
• To prove that the process is consistently doing what it is
supposed to do (i.e., that the process is under control)
• To determine the process variables and acceptable limits
for these variables, and to set up appropriate in- process
controls.
Validation in Pharmaceutical Industry:
• Assurance of Quality
• Cost Reduction
• Government Regulation
6. Documentation associated with validation includes:
• Standard Operating Procedures (SOPs):
• Specifications
• Validation Master Plan (VMP)
• Qualification Protocols and Reports
• Validation Protocols and Reports.
Standard Operating Procedures (SOPs):
• 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)
7. Validation protocol (or plan) (VP):
• A document describing the activities to be performed in a
validation, including the acceptance criteria for the
approval of a manufacturing process or a part thereof for
routine use.
Validation report (VR):
• A document in which the records, results and evaluation
of a completed validation programme are assembled and
summarized.
• It may also contain proposals for the improvement of
processes and/or equipment.
8. Resources required to implement validation:
• Time:
• rigorous time schedules.
• Financial:
• time of specialized personnel and
• expensive technology.
• Human:
• collaboration of experts from various disciplines
• e.g. a multidisciplinary team, comprising quality
assurance, engineering, manufacturing and other
disciplines, depending on the product and process to be
validated.
9. Scope of Validation
• Appropriate and sufficient system – to perform validation
tasks in a timely manner.
• organizational structure and
• documentation
• infrastructure,
• sufficient personnel – with specific qualification and
• financial resources
• Proper preparation and planning before performing
validation activities
• Validation performed in a structured way according to
protocols and documented procedures.
10. Scope of Validation
• A written report on outcome of validation should be
produced for documentation.
• Validation should be performed:
• for new premises, equipment, utilities and systems, and processes
and procedures;
• at periodic intervals; and
• when major changes have been made.
• Validation should be done over a period of time.
• e.g. at least three consecutive batches should be validated, to
demonstrate consistency.
11. Scope of Validation
• In-process controls and validation:
• In-process tests are performed during the manufacture of each
batch according to specifications and methods devised during the
development phase.
• Objective of in-process controls - to monitor the process
continuously.
• Significant changes to the facilities or the equipment,
and processes that may affect the quality of the
product should be validated.
• A risk assessment approach should be used to
determine the scope and extent of validation
required.
12. Validation Master Plan (VMP)
• Definition: It 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 and
• defines details of and timescales for the validation
work to be performed
• It should reflect the key elements of the validation
programme.
13. Validation Master Plan
• It should be concise and clear and contain at least the
following:
• a validation policy
• organizational structure of validation activities
• summary of facilities, systems, equipment and
processes validated and to be validated
• documentation format (e.g. protocol and report format)
• planning and scheduling
• change control
• references to existing documents.
14. Validation Protocol
• Definition: A document describing the activities to be
performed in a validation, including the acceptance
criteria for the approval of a manufacturing process or a
part thereof for routine use.
• A protocols should include
• the objectives of the study
• the site of the study
• the responsible personnel
• description of SOPs to be followed
• equipment to be used; standards and criteria for the relevant
products and processes
• the type of validation
• the processes and/or parameters
• sampling, testing and monitoring requirements
• predetermined acceptance criteria for drawing conclusions
15. Validation and Qualification
• Validation: Action of proving and documenting that any
process, procedure or method actually and consistently
leads to the expected results.
• Qualification: Action of proving and documenting that
any equipment, utilities and systems actually and
consistently leads to the expected results
• Validation and qualification are essential components of
the same concept.
• Qualification is part of validation
16. Qualification
• Qualification: Action of proving and documenting that
any equipment, utilities and systems actually and
consistently leads to the expected results
• Qualification should be completed before process
validation is performed.
• The process of qualification –
• logical,
• systematic process
• should start from the design phase of the premises,
equipment, utilities and equipment.
17. Qualification
• There are four stages of qualification:
• design qualification (DQ)
• installation qualification (IQ)
• operational qualification (OQ)
• performance qualification (PQ).
• All SOPs for operation, maintenance and calibration
should be prepared during qualification.
• Training should be provided to operators and training
records should be maintained.
18. Design Qualification:
• Documented evidence that the premises, supporting
systems, utilities, equipment and processes have been
designed in accordance with the requirements of GMP
Installation qualification (IQ):
• Installation qualification should provide documented
evidence that the installation was complete, satisfactory
and operate in accordance with established specifications.
• Installation qualification verified –
• The purchase specifications,
• drawings, manuals,
• spare parts lists and
• vendor details
19. Operational qualification (OQ):
• Operational qualification should provide documented
evidence that utilities, systems or equipment and all its
components operate in accordance with operational
specifications.
• Operation controls, alarms, switches, displays and other
operational components should be tested.
Performance qualification (PQ):
• Performance qualification should 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 be collected over a suitable period of
time to prove consistency.
20. Requalification
• Requalification should be done in accordance with a
defined schedule.
• The frequency of requalification may be determined on
the basis of factors such as the analysis of results relating
to calibration, verification and maintenance.
• There should be periodic requalification, as well as
requalification after changes (such as changes to utilities,
systems, equipment; maintenance work; and movement).
• Requalification should be considered as part of the
change control procedure.
21. Advantages of Validation
Main advantages of Validation:
Assurance of quality
• Validation is an extension of the concepts of quality
assurance since close control of the process is necessary
to assure product quality.
• It is not possible to control a process properly without
thorough knowledge of the capabilities of that process.
• Without validated and controlled processes, it is
impossible to produce quality products consistently
22. Process optimization
• Optimize – to make as effective, perfect or useful as
possible
• Validation helps to optimize the process for its maximum
efficiency with maintaining its quality standards.
• The optimization of the facility, equipment, systems, and
processes results in a product that meets quality
requirements at the lowest cost.
Reduction of quality costs
• Any validated and controlled process will result in fewer
internal failures like
• Fewer rejects
• Reworks
• Re-tests
• Re-inspection
23. Process Validation
Process Validation – Statutory and Regulatory
requirement
• Requirement of cGMPs for finished pharmaceuticals (21
CFR 211)
• Requirement of GMPs for medical devices (21 CFR 810)
• Apply to manufacturing of both drug product and medical
devices
24. Definition of Process Validation (as per US FDA):
• Process validation is establishing documented evidence
which provides a high degree of assurance that a specific
process will consistently produce a product meeting its
predetermined specifications and quality characteristics.
In short,
• Process validation is defined as the collection and
evaluation of data, from the process design stage through
commercial production, which establishes scientific
evidence that a process is capable of consistently
delivering quality product.
25. Process Validation Activities
• Process validation involves a series of activities taking
place over the lifecycle of the product and process.
• Process validation activities in three stages
• Stage I: Process Design
• Stage II: Process qualification
• Stage III: Continued process verification
26. Stage 1 – Process Design:
• The commercial manufacturing process is defined during
this stage based on knowledge gained through
development and scale-up activities.
Stage 2 – Process Qualification:
• During this stage, the process design is evaluated to
determine if the process is capable of reproducible
commercial manufacturing.
Stage 3 – Continued Process Verification:
• On-going assurance is gained during routine production
that the process remains in a state of control.
27. Types of Process Validation
The guidelines on general principles of Process Validation
mention four types of validation.
• Prospective Validation (Premarket validation)
• Retrospective Validation
• Concurrent Validation
• Revalidation
28. Prospective Validation
• Definition: It is establishing documented evidence prior
to process implementation that a system does what it
proposed to do based on pre-planned protocols.
• An experimental plan called the validation protocol is
executed before the process is put into commercial use.
• It is normally undertaken for a new drug product or new
facilities are introduced into a routine pharmaceutical
production.
• Objective: To prove that the process will work in
accordance with a validation protocol
29. • During Product development stage
• Production process broken down into individual steps
• Each steps evaluated on the basis of experience or theoretical
considerations
• Critical factors that may affect the quality of the finished product
are determined.
• Personnel involved in Prospective validation are
• Representatives from Production
• QC/QA, Engineering
• Research and Development
• It is a challenge element to determine the robustness of
the process. Such a challenge is generally referred to as a
"worst case" exercise.
30. Everything should be planned and documented fully in an
authorized protocol. It contains…
a) Objective, scope, responsibilities
b) Process Flow
c) A description of the process,
d) A description of the experiment,
e) Details of the equipment/facilities to be used together
with its calibration status,
f) The variables to be monitored,
g) The samples to be taken - where, when, how and how
many,
h) The product performance characteristics/attributes to
be monitored, together with the test methods,
i) The acceptable limits,
j) Time schedules,
k) Details of methods for recording and evaluating
results, including statistical analysis.
l) Summary / Conclusion
31. Pre-Requisite of process validation
• All equipment to be used should have been qualified
(Installation/Operational Qualification),
• The production Facility and area should be validated.
• Analytical testing methods to be used should have been
fully validated,.
• Critical support systems like water system, compressed
air system etc, should be validated.
• Raw and packaging material specifications are approved.
• Staff taking part in the validation work should have been
appropriately trained.
32. Retrospective Validation
• Definition: It is an establishing documented evidence that
a process does what it is supposed to do based on review
and analysis of historic data.
• Many process – routine use – not validated
• Validation of these processes - historical data to provide
the necessary documentary evidence that the process is
doing what it is supposed to do.
• Steps require for validation
• Protocol preparation
• Validation reports
• Data analysis
• Conclusion
• Recommendations
33. Concurrent Validation
• Definition: Concurrent Validation means establishing
documented evidence a process does what it is supposed
to do based on data generated during actual
implementation of the process.
• Validation – during routine production
• Validation involves –
• In-process monitoring
• End product testing
• Personnel – Authorized staff
• Documentation – as per Prospective Validation
34.
35. Revalidation
• Definition: Re-validation provides the evidence that
changes in a process and/or the process environment,
introduced either intentionally or unintentionally, do not
adversely affect process characteristics and product
quality.
• There are two basic categories of Re-validation:
• Re-validation in cases of known change (including
transfer of processes from one company to another or
from one site to another),
• Periodic Re-validation carried out at scheduled
intervals
36. Changes that are likely to require Re-validation are as
follows:
• Changes of raw materials (physical properties such as
density, viscosity, particle size distribution may affect the
process or product),
• Change of starting material
• Changes of packaging material (e.g. substituting plastic
for glass),
• Changes in the process (e.g. mixing times, drying
temperatures),
• Changes in the equipment (e.g. addition of automatic
detection systems).
• Changes of equipment
• Production area and support system changes (e.g.
rearrangement of areas, new water treatment method),
• Transfer of processes to another site