This document outlines regulatory perspectives on advanced GMPs for the 21st century. It discusses the FDA's 21st century initiatives to modernize pharmaceutical regulations using a risk-based approach focused on quality systems. The concepts of advanced GMPs emphasize building quality into products and processes rather than relying solely on end-product testing. A key aspect is implementing a robust quality system approach across the organization.
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 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.
Mechanical Engineer (A.M.I.E), Statistics, NDT, P.G.Diploma in Materials Management with 22.5 years experience seeks change with organization of repute
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 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.
Mechanical Engineer (A.M.I.E), Statistics, NDT, P.G.Diploma in Materials Management with 22.5 years experience seeks change with organization of repute
How Project Quality Is Managed Powerpoint Presentation SlidesSlideTeam
Incorporate How Project Quality Is Managed PowerPoint Presentation Slides to determine how quality will be managed throughout by handling processes and procedures. Analyze the quality-related concerns of the firm by using this effective PPT slideshow. Showcase the information regarding the quality standards that are defined in order to manage overall quality by taking the assistance of the project quality management PowerPoint slideshow. Provide detailed information about product development, design, and testing with the help of quality management plan PPT slideshow. Showcase various quality-related initiatives, product quality assurance checklist, etc by incorporating this PowerPoint slide deck. Highlight detail about various quality control initiatives, product quality control checklist, quality assurance, etc. by using project management PPT themes. Explain control log, quality control, and assurance issues reporting plan. You can also present information on the project inspection checklist. Present testing techniques that are used to evaluate materials, components properties, in order to determine defects and discontinuities by taking the assistance of project quality assurance PowerPoint slides. The project quality PPT also allows you to present key quality management tools, weekly quality defect occurrence with check sheet, etc. https://bit.ly/3f4lPvZ
The VDA recommends it’s members to apply VDA 6.3 (2010) standard for the implementation and maintenance of Quality management System. This presentation explains the features and plus points of this system of process auditing, which sets it apart from other methods in today's automotive industry.
According to new syllabus of PCI M.Pharm 1st sem. students can directly utilize this ppt for their study. As per PCI new syllabus QA STUDENTS find this ppt very use full.
How Project Quality Is Managed Powerpoint Presentation SlidesSlideTeam
Incorporate How Project Quality Is Managed PowerPoint Presentation Slides to determine how quality will be managed throughout by handling processes and procedures. Analyze the quality-related concerns of the firm by using this effective PPT slideshow. Showcase the information regarding the quality standards that are defined in order to manage overall quality by taking the assistance of the project quality management PowerPoint slideshow. Provide detailed information about product development, design, and testing with the help of quality management plan PPT slideshow. Showcase various quality-related initiatives, product quality assurance checklist, etc by incorporating this PowerPoint slide deck. Highlight detail about various quality control initiatives, product quality control checklist, quality assurance, etc. by using project management PPT themes. Explain control log, quality control, and assurance issues reporting plan. You can also present information on the project inspection checklist. Present testing techniques that are used to evaluate materials, components properties, in order to determine defects and discontinuities by taking the assistance of project quality assurance PowerPoint slides. The project quality PPT also allows you to present key quality management tools, weekly quality defect occurrence with check sheet, etc. https://bit.ly/3f4lPvZ
The VDA recommends it’s members to apply VDA 6.3 (2010) standard for the implementation and maintenance of Quality management System. This presentation explains the features and plus points of this system of process auditing, which sets it apart from other methods in today's automotive industry.
According to new syllabus of PCI M.Pharm 1st sem. students can directly utilize this ppt for their study. As per PCI new syllabus QA STUDENTS find this ppt very use full.
Productivity & Total Quality ManagementVaibhav Bhatt
Productivity and Total Quality Management Importance For An Organisation And How Can They Develop And Overall Efficiency Through Proper Quality Management Techniques
Greg has expertise for over 20 years in the areas of applied data analysis techniques, instructional design, training and development.Root Cause and Corrective Action (RCCA) Workshop
Vastu is the exact science but some people have connected it with the orthodox practices to misguide the people.Vastu is based on the following principles of science:
1. Principle of energy flow
2. Principle of open space
3. Principle of shapes
4. Principle of angles
5. Principle of directions
6. Principle of gravity(Mass)
7. Principle of height
8. Principle of slope
9. Principle of placement of rooms
10.Principle of elements
9.
Sai Pharma Solutions Inc. has has been instrumental in providing services on consultation and turnkey project basis in Regulatory Affairs, Quality Management and GMP compliance since 2008. We offer consultation and undertake turnkey projects in development and implementation of Quality Systems which incorporates Regulatory Affairs, Quality and cGMP documentation, DMF and Dossier Management, SOP Management, Technical and Scientific Advice management, Validation and Qualification Management, Gap Analysis, Review, Assessment, Audits and Training. Our clientele includes the upcoming and existing pharmaceutical industries. We are known for the best"QQS" worldwide. The quality of our work speaks volumes about our efforts and endeavours".
Knee anatomy and clinical tests 2024.pdfvimalpl1234
This includes all relevant anatomy and clinical tests compiled from standard textbooks, Campbell,netter etc..It is comprehensive and best suited for orthopaedicians and orthopaedic residents.
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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!
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.
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
Acute scrotum is a general term referring to an emergency condition affecting the contents or the wall of the scrotum.
There are a number of conditions that present acutely, predominantly with pain and/or swelling
A careful and detailed history and examination, and in some cases, investigations allow differentiation between these diagnoses. A prompt diagnosis is essential as the patient may require urgent surgical intervention
Testicular torsion refers to twisting of the spermatic cord, causing ischaemia of the testicle.
Testicular torsion results from inadequate fixation of the testis to the tunica vaginalis producing ischemia from reduced arterial inflow and venous outflow obstruction.
The prevalence of testicular torsion in adult patients hospitalized with acute scrotal pain is approximately 25 to 50 percent
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
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.
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
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
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.
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
Maxilla, Mandible & Hyoid Bone & Clinical Correlations by Dr. RIG.pptx
Advanced gm ps for 21st century from regulatory perspectives
1. ADVANCED GMPs for 21st Century
Regulatory Perspective
Mr.J.Ramniwas
Founder and CEO
SAI PHARMA SOLUTIONS INC. VADODARA
2. Outline
Changing Paradigm for GMPs
21st Century Initiatives
Concept of Modern Quality Systems
Basis of Advanced GMPs
Quality System Approach
What’s new to meet challenges
GMP Improvements
Global Registration Requirements
Expectations
Summary J.Ramniwas 2
3. Changing Paradigm for GMPs
Product Process Systems
-1970 1980 - 1990 21st
[QC] [QA] Century
[QS]
J.Ramniwas 3
4. Background of FDA’s 21st
Century Initiatives
Limited resources and increased volume of work
August 2002 – FDA announced the Pharmaceutical
cGMPs for the 21st Century – A Risk Based Approach
Focus on the greatest potential risk to the public
FDA’s intent to integrate quality systems and risk
management approaches - to modernize FDA’s
regulations
Encourage industry to adopt modern and innovative
manufacturing technologies as well as modern quality
system approaches
Necessary to harmonize the cGMPs with other non-
U.S. pharmaceutical regulatory systems
Need to harmonize with FDA’s own medical device
quality systems regulations
J.Ramniwas 4
5. Background of FDA’s 21st
Century Initiatives contd...
Encourage Risk-Based approaches which focus on critical elements
Ensure FDA’s Review, Compliance and Inspection
Policies –based on state-of-art pharmaceutical
science
! Risk-Based Approach to Manufacturing and
Regulation
•#Pharmaceutical Inspectorate
– Experienced Field Investigators
•#Process Analytical Technology (PAT) Guidance
– Real-time measurements
•#Process Validation Guidance
– Life Cycle Approach - Built-in Quality, not tested into
product
•#21 CFR 11 Electronic Records Guidance
•#Quality Systems Guidance - September 2006 – FDA issued the final
version of the “,-./0123#456#71/-896:#51#;-0<.9:#=:893>8#?@@6502A#95
Pharmaceutical cGMP Regulations”
•#Systems-Based Inspection
•#6 systems J.Ramniwas 5
6. Philosophy of cGMP and
Modern Quality Systems
Quality should be built into
the product, and testing
alone cannot be relied
on to ensure product
quality.
J.Ramniwas 6
14. A. Management Responsibilities Contd..
j Structure the organization to ensure the
assigned authorities and responsibilities
l
k Organizational structure is documented
n
m Support the total quality model
p
o Quality Systems departments have equal
standing with other departments within an
organization
r
q The Quality Manager has the authority to
detect problems, implement solutions, and
provide prompt feedback on quality issues to
the organization.
organization.
J.Ramniwas
15. A. Management Responsibilities Contd..
Play a key role in the design, implementation, and
management of a robust quality systems.
t
s Align quality plans with company’s visions and
mission
v
u Actively participate in Management Review meetings
– to ensure continuing suitability, adequacy and
effectiveness
x
w Articulate their vision of and commitment to quality to
all levels of the organization.
z
y Advocate continuous improvement of the operation
of Quality System
•#Strong
•#Strong and visible support for the quality system
•#Internal
•#Internal communication on quality issues at all levels
€
• Commit necessary resources
J.Ramniwas
16. A. Management Responsibilities Contd..
‚
• Management controls are always reviewed
by FDA
•#CAPA
•#CAPA
•#People
•#People qualifications
•#Change
•#Change control
•#Validation
•#Validation
J.Ramniwas
17. B. RESOURCES.
Œ
‹ General Arrangements
Personnel Development
– Communicative
Facilities and Equipment
Control Outsourced Operations
J.Ramniwas
18. B. RESOURCES Contd...
• Appropriate allocation of resources
intended purpose
– collection, storage,
examination of in-process, stability, and reserve samples
in-
Personnel
knowledge
-solving and communicative culture
– Education, training and experience
– GMP
J.Ramniwas
19. C. MANUFACTURING
! Design, develop and document Product and
Processes
•#$%&'()*
•#-./01'2)3)4.2
•#7(4)4/38#&(./'**'*
;
: Examine Inputs <#=3)'(438*
>#=3)'(438*
@
? Perform and Monitor A&'(3)4.2*
B&'(3)4.2*
•#$2)4('#D(.E0/)#F4G'#7H/8'
•#7(4)4/38#D(./'**'*#– N3(43M484)H
•#7(4)4/38#D(./'**'*# – L3(43M484)H
•#P)3)4*)4/38#D(./'**#7.2)(.8#QPD7R
•#DUV#–
•#DUV#– Monitor & reduce QC testing
Y
X Address Nonconformities J.Ramniwas
20. C. MANUFACTURING Contd...
•
Ž Address Nonconformities
•#Investigations,
•#Investigations, conclusion and follow -up must
follow-
be documented.
•#
•#CAPA
•#CAPA
J.Ramniwas 2
21. D. EVALUATION ACTVITIES
– Analyze Data for Trends
Conduct Internal Audits
sustainability of Quality Systems
– FDA is to refrain from
both reviewing and copying reports or records that result
from internal audits
J.Ramniwas 2
22. D. EVALUATION ACTVITIES Contd...
Quality Risk Management
•#Understanding
•#Understanding of quality issues
Effective decision- making
decision-
•#Risk
•#Risk assessment
and the severity of harm
•#Engage
•#Engage appropriate parties in risk assessment, e.g.
regulatory affairs, customers, appropriate manufacturing
personnel, development scientist, other stakeholders
•#Risk
•#Risk management – as a tool in the development of
product specifications and critical process parameters
•#Repeat
•#Repeat risk assessment – to improve processes
•#Proactive
•#Proactive approach to quality
Mitigate risk
J.Ramniwas 22
23. D. EVALUATION ACTVITIES Contd...
Corrective Action
significant problems do not recur
Preventive Actions
– Identify potential problems and root causes
– Assess possible consequences
– Consider appropriate actions
CAPA
level of detail of the evaluation process
J.Ramniwas 23
24. D. EVALUATION ACTVITIES Contd...
£ Sources of recurring problems
¤
– Non-conformance reports and re
Non-
– Product Returns
– Complaints
– Internal and External audits
– Trending data and risk assessment
– Management review decisions
•#Effectiveness
•#Effectiveness of CAPA
J.Ramniwas 24
25. D. EVALUATION ACTVITIES Contd...
Promote Improvement
•#´44329.µ31388#01/#344.2.312:#54#0#¶-0<.9:#8:893>
•#=31.56#G010F3>319#–
•#=31.56#G010F3>319#– involve in the evaluation of
improvement process
•#½33@#0¾63089#54#2A01F38#.1#82.319.4.2#/3µ3<5@>3198#####
and regulatory requirements
J.Ramniwas 25
26. System Based cGMP Inspection
1. Quality System
2. Facility
6. Packaging
Full Inspection
the five systems
Abbreviated Inspection
system and one of the five systems
J.Ramniwas 26
27. State of Control
Á
À FD
are developed, manufactured and held in a state
of control, i.e. contribute to SISPQ
Identity, Strength, Purity, Quality
Ã
 Detailed inspection of a system so that the
findings reflect the state of control in that system
for every product
Å
Ä If one of the six systems is out of control, the
company is considered out-of-control
out-of-
J.Ramniwas 27
28. It is not the strongest species that
surviveÇ
surviveÆ nor the most intelligentÈ but
intelligentÉ
the ones most responsive to
change”
Charles Ì06Í.1
Î06Í.1
See today with the eyes of
tomorrow and change before the
change comes.
comes.
J.Ramniwas 28
29. A Unique Feature of Indians
………#………Ð……#……Ñ#71/.01#
Pharmaceutical Ó#71/.01#HA06>023-9.20<#
Ô#71/.01#HA06>023-9.20<#
Community has got fantastic flexibility
to accept any challenge Õ#0/0@9#95#
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accept any challenge ×#0/0@9#95#
Ø#0/0@9#95#
Change ………………#………………Ñ#
J.Ramniwas 29
31. Advantages
Quality by design
Logical movement of personnel and material
Control at every stage of manufacture
Reduced risk of cross-contamination
Science based approach
Risk based approach
Confidence building
J.Ramniwas 3
32. Number ICH Guidelines
Q7 Good Manufacturing Practice Guide for
Active Pharmaceutical Ingredients
Q8 Pharmaceutical Development
Q9 Quality Risk Management
Q10 Quality Management System
Q11 Development and Manufacturing of Drug
Substances
FDA Process Validation Guidelines
J.Ramniwas 32
35. Quality of Operation reflected
through SOPs.
IQ, OQ, PQ and higher levels of
scientific skills in validations
Plant upgradations to the latest
in Pharma standards.
J.Ramniwas 35
36. Quality of Water and HVAC
systems
Stringent controls for sterile
products manufacture and
asceptic manufactured products
J.Ramniwas 36
37. Recent Changes to PIC
Product Quality Review (new clause 1.
î Commenced on 1 ï01-06:#ðññòÑ
ó01-06:#ðññòÑ
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ô Requires annual quality reviews of all products to verify the
consistency of the existing process to highlight trends ö#95
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identify the need for productø@652388#.>@65µ3>3198Ñ
productù@652388#.>@65µ3>3198Ñ
û
ú Requires reviews ofü ofý
•
þ Starting ‚ pacƒing materials„ especially from new sources…
• Critical in•process controls and finished product results…
in•
• All batches that failed to meet specifications…
• All significant deviations…
• All changes to processes and analytical methods…
• Marƒeting Authorisation variations…
• Stability monitoring and any trends…
• Recalls„ complaints and returns…
• Qualification status of equipment ‚ utilities…
• †echnical agreements… J.Ramniwas 37
38. Upcoming Changes to PIC
On-
On-going stability (new clauses 6.2 – 6.
Expected to commence on 1 June 2006 or soon after.
Requires monitoring of stability after marketing, against
a written protocol.
Stability program should be extended to the end of the
shelf life of the product.
One batch per year of each product strength
primary packaging type.
Maintain a written summary of the data generated.
J.Ramniwas 38
39. Upcoming Changes to PIC
Reference Samples "#$%&%'&()'#*+,-.%/#0'%1#2''%3#4 !
6
5 Expected to commence on 1 June 2006 or soon after.
8
7 Purpose and definitions.
:
9 Duration of storage.
<
; Size of samples.
>
= Storage conditions.
@ EB(&&%'#+CB%%,%'&/D
? AB(&&%'#+CB%%,%'&/D
G OI+&#&)#J)#('#&I%#%K%'&#)L#&I%#M.)/NB%#)L#+#
F HI+&#&)#J)#('#&I%#%K%'&#)L#&I%#M.)/NB%#)L#+#
manufacturer.
J.Ramniwas 39
40. Upcoming Changes to PIC*#]^_
Sterile Products (changes to Annex 1)
Q
P Expected to commence on 1 June 2006 or soon after.
S
R Changes to some particle size limits for clean -room
clean-
classification purposes.
U
T Media fill limits specified for the validation of aseptic
processing.
W Pre-
V Pre-sterilization bioburden assays required for aseptic
processing and terminal sterilization.
Y
X Grade A environment required forZ for[
- Partially stoppered freeze drying vials.
- Area where aluminium caps on aseptically filled vials are
crimped.
J.Ramniwas 4
41. Clean Room Environment Control
Environment monitoring
Scheduled programmes
Establishment of limits and training.
Sanitization, efficacy and monitoring
methods.
J.Ramniwas 4
42. Activities for Advanced GMP Compliance
Quality System Improvements
– Calibration
– Maintenance
– Change Control
– ZAP[#-'43)4.2#1323]'1'2)[#7UDU
^AP[#-'43)4.2#1323]'1'2)[#7UDU
– Training
– Complaints and recall procedures
– Critical utility and environmental monitoring and
sampling
– Gowning, personnel monitoring
– Material control
– Cleaning , sterili_3)4.2#32E#*324)4_3)4.2
sterili`3)4.2#32E#*324)4_3)4.2
42
43. Activities for Advanced GMP Compliance
Documentation
– Site Master File
– Quality Manual
– Master Batch Records
– SOPs and associated forms
– Trending Records
– Log books
– Approved critical drawings
– Documentation to support CTD
•#a%K%.)-,%'&+.#-B)&)M)./#+'J#B%-)B&/
•#*&+d(.(&e#&%/&('C#-B)&)M)./#+'J#B%-)B&/
J.Ramniwas 43
44. Activities for Advanced GMP Compliance
Upgrading Environments
– layout of facility
– Classification of environment
– gh_2#L(.&%B#('&%CB(&e#&%/&('C
ih_2#L(.&%B#('&%CB(&e#&%/&('C
– Room pressure differentials
– Air flows
– Air velocity and volume
– Monitoring and control
– Access of materials and personnel
J.Ramniwas 44
45. Activities for Advanced GMP Compliance
•#Upgrading l+&%B#*e/&%,/
m+&%B#*e/&%,/
– Overall design
– Instrumentation
– Dead legs, Slopes
– Valves
– Backflow prevention
– Materials, finishes
– Spray balls, vent filters, sanitary heat
exchangers
– Sanitisation and operation
– Recirculation, Flow rate
– Monitoring and control J.Ramniwas 45
47. Activities for Advanced GMP Compliance
Upgrading Equipment
•#
– Equipment Capability – 6 sigma
– Materials, Finishes
– Local environment
– Cleaning, sanitisation
– Monitoring and control
– “x+.(J+&+d(.(&e”#– 21 CFR Part 11
“x+.(J+&+d(.(&e”#–
J.Ramniwas 47
48. The Common Technical Document (CTD)
•#|I%#p|a#(/#+#L)B,+&#+CB%%J#de#hos#o*2#+'J###
Japan for submitting applications for new
products.
•#•&#(/#)BC+'(/%J#('#€#,)JN.%/D#^)JN.%#4#(/#
unique to each region. Modules 2 to ‚#+B%#
ƒ#+B%#
common across all regions
• Module 1 – Administrative Requirements
•#^)JN.%#…#– ‰(CI#.%K%.#/N,,+B(%/#)L#ˆN+.(&es#
•#^)JN.%#…#– ‡(CI#.%K%.#/N,,+B(%/#)L#ˆN+.(&es#
Clinical and Non clinical
J.Ramniwas 48
49. The Common Technical Document (CTD)
• Module Š#– Quality - Chemical, Pharmaceutical
‹#–
and Biological Documentation
•#^)JN.%#•#–
•#^)JN.%#•#– Toxicological and Pharmacological
(non clinical) study reports
•#^)JN.%#€#–
•#^)JN.%#€#– Clinical Study Reports
J.Ramniwas 49
50. The Common Technical Document (CTD)
• Generally dossier must be in English or the
language of the Reference Member State
• eCTD format was obligatory. But now
obligatory.
mandatory
• Mock up of packaging, specimen of packaging
and leaflet also required in language of
Reference Member State
J.Ramniwas 5
51. VALIDATION
•#Usually a ma—)B#L+(.('C#L)B#,+'e#,+'NL+M&NB%B/
ma˜)B#L+(.('C#L)B#,+'e#,+'NL+M&NB%B/
•#*&B+&%C(M#a)MN,%'&+&()'
– Production of an overall Validation Master Plan
and Validation Plans for specific areas.
– Production of a validation schedule
– Production of System Boundary drawings
– System Impact Assessment
J.Ramniwas 5
52. VALIDATION
• Design Qualification
– GMP review of Facility Design
– DQ (protocols execution and reports) of ma•)B
maž)B
Direct Impact Systems and Equipment
• Equipment Facilities and Utilities Qualification
– IQ, OQ, PQ Protocols execution and reports for
Direct Impact Systems including ¡x2ps Critical
¢x2ps
Utilities, Process Equipment and Laboratory
Equipment
J.Ramniwas 52
53. VALIDATION
• Validation
– Protocols execution and reports for
Process Simulation (Media Fills),
Cleaning Validation, Process
Validation and Method
Validation¤K%B(L(M+&()'
Validation£K%B(L(M+&()'
J.Ramniwas 53
54. Environment Monitoring Sterile Areas
Monitoring Methods :
Surface Monitoring
Active Air Monitoring
Passive Air Monitoring
Particulate Monitoring
J.Ramniwas 54
55. Some of the points cited in the
Regulatory Inspections
Restricted access to computers and
data handling.
Total traceability of Unit operation
in BMR with respect to machine
no., room no., time logs, operation
logs and verification
J.Ramniwas 55
56. Some of the points cited in the
Regulatory Inspections Contd…..
Risk assessment for critical facilities and
equipments which can cause product
quality to be altered e.g. air handling
systems in sterile product manufacture
Air handling system with single pass with
HEPA filters not re-circulation type.
J.Ramniwas 56
57. Some of the points cited in the
Regulatory Inspections Contd…..
Validation Master Plan, detailed
execution through protocols and
executive summary on the study.
100% identification of Raw Materials in
QC
TSE/BSE certification and SOP for
incoming materials assessment through
vendor approval system
J.Ramniwas 57
58. Some of the points cited in the
Regulatory Inspections Contd…..
Pest control, procedure with schematic
diagrams, effectiveness of chemicals and
disposal of dead rodents.
Water systems with respect to plant
design, system validation, chemical and
microbial attributes and monitoring of
pesticides and radioactive traces.
J.Ramniwas 58
59. Laboratory
Reference standards, working
standards, instrument logs, column
register, calibration, stability
monitoring and instrument audit
trials.
Annual Reports on each product is
scrutinized.
J.Ramniwas 59
60. Laboratory Contd…
Deviations and change control
mechanism thoroughly
investigated.
Approved suppliers list and its tally
with vendor approval system.
OOS handling.
J.Ramniwas 6
61. Laboratory Contd…
Technical agreements and its
executions.
Sterility assurance in bulk APIs
and dosage forms.
Media simulation trials and its
applicability to production run.
J.Ramniwas 6
62. Some of the USFDA Inspections
and Non-compliance
Deficiency in validation work.
Process validation as well as
analytical validation.
Process validation not done on
worst case simulation.
J.Ramniwas 62
63. In a multiple product manufacturing site,
effectiveness of cleaning validation not
demonstrated through worst case in a
multiproduct matrix.
Back-up system of stability chamber
inadequate.
Inadequate temperature mapping in
warehouses.
J.Ramniwas 63
64. Inadequate validation of vacuum
transfer system for cleaning operations.
Changes in production, QC and
warehouse without change control.
Complaint investigation lacking depth,
tracebility and time frame commitment.
J.Ramniwas 64
65. ADVANCED GMPs CONCERNS
Lab Controls SOPs
Records and Reports Reprocessing /
Process Controls Reworks
Equipment Cleaning Ingredients controls
Process Validation Buildings and
Water Systems Facilities
Stability Programs Training
Investigations
J.Ramniwas 65
70. GMP -Improvements
Renovation of facilities
Ò
Ñ Plant
Ô Ö+&%B
Ó Õ+&%B
Ø Úx2p
× Ùx2p
Ü
Û Storage
Þ
Ý Disposal
à
ß Training of personnel
â
á Upgrading equipment
ä
ã Identifying critical steps
æ In-
å In-process parameters
è
ç Validation
ê
é Self inspection J.Ramniwas 7
71. Global Registration Requirements
GMP •Basic prerequisite
ˆ Semi•regulated countries also need GMP compliant
Semi•
facilities
ˆ Many countries require pre•approved facilities
pre•
ˆ General GMP inspection of the facility
ˆ Some countries inspect the product manufacturing line
before granting marƒeting authorisation
ˆ Product specific GMP inspection
J.Ramniwas 7
72. †he Expectations
The evaluation of the risk should ultimately link back to
the potential risk to the patient.
patient.
The extent of the risk management process should be
commensurate with the level of risk associated with the
decision.
decision.
A more robust data set will lead to lower uncertainty.
uncertainty.
It is essential to have a clear delineation of the risk
question.
question.
Risk management should be an iterative process.
process.
J.Ramniwas 72
73. †he Expectations Contd……
People who apply risƒ management should have
the appropriate training„ sƒills and experience…
experience…
†he risƒ management process should be
appropriately documented and verifiable…
verifiable…
Šefining specifically the risƒ management problem
or question„ including the assumptions leading to
the question…
question…
Assembling bacƒground information and data on
the ha‹ard„ harm or human health impact relevant
to the assessment…
assessment…
J.Ramniwas 73
74. †he Expectations Contd……
Identifying the necessary resources„ members of
the team who have the appropriate expertise„ with
the leader clearly identified…
identified…
Asƒing the right risƒ assessment questions…
questions…
Stating clearly the assumptions in the risƒ
assessment…
assessment…
Assessing the quality and sufficiency of relevant
data…
data…
Specifying and deliverables for the risƒ
assessment…
assessment…
J.Ramniwas 74
75. Summary
Use regular internal audits to identify those areas
that require attention to comply with the GMP Guides.
Guides.
Utilise external consultant(s) if necessary.
necessary.
Prioritise implementation of corrective actions using a
risk based approach.
approach.
Establish a budget to enable appropriate corrective
actions to be implemented.
implemented.
ë%%- watch on Regulatory authority websites for
ì%%-
changes in GMPs coming up in the future.
future.
Establish industry networking system to monitor and
report on inspection trends by GMP regulators.
regulators.
75
76. †hanƒ you for your attentionŒ
Any Questions•
Contact for consulting or technical advisory servicese
J.RAMNIWAS
Founder & CEO
SAI PfUg=U#PAFhViAjP#ij7k
Phone No
76
l0(#=.)).m#P)3()#).#G424*n[#''(H)n42]#42#M')o''2mk