In Process Quality Control Tests (IPQC) for Solid Dosage FromSagar Savale
IPQC is concerned with providing accurate, specific, & definite descriptions of the procedures to be employed, from, the receipt of raw materials to the release of the finished dosage forms.
In Process Quality Control Tests (IPQC) for Solid Dosage FromSagar Savale
IPQC is concerned with providing accurate, specific, & definite descriptions of the procedures to be employed, from, the receipt of raw materials to the release of the finished dosage forms.
WHO Guideline & Stability Protocols for Liquid Dosage FormsAnindya Jana
These guidelines seek to exemplify the core stability data package required for registration of active pharmaceutical ingredient (APIs) & finished pharmaceutical protocols (FPPs), replacing the previous WHO guidelines in this area. However, alternative approaches can be used when they are scientifically justified. Further guidelines can be found in International Conference on Harmonisation (ICH) guidelines and in the who guidelines on the active pharmaceutical ingredient master file procedure.
This guideline is a revised of the ICHQ1A –stability data package for new drug substance /DRUG PRODUCT .The [urpose of guideline to define stability data package that sufficient for a registration application within the 3 regions of EU ,JAPAN & USA & to maintain the quality of drug products, in relation to safety , efficacy & acceptability throughout the propose shelf life.
ICH Stability testing of new drug substances and products QA (R2) - 2015
Almudena Camacho
Mohammad Koosha
Rocio Monroy
Professor Peivand Pirouzi Inc. -
Copyright 2015 - Professor Peivand Pirouzi Inc., International Corporate Training, Canada
All rights reserved
A detailed study on the guidelines that are taken for ICH which is also known as the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use. The chapter deals with an overview of Quality, Safety, Efficacy and Multidisciplinary guidelines and then a detailed study on the Quality Guidelines. Also a detailed learning of Stability Testing Guidelines proposed by the International Conference for Harmonization.
WHO Guideline & Stability Protocols for Liquid Dosage FormsAnindya Jana
These guidelines seek to exemplify the core stability data package required for registration of active pharmaceutical ingredient (APIs) & finished pharmaceutical protocols (FPPs), replacing the previous WHO guidelines in this area. However, alternative approaches can be used when they are scientifically justified. Further guidelines can be found in International Conference on Harmonisation (ICH) guidelines and in the who guidelines on the active pharmaceutical ingredient master file procedure.
This guideline is a revised of the ICHQ1A –stability data package for new drug substance /DRUG PRODUCT .The [urpose of guideline to define stability data package that sufficient for a registration application within the 3 regions of EU ,JAPAN & USA & to maintain the quality of drug products, in relation to safety , efficacy & acceptability throughout the propose shelf life.
ICH Stability testing of new drug substances and products QA (R2) - 2015
Almudena Camacho
Mohammad Koosha
Rocio Monroy
Professor Peivand Pirouzi Inc. -
Copyright 2015 - Professor Peivand Pirouzi Inc., International Corporate Training, Canada
All rights reserved
A detailed study on the guidelines that are taken for ICH which is also known as the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use. The chapter deals with an overview of Quality, Safety, Efficacy and Multidisciplinary guidelines and then a detailed study on the Quality Guidelines. Also a detailed learning of Stability Testing Guidelines proposed by the International Conference for Harmonization.
a substance can absorb any visible light or external radiation and then again emit it. this called fluorescence and the process of reduction in fluorescence intensity is called quenching. this presentation is all about quenching of fluorescence.
Method validation for drug substances and drug product _remodified_2014Ramalingam Badmanaban
Method validation is the process of proving that an analytical method is acceptable for its intended purposes.
METHOD VALIDATION = ERROR ASSESSMENT
Method validation is the process of demonstrating that analytical procedures are suitable for their intended use and that they support the identity, strength, quality, purity and potency of the drug substances and drug products
Validation: Prior ConsiderationsSuitability of Instrument Status of Qualification and Calibration Suitability of Materials Status of Reference Standards, Reagents, Placebo Lots Suitability of Analyst Status of Training and Qualification Records Suitability of Documentation Written and approved standard test procedure and proper approved protocol with pre-established acceptance criteria
Compendial vs. Non-compendial Methods
Compendial methods-Verification
Regulatory analytical procedure in USP/NF
Non- compendial methods-Validation
Alternative analytical procedure proposed by the applicant for use instead of the regulatory analytical procedure
Chromatographic Methods
Demonstrate Resolution
Impurities/Degradants Available
Spike with impurities/degradants
Show resolution and a lack of interference
Impurities/Degradants Not Available
Stress SamplesFor assay, Stressed and Unstressed Samples should be compared.
Ability of an analytical method to measure the analyte free from interference due to other components.
Selectivity describes the ability of an analytical method to differentiate various substances in a sample
Original term used in USP
Also Preferred by IUPAC and AOAC
Also used to characterize chromatographic columns
Degree of Bias (Used in USP)
The difference in assay results between the two groups
the sample containing added impurities, degradation products, related chemical compounds, placebo ingredients
Selectivity: For impurity test, impurity profiles should be compared.
Temperature (50-60℃)
Humidity (70-80%)
Acid Hydrolysis (0.1 N HCl)
Base Hydrolysis (0.1 N NaOH)
Oxidation (3-30%)
Light (UV/Vis/Fl)
Intent is to create 10 to 30 % Degradation
Change in the analytical procedure, drug substance, drug product, the changes, may necessitate revalidation of the analytical procedures.
“The degree of revalidation depends on the nature of the change.”
“FDA intends to provide guidance in the future on post-approval changes in analytical procedures.”
By Visual Inspection of plot of signals vs. analyte concentration
By Appropriate statistical methods
Linear Regression (y = mx + b)
Correlation Coefficient, y-intercept (b), slope (m)
Acceptance criteria: Linear regression r2 > 0.999
Requires a minimum of 6 concentration levels
Normally derived from Linearity studies.
Established by confirming that the method provides acceptable degree of linearity, accuracy, and precision.
Specific range dependent upon intended application of the procedure.
Presentation on-stability-study of pharmaceutical productMd Mohsin
this content takes important information about stability & stability study of pharmaceutical products including guidelines,climate zone,testing conditions,sampling plan,extension of shelf life,re test,current trends in stability study etc.
stability The ability of a pharmaceutical product to retain its chemical, physical, microbiological and biopharmaceutical properties within specified limits throughout its shelf-life.Why is stability of a drug important?
Drug stability affects the safety and efficacy of the drug product; degradation impurities may cause a loss of efficacy and generate possible adverse effects. Therefore, achieving the chemical and physical stability of drugs is essential to ensure their quality and safety.Common factors that affect this stability include temperature, light, pH, oxidation and enzymatic degradation. Special considerations are also required when dealing with chiral molecules, deuterated internal standards and large biomolecules.
Comparison of stability testing requirements of ich with otherJun Brown
Stability plays an important role in the drug development process. Present work aims to compare the stability
testing (ST) requirements of International Conference on Harmonization (ICH) with other international regulatory
agencies like World Health Organization (WHO), Association of South East Asian Nations (ASEAN) and
European Agency for Evaluation of Medicinal and Health Products (EMEA). ICH guidelines describe stability
testing requirements for new drug substance and drug product. WHO guidelines describe stability testing
requirements for both new and existing Active pharmaceutical ingredients (APIs) and addresses information
to be submitted in original and subsequent applications for marketing authorization of their related Finished
pharmaceutical products (FPP) for human use. ST requirements for WHO are similar, except for the parameters
like selection of batches and storage conditions. WHO guidelines have an additional requirement for long term
storage condition (general case) and accelerated storage conditions (substance/product intended to be stored
in refrigerator). ASEAN guideline mainly focuses on the requirements for stability testing of drug products along
with new chemical entities (NCE’s). The differences were observed in stress testing, selection of batches and
real time storage conditions. EMEA guidelines discussed here are an extension of the note for guidance on
stability testing requirements for new active substance and related products. It sets out the stability testing
requirements for existing active substance and related finished product. The minimum time period to be covered
by data at the time of submission during long term storage conditions differs from ICH guidelines.
ICH Guideline Stability Testing of New Drug Substances and Product Q1A(R2).pptxTrishala Bhatt
This presentation outlines the ICH Guideline for Stability Testing of New Drug Substances and Products, Q1A(R2). It serves as a comprehensive framework for ensuring the stability of new pharmaceuticals, with a focus on the requirements for registration applications within the EC, Japan, and the United States. The guideline emphasizes a balance between a standardized approach and the flexibility to adapt to specific scientific considerations and characteristics of the materials under evaluation.
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.
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.
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.
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.
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
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
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Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
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
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
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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!
2. CONTENTS
What is stability
What is the need of stability in pharmaceuticals
What is the requirements of physicals stability under Indian drug
law
Possible changes
Factor affecting stability
Stages of Drug and Product Development and Stability Testing
Types of stability
Physical stability of Pharmaceuticals
Different Organization regulating stability guidelines
ICH Guidelines
ICH Q1AR2
Conclusion
References
3. What is Stability?
Drug Stability refers to the capacity of a drug substance or
product to remain within established specifications of
identity, strength, quality, and purity in a specified period
of time.
Stability is officially defined as the time lapse during which
the drug product retains the same properties and
characteristics that it possessed at the time of manufacture.
The stability of a product is expressed as the expiry
period or technically as shelf life.
4. What is the Need of Stability in Pharmaceuticals
KEY ASSURANCE OF QUALITY OF PHARMACEUTICALS
To gather information during Preformulation Stage to
produce a stable product.
To determine maximum Expiration Date.
To get an idea of storage condition.
To determine the packaging components.
To establish retest period of pharmaceuticals.
Transport conditions.
Provide an evidence on how the quality of a drug
substance or drug product varies with the time under the
influence of environmental factor
5. Requirement of Stability Testing under Indian Drug Law
With reference to Schedule M serial No 16 Quality
Control System 16.10: The quality control department shall
conduct Stability Studies of the products to ensure and assign their
shell life at the prescribed conditions of storage. All records of such
studies shall be maintained
6. The Possible Changes{Visible & Invisible}
Loss of active ingredient
Alteration in bioavailability
Loss of content uniformity
Decline of microbiological status
Loss of pharmaceutical elegance and patient
acceptability
Formation of toxic degradation products
Loss of package integrity
Reduction of label quality
Modification of any factor of functional relevance
(dissolution, release, etc.)
7. Why so much emphasis on right practice in Stability
The ideal production The non-ideal shipment and
environment storage environment
- Transport
- Regulations and
Controls - Wholesalers
- GMP
- Retailers
- GLP
- Patients
The ideal formulation
Mishandling
8. Factor Affecting Drug Stability
1- Environmental factors
- Temperature
- Light
- Moisture
2- Drugs or excipients in the dosage form
-Particle size of drug
-pH of the vehicle
3- Microbial contamination
4- Trace metal Contamination
5- Leaching from containers
9. Types of Stability In Pharmaceuticals
Stability of Drug
Physical Chemical Packaging Microbiological
Physical Stability of
Pharmaceuticals
10. Physical stability of Pharmaceuticals
Physical stability implies that:
-The formulation is totally unchanged (appearance, organoleptic
properties, hardness, brittleness, particle size etc).
-It is significant as it affects:
pharmaceutical elegance
drug content uniformity
drug release rate.
18. Different regulatory Authorities which regulates guidelines for stability
ICH: international Conference on Harmonization of
technical requirements for registration of
pharmaceuticals for human use
WHO : World Health Organization
USFDA: United state food drug Administration
CPMP: Committee for Medicinal Products for
Human Use formerly known as Committee for
Proprietary Medicinal Products
19. What is ICH
The International Conference on Harmonisation of Technical
Requirements for Registration of Pharmaceuticals for Human Use.
ICH is unique project that brings together the regulatory authorities of
Europe, Japan & U.S. and experts from the pharmaceutical industries to
discuss the scientific and technical aspects of the product registration.
Mission of ICH
ICH’s mission is to make recommendations towards achieving greater
harmonisation, thereby reducing or obviating duplication of testing carried
out during the research and development of new human medicines.
Global Cooperation Group
In 1999 ICH made five regions
INDIA has joined ICH in 2007 in GCC Region
20. Body of ICH
1. Founder members in steering committee of ICH
European Union: represents 15 current EU member states
European Federation of Pharmaceutical Industries
Association (EFPIA): located in Brussels, mainly medicines
research based pharma companies from 15 countries.
Ministry of Health and Welfare (MHW)- Japan.
Japan Pharmaceutical Manufacturer’s Association (JPMA): it
represents all the 90 major research based pharmaceutical
companies.
US Food and Drug Administration (USFDA)
Pharmaceutical Research and Manufacturers of America
(PHRMA): it represents 67 research based companies and 25
research affiliates.
21. 2. Observers: the following observers act as a link between
ICH countries and regions.
i. WHO
ii. Canada
iii. IFPMA
3. ICH co- ordinator: nominated by each of the six co
sponsors.
4. The ICH secretariat: its primary function is the organization
of steering committee and experts meeting and associated
documentation.
5. ICH expert working group: carried by experts.
6.The harmonisation process: process development and the
progress of each guideline during harmonisation process.
22. ICH GUIDLINES
GUIDELINES {QSEM}
Quality guidelines Safety guidelines
Efficacy guidelines Multi disciplinary guidelines
24. The ICH Q1 series of guidelines are designed for
stability programs which consists of 6 separate
guidelines
25. ICH GUIDILINES
Objectives
Defines stability data package for drug substance and drug
product for registration application, Within there region
Exemplify the core stability package for new substance &
products.
General principle of Q1AR2
The purpose of stability testing is to provide evidence on how
a drug substance or drug product varies with in time under the
influence of environmental factor such as
Temperature
Humidity
Light
To establish a re test period for the drug substance/shelf life
Recommended storage condition
26. ICH GUIDLINES
Stress Testing : Studies undertaken to asses the effects of
the sever conditions on the drug product.
Carried out at 10 o c increment
50 o c….to 70 o c
Humidity 75% RH
Selection of Batches :at least three batches shall
be studied for stability, out of which 2 batches shall
be at least pilot batches and third one can be small if
justified.
Stability study can be performed on each individual
strength and container size of the product.
27. ICH GUIDELINES
Container Closure system
Stability testing should be conducted on the dosage
form packaged in the container closure system
proposed for marketing
Specification
These guidelines states the list of test, reference to
analytical procedure, and proposed acceptance
criteria, include the concepts of different acceptance
criteria for release and shelf life specification is
addressed in ICH Q6A & Q6B.
28. ICH GUIDELINES
Testing frequency
For products with a proposed shelf life of at least 12
months
the frequency of testing at the long term storage condition
should normally be every 3 months over the first year, every 6
months over the second year, and annually thereafter through
the proposed re-test period.
First year------------------3 month
Second --------------------6 month
Thereafter------------------annually through out the proposed re-test
period
Testing frequency at accelerated storage condition min
three point , at 0 , 3 , 6 month
33. ICH GUIDELINES
3.Drug products packaged in impermeable containers
The stability studies for product stored in impermeable container can be
conducted under any controlled or ambient humidity condition.
4.Drug products intended for storage in a refrigerator
34. ICH GUIDELINES
5.Drug products intended for storage in a freezer
stability commitment
submission includes data from stability studies on at least three
production batches, a commitment should be made to continue
these studies through the proposed re-test period.
39. In general significant change for drug product is defined
as one or more of the following:
1. A 5%change in assay from its initial value
2. Any degradation product exceeding its acceptance
criteria
3. Failure to meet the acceptance criteria for appearance,
physical attributes and hard ness , dose delivery per
actuation, etc.
4. Failure to meet the acceptance criteria for pH.
5. Failure to meet the acceptance criteria for dissolution for
12 dosage units.
40. Evaluation
A systematic approach should be adopted in the presentation and
evaluation of the stability information.
Where the data show so little degradation and so little variability that it
is apparent from looking at the data that the requested shelf life will be
granted, it is normally unnecessary to go through the formal statistical
analysis; providing a justification for the omission should be sufficient.
An approach for analysing data on a quantitative attribute that is
expected to change with time is to determine the time at which the 95%
one-sided confidence limit for the mean curve intersects the (lower)
acceptance criterion (95% assay).
41. EVALUATION – BEST CASE
4. No significant change at accelerated conditions within six (6)
months.
5. Long-term data show little or no variability and little or no
change over time.
6. Accelerated data show little or no variability and little or no
change over time.
7. Statistical analysis is normally unnecessary.
8. Proposed retest period or shelf life = double of period
covered by long-tem data
9. A retest period or shelf life granted on the basis of
extrapolation should always be verified by additional long-
term stability data
42. CONCLUSION
Stability studies should be planned on the basis of
pharmaceutical R+D and regulatory requirements.
Forced degradation studies reveal the intrinsic chemical
properties of the API, while formal stability studies establish
the retest date.
The shelf life (expiry date) of FPPs is derived from formal
stability studies.
Variability and time trends of stability data must be
evaluated by the manufacturer in order to propose a retest
date or expiry date.
43. References
Drug Stability: Principles and Practices, 3rd Edition, edited by
Jens T. Carstensen and C. T. Rhodes
www.pharmpedia.com
www.ich.org
www.fda.gov
www.whoindia.org
www.ema.europa.eu
Remington the science and practice of pharmacy p1025
Since its inception in 1990, ICH has evolved, through its ICH Global Cooperation Group, to respond to the increasingly global face of drug development, so that the benefits of international harmonisation for better global health can be realised worldwide
The design assumes that the stability of an intermediate levels is represented by the stability of the extremes tested.
Bracketing can be applied to studies with multiple strengths of identical or closely related formulations. Examples include: Capsules, tablets and oral solutions of different strengths. In cases, where different excipients are used among strengths, bracketing generally should not be applied. Bracketing can be applied to studies of the same container closure system where either the container size or fill varies while the other remains constant.