An out of specification (OOS) occurs when analytical results fall outside established specification ranges. There are guidelines from organizations like MHRA, CDER, and PIC/S for handling OOS events. OOS can occur during stability studies, finished products, or raw materials due to laboratory errors, process issues, or sample homogeneity problems. Investigations follow a phased approach starting with the quality control laboratory and then involving manufacturing operations if needed. The fate of an OOS batch may include reprocessing, reworking, or destruction depending on the investigation conclusions.
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.
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.
Fundamental knowledge on pharmaceutical
product development and translation from laboratory to market.
Quality management systems: Quality management & Certifications.
Introduction to OOS
Identification of OOS: Reports of Laboratory Investigation
Responsibility of Analyst and Supervisor
Identification of OOS:
Reports of Full Scale Investigation
Review of Manufacturing, Production and Sampling
Review of Lab Investigation Result
Supplementary Laboratory Testing Procedure
Analysis of Investigated Results
Pilot Plant:-
“Defined as a part of pharmaceutical industry where a lab scale formula is transformed into viable product by the development of liable practical procedure for manufacture”.
Scale-up:-
“The art of designing of prototype using the data obtained from the pilot plant model”
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.
Objectives of CGMP
Layout of buildings, services, equipments & maintenance
Production organization
material management
handling and transportation
inventory management &control
Production and planning control
Sales forcasting
Budget and cost control
Industrial and personnel relationship
Total quality management
Technology Transfer in Pharma Industry, Technology Transfer in Pharmaceutical Industry, Pharmaceutical Technology Transfer, Pharma Tech Transfer, Naseeb basha, Pharmaceutical Tech Transfer, Naseeb basha Technology Transfer in Pharma Industry, Naseeb basha Pharmaceutical Technology Transfer
Fundamental knowledge on pharmaceutical
product development and translation from laboratory to market.
Quality management systems: Quality management & Certifications.
Introduction to OOS
Identification of OOS: Reports of Laboratory Investigation
Responsibility of Analyst and Supervisor
Identification of OOS:
Reports of Full Scale Investigation
Review of Manufacturing, Production and Sampling
Review of Lab Investigation Result
Supplementary Laboratory Testing Procedure
Analysis of Investigated Results
Pilot Plant:-
“Defined as a part of pharmaceutical industry where a lab scale formula is transformed into viable product by the development of liable practical procedure for manufacture”.
Scale-up:-
“The art of designing of prototype using the data obtained from the pilot plant model”
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.
Objectives of CGMP
Layout of buildings, services, equipments & maintenance
Production organization
material management
handling and transportation
inventory management &control
Production and planning control
Sales forcasting
Budget and cost control
Industrial and personnel relationship
Total quality management
Technology Transfer in Pharma Industry, Technology Transfer in Pharmaceutical Industry, Pharmaceutical Technology Transfer, Pharma Tech Transfer, Naseeb basha, Pharmaceutical Tech Transfer, Naseeb basha Technology Transfer in Pharma Industry, Naseeb basha Pharmaceutical Technology Transfer
Data Integrity II - Chromatography data system (CDS) in PharmaSathish Vemula
- Introduction
- Functions of CDS
- Validation of CDS
- Regulatory requirements
- Procedures required
- Areas for ensuring CDS Data Integrity
- Previous observations
- FDA Warning Letters – 2013
- FDA Warning Letters – 2014
- FDA 483’s related to CDS
- EU – Non compliance Reports
- WHO - Notice of Concern
- How to avoid observations ?
- Conclusion
HPLC Principle,Instrumentation and ApplicationAlakesh Pradhan
HPLC Chromatography and its principle
Liquid chromatography
High Performance Liquid Chromatography ( HPLC )
The components of the high performance liquid chromatograph (HPLC).
The separation process.
The chromatogram
OOS and OOT investigation is always a challenging task. This slide may help for a better understanding of investigation procedure according to regulatory requrement.
Documentation with respect to release of finished pharmaceutical productMadhuraNewrekar
Documentation is a crucial part of the quality assurance system and is needed in every aspect of pharmaceutical manufacturing. Important documentation with respect to final product release in pharmaceutical industry is explained in brief.
It is difficult to maintain the sterility and It is more difficult to investigate when the status is Non sterile. So this ppt narrate the way for you to investigate the Non sterility.
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
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.
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
- 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
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.
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.
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.
2. 2
Definition
If the analytical result(s) of a batch or material is/are
falling out side of the established specification
ranges, is called / considered as Out of Specification.
Or
The term OOS test results includes all suspect results
that fall outside the predetermined Specification
3. 3
Out of Specifications
There are lot of guidelines are available for defining
to handle the OOS products/materials/batches as:
MHRA guideline for OOS
CDER guideline for OOS
PIC/S guideline for OOS
4. 4
Out of Specifications
The OOS may be observed during the analysis of:
Stability study
Finished API
Intermediates
In-process
Raw materials
Packing materials
5. 5
Out of Specifications
OOS found due to the following reasons but not
limited to:
OOS
Laboratory
Process
related
Sample
homogeneity
6. 6
Out of Specifications
Laboratory errors:
Laboratory errors
Method of
Analysis
Use of Non
Calibrated
instruments
Error in
calculation
Analyst
error
Instrument
Failure
7. 7
Out of Specifications
Process Related:
Process Related
Operator Error Equipment
Failure
Deviation form
the validated
procedure
Quality of Raw
material /
Intermediate
used
In-Process
Control During
Manufacturing
9. 9
OOS Investigations
As per MHRA (EU GMP)
Phase – I Investigation
(Primary & extended lab investigation)
Phase – II Investigation
(Manufacturing investigation)
Phase – III Investigation
(Extended manufacturing, Re-sampling
and re-analysis)
Procedures of OOS investigations
As per CDER (US FDA)
Phase – I Investigation
(Primary & extended lab investigation)
Phase – II Investigation
(Manufacturing investigation and re-
sampling and re-analysis)
10. 10
OOS Investigations
Phase – I Investigation: Laboratory investigation
Laboratory investigation is related to the Quality control
department along with rechecking of documents with same
analyst and re-testing with different analyst with original sample.
Phase – I is sub divided in to two sections as:
Phase – Ia (Primary Lab investigation), and
Phase -Ib (Extended Lab investigation)
As per MHRA (EU GMP)
11. 11
OOS Investigations
Phase – II Investigation: Manufacturing Investigations
In manufacturing investigation, production person investigate :
Process parameters
Drying parameters
Input raw materials quality
training of persons
Cleaning of equipment
Environmental information
Contamination & etc….
As per MHRA (EU GMP)
12. 12
OOS Investigations
Phase – III Investigation: Extended Manufacturing Investigations
In Phase III investigation, Quality Control / Quality Assurance & Production
department investigate the following:
Sampling error by person
Authorized for re sampling (if required)
Re-analysis of re-sampled material with different Analyst
If root cause found, define the CAPA or if not
Diverted the matter to R&D / ADL or PD Lab
Conclusion by all team member (QA, QC, PRD, ADL R&D, PD Lab)
Decide the fate of batch by QA Head
As per MHRA (EU GMP)
13. 13
OOS Investigations
Re-testing:
The analysis of original sample at the time of phase- I laboratory investigation.
Re-sampling:
The original batch is sampled by QA second time after QA head authorization for re-
analysis.
Re-analysis:
The analysis of re-sampled material for the verification of results, if
manufacturing investigation does not have root cause.
14. 14
OOS Investigations
Phase – I Investigation: Laboratory investigation
Laboratory investigation is related to the Quality control
department along with rechecking of documents with same
analyst and re-testing with different analyst with original
sample.
Phase – II Investigation: Manufacturing investigation
Process related investigation is to be carried out by
Production department along with re-sampling and re-
analysis.
As per CDER (US FDA)
15. 15
OOS Investigations
Phase – I Investigation: Laboratory investigation
Analyst observed the OOS result
Re-calculate the results (if required)
If analytical results remain same
Report the OOS result to QC In-charge
Log the OOS
Start the Primary Laboratory investigation
Review the documents along with solutions as (Potency / STP
& Specs / buffer solutions / calibration of instruments /
standard solutions / Column efficiency / weights / storage
condition of sample and many more)
16. 16
OOS Investigations
Phase – I Investigation: Laboratory investigation
If there is no abnormality observed during the primary
lab investigation then
Report same results and considered as valid OOS and report
Quality Head review the primary lab investigation and
evaluate for re-testing (if QA Head permits)
Repeat the analysis as thrice with original sample with
different analyst
Report the average result of repeat analysis
Report the average result
17. 17
OOS Investigations
Phase – I Investigation: Laboratory investigation
If the result complies
Report as complies and invalidate the OOS
Release the batch
If any of result if not complies (among three)
Report as OOS and continue the OOS
Report to QA head
QA head will recommend for the Phase – II investigation (manufacturing
investigation)
18. 18
OOS Investigations
Phase – II Investigation: Manufacturing investigation
Production persons shall investigate the following:
Input quantity of raw material
Input RM quality
Process parameters details
Critical process parameter details (time / temp)
In-process results
Out put of the material
Re-conciliation of raw materials
Utility pressures
Calibration / Preventive maintenance of equipment
Attached ancillaries status
19. 19
OOS Investigations
Phase – II Investigation: Manufacturing investigation
Production persons shall investigate the following:
Cleaning of equipments
Training of personnel
Brain storming with operators
Contamination verifications
Environmental review
If there is no assignable cause observed during manufacturing
investigations, same is to be reported to Quality Assurance Head.
20. 20
OOS Investigations
Phase – II Investigation: Manufacturing investigation
QA, QC and production department will evaluate the investigations and after that:
Sampling procedure review, if suspected
QA head may recommend for re-sampling
QC analyst shall analyze the sample as per STP
Report the result (Pass / Failed)
If Pass
Define the CAPA
Release the Batch
If failed
Reject the batch
Divert the matter to R&D / ADL / PD Lab
21. 21
OOS Investigations
Phase – II Investigation: Manufacturing investigation
R&D / ADL / PD Lab shall:
Take the user trial with the material
Investigate the failure based on experiments / experiences
Various types of experiments
To find out the root cause
To identify, is this material can b e reprocessed / reworked
Make a summary report
Defined the corrective actions
22. 22
OOS Investigations
Phase – II Investigation: Manufacturing investigation
QA/QC/Production department shall:
QA head shall define the fate of batch for reprocess / rework /
destruction
Accept the corrective and preventive actions
Training to all concerned for root cause / corrective action / preventive
action
Monitor the activity for corrective actions
Evaluate the results of corrective actions
Implement the preventive actions
Verify the implementation of preventive actions
After satisfactory implementation close the OOS & CAPA
23. 23
OOS Investigations
All these activity for investigation / corrective actions / preventive
actions should be recorded and reviewed and archived.
24. 24
OOS Investigations
If OOS batch is to be reprocessed / re-work:
Follow the written approved BMR for re-process / Rework
Sample as per SOP for sampling of material
Analyze the material according to the specification and STP
Evaluate the quality of the batch
Keep this batch for stability (Accelerated / Long term)
Evaluate the stability results of the batch
Communicate the OOS to the customers (as mentioned in to the
Quality agreement)
25. 25
OOS Investigations
Impact of OOS on REGULATORY:
Stability study required
OOS should be reported to RA
OOS batch should not be sold to Regulatory market
OOS batch can not be blend with fresh approved batch
OOS batch can not be directly sell to the market
26. 26
Abbreviations
CDER : Center for drug evaluation and research
OOS : Out of specification
RA : Regulatory affairs
STP : Standard testing procedure
EU-GMP : European good manufacturing practices
PIC/s : Pharmaceutical inspection co-operation
scheme