This document discusses deviation handling and root cause analysis. It defines deviations as departures from standard procedures and outlines regulatory expectations to investigate deviations and prevent reoccurrence. The basic process flow for handling deviations includes identification, assessment, classification, investigation and corrective actions. Root cause analysis is presented as a method to systematically identify underlying causes of problems using techniques like brainstorming, 5 whys, and cause-and-effect diagrams. The goals of root cause analysis are failure identification, analysis, and resolution through an iterative process.
This presentation describes approaches for software validation used to automate laboratory research procedures, consolidate data collection and analysis and/or run sophisticated QC or manufacturing operations.
Several approaches to software validation exist and may be appropriate for a specific project.
The scope of any validation effort depends upon a number of factors
Size and complexity of the software,
Origin of the software (custom vs. off-the-shelf) and
Whether the functions are critical or non-critical in nature.
By effectively planning the process, validation time and resources can be reduced while meeting regulatory requirements.
This presentation describes approaches for software validation used to automate laboratory research procedures, consolidate data collection and analysis and/or run sophisticated QC or manufacturing operations.
Several approaches to software validation exist and may be appropriate for a specific project.
The scope of any validation effort depends upon a number of factors
Size and complexity of the software,
Origin of the software (custom vs. off-the-shelf) and
Whether the functions are critical or non-critical in nature.
By effectively planning the process, validation time and resources can be reduced while meeting regulatory requirements.
Corrective Actions and Preventive Actions.Corrective Action Preventive Action (CAPA) is a process which investigates and solves problems, identifies causes, takes corrective action and prevents recurrence of the root causes. The ultimate purpose of CAPA is to assure the problem can never be experienced again. Corrective vs. Preventive Action. Quality professionals frequently express confusion as to the difference between corrective and preventive action. A corrective action deals with a nonconformity that has occurred, and a preventive action addresses the potential for a nonconformity to occur.
CAPA management, corrective and preventive action, Rootcause analysis, RCA, Problem mapping, FMEA, Failure Mode effect and Analysis, Fault Tree analysis, Fishbone : ISHIKAWA, CTQ Tree (Critical to Quality Tree), AFFINITY DIAGRAM, 5 Why’s, Human errors,
Corrective Actions and Preventive Actions.Corrective Action Preventive Action (CAPA) is a process which investigates and solves problems, identifies causes, takes corrective action and prevents recurrence of the root causes. The ultimate purpose of CAPA is to assure the problem can never be experienced again. Corrective vs. Preventive Action. Quality professionals frequently express confusion as to the difference between corrective and preventive action. A corrective action deals with a nonconformity that has occurred, and a preventive action addresses the potential for a nonconformity to occur.
CAPA management, corrective and preventive action, Rootcause analysis, RCA, Problem mapping, FMEA, Failure Mode effect and Analysis, Fault Tree analysis, Fishbone : ISHIKAWA, CTQ Tree (Critical to Quality Tree), AFFINITY DIAGRAM, 5 Why’s, Human errors,
The RCCA PPT is an excellent training tool to implement into your functional group or business.
It basically forces you to peel the onion on a failure as far back until you’ve reached the root cause whereas in some cases it could be several.
It incorporates the 5 whys and the problem solving technique.
Auditing Manufacturing Process and Product and Process Information.pdfDr. Dinesh Mehta
Manufacturing process audits should ensure that procedures are properly followed, problems are quickly corrected, there is consistency in the process, and there is continuous improvement and corrective action as needed.
THE IMPORTANCE OF MARTIAN ATMOSPHERE SAMPLE RETURN.Sérgio Sacani
The return of a sample of near-surface atmosphere from Mars would facilitate answers to several first-order science questions surrounding the formation and evolution of the planet. One of the important aspects of terrestrial planet formation in general is the role that primary atmospheres played in influencing the chemistry and structure of the planets and their antecedents. Studies of the martian atmosphere can be used to investigate the role of a primary atmosphere in its history. Atmosphere samples would also inform our understanding of the near-surface chemistry of the planet, and ultimately the prospects for life. High-precision isotopic analyses of constituent gases are needed to address these questions, requiring that the analyses are made on returned samples rather than in situ.
Cancer cell metabolism: special Reference to Lactate PathwayAADYARAJPANDEY1
Normal Cell Metabolism:
Cellular respiration describes the series of steps that cells use to break down sugar and other chemicals to get the energy we need to function.
Energy is stored in the bonds of glucose and when glucose is broken down, much of that energy is released.
Cell utilize energy in the form of ATP.
The first step of respiration is called glycolysis. In a series of steps, glycolysis breaks glucose into two smaller molecules - a chemical called pyruvate. A small amount of ATP is formed during this process.
Most healthy cells continue the breakdown in a second process, called the Kreb's cycle. The Kreb's cycle allows cells to “burn” the pyruvates made in glycolysis to get more ATP.
The last step in the breakdown of glucose is called oxidative phosphorylation (Ox-Phos).
It takes place in specialized cell structures called mitochondria. This process produces a large amount of ATP. Importantly, cells need oxygen to complete oxidative phosphorylation.
If a cell completes only glycolysis, only 2 molecules of ATP are made per glucose. However, if the cell completes the entire respiration process (glycolysis - Kreb's - oxidative phosphorylation), about 36 molecules of ATP are created, giving it much more energy to use.
IN CANCER CELL:
Unlike healthy cells that "burn" the entire molecule of sugar to capture a large amount of energy as ATP, cancer cells are wasteful.
Cancer cells only partially break down sugar molecules. They overuse the first step of respiration, glycolysis. They frequently do not complete the second step, oxidative phosphorylation.
This results in only 2 molecules of ATP per each glucose molecule instead of the 36 or so ATPs healthy cells gain. As a result, cancer cells need to use a lot more sugar molecules to get enough energy to survive.
Unlike healthy cells that "burn" the entire molecule of sugar to capture a large amount of energy as ATP, cancer cells are wasteful.
Cancer cells only partially break down sugar molecules. They overuse the first step of respiration, glycolysis. They frequently do not complete the second step, oxidative phosphorylation.
This results in only 2 molecules of ATP per each glucose molecule instead of the 36 or so ATPs healthy cells gain. As a result, cancer cells need to use a lot more sugar molecules to get enough energy to survive.
introduction to WARBERG PHENOMENA:
WARBURG EFFECT Usually, cancer cells are highly glycolytic (glucose addiction) and take up more glucose than do normal cells from outside.
Otto Heinrich Warburg (; 8 October 1883 – 1 August 1970) In 1931 was awarded the Nobel Prize in Physiology for his "discovery of the nature and mode of action of the respiratory enzyme.
WARNBURG EFFECT : cancer cells under aerobic (well-oxygenated) conditions to metabolize glucose to lactate (aerobic glycolysis) is known as the Warburg effect. Warburg made the observation that tumor slices consume glucose and secrete lactate at a higher rate than normal tissues.
Professional air quality monitoring systems provide immediate, on-site data for analysis, compliance, and decision-making.
Monitor common gases, weather parameters, particulates.
Seminar of U.V. Spectroscopy by SAMIR PANDASAMIR PANDA
Spectroscopy is a branch of science dealing the study of interaction of electromagnetic radiation with matter.
Ultraviolet-visible spectroscopy refers to absorption spectroscopy or reflect spectroscopy in the UV-VIS spectral region.
Ultraviolet-visible spectroscopy is an analytical method that can measure the amount of light received by the analyte.
1. Title: Deviation and
Root Cause Analysis
Content
Deviation and Type of Deviation
Regulatory expectation
Basic process flow for Deviation handling
Root Cause Analysis
Tools and Technique for Root Cause Analysis
Presented By: Subhash Sanghani
2. WHAT IS DEVIATION?
Deviation is a departure from a documented standard or procedure
Deviations are measured differences between observed value and expected or normal value for a process or product
condition, or a departure from approved procedure or established standard or specification
There are two types of deviations
1)Planned Deviation : Planned deviations, which are described, and pre-approved deviation from the current operational
document/system, covering a specified period of time or number of batches. Planned deviation shall be approved before
execution
2)Unplanned Deviation: Unplanned deviations also called as incident.
It is defined as unplanned or uncontrolled event in the form of non-compliance from the designed systems or
procedures at any stage of manufacturing, packaging, testing, holding and storage of drug product due to system
failure or equipment breakdown or manual error.
WHY INVEISTIGATE DEVIATION?
To prevent reoccurrence
Failures are cost to company
Failures can have adverse health impact on the consumers if go undetected
To identify the cause and take corrective actions
To identify other similar situations and take preventive actions
Continuous improvement
Regulatory requirement
3. Regulatory Expectation
• “Any unexplained discrepancy…shall be thoroughly investigated…The
investigation shall extend to other batches …that can have been associated with the
specific failure or discrepancy. A written record of the investigation shall be made
and shall include the conclusions and follow-up
21 CFR 211.192
•“Any deviations from instructions or procedures should be avoided as far as
possible. If a deviation occurs, it should be approved in writing by a competent
person…”
• Any significant deviations [from defined procedures and instructions] are fully
recorded and investigated
EC Guide to GMP, Chapter 5
(5.15)
• Any deviation from established procedures should be documented and explained.
Critical deviations should be investigated, and the investigation and its conclusions
should be documented.
ICHQ7A
• The organization should ensure process outputs, products, and services that do not conform to
requirements are identified and controlled to prevent unintended use or delivery. The
organization should take appropriate action based on nature of nonconformity and its impact on
conformity of products and services. This is applicable also to nonconforming products and
services detected after delivery of products during or after provision of service
ISO 9001:2015,Clause 8.7
When a deviation occurs the responsible firm must undertake and investigation to determine what went wrong
and what damage, if any , the product might have suffered.
4. Basic Process flow for Deviation handling
Identification of deviation
Immediate correction & initial
impact assessment
(Containment action)
Define and classified
deviation
Major :Impact on product
quality
Critical: Impact on
product quality, safety &
efficacy
Minor: No impact on
product quality, safety
& efficacy
•Impact
Assessment
•Corrections &
closure of incident
•Impact Assessment
•Investigation
•Corrections / CAPA
•Closure of incident
•CAPA
implementation &
effectiveness check
Related to
what?
When and
Where?
What is the
extent?
What are the
immediate
action taken
Any interim
control
5. Root Cause Analysis
Root cause analysis(RCA) is a method that used to address a deviation or non conformance in order to get to the true root
cause of the problem.
RCA is application of a series of well known technique which can produce a systematic, quantified and documented
approach to the identification, under stand and resolution of under causes.
As a PROCESS it is more effective when it’s adequately defined, provisioned with appropriate resources, and performed by
trained personnel.
Goals - Failure identification - Failure analysis - Failure resolution
Iterative Process: - Complete prevention of recurrence by a single intervention is not always possible.
Basic steps involved in Root Cause Analysis Define
Event
Gather
data
Investig
ation
Identify
the Root
CausesEliminat
e items
that are
not root
causes
Recomm
endation
s
CAPA
Improve
ment
6. RCATools and Technique
Brainstorming
A creative approach to generate a high volume of ideas free of criticism and judgment.
What are the rules?
Every idea is captured.
Ideas are written as said.
No comments, discussion, or criticism.
Everyone contributes.
Five Whys?
The 5 Whys is a questions‐asking method used to explore the cause/effect relationships underlying a particular problem.
Ultimately, the goal of applying the 5 Whys method is to determine a root cause of a defect or problem.
Keep asking Why till you reach root cause
Cause and Effect Diagram
Technique to graphically identify and organize many possible causes of a
problem
Advantages - Helps to discover the most likely ROOT CAUSES of a
problem
Teach a team to reach a common understanding of a problem.
Fishbone Analysis Components : -
Head of a Fish : Problem or Effect
Horizontal Branches : Causes
Sub – branches : Reason