-
Session 3Validation, Risk and Criticality
Presented by Trevor Schoerie
14 May, 2014
-
Slide 2 © PharmOut 2014
Validation, Risk and Criticality
• In process validation we want to understand and control the variationnot the risk.
• The “drug” benefit vs risk should have already been determined, (hopefully).
“GAMP 5 – Risk Based ……”
“We talk about QRM every time we meet!”
-
Slide 3 © PharmOut 2014
“Process Variation”
1. Sample Variation
2. Analytical Variation?
3. Process Variation – normally associate
Is the sample representation of the batch?
Blinded samples in lab = STD DEV
Real process variation
-
Slide 4 © PharmOut 2014
This session
Using Risk to determine no of batches
Risk vs criticality
-
Slide 5 © PharmOut 2014
How we get to validation…..
• New Chemical Entity *Stage 1 data
• Generic manufacturer
• Contract manufacturer
• New manufacturing site – Tech. Transfer
• Country where validation is a new requirement
• Expansion of regulations, i.e. export to Australia
No concurrent release of validation batches
No retrospective validation
-
Slide 6 © PharmOut 2014
Typical validation NCE – Stage 2a/b?
Real life
Start
Registration / QbD
-
Slide 7 © PharmOut 2014
How many PPQ batches?
QTPP
CQAs/
CPPs
Process Description
Analytical Methods
SOPs & Batch
Records
Design Reports
FSE Qualified
PVMP
Training Completed
Approved PV
Protocols
-
Slide 8 © PharmOut 2014
Knowledge vs # of PV batches
Prior Knowledge Process Design
Prior Knowledge
PV
Process Design PV
Comprehensive Prior Knowledge may support fewer PV batches
Limited Prior Knowledge may require more PV batches
-
Slide 9 © PharmOut 2014
How many PPQ batches?
This depends on the risk and the following elements:
Based on science, experience and justified (documented).
Based on statistics.
-
Slide 10 © PharmOut 2014
-
Slide 11 © PharmOut 2014
How many PPQ batches?
Step 2:Risk Assessment of Control
Strategy
Step 3:Determine Overall Residual
Risk
Step 4:Translate Overall Residual
Risk into # of PPQ Batches
Stage 1Assessment
Stage 2 ActivitiesPrepare PPQ BatchesCompare results to Acceptance Criteria
Risk Level AcceptableStep 1:Risk Assessment of Product
Knowledge & Process Understanding
Reference ISPE
-
Slide 12 © PharmOut 2014
Risk Assessment of Stage 1
Product Knowledge• Analytical understanding
of product structure• Mechanistic
understanding of product profile
• Contextual understanding of CQA’s
Process Understanding• Depth of understanding
unit operations• Level of knowledge of
process response to input variability
• Process predictability• Understanding of scale
Control Strategy• Application of
process/product understanding to production controls
• Control of raw material inputs
• Equipment capability vsprocess requirements
Assess each CQA
Can use:• Risk Charts• Relative level of
risk based on RPN
• Other QRM tools
-
Slide 13 © PharmOut 2014
Step 1: Risk Assessment of Product Knowledge
Identification of CQA and impact of CQA variation on patient:
• Level of understanding of product attributes (i.e. how a particular attribute affects patient safety & efficacy)
Product Characterisation:
• The strength of the link between the CQA and clinical performance
-
Slide 14 © PharmOut 2014
Product Knowledge Risk Ranking
Product Knowledge
Factor
Relative Risk RankingCharacteristics of ranking assignments
Low Risk Medium Risk High Risk
Identification of CQA and impact of CQA variation on patient
• Physiochemical/ biological, pharmacokinetic knowledge, and QbDapproach used to design the formulation of drug product
• Impact of variation on bioavailability explored & understood
• CQAs identified and justified
• Physiochemical/ biological, pharmacokinetic properties identified
• Some exploration of impact of variation
• Product specifications established from development trial and error
• Impact of variation known only from evaluation of incidents
Product Characterisation
• Analytical method has direct measurable linkage to clinical performance
• Complete product
• Analytical method development based on mechanism of action for the therapeutic agent but linkage to clinical performance
• Product characterisation measures quality against established empirical limits
-
Slide 15 © PharmOut 2014
Process Understanding Risk Ranking
Process Understanding
Factor
Relative Risk RankingCharacteristics of ranking assignments
Low Risk Medium Risk High Risk
Degree of process understanding/ unit operation
-First principles understanding: based on an understanding of prevailing mechanisms and rationale
-Casual knowledge: that based on what causes interrelationships between variables
-Descriptiveknowledge: derived only from observation, reflecting basic facts
Process predictably and modelling
-Models based on first principles-Extension of empirical and mechanistic models-Highly predictable process and scale-up
-Use of models derived from basic physical, chemical, biological or microbial mechanisms of observed phenomena-Sufficient knowledge to employ PAT methods, if applicable and desired
-Primitive models reflecting only basic understanding of process and scale effects-Process predictability is questionable
Table continued on the next slide
-
Slide 16 © PharmOut 2014
Process Understanding Risk Ranking
Process Understanding
Factor
Relative Risk RankingCharacteristics of ranking assignments
Low Risk Medium Risk High Risk
Process Response to input variability
-Design space identified using multivariate data and statistical methods-Impact of material attributes on product quality explored extensively in development-Material specific CQAs identified and well understood or no material specific CQAs
-Well-defined criticality for process based on multivariativeexperiments-Impact of material attributes on product quality explored to some degree-Material specific CQAs identified-full range of variability not explored in development
-Partially defined, primarily through univariateexperimentation-Impact of materials attributes to product quality are minimally explored-Materials specific CQAs not identified
Effects of scale -Highly predictable-dataacross different scales can be projected.
-Predictable-data across scales can be projected
-Unpredictable-Scale impact
-
Slide 17 © PharmOut 2014
How many PPQ batches?
Step 2:Risk Assessment of Control
Strategy
Step 3:Determine Overall Residual
Risk
Step 4:Translate Overall Residual
Risk into # of PPQ Batches
Stage 2 ActivitiesPrepare PPQ BatchesCompare results to Acceptance Criteria
Risk Level AcceptableStep 1:Risk Assessment of Product
Knowledge & Process Understanding
Stage 1 ActivitiesAssessments of Product Knowledge and Process Understanding
-
Slide 18 © PharmOut 2014
Step 2: Risk Assessment of Control Strategy
• How the specifications were developed.Raw Materials Specifications
• How easily the requirements for the process are accommodated by the manufacturing equipment.
Equipment Capability vs. Process
Requirements
• How consistently the process has performed historically and during development studies.
Experience with Process Performance
• How the process is monitored and variability is detected
Monitoring capability & detectability
-
Slide 19 © PharmOut 2014
Control Strategy - Risk Ranking
Control Strategy Factor
Source of Potential
Variability and/or Uncertainty
Relative Risk RankingCharacteristics of ranking assignments
Low Risk Medium Risk High Risk
Raw Material Specifications
-Different suppliers; different manufacturing processes, -Material attributes test method-Different batches-Basis for material specification-Specification wider than experience
-Specifications of material attributes impacting product quality based on development data
-Limited justification of specifications of material attributes
-Specifications are not justified.-Compendial or supplier limits accepted without further investigation
-
Slide 20 © PharmOut 2014
Control Strategy - Risk Ranking
Control Strategy Factor
Source of Potential
Variability and/or Uncertainty
Relative Risk RankingCharacteristics of ranking assignments
Low Risk Medium Risk High Risk
Equipment Capability vs.
-Capability of equipment to
-Comparison of parameter control
-Comparison of control ranges from
-Comparison of parameter control
Process Requirements
-Control operating parameters within acceptable ranges
-Ranges from equipment qualification with process requirements indicates all parameters are well within equipment control capabilities and supported by qualification data
-Equipment qualification with process requirements indicates marginal capability to meet requirements for a limited number of process parameters
-Ranges from equipment qualification with process requirements indicates a significant number of parameters are similar to equipment control capabilities
-
Slide 21 © PharmOut 2014
Control Strategy - Risk Ranking
Control Strategy Factor
Source of Potential Variability
and/or Uncertainty
Relative Risk RankingCharacteristics of ranking assignments
Low Risk Medium Risk High Risk
Experience with process performance to date
-Variationobserved-Scaling effectsConsistency of past performance
-Underlying cause(s) for variation is understood & addressed (or variation not observed during manufacture)-Impact of scale is well understood-Process has consistently performed as expected
-Variation is managed empirically, but underlying causes are not well understood-Some understanding of scaling issues-Minor departures from expected results that were investigated and satisfactorily explained
-Variation has been observed, but has not been successfully managed-Impact of scale changes has not been explored-Unexplainedfailure has been experienced
Monitoring capability & detectability
-Ability of monitoring tools & methods to detect variation
-Attributes measured in real time at a sensitivity where performance variability is likely to be observed
-Attributes measuredoff-line (after batch completion) at a sensitivity where performance is likely to be observed
-Attribute measurement accuracy is inadequate
-
Slide 22 © PharmOut 2014
Stage 2
Step 2:Risk Assessment of Control
Strategy
Step 3:Determine Overall Residual
Risk
Step 4:Translate Overall Residual
Risk into # of PPQ Batches
Stage 1 ActivitiesAssessments of Product Knowledge and Process Understanding
Stage 2 ActivitiesPrepare PPQ BatchesCompare results to Acceptance Criteria
Risk Level AcceptableStep 1:Risk Assessment of Product
Knowledge & Process Understanding
-
Slide 23 © PharmOut 2014
Step 3: Determine overall residual risk
The residual risk level reflects the confidence in performance of the commercial process:
Residual Risk Level
Description
Severe (5)
Multiple factors have high risk ratings
High (4)
Few factors have high risk ratings or all have medium risk rating
Moderate (3)
Medium risk level for multiple factors or high risk level for one factor
Low (2)
Medium risk level for a few factors, the others are low risk
Minimal (1)
Low risk level for all factors
-
Slide 24 © PharmOut 2014
How many PPQ batches?
Step 2:Risk Assessment of Control
Strategy
Step 3:Determine Overall Residual
Risk
Step 4:Translate Overall Residual
Risk into # of PPQ Batches
Stage 1Assess
Stage 2 ActivitiesPrepare PPQ BatchesCompare results to Acceptance Criteria
Risk Level AcceptableStep 1:Risk Assessment of Product
Knowledge & Process Understanding
-
Slide 25 © PharmOut 2014
Step 4: Translate overall residual risk into the number of PV Batches
1. Based on rationales and experience
2. Target Process Confidence and Target Process Capability
• Statistical-includes measures of variability & confidence level
3. Expected Coverage
• Statistical-includes measure of probability of batch success rate
Note: Other approaches may be appropriate
-
Slide 26 © PharmOut 2014
How many PV batches?
Approach 1:Rationales and
experience
Approach 2:Target process confidence &
target process capability
Step 4:Translate Overall
Residual Risk into # of
PPQ Batches
2 Approaches to Translate Overall Residual Risk into # of PV Batches
-
Slide 27 © PharmOut 2014
Approach 1: Rationales and Experience
ResidualRisk Level
Number of Batches
Rationale
Severe (5)
Not Ready for PV
Encourage additional development to reduce risk level
High (4)
10 High # of consecutive successful batches unlikely if controls are not adequate
Moderate (3)
5 Increased residual risk addressed by preparing 2 additional PV batches to provide further demonstration of process consistency
Low (2)
3 Knowledge & Control Strategy regarded as sufficient. 3 PPQ batches has historically been appropriate for demonstrating process consistency for many low-risk processes
Minimal (1)
1-2 Minimal residual risk with less than 3 PPQ batches required, e.g. for verifying specific controls associated with a well-understood change to a process
-
Slide 28 © PharmOut 2014
Approach 2: Target process confidence & target process capability
• Process Capability (CpK) is used as a measure of the capability of the process to consistently meet the quality requirements
• Assumption: CpK ≥1 as a starting point for assessing the capability of a process undergoing validation
-
Slide 29 © PharmOut 2014
Approach 2: Target process confidence & target process capability
• Used as a measure for level of confidence needed in the CpK and thereby as a degree of assurance
• High level of confidence in the CpK can be built only with time and experience (during Stage 3)
• Residual Risk Level used to define the confidence needed at completion of Stage 2.
-
Slide 30 © PharmOut 2014
Approach 2: Target process confidence & target process capability
ResidualRisk Level
TargetConfidence
Comments
Severe (5) N/A Major gaps in knowledge & understanding.Additional effort on product/process/control strategy development may be necessary. High confidence level needed to provide high degree of assurance.
High (4) 97%
Moderate (3)
95% Target confidence levels designed to provide reasonable assurance of process capability. Higher confidence levels would be achieved during Stage 3.Low (2) 90%
Minimal (1) N/A High “confidence” based on existing understanding and capability of control strategy. Does not require additional assurance during PV beyond demonstration that commercial systems and procedures are appropriate.
-
Slide 31 © PharmOut 2014
Approach 2: Target process confidence & target process capability
Residual Risk Level
Min # of batches
Target Confidence for CpK 1.0
Acceptance Criteria
Readily Pass Calculated
CpK
Marginally Pass Calculated CpK
Fail Calculated CpK
Severe (5) Not Ready for PPQ
N/A
High (4) 11 97%
≥ 1.6≥ 1.0and
< 1.6< 1.0
Moderate (3)
8 95%
Low (2) 5 90%
Minimal (1) 1-3 N/A
• Based on a Target CpK of 1.0 and an actual CpK of 1.6. • May include clinical manufacture, demonstration, or other at-scale lots.
Assumes process will be under statistical control & data will show normal distribution.
-
Slide 32 © PharmOut 2014
Approach 2: Target process confidence & target process capability
PPQ Outcome Pass / Fail Other Considerations
Impact on Initial CPV Sampling Approach*
Readily Pass calculated CpK
Pass N/A Supports Stage 3 routine sampling
Marginally Pass calculated CpK
Pass All input/output parameters within range
Consider enhanced monitoring for CQA’s not meeting “Readily Pass”
Fail calculated CpK
Investigate -Parameter values-Intra-lot CpK-Probability of detection-Process improvement options
Consider enhanced monitoring; May include some testing beyond PPQ.
*PPQ outcome is one consideration in establishing CPV Plan
-
Slide 33 © PharmOut 2014
This session
Using Risk to determine no of batches
Risk vs criticality
-
Slide 34 © PharmOut 2014
FMEA - recap
• Study the Failure Mode and Effect Analysis
• It involves reviewing as many components, assemblies, and subsystems as possible to identify failure modes, and their causes and effects.
-
Slide 35 © PharmOut 2014
Ishikawa – Cause and Effect Diagram
-
Slide 36 © PharmOut 2014
Quality Risk Management (QRM)
• This session will take a step back and look at the basics
• We will ponder some topics:
• Is the “Criticality Assessment” a “Variability Assessment” when discussing CQAs/CPPs for Qualification & Validation activities?
• Do we throw out our innate understanding of the hazard because we are “FMEA” driven?
FMEA does not help identify sources of variation
-
Slide 37 © PharmOut 2014
ICH Q9 Quality Risk Management (& Annex 20 of PIC/S PE 009-8)
• ICH Q9 explains the “What” of QRM [10 pages]
• Annex I of ICH Q9 provides concepts and ideas on the “How to”-formal and informal [4 pages]
• Annex II of ICH Q9 details the potential “Where” of QRM [5 pages]
• A “roadmap” is presented to us within the document, but do we follow it for Qualification & Validation activities?
• For example, do we make use of QRM tools other than FMEA (or FMECA) effectively?
-
Slide 38 © PharmOut 2014
Quality Risk Management (QRM)
• Risk is defined as the combination of the probability of occurrenceof harm and the severityof that harm
• Harm: Damage to health, including the damage that can occur from loss of product quality or availability.
• Severity: A measure of the possible consequences of a hazard.
Begin the QRM Process
Risk Identification
Risk Analysis
Risk Evaluation
Risk Reduction
Risk Acceptance
Risk Assessment
Risk Control
Output of the QRM Process
Review Events
Risk Review
QRMTools
Risk C
om
mu
nicatio
n
-
Slide 39 © PharmOut 2014
Quality Risk Management (QRM)
Wet Floor (Hazard: The potential source of harm)
Broken Leg(Harm: Damage to health, including the damage that can occur from loss of product quality or availability)
Severity: A measure of the possible consequences of a hazard.
Risk is defined as the combination of the probability of occurrence of harmand the severity of that harm
-
Slide 41 © PharmOut 2014
Deductive vs Inductive Reasoning
Destroyed my car.How did this happen?
Intoxicated?What will happen if I
drive?
Inductive (forward logic)Deductive
?
FMEAPHA
FTA STA C&E Analysis
-
Slide 42 © PharmOut 2014
Inductive Reasoning
Outcome
Hypothesis
Observation
Confirmation
Risk Identification
Risk Analysis
Risk Evaluation
Risk Reduction
Risk Acceptance
“Top-down" “Think up” Failures!
More Proactive?
-
Slide 43 © PharmOut 2014
Deductive Reasoning
Theory
Tentative Hypothesis
Pattern
ObservationRisk
Identification
Risk Analysis
Risk Evaluation
Risk Reduction
Risk Acceptance
“Bottom-up" “Narrow down”
Failure!More Reactive?
-
Slide 44 © PharmOut 2014
Inductive vs Deductive QRM
QRM Tool Inductive Deductive “Complexity”
FMEA Yes No Medium
FMECA Yes No Medium
FTA No Yes High
HACCP Yes Yes Low
HAZOP Yes No Medium
PHA Yes No Low
Risk Ranking and Filtering
Yes Yes Low
Supporting Statistical Tools
Yes Yes Low
-
Slide 45 © PharmOut 2014
Appendix I: Risk Management Methods & Tools
• General overview-references some primary tools
“It is important to note that no one tool or set of tools is applicable to every situation in which a QRM procedure
is used”
FMEA FMECA FTA HACCP
HAZOP PHARisk Ranking & Filtering
Supporting Stats Tools
-
Slide 46 © PharmOut 2014
Appendix I: Risk Management Methods & ToolsQRM Tools Input Process Output
FMEA Relies on product & process understanding. Manageable process steps.
Once potential failure modes are established, risk reduction can be used to eliminate, contain, reduce or control the potential failures.
Summarises modes of failure, factors causing these failures and the likely effects of these failures.
FMECA Relies on product & process understanding. Manageable process steps.
Once potential failure modes are established, risk reduction can be used to eliminate, contain, reduce or control the potential failures.
The output of an FMECA is a relative risk “score” for each failure mode, which is used to rank the modes on a relative risk basis.
FTA System (or sub-system) failures
Evaluates system (or sub-system) failures one at a time but can combine multiple causes of failure by identifying causal chains.
The output of an FTA includes a visual representation of failure modes.
-
Slide 47 © PharmOut 2014
Failure Mode Effects Analysis (FMEA)
Item or process
Step
Potential Failure Mode
Potential Effect(s) of Failure
Se
ve
rity
Potential Cause(s)
Occu
rren
ce
Current Controls
De
tectio
n
RP
N
Recommended Action
Responsibility & Target Date
Action Taken
Se
ve
rity
Occu
rren
ce
De
tectio
n
RP
N
FMECA: Extended to incorporate an investigation of the degree of severity of the consequences, their respective probabilities of occurrence and their detectability
-
Slide 48 © PharmOut 2014
Appendix I: Risk Management Methods & ToolsQRM Tools Input Process Output
HACCP Product and process understanding.
It is a structured approach that applies technical & scientific principles to analyze, evaluate, prevent, and control the risk or adverse consequence(s) of hazard(s)
Risk management information that facilitates monitoring of critical points not only in the manufacturing process but also in other life cycle phases.
HAZOP All processes & safety hazards.
It is a systematic brainstorming technique for identifying hazards using so-called “guide-words”.
As is the case with HACCP, the output of a HAZOP analysis is a list of critical operations for risk management.
PHA Product, process and facility design information
1) Identification, 2) Evaluation 3) Ranking, and 4) Remediation
Typically, hazards identified in the PHA are further assessed with other risk management tools such as those in this section.
-
Slide 49 © PharmOut 2014
Preliminary Hazard Analysis (PHA)
• Early in the development: little information on design details or operating procedures will often be a precursor to further studies
• For product, process and facility design
• Further assessed with other risk management toolsHazards Arising from Product Design
Hazard Investigation/ Controls
Severity (S)
Frequency (F)
Impact (SxF)
-
Slide 50 © PharmOut 2014
Appendix I: Risk Management Methods & ToolsQRM Tools Input Process Output
Risk Ranking and Filtering
Risk ranking and filtering can be used to prioritize manufacturing sites for inspection/audit by regulators or industry.
Forms a single relative risk score that can then be used for ranking risks. “Filters,” in the form of weighting factors or cut-offs for risk scores, can be used to scale or fit the risk ranking to management or policy objectives.
Risk ranking methods are particularly helpful in situations in which the portfolio of risks and the underlying consequences to be managed are diverse and difficult to compare using a single tool.
Supporting Statistical Tools
Statistical data They can enable effective data assessment, aid in determining the significance of the data set(s), and facilitate more reliable decision making.
Control Charts, Design of Experiments (DOE), Histograms, Pareto Charts, Process Capability Analysis
-
Slide 51 © PharmOut 2014
Appendix II: Potential Applications for QRM
In II.1: Integrated Quality Management
• To interpret monitoring data (e.g., to support an assessment of the appropriateness of revalidation or changes in sampling).
• To determine appropriate actions preceding the implementation of a change, e.g., additional testing, (re)qualification, (re)validation or communication with regulators.
-
Slide 52 © PharmOut 2014
Appendix II: Potential Applications for QRM
In II.4: Facilities, Systems & Equipment
• To determine the scope and extent of qualification of facilities, buildings, and production equipment and/or laboratory instruments (including proper calibration methods).
• To determine acceptable (specified) cleaning validation limits.
-
Slide 53 © PharmOut 2014
Appendix II: Potential Applications for QRM
In II.4: Facilities, Systems & Equipment
To select the design of computer hardware and software (e.g., modular, structured, fault tolerance);
To determine the extent of validation, e.g.,
• identification of critical performance parameters; selection of the requirements and design;
• code review;
• the extent of testing and test methods;
• reliability of electronic records and signatures.
-
Slide 54 © PharmOut 2014
Appendix II: Potential Applications for QRM
II.6 Production
• To identify the scope and extent of verification, qualification and validation activities (e.g., analytical methods, processes, equipment and cleaning methods;
• To determine the extent for follow-up activities (e.g., sampling, monitoring and re-validation);
• To distinguish between critical and non-criticalprocess steps to facilitate design of a validationstudy.
-
Slide 55 © PharmOut 2014
Uses in Qualification & Validation
QRM ToolsTools
Uses in Q&V
FMEA All Q&V Stages-prioritize potential risks and monitor the effectiveness of risk control activities.
FMECA All Stages-Prioritize potential risks and monitor the effectiveness of risk control activities. Understand the impact of detectability
FTA Establish the pathway to the root cause of the failure during Q&V. Is useful both for risk assessment and in developing monitoring programs as an output of Q&V.
HACCP Used to identify and manage risks associated with physical, chemical and biological hazards (including microbiological contamination).
HAZOP This facilitates regular monitoring of critical points in the manufacturing process. Used early in the design stage. Q&V input.
PHA Used early in the development of a project when there is little information on design details or operating procedures; thus, it will often be a precursor to further studies. Useful “first cut” for Q&V.
Risk Ranking and Filtering
Risk ranking is useful when management needs to evaluate both quantitatively-assessed and qualitatively-assessed risks within the same organizational framework.
Stats Tools They can enable effective data assessment throughout Q&V activities
-
Slide 56 © PharmOut 2014
QRM vs Impact Assessment Example
“Top Down”
Critical Quality Attributes
Critical Process Parameters
System
Subsystem
Component
End
End
Product carryover exceeds acceptance criteria
Cleaning Agent Concentration
CIP System
Chemical Addition
Chemical Feed Pump
“Bottom Up”
From ISPE GPG Applied Risk Management for C&Q
-
Slide 57 © PharmOut 2014
QRM vs Impact Assessment
Characteristics Impact Assessment (Baseline® Guide 5)
Formal Risk Assessment
“Top Down” or “Bottom Up” “Bottom Up” “Top Down”
Ability to identify specific process risks Low High
Ability to identify specific Critical Aspects
Low High
Ability to prioritise Qualification efforts Medium High
Cost in time and resources Medium High
Need for SMEs experienced in the tool to be used
Low High
Acceptability to regulators Medium High
Usefulness as “lifecycle” document in future
Low High
From ISPE GPG Applied Risk Management for C&Q
-
Slide 58 © PharmOut 2014
“Criticality” in Annex 15
• “It is a requirement of GMP that manufacturers identify what validation work is needed to prove control of the critical aspects of their particular operations.”
• “The protocol should specify critical steps and acceptance criteria.”
• “Evidence should be available to support and verify the operating parameters and limits for the critical variables of the operating equipment.”
• “Risk analysis: Method to assess and characterise the critical parameters in the functionality of an equipment or process.”
-
Slide 59 © PharmOut 2014
Going from QTPP to CQA
• We assume that during product development the clinicians and toxicologists have established that these parameters are high risk to the patient.
• So we are looking at reducing the variability of these attributes.
-
Slide 60 © PharmOut 2014
Connecting a CQA to a CPP
• The manufacturer during product development and based on prior product and process knowledge establishes that these process parameters have a high impact on variability.
• “Validation” looks at ways to provide confidence that the variability is controlled.
-
Slide 65 © PharmOut 2014
Ishikawa – Cause and Effect Diagram
-
Slide 66 © PharmOut 2014
The PharmOut “STIC-man”!
Summary Table from Ishikawa Criticality
-
Slide 67 © PharmOut 2014
Activity 3: QRM
Please complete the Blue Sheets as a group and return them to us
Please assign a Speaker/Scribe at
each table
If there are any questions, please ask!
-
Slide 68 © PharmOut 2014
Thank you for your time.Questions?
Trevor Schoerie
Lead Consultant
www.pharmout.net