Introduction to Validation December 9th and 10th, 2021
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Day 1
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Introductions
Source: https://pulmonaryfibrosisnews.com
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Instructors • Sharon McGuire, M.A., PDI, The University of Rhode Island • Cahil McGovern, Ph.D., PDI, The University of Rhode Island
Source: https://afrief.org
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History of Validation
Source: https://www.ducksters.com
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Origins of Validation • Failed Apollo Mission (Apollo 1 Mission, 1967) • Fire aboard the capsule ignited the oxygen led to the crew perishing • Cause was determined to be deficiencies in design, manufacture, installation, rework and •
quality control in the electrical wiring Ultimately led to changes in design of subsequent lunar modules
•
• • •
Recommendation: Review of specification be conducted, 3-dimensional jigs be used in manufacture of wire bundles and rigid inspection at all stages of wiring design, manufacture, and installation be enforced. Overseeing all modification to the spacecraft design more rigorously scrutinized Hatch redesign Replacement of flammables (from oxygen to an oxygen/nitrogen mix)
• Although not (bio)pharmaceutical related, this event went through several
industries simultaneously changing the methods of verification (i.e. validation)
Source: https://lh3.googleusercontent.com
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What is Validation?
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Introduction • Definition:
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• Validation is the process of establishing documented evidence that demonstrates a procedure, process, or activity executed in a controlled manner maintains the desired level of compliance at all stages.
• Purpose: • The purpose of validation is to establish the validity of the input and output of the activity and provides documented evidence that the inputs produce the expected and desired result.
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Introduction – Regulations Related to Validation • 21 CFR 211.100A and 110 • The cGMP regulations for validating pharmaceutical (drug) manufacturing require that
drug products be produced with a high degree of meeting all the attributes they are intended to possess. Effective validation contributes significantly to assuring drug quality.
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Control procedures shall be established to monitor the output and validate the performance of those manufacturing processes that may be responsible for causing variability in the characteristics of in-process material and the drug product.
• ICH Q7 Good Manufacturing Practice for Active Pharmaceutical Ingredients • The company’s overall policy, intensions, and approach to validation, including the validation of production processes, cleaning procedures, analytical methods, inprocess control test procedures, computerized systems, and persons responsible for the design review, approval and documentation of each validation phase, should be documented.
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Source: http://guardianpharmacy.net
Introduction - Regulations Related to Validation • ICH Q8 Pharmaceutical Development • Process development studies should provide the basis for process improvement, process validation, continuous process verification (where applicable), and any process control requirements.
• ICH Q9 Quality Risk Management • 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 noncritical process steps to facilitate design of a validation study. 10
Source: http://guardianpharmacy.net
Introduction - Regulations Related to Validation • ICH Q10 Pharmaceutical Quality Systems • Sources of knowledge include, but are not limited to, prior knowledge (public domain or internally documented); pharmaceutical development studies; technology transfer activities; process validation studies over the product lifecycle; manufacturing experience; innovation; continual improvement; and change management activities.
• ICH Q11 Development and manufacture of Drug Substances • Process validation can include the collection and evaluation of data, from the process design stage throughout production, that establish scientific evidence that a process is capable of consistently delivering a quality drug substance.
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Source: http://guardianpharmacy.net
Introduction – Areas that Validation Impacts • • • • • •
Development (Technology Transfer) Quality Control Manufacturing Facilities and Engineering Information Technology and Systems Quality Assurance
Everyone Plays a Role “Team Sport”
Source: https://www.forbes.com
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Introduction – Validation Approaches •
The guidelines on general principles of validation mentions four approaches to validation: • • • •
•
Prospective validation - Occurs during the initial installation of the equipment, system or process prior to process implementation based on preapproved protocols. Concurrent validation – Conducted in parallel with routine production (exceptional circumstances). Retrospective validation – Occurs after production operations have started and based a review and analysis of data or historical information (not typical or ideal). Revalidation-Periodic evaluation of equipment that has not undergone a major change or modification.
All these approaches establish documented evidence that the equipment, systems and processes operate as expected based on predetermined criteria called out in approved plans and protocols. 13
Introduction – Validation Categories • • • • • • •
Facilities and Equipment Computer Analytical Methods Cleaning (Hold times, CIP, SIP, Facility) Manufacturing (Process Validation) Packaging Transport/Shipping
Everything is Validated
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Introduction – Facilities and Equipment Validation • Is performed for facilities, utilities and equipment as it applies to the manufacturing processes. • HVAC, water, compressed gases • Media vessels, bioreactors, centrifuge, hold vessels, lab equipment • Data is generated and documented in protocols to ensure the facilities, utilities and equipment perform as expected. • These activities are typically performed during initial startup. Source: https://www.standrewlutheran.org
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Introduction – Computer Relates Systems Validation • Computerized system validation is the process to ensure that the system performs as designed and maintains the integrity of its data (accurate, reliable, retrievable and secure data) to ensure the safety and effectiveness of the product. • It creates an electronic data trail that can be considered equivalent to paper records. • This applies to off the shelf software and custom software. • Guidance • 21 CFR Part 11 • Good Automated Manufacturing Practice (GAMP)
21-CFR-Part-11
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Introduction – Analytical Method Validation •
Method validation is a procedure for performing numerous laboratory studies designed to verify that an analytical test methods are suitable for their intended purpose.
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Validation data must be generated under a protocol with the description of methodology of each validation characteristic and predetermined and justified acceptance criteria, using qualified instrumentation.
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Validation characteristics • Specificity • Linearity • Accuracy • Precision (repeatability, precision, and reproducibility) • Range • Quantitation limit • Detection limit
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Guidance • Bioanalytical Method Validation Guidance for Industry Source: https://www.safebridge.com
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Introduction – Cleaning Validation •
Cleaning Validation is a methodology used to assure that a cleaning process consistently removes residues of active, inactive and detergent ingredients from the surfaces of equipment used in a manufacturing process.
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Approaches to cleaning validation are dependent on the facility use (single product vs. multiple product).
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Single use equipment and materials can change the approach to cleaning.
Methods associated with cleaning validation:
• • • • • •
Visual Inspection Total Organic Carbon (TOC) - Swab/Rinse Conductivity Bioburden Endotoxin
Guidance
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21 CFR 211.67 ICH Q3C (R4) – Impurities: Guideline for residual solvents
18 Source: https://pharmsolution.org
Introduction – Process Validation • Process Validation is defined as the collection and evaluation of data, from the process design stage through commercial production, which establishes scientific evidence that a process is capable of consistently delivering quality product. • Process validation involves a series of activities taking place over the lifecycle of the product and process. • The Process Validation life cycle is broken out into three stages. • Stage 1: Process Design • Stage 2: Process Performance and Qualification (PPQ) • Stage 3: Continued Process Verification • Guidance • ICH Q11 - Development and manufacture of Drug Substances • Guidance for Industry - Process Validation: General Principles and Practices Source: https://blog.minitab.com
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Introduction – Packaging (Container Closure) •
• • • •
A primary packaging component means a packaging component that is or may be in direct contact with the dosage form.
A secondary packaging component means a packaging component that is not and will not be in direct contact with the dosage form. Leachable and Extractable (biocompatibility) • 103993 Materials of Construction (MOC) Container Closure Methods • Dye Ingress • Microbial Ingress • Vacuum Decay • Pressure Decay Guidance • PDA Technical report 27- Pharmaceutical Package Integrity • ISO 11607 - Packaging for Terminally Sterilized Medical Devices • AAMI TIR17 - Compatibility of Materials Subjected to Sterilization
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Introduction – Transport/Shipping • Transport validation • Demonstrates the product is unaffected by environmental conditions. • Provide valuable data on the expected performance of packaging during the transport. • Modes of transportation, such as road, which can differ by car or truck, train, sea, and air are include.
• Parameters for evaluation • Temperature • Vibration • Shipping conditions cover 4 seasons and modes of transportation • Product testing (release testing) • Guidance • PDA tech report # 39 • ICHQ7- Good Manufacturing Practice for Active Pharmaceutical Ingredients 21
Why is Everything Validated?
Validation is Your Best Defense • • • •
Supports your claims and design Provides documented evidence Ensures safety Ensures a state of control
Source: https://miro.medium.com
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When Do You Validate & How?
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Validation Activities • Validation is performed: • As part of initial start up. • For the implementation of new equipment, utility systems, processes, procedure. • During defined periodic intervals and when major changes that impact the current validation state occur.
Source: https://miro.medium.com
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Validation Documents •
• •
Master Plans Project Plan Validation Protocols • • • •
Installation Qualification (IQ) Operational Qualification (OQ) Performance Qualification (PQ) Process Validation (PVQ) •
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Process Performance Qualification (PPQ)
Summary Reports
Source: https://www.webinarcompliance.com
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Validation - It All Starts with a Plan • Master Validation Plan (MVP) is a revisable document that is updated periodically. • Master Plans define the systems, scope and procedures and is designed to layout the overall approach to validating the facility, major systems, equipment and processes. • What types of Master Plans might a company generate and maintain? • Site • Equipment • Computer • Cleaning • Steaming • Process Source: https://www. encrypted-tbn0.gstatic.com
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Regulatory Inspections and Observations
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What happens when you don’t validate? • •
• • •
“Your firm failed to validate the manufacturing process for your over the counter (OTC) drug product. You also lacked validation of your ICP-OES instrument. Furthermore, you lacked appropriate written cleaning procedures and cleaning validation for the product. Your responses are inadequate because you did not provide a detailed validation plan for your products or equipment.” (March, 2020) “During the inspection we observed that your sterilization operations have not been adequately validated to demonstrate that all component materials, sizes, solutions, types, etc. can undergo and withstand your sterilization process and method.” (December, 2019)
“Your firm’s Process Validation Procedure does not identify the frequency for validating and revalidating manufacturing processes. Your validation records do not show these processes have been evaluated with any uniformity proportionate with risk it poses to the finished device.” (December, 2019) ”Your firm also failed to perform water system validation studies.” (July, 2019)
"Furthermore, you lacked appropriate written cleaning procedures and cleaning validation .” (September, 2019) 28
What happens when you don’t validate? • “You have failed to validate with a high degree of assurance, a process where the
results cannot be fully verified by subsequent inspection and test.” (January, 2014)
• “The aseptic process used to manufacturing your products have not been validated
since manufacturing operations began in April 2018. Based on your labeling, these products are expected to be sterile. Also, you are lacking the validation of sterilization processes.” (June, 2020)
• "Our inspection indicated that your water quality is not suitable for its intended use. Your firm also lacked water system validation and did not demonstrate that it can consistently produce water that is suitable for pharmaceutical use.” (June, 2019)
• "Your response is inadequate because you did not provide a detailed validation plan for your products or equipment.” (June, 2019)
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Assessment 1
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Source: https://www.cheatsheet.com
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Basics of Equipment Validation
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Equipment Validation • What Documents Support Equipment Validation? • User Requirements Specification (URS) • Comprehensive description of the requirement and performance of the facility’s systems, equipment, or processes that must be met to produce a drug product of the intended quality.
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Design Qualification (DQ)
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Never too early to have Quality Oversight!!
Verification and documentation to demonstrate that the design of the facility’s systems or equipment meets the requirements of the URS and GMP
• Quality Risk Assessment - Looks at the critical process parameters and critical quality attributes
• • • •
Identifies risk to product Mechanisms for identifying risks Identifies risks associated with design Identifies and implement Quality controls
Source: https://http://www.mkbestcalibrationservices.com
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Order of Validation Activities…… Installation Qualification
Operational Qualification
Performance Qualification Source: https://encrypted-tbn0.gstatic.com
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Installation Qualification
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Installation Qualification Protocol • •
Verification and documentation to demonstrate that the facility’s systems or equipment as installed or modified, comply with the approved design and that all the manufacturer’s recommendation have been considered. The Installation Qualification Protocol includes:
• • • • • • • • • • • • • •
Signature Verification Test Equipment and Materials Specifications of Purchase Order Operation and Maintenance Manual SOP (draft) Recommended Maintenance Instrument List (Calibration) Equipment Data Sheet Material of Construction Data Sheet Utility Data Sheet Minor Component Sheet Recommended Spare Parts Software identification Corrective Action Form
https://pharmafesta.com
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IQ - Signature Approval
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A signature approval page will identify the author of the protocol and will be completed by the responsible individuals participating in the execution/review of the protocol.
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Post approval of protocol or final report are both considered final document approval.
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IQ - Signature Verification
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A signature reference will be completed by the responsible individuals participating in the execution of the protocol and/or review of individual data sheets.
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IQ - Test Equipment and Materials A record of test equipment and materials will be completed. • Test equipment not owned by the Company X that is used during execution of the protocol will be accompanied by a current calibration verification. • Test equipment owned by the Company X that is used during execution of the protocol will be accompanied by a current calibration verification or the calibration record will be referenced. • Manufacturer and lot numbers of test materials used during execution of the protocol will be recorded. •
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IQ - Specifications of Purchase Order
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A list of specifications and purchase orders for major components will be completed. These documents are to be reviewed for conformance to the vendor drawings.
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IQ - Operation and Maintenance Manual
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A list of equipment Operation and Maintenance (O & M) manuals will be completed verifying the status of their location.
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IQ - SOP (draft)
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The Company X Standard Operating and Maintenance Procedures relating to the proper and safe routine operation of the refrigerator will be reviewed and recorded.
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SOPs are not required to be approved at this time.
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IQ - Manufacturer’s Recommended Maintenance
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A list of the manufacturer's recommended maintenance for each major component of the system will be completed.
Usually linked to your work order system 43
IQ - Instrument List (Calibration)
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A list of instruments for the system will be completed including verification of instrument labeling and calibration.
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IQ - Equipment Data Sheet
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A data sheet for each major/critical component as defined by the system/equipment vendor drawings will be completed to ensure the installed component is the correct component.
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Software/firmware are usually captured as part of this section or may have its own data sheet (if applicable).
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IQ – Material of Construction Data Sheet
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All exposed surfaces in the refrigerator will be inspected for appropriate construction. All surfaces will be noncorroding and non-shedding.
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IQ - Utility Data Sheet
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A data sheet for each associated utility will be completed as defined on the vendor drawings.
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Confirmation of equipment electrical rating versus circuit rating will be performed.
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IQ – Minor Component Sheet
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A list of the minor components as defined by the system/equipment vendor drawings will be completed to ensure the installed component is the correct component.
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IQ - Recommended Spare Parts
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An itemized list of the manufacturer's recommended spare parts for the entire system will be completed or referenced.
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IQ - Corrective Action Form
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The Corrective Action Form (or equivalent) is used to list and describe any deviations that may occur during testing procedures and their corrective actions. Protocol deviations are a result of errors related to protocol development, can be corrected, and require no further action. Equipment/Test errors are inconsistencies with the documentation and require investigation.
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Assessment 2
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Order of Validation Activities…… Installation Qualification • • •
If IQ is not complete, can OQ activities be initiated? How are major deviations handled? Approval to Proceed (QA)
Operational Qualification • •
When do SOPs get approved? Once the SOP is approved, what does this mean?
Performance Qualification • •
Source: https://www.illumina.com
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If OQ is not complete can PQ activities be initiated? What equipment/systems are subjected to PQ? Duration? Specifications?
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Operational Qualification
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Operational Qualification Protocol • Verification and documentation to demonstrate that the facility’s systems or
equipment perform as intended throughout the anticipated operating ranges.
• Requires completion of IQ (or approval to proceed) • Operational Qualification: • Signature Verification • Test Equipment and Materials • Procedures List • Functional Operations • Software Operations • Alarms and Indicators • SOP (finalized at completion of OQ) • Temperature/Thermal Mapping studies • Establish training program for relevant staff • Corrective Action Form 54
OQ - Signature Approval
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A signature approval page will identify the author of the protocol and will be completed by the responsible individuals participating in the execution/review of the protocol.
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Post approval of protocol or final report are both considered final document approval.
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OQ - Signature Verification
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A signature reference will be completed by the responsible individuals participating in the execution of the protocol and/or review of individual data sheets.
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OQ – Test Equipment and Materials A record of test equipment and materials will be completed. • Test equipment not owned by the Company X that is used during execution of the protocol will be accompanied by a current calibration verification. • Test equipment owned by the Company X that is used during execution of the protocol will be accompanied by a current calibration verification or the calibration record will be referenced. • Manufacturer and lot numbers of test materials used during execution of the protocol will be recorded. •
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OQ – Procedure List •
A list of equipment/system Standard Operating Procedures used during execution of the protocol will be recorded.
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A "Draft" SOP may be used for protocol development and execution but the SOPs must be approved before this OQ is completed.
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Acceptance criteria will be met when the list of operating procedures are complete and all standard operating procedures for the safe and routine operation of the ThermoScientific Refrigerators are approved.
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OQ – Operational Parameters •
A list of operational parameters will be recorded prior to execution of the protocol.
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Operational parameters will include the operating ranges and setpoints.
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Verification that operating setpoints have been returned to the original settings will be confirmed upon completion of the executed protocol.
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Acceptance criteria will be met once the operating parameters are listed and returned to their original settings after execution of the protocol.
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OQ – Functional Operations - Temperature
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The functionality of the operator controls and indicators will be verified.
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Acceptance criteria will be met when the actual results conform to the expected results or explained.
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OQ – Functional Operations- Temperature Mapping and Distribution
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The ThermoScientific Refrigerator will be mapped.
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The distribution and placement of the thermocouples will be verified and documented.
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OQ – Functional Operations- Temperature Mapping and Distribution (Empty)
The ThermoScientific Refrigerator will be temperature mapped empty as a worst case scenario. • The distribution and placement of the thermocouples will be in agreement with Attachment X, verified, and documented. • A map and/or digital image of the thermocouple placement will accompany the attachment. • Acceptance criteria will be met when the actual results conform to the expected results or explained. •
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OQ – Functional Operations- Temperature Mapping and Distribution (Loaded) The ThermoScientific Refrigerator will be temperature mapped with a media packages and conicals/bottles containing 50 mls of sterile water. • The distribution and placement of the thermocouples will be in agreement with Attachment X, verified, and documented. • A map and/or digital image of the thermocouple placement will accompany the attachment. • Acceptance criteria will be met when the actual results conform to the expected results or explained. •
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OQ – Functional Operations - Recovery
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The recovery time of the refrigerator with respect to it’s temperature setpoint will be examined and the recovery time will be documented.
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OQ – Functional Operations – Alarms and Indicators
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The functionality of the refrigerator temperature alarm will be verified.
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The alarm will be tested in a manner that does not jeopardize the equipment/system integrity.
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Acceptance criteria will be met when the actual results conform to the expected results or explained.
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OQ – Functional Operations – Alarms and Indicators
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The functionality of the refrigerator temperature alarm will be verified.
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The alarm will be tested in a manner that does not jeopardize the equipment/system integrity.
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Acceptance criteria will be met when the actual results conform to the expected results or explained.
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OQ - Corrective Action Form
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The Corrective Action Form is used to list and describe any deviations that may occur during testing procedures and their corrective actions. Protocol deviations are a result of errors related to protocol development, can be corrected, and require no further action. Equipment/Test errors are inconsistencies with the documentation and require investigation.
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Assessment 3
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Order of Validation Activities…… Installation Qualification • • •
If IQ is not complete, can OQ activities be initiated? How are major deviations handled? Approval to Proceed (QA)
Operational Qualification • •
When do SOPs get approved? Once the SOP is approved, what does this mean?
Performance Qualification • • • •
If OQ is not complete can PQ activities be initiated? What equipment/systems are subjected to PQ? Duration? Specifications?
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Performance Qualification
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Performance Qualification Protocol • Verification and documentation to demonstrate that the system consistently performs as expected under operating conditions meeting pre-determined acceptance criteria.
• Requires completion of IQ and OQ • Performance Qualification: • Signature Verification • Test Equipment and Materials • Applicable SOPs (approved) • Temperature/Thermal Mapping studies (equipment dependent) • Test Results and Specifications • Establish training program for relevant staff • Corrective Action Form
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PQ – Performance Qualification •
What Systems are subjected to PQ studies? • HVAC (EM PQ) • Water • Compressed Gas • CCA • Autoclave (load patterns) • Glass Washer (load patterns) • Steam Distribution Lines and vessels (SIP) • Clean in Place of lines and vessels (CIP)
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PQ – Performance Qualification •
What are the objectives of PQ studies? Demonstrate the consistent quality of the utilities over time (USP purified water). • Demonstrate an effective cleaning procedure in a defined load pattern (glasswasher). • Demonstrate effective sterilization in a defined load pattern (autoclave, process piping). • Demonstrate effective cleaning and sterilization of lines and vessels (CIP/SIP). •
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How do the acceptance criteria differ from the OQ?
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Typical duration/number of runs of these studies? 73
Assessment 4
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Lunch/Break
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Temperature Mapping Exercise
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Temperature Mapping Exercise •
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Demonstrates proper operation of the incubator and the proper storage of cells and test sample materials. Equipment: • • • •
• • • •
IRTD Thermocouples Dry bath Validator
Thermocouples will be precalibrated at -10°C and 50°C and a check at 20°C. Thermocouples will be distributed throughout the incubator. Once stabilized, we will begin recording the temperatures in accordance with the protocol. Mapping study will be minimum of 24 hours. 77
Temperature Mapping Equipment
Intelligent Resistant Temperature Device
LTR 90
Kaye Validator AVS
Source: https://www.kayeinstruments.com
TC Wire
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Temperature Mapping Equipment
Kaye Valprobe RT Validation System
Source: https://www.kayeinstruments.com
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Video 1: Introduction to Validation Equipment
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OQ – Functional Operations- Temperature Mapping and Distribution
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The Eppendorf 170S Galaxy incubator will be mapped.
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The distribution and placement of the thermocouples will be verified and documented.
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OQ – Functional Operations- Temperature Mapping and Distribution (Empty)
The Eppendorf incubator will be temperature mapped empty as a worst-case scenario. • The distribution and placement of the thermocouples will be in agreement with Attachment X, verified, and documented. • A map and/or digital image of the thermocouple placement will accompany the attachment. • Acceptance criteria will be met when the actual results conform to the expected results or explained. •
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TC Pitfalls
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Temperature Mapping Pitfalls
+ + -
+ -
Root Cause: Incorrect wiring of SIM
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Temperature Mapping Pitfalls
Root Cause: Loose wiring in SIM
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Temperature Mapping Pitfalls
SIM not fully Inserted SIM fully Inserted
Root Cause: Incorrect seating of SIM in AVS
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Video 2: Wiring a SIM
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Source: https://www.cheatsheet.com
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Creating a Program/Introduction to AVS Software
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Opening AVS Software
Desktop screen
Source: https://www.kayeinstruments.com
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Credentials (Username and Password)
Log in screen Source: https://www.kayeinstruments.com
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Main Screen Navigation
Main screen
Source: https://www.kayeinstruments.com
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Defining Equipment • Create an asset for all your Kaye equipment which will notify you of upcoming calibrations. • You can add a new piece of equipment by pressing the (+) sign which directs you to the New Equipment Screen.
Equipment Hub screen Source: https://www.kayeinstruments.com
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New Equipment Information • Use the text box and dropdown menus to enter equipment serial numbers, calibration date, model and serial numbers and equipment type. • You can upload an image of the equipment using the camera on the tablet. • Once completed, hit the save button. New Equipment Screen Source: https://www.kayeinstruments.com
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Creating an Asset • Each piece of equipment/ process you validate can be setup and defined as an asset.
• To open the Asset Hub, press the Assets on the Main Screen.
Main screen Source: https://www.kayeinstruments.com
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Creating an Asset • The Asset Hub lists the various assets that have been validated. • You can display your assets by type, manufacturer or location.
• The assets can be listed with model numbers. • Use the magnifying glass to search for assets.
Asset Hub
• To add an asset, press the (+) icon and be directed to the New Asset Screen. Source: https://www.kayeinstruments.com 96
Creating an Asset • The New Asset Screen has text boxes and pull down menus for equipment names, ID, type, location, model, size, last validation date and validation frequency. • You can add further detail in the Description box on the right. • Once entered, press the save key or cancel to move on without changes. New Asset Screen
Source: https://www.kayeinstruments.com
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Creating an Asset • Navigate back to the Asset Hub using the back arrow. • Using the (+) icon to create a new asset.
Asset Hub Source: https://www.kayeinstruments.com
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Defining an Setup • To create a setup file from the Asset Details Screen, press Setups.
• In the Setup Hub Screen, press the New key. • From here, you can define sensors, assign sensors to calculation groups, set calibration parameters and criteria, and detail qualification studies. Setup Hub Screen
• You can also modify existing setup files using the pen icon. Source: https://www.kayeinstruments.com 99
Setting up an Asset • Define descriptive information to detail a Setup. • Use text boxes and dropdown menus to enter setup name, number of sensors, equipment ID, SOP, the load description and any additional comments. • Once entered use the light blue banner(s) labeled Sensor Configuration. Define Set Up screen Source: https://www.kayeinstruments.com
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Configuring Sensors • The 7 process steps we need to go through will be displayed just below the Setup name.
• The sensor configuration is broken down into two steps, Select and Configure Sensors. • The grade of the wire plays a role in the sensor configuration.
Sensor Configuration screen Source: https://www.kayeinstruments.com
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Grouping Sensors • The next step is to group the sensors by pressing the Group Sensor key.
• This screen will display the existing groups and a New Group button. • The Default Group button will automatically generate groups for sensors measuring temperature.
Group sensor screen
• To assign groups, press the New Group button and the textbox appears on the screen. Enter the information you want and hit save. Source: https://www.kayeinstruments.com
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Calculations • Once sensors have been defined, you can specify calculations to be performed during a qualification study. • These include lethality, interval, saturation pressure of steam, etc.
Calculations
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Specifying Calibration Temperatures • Before running a qualification study, you need to perform sensor calibrations for accuracy and ensure the system meets required deviation criteria. • The validator will compare each TC to the IRTD.
• The variation for each sensor at the high and low temperature points is stored in the SIM as an offset. Calibration Parameters screen
• The off sets are applied to the qualification study.
Source: https://www.kayeinstruments.com
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Define the Qualification Details/Create setup report • You can choose to manually Start/Stop studies or program times.
• Once completed use the blue banner to advance to review.
Qualification Parameters screen
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Set Up Review • You can choose to manually Start/Stop studies or program times.
• Once completed use the blue banner to advance to review. • Save
Set up Review screen Source: https://www.kayeinstruments.com
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Initiating a Calibration/Qualification/Verification • Return to the Asset Screen • Select the desired Setup
• Select and Initiate the operation • You will be prompted to Start operation
Initiate a Calibration from the Asset Screen Source: https://www.kayeinstruments.com
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Video 3: Creating a Program
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Assessment 5
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Day 2
110
Pre-calibration
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Pre Calibration
Asset Details screen
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Sensor Calibration
Calibration Study Screen
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Temperature Mapping- Pre-calibration Setpoints
Activity Pre-Calibrations Number of Thermocouples
Low Temp Calibration Setpoint
12
-10.0°C
Check Temp Calibration Setpoint
20°C
High Temp Calibration Setpoint
50°C
Source: Amphenol Advanced Sensors
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Calibration Pitfalls
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Temperature Mapping Pitfalls
Root Cause: Incorrectly Seated TC(s) in LTR 116
Video 4: TC Pre-calibration
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Wiring the Incubator
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Temperature Mapping- Placing TCs
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Temperature Mapping-Qualification Helpful hints: TC 12
TC 10
•
Thermocouples can be strung through door gasket but always look for a validation port first
•
One thermocouple should be placed near the unit RTD (resistance temperature detector) with the remaining distributed throughout the mapping chamber
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Remember to stay off the walls and avoid contacting inner surfaces
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“Stabilization” is protocol dependent and can differ…rule of thumb is 30 minutes
•
Qualification run time is protocol dependent and can also differ…rule of thumb is 24 hours
TC 11 TC 2 TC 1
TC 3 TC 5
TC 4
TC 6 TC 8
TC 7
TC 9
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Video 5: Wiring the Incubator
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Qualification
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Initiating Qualification • Return to the Asset Screen • Select the desired Setup
• Select Initiate Qualification • You will advance to the Qualification Study View Screen
Initiate a Qualification from the Asset screen
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Qualification Study • Start the Qualification Study by selecting Start Qual button. • You will be promted to confirm “Yes/No” • Once Yes is Selected, the study will begin.
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Video 6: Performing the Qualification Run
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Calibration Verification
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Calibration Verification • Following the Qualification Study, return to the Asset Screen and press the Initiate Verification button. • The parameters have already been established in the initial setup. • Ensure the TCs are seated properly in the LTR unit as done for calibration.
Set up Screen
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Calibration Verification • The Kaye System will drive the LTR to the verification points.
Calibration Parameters screen
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Temperature Mapping-Verification
Activity Verification Temperature Setpoints Number of Thermocouples
12
Low Temp Calibration Setpoint
-10.0°C
High Temp Calibration Setpoint
50.0°C
Verification Temperature Check
20°C
129
Video 7: TC Verification
130
Assessment 6
131
Reports and review/analysis of data
132
Temperature Mapping-Reports (Setup)
Report Highlights: •
Identifies SIM used
•
Identifies TC designations
•
Identifies Calibration Parameters (setpoints, deviation criteria, and logging intervals).
•
Identifies qualification parameters and preferences)
133
Temperature Mapping-Reports (Pre-Calibration)
Report Highlights: •
Identifies SIM used
•
Identifies Calibration setpoints
•
Identifies stability criteria
•
Identifies deviation criteria
•
Shows TC performance
134
Temperature Mapping-Reports (Qualification)
Report Highlights: •
Identifies SIM/slot used
•
Identifies study start/stop time
•
Shows TC performance
135
Temperature Mapping-Reports (Qualification)
136
Temperature Mapping-Reports (Verification)
Report Highlights: •
Identifies SIM used
•
Identifies temperature verification points
•
Identifies stability
•
Identifies deviation criteria
137
Temperature Mapping-Reports (Summary)
Report Highlights: • Review of the mapping run
138
Identifying Cold and Warm Locations Coolest location-Near the RTD
TC 12
TC 10
TC 11 TC 2 TC 1
TC 3 TC 5
TC 4
TC 6 TC 8
TC 7
TC 9
Warmest location-upper middle of the incubator
139
Identifying Cold and Warm Locations
140
Did Incubator PDI-001 Meet Acceptance Criteria (i.e. Pass Thermal Mapping)? • •
•
•
•
All thermocouples will be stable prior to initiating study. Yes, all TC stable for at least 30 minutes The distribution and placement of the thermocouples will be in agreement with Attachment X, verified, and documented. Yes, all TC locations agree with protocol and were verified A map and/or digital image of the thermocouple placement will accompany the attachment. Yes, attached Acceptance criteria will be met when the actual results conform to the expected results or explained. Yes, all TCs were within 1°C of setpoint and maintained for the entirety of the study Location of maximum and minimum thermocouples identified. Yes, the location of TC2 was the maximum temperature at 37.16°C (center) and TC11 was identified as the minimum temperature at 36.64°C (near RTD). 141
Did Incubator PDI-001 Meet Acceptance Criteria (i.e. Pass Validation)? • • • • • • •
•
Attachment 1 completed? Yes, signatures have been collected. Attachment 2 completed? Yes, test equipment have been listed with calibration certificates attached or identified. Attachment 3 complete? Yes, SOP has been approved Attachment 4 complete? Yes, operational parameters have been identified Attachment 5 complete? Yes, we have demonstrated control of temperature/CO2 parameters Attachment 6 complete? Yes, mapping studies completed Attachment 7, 7A, and 7B complete? Yes, mapping studies and recovery complete. All reports have been attached. Attachment 8 complete? Yes, alarms have been tested and performed as expected 142
Did Incubator PDI-001 Pass Validation?
https://www.thecampuscurrent.com
143
Helpful Hints
144
Helpful hints– Temperature Mapping Autoclaves/Process Piping • Standard Acceptance Criteria • Fo • 121.1°C • Steaming, in general, is hard on TCs, typically have dedicated TCs for steaming studies (tipped TCs). • Beware of water traveling up the TC to the SIM port. Hint: create slits in the casing which will allow the water to weep out. • TCs usually have biological indicators fastened to the ends (autoclave tape)
Source: https://www.zirbus.com/
145
Helpful hints– Temperature Mapping Cryostorage Units • Calibrate using liquid nitrogen (physical constant). Calibrating with colder temperatures are difficult with LTR90. • Standard Acceptance Criteria • >135°C • Run for a minimum of three fills • Open door recovery is very important
Source: https://www.mitegen.com
146
Thank You! Contact Information: Cahil McGovern, Ph.D. (email: cahilmcgovern@uri.edu) Sharon McGuire, MS (email: smcguire@uri.edu)
147
Notes:
148