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Equipment Qualification
- 1. Equipment Qualification Considerations When Purchasing, Designing, or Qualifying Storage Units Robert Craig Miller Senior Validation Specialist VaLogic, LLC
- 2. Purpose of Today’s Meeting • Discuss the regulatory requirements driving our processes and the relationship to test scripts. • Discoveries encountered in Validations. • Q & A
- 3. Receipt Storage Distribution Shipper Qualification Temperature Monitoring Shipper Qualification Equipment Certification Preventive Maintenance Document Control Equipment Qualification Equipment Certification Document Control Change Control Equipment Qualification Document Control Cradle To Grave
- 4. Definitions • Acceptance Criteria – The standards a product or process must meet to successfully complete a test phase or to meet delivery requirements. • As-Found-Data – Data comparing the response of an instrument to known standards, as determined without adjustment, after the instrument is made operational. • Calibration: The process of adjusting an instrument or compiling a deviation chart so that its reading can be correlated to the actual value being measured. • Certification – A documented statement, by authorized and qualified individuals, that an equipment/system validation, revalidation, qualification, re-qualification, or calibration has been performed appropriately with acceptable results. • Change Control – A formal monitoring system by which qualified representatives of appropriate disciplines review proposed or actual changes that might affect a validated status.
- 5. Definitions (Continued) • Corrective Action – An action, specified in Standard Operating Procedures, that is taken in response to information gathered from environmental monitoring data. This may be implemented when Alert or Action Limits are exceeded or when Trend Analysis indicates a developing problem. • Critical – Of or pertaining to a condition causing an abrupt change in the quality or property of an environment, process or product. • Critical Component – Any component of a critical device that’s failure to perform can be reasonably expected to cause the failure of a critical device, or to affect the device’s safety or effectiveness. • Critical Instrumentation – Those instruments which are pertinent to the proper operation, control, and recording of critical process parameters. • Critical Process Parameter – A control parameter that has a direct relationship to the quality, safety, effectiveness, or performance of the intermediate or final product.
- 6. Definitions (Continued) • Final Report – A document summarizing the results derived from the execution of a protocol. The final report shall include a conclusion, which indicates validation success or failure and designates proven acceptable ranges for all critical process parameters as determined by the execution of the validation protocol. • Installation Qualification – The performance of documented verification that an equipment/system installation adheres to approved contract specification and achieves design criteria. • Operational Qualification – The documented verification that the equipment/system performs per design criteria over all defined operating ranges. • Performance Qualification – Documented verification that equipment, systems, or processes operate the way they are purported to do. This operation must be reliable and reproducible within a specified, predetermined set of parameters under normal production conditions and must be in a state of control.
- 7. Definitions (Continued) • Protocol – The written and approved document of an experimental sequence of tests that, when executed as prescribed, are intended to produce documented evidence that the equipment or system does what it is designed or claims to do reproducibly. • Qualification – Operation aimed at proving, with regard to materials, equipment, or personnel, that the required conditions are met and that they actually provide the expected results. • Trend Analysis – Periodic review and analysis of environmental monitoring program results that can be related to time, shift, facility, etc. for patterns that may suggest underlying or developing problems. • Validation – The overall term for establishing documented evidence through defined tests and challenges, that a system, manufacturing process, analytical method, and/or piece of equipment meets design criteria and that adequate provisions have been established to keep it in a state of control so it will produce a product that meets predetermined specifications and quality attributes. Validation can be performed prospectively, concurrently, or retrospectively. • Validation Master Plan – The establishment of a dynamic written plan that defines the overall approach to a validation project.
- 8. So . . . what is Validation? • Legal responsibility? • Ethical responsibility? • Sound Business Practice?
- 9. Regulatory Requirements Validation and Documentation The FDA’s 1987 guideline defines validation as: • Establishing documented evidence, which provides a high degree of assurance that a specific process will consistently produce a product meeting its pre-determined specifications and quality characteristics.
- 10. Key Validation Documents • Validation Master Plan (VMP) • User Requirements • Functional Specifications • Validation Protocols • Standard Operating Procedures (SOPs) • Validation Final Reports • Change Control System
- 11. User Requirements • Can you identify your needs – In writing? • Musts vs. Wants • Simple, yet has a large impact on the design and validation processes • Provides basis for PQ acceptance criteria
- 12. Functional Specifications • The “How To’s” of meeting the User Requirements • Other Terms – User Requirement Specification – Purchasing Specification – Technical Specification • Provides basis for OQ and PQ acceptance criteria
- 13. Detailed Design • The hard specifics of the design • Detailed specifications and drawings – Cut sheets – Technical specs – P&ID’s – Manufacturer’s documentation • Provides the basis for IQ
- 14. Design / Validation Relationship User Requirements PQ Functional Spec OQ Detailed Design IQ Build
- 15. Typical Things Done – Summary Reports • Completed following protocol execution – Following completion of each protocol – May “lump” IQ / OQ together • Content – Defined by Validation Master Plan / SOPs – Clearly states whether equipment met acceptance criteria as stated in the approved protocols – Clearly states user limitations on the equipment, if any – Provides raw data obtained during the studies, along with information regarding performance of the unit during the studies, for example: • How long the unit maintained acceptable temperatures following power loss? • Hot and Cold spots in the unit
- 16. GMP Relevance & Risk Assessment Section 21 CFR Relevance Product Equipment Section 21 CFR Relevance Product Equipment Installation Qualification Performance Qualification Purchase Order Verification 211.63 N/A Moderate Operational Qualification Verification 211.22, 211.63, and 211.100 High Low Manufacturer’s. Documentation Verification 211.67, 211.68, and 211.100 N/A Moderate Equipment Set-up and Thermocouple Placement Verification 211.68 and 211.100 Low Low Environmental Conformance Verification 211.63 N/A High Operating Temperature Thermal Mapping 211.63, 211.68, 211.100, and 211.142 High N/A Electrical Utilities Verification Same as above N/A High Thermocouple Calibration Verification 211.68 and 211.100 Low N/A Standard Operating Procedure Verification 211.67, 211.68, 211.100, and 211.142 N/A Moderate Validation Test Equipment Verification 211.68 Low Moderate Operational Qualification Re-qualification Installation Qualification Verification 211.22, 211.63, and 211.100 Low Moderate Preventive Maintenance Verification 211.67, 211.68, and 211.100 Low High Validation Test Equipment Verification 211.68 Low Moderate Critical Instrumentation Calibration/Certification Verification 211.68 and 211.100 High Low Critical Instrumentation Calibration/Certification Verification 211.68 and 211.100 High Low Electrical Utilities Verification 211.63 N/A High Equipment Set-up and Thermocouple Calibration Same as above Moderate N/A Validation Test Equipment Verification 211.68 Moderate N/A Temperature Distribution Thermal Mapping 211.63, 211.68, 211.100, and 211.142 High N/A Equipment Set-up and Thermocouple Calibration 211.68 and 211.100 Moderate N/A Open Door Analysis Thermal Mapping Same as above Moderate N/A Operating Temperature Thermal Mapping 211.63, 211.68, 211.100, and 211.142 High N/A Power Failure Analysis Thermal Mapping Same as above Moderate N/A Thermocouple Calibration Verification 211.68 and 211.100 Moderate N/A Alarms and Controls Testing 211.68, 211.100, Alarms and Controls Testing 211.68, 211.100,
- 17. Re-qualification • Event Driven – Replacement of critical components – Change in process or procedures – Change in personnel – Failure Investigation • Time Driven – Change of “the little things” over time – Poorly maintained systems – Routine system failure – Environment dependent
- 18. Change Control • The modification, relocation or decommissioning of any equipment that has been tested under validation conditions must be documented. • Change Control is necessary to perpetuate validation • When should Change Control begin? – After the validation report is approved? – Before qualification begins?
- 19. Difficulties in Validation • Inadequate definition of system requirements / specifications • Poor protocols • Inadequate resolution / explanation of failures / deviations • Poor planning • Poor communication
- 20. Success in Validation • Getting Validation personnel involved early in the process • Well defined user requirements and specifications • Good Communication • Integrating Validation into design-build- test-use cycle
- 21. Discoveries • What we have learned in our supporting role to Operations. – Identifying hot and cold spots. – Affects of TC placement on loaded upright, ultra-low storage unit. – Same is often different. – Hidden costs of being economical. – Helping is sometimes hurting. – When up is down and when down is up.
- 22. Typical TC Placement Diagram TC 01 TC 02 TC 06 TC 04 TC 05 TC 07 TC 08 TC 09 TC 10 TC 11 TC 12 TC 03 TC Shelf Location Suspension 01 Top Back Left Liquid 02 Top Front Right Airborne 03 Second Front Left Airborne 04 Second Controller Airborne 05 Third Back Left Airborne 06 Third Center Airborne 07 Third Front Right Airborne 08 Fourth Front Left Airborne 09 Fourth Back Right Airborne 10 Bottom Center Liquid 11 Bottom Front Right Airborne 12 External Filter Airborne
- 23. Probe Placement on a Walk-in FRONT OF UNIT RTD 8.8' 8.5' 7.4' Probe 01 Back Back Back Front Front Front Back Middle Probe 02 Front Probe 03 Middle Probe 04 Probe 05 Probe 11 Probe 06 Probe 07 Probe 09 Probe 10 HighLevel 6' fromfloor MidLevel 4' fromfloor LowLevel 2' fromfloor Middle Probe 08 Middle Probe 12
- 24. Affects Upon Temperature During TC Placement -100 -90 -80 -70 -60 -50 -40 -30 -20 -10 0 10 20 30 40 11:42:40 12:20:00 13:00:00 13:40:00 14:20:00 15:00:00 15:40:00 16:20:00 17:00:00 17:40:00 18:20:00 19:00:00 19:40:00 20:20:00 21:00:00 21:40:00 22:20:00 23:00:00 23:40:00 0:20:00 1:00:00 1:40:00 2:20:00 3:00:00 3:40:00 4:20:00 5:00:00 5:40:00 6:20:00 7:00:00 7:40:00 8:20:00 9:00:00 9:40:00 10:20:00 11:00:00 11:40:00 Time Temperature 201A-T13 202A-T14 203A-T15 204A-T16 205A-T17 206A-T18 207A-T19 208A-T20 209A-T21 210A-T22 211A-T23 Ambient TC placement Temperatures below -70C Undocumented entry by Operations -100 -90 -80 -70 -60 -50 -40 -30 -20 -10 0 10 20 30 40 11:42:40 12:20:00 13:00:00 13:40:00 14:20:00 15:00:00 15:40:00 16:20:00 17:00:00 17:40:00 18:20:00 19:00:00 19:40:00 20:20:00 21:00:00 21:40:00 22:20:00 23:00:00 23:40:00 0:20:00 1:00:00 1:40:00 2:20:00 3:00:00 3:40:00 4:20:00 5:00:00 5:40:00 6:20:00 7:00:00 7:40:00 8:20:00 9:00:00 9:40:00 10:20:00 11:00:00 11:40:00 Time Temperature 101A-T01 102A-T02 103A-T03 104A-T04 105A-T05 106A-T06 107A-T07 108A-T08 109A-T09 110A-T10 111A-T11 Ambient TC placement Temperatures below -70C • Same model; same set point; same TC diagram. • Different load; different age; different ambient. • Recovery time: 8 hours and 16 hours, respectively.
- 25. All units of same model are created equal; some operate more efficiently than others. -90 -88 -86 -84 -82 -80 -78 -76 -74 -72 -70 -68 -66 12:16:05 12:55:00 13:35:00 14:15:00 14:55:00 15:35:00 16:15:00 16:55:00 17:35:00 18:15:00 18:55:00 19:35:00 20:15:00 20:55:00 21:35:00 22:15:00 22:55:00 23:35:00 0:15:00 0:55:00 1:35:00 2:15:00 2:55:00 3:35:00 4:15:00 4:55:00 5:35:00 6:15:00 6:55:00 7:35:00 8:15:00 8:55:00 9:35:00 10:15:00 10:55:00 11:35:00 12:15:00 Time Temp TC 01 TC 02 TC 03 TC 04 TC 05 TC 06 TC 07 TC 08 TC 09 TC 10 TC 11 -90 -88 -86 -84 -82 -80 -78 -76 -74 -72 -70 -68 -66 12:16:05 12:55:00 13:35:00 14:15:00 14:55:00 15:35:00 16:15:00 16:55:00 17:35:00 18:15:00 18:55:00 19:35:00 20:15:00 20:55:00 21:35:00 22:15:00 22:55:00 23:35:00 0:15:00 0:55:00 1:35:00 2:15:00 2:55:00 3:35:00 4:15:00 4:55:00 5:35:00 6:15:00 6:55:00 7:35:00 8:15:00 8:55:00 9:35:00 10:15:00 10:55:00 11:35:00 12:15:00 Time Temp TC 01 TC 02 TC 03 TC 04 TC 05 TC 06 TC 07 TC 08 TC 09 TC 10 TC 11 -90 -88 -86 -84 -82 -80 -78 -76 -74 -72 -70 -68 -66 12:16:05 12:55:00 13:35:00 14:15:00 14:55:00 15:35:00 16:15:00 16:55:00 17:35:00 18:15:00 18:55:00 19:35:00 20:15:00 20:55:00 21:35:00 22:15:00 22:55:00 23:35:00 0:15:00 0:55:00 1:35:00 2:15:00 2:55:00 3:35:00 4:15:00 4:55:00 5:35:00 6:15:00 6:55:00 7:35:00 8:15:00 8:55:00 9:35:00 10:15:00 10:55:00 11:35:00 12:15:00 Time Temp TC 01 TC 02 TC 03 TC 04 TC 05 TC 06 TC 07 TC 08 TC 09 TC 10 TC 11 -90 -88 -86 -84 -82 -80 -78 -76 -74 -72 -70 -68 -66 14:56:15 15:30:00 16:05:00 16:40:00 17:15:00 17:50:00 18:25:00 19:00:00 19:35:00 20:10:00 20:45:00 21:20:00 21:55:00 22:30:00 23:05:00 23:40:00 0:15:00 0:50:00 1:25:00 2:00:00 2:35:00 3:10:00 3:45:00 4:20:00 4:55:00 5:30:00 6:05:00 6:40:00 7:15:00 7:50:00 8:25:00 9:00:00 9:35:00 10:10:00 10:45:00 11:20:00 Time Temp TC 01 TC 02 TC 03 TC 04 TC 05 TC 06 TC 07 TC 08 TC 09 TC 10 TC 11
- 26. Cost of Quality Acceptance Criteria: -195°C to -135°C Slot Brand X - Economical Brand Y – Top of the Line 1 -88.5°C -178.6°C 2 -94.5°C -182.1°C 3 -118.3°C -186.4°C 4 -127.0°C -187.8°C 5 -154.9°C -188.8°C 6 -159.5°C -189.8°C 7 -171.1°C -190.9°C 8 -187.9°C -192.2°C 9 -192.2°C -192.6°C 10 -194.6°C -192.8°C 11 -194.8°C -193.5°C 12 -196.5°C -194.1°C 13 -196.6°C -194.3°C
- 27. Quick “Fix” Acceptance Criteria: -195°C to -135°C Slot Temperature – High Fill Set Point of 7” Temperature – High Fill Set Point of 10” 1 -88.5°C -125.3°C 2 -94.5°C -134.7°C 3 -118.3°C -139.3°C 4 -127.0°C -149.2°C 5 -154.9°C -153.4°C 6 -159.5°C -160.9°C 7 -171.1°C -167.5°C 8 -187.9°C -184.3°C 9 -192.2°C -192.1°C 10 -194.6°C -196.8°C 11 -194.8°C -196.9°C 12 -196.5°C -196.9°C 13 -196.6°C -197.1°C
- 28. Criticality of Temperature Set Point Temperature Control Set Point at -85.0C -90 -88 -86 -84 -82 -80 -78 -76 -74 -72 -70 -68 -66 -64 -62 -60 12:50:00 12:55:00 13:00:00 13:05:00 13:10:00 13:15:00 13:20:00 13:25:00 13:30:00 13:35:00 13:40:00 13:45:00 13:50:00 13:55:00 14:00:00 14:05:00 14:10:00 14:15:00 14:20:00 14:25:00 14:30:00 14:35:00 14:40:00 14:45:00 14:50:00 14:55:00 15:00:00 15:05:00 15:10:00 15:15:00 Time Temperature(DegC) Min Max Avg Temperature Control Set Point at -80.0C -90 -88 -86 -84 -82 -80 -78 -76 -74 -72 -70 -68 -66 -64 -62 -60 12:50:00 12:55:00 13:00:00 13:05:00 13:10:00 13:15:00 13:20:00 13:25:00 13:30:00 13:35:00 13:40:00 13:45:00 13:50:00 13:55:00 14:00:00 14:05:00 14:10:00 14:15:00 14:20:00 14:25:00 14:30:00 14:35:00 14:40:00 14:45:00 14:50:00 14:55:00 15:00:00 15:05:00 15:10:00 15:15:00 Time Temperature(DegC) Min Max Avg
- 29. Affects of Dynamic Testing -2 -1 0 1 2 3 4 5 6 7 8 9 10 11 11:00:00 12:10:00 13:20:00 14:30:00 15:40:00 16:50:00 18:00:00 19:10:00 20:20:00 21:30:00 22:40:00 23:50:00 01:00:00 02:10:00 03:20:00 04:30:00 05:40:00 06:50:00 08:00:00 09:10:00 10:20:00 11:30:00 12:40:00 13:50:00 15:00:00 16:10:00 17:20:00 18:30:00 19:40:00 20:50:00 22:00:00 23:10:00 00:20:00 01:30:00 02:40:00 03:50:00 05:00:00 06:10:00 07:20:00 08:30:00 09:40:00 10:50:00 Time Temperature(DegC) B090 B131 B135 B145 B277 B353 B354 B403 D002 D003 D685 D686 D687 D691 D692 D693 D694 D695 D697 D698 D699 D700 D701 D703 D704 D705 D706 D707 D709 D710 D711 D712 D713 D714 D721 D722 Open Door Test #1 Open Door Test #2 Open Door Test #3
- 30. To Summarize • As the User, know your requirements and processes. • Validation is a lifecycle approach. It’s not a one and done. • Be cognizant of change control. • Have a thorough TC/logger placement diagram to detect hot and cold spots. • Understand the functionality of the units being qualified. • But, above all, the most import thing to remember is that . . .
- 31. OUR PRIMARY OBLIGATION IS TO THE END USER • Family • Friends • Co-workers • Strangers
- 32. Thank You For Your Participation Questions, comments, complaints?
- 33. About the Presenter Robert “Craig” Miller has over twenty years experience working in the pharmaceutical and biotech support industry. Starting off as a Repository Technician at the National Cancer Institute Clinical Repository, he has held increasing key positions and recently left Fisher BioServices (formerly McKesson BioServices, Ogden BioServices) after ten years as the Validation Manager to join VaLogic, LLC, a calibration and validation consulting firm supporting life sciences. Contact Information: Email: cmiller@valogic.us Office: 240-529-1673 Cell: 240-602-1424 Fax: 240-529-1678 Web: www.valogic.us
Editor's Notes
- One thing that I am going to ask of you is to not take what I have to say as gospel but challenge what I am saying. I want to use you find areas of weakness and offer up solutions to either increase quality or efficiency without sacrificing quality in the process. In addition, you are the lab rats for this particular experiment and I want your feedback upon this presentation, which I hope to roll out to the masses as part of annual GMP and/or Continuing Education training.
- Our core business is in the receipt, storage, labeling, and/or distribution of pharmaceuticals/biologics in support of clinical trials. This simple slide shows how we support Operations in ensuring Down Stream Control to prevent adulteration of pharmaceuticals or degradation of biologics that may result in adverse events, such as patient illness or death.
- I am going to focus primarily on Equipment Qualification today as this is, perhaps, the most pervasive and critical aspect of cold chain supply management. So, before we get into nuts and bolts of Equipment Qualification I would like to briefly go over some key definitions first. Acceptance criteria is pre-determined at the on-set of validation. All we are doing is testing the system, documenting, and reporting the results. So don’t kill the messenger when we report failures that may affect product quality or equipment performance. We are not here to “make it pass” but to provided documented evidence that a unit is fit for its intended purpose.
- Can anybody provide me with examples of a critical component? (evaporator, compressor) What about a gasket to a door seal? How about critical instrumentation? (controller, external alarm probe) And critical process parameter? (Control set point, storage range, alarm set points)
- What is the order of sequence for qualification?
- <number> .
- <number> Validation Master Plan (VMP) Top Level Document An outline describing your approach to validation at your facility It provides the opportunity to discuss the rationale for the mechanics of how systems will be validated May be broad or narrow in scope Validation protocols Installation Qualification (IQ) Operational Qualification (OQ) Performance Qualification (PQ) Process, packaging, and cleaning SOPs Process Operation and Preventive Maintenance Calibration Validation reports IQ, OQ and PQ summary reports Annual review reports Change control system Maintenance of validated system
- Defines the equipment or system that meets the user’s operational tolerances
- <number> The process flow starts with the User Requirements and runs counter-clockwise.
- <number> Following completion of each phase of qualification a Final/Summary Report is written.
- This table illustrates the relationship of test scripts to the regulations and its impact upon product and/or equipment. Note: I have only cited 210 and 211 for finished pharmaceuticals but other regulations apply based upon what you are storing and distributing. Let me know whether you would like to go into these regulations in further detail or simply read them at your leisure.
- Documented Procedure Planned Change Emergency Change Levels of Notification and Approval Product Quarantine Evaluation for Revalidation
- Bullet #1: Design a storage unit (WIR or RT Vault) to meet temperature requirements but not relative humidity, which is key to your product’s quality. Bullet #2: Protocols do not capture or test critical components, instrumentation, or processes that have a direct or indirect impact upon product’s quality, purity, strength, and efficacy. A flawed diagram that doesn’t capture areas that may adversely affect product; failure to perform utilities verification; confirm calibration of equipment; documentation of key process parameters such as control set point. Bullet #3: Denoting failed without further comment on impact upon study. Bullet #4: Not having your ducks in row prior to start of qualification. Purchasing several storage units to arrive two days prior to product showing up. Bullet #5: Clear understanding of directives, acceptance criteria, readiness, and timelines. Operations informs you a unit has arrived and to go validate it but Facilities personnel haven’t even uncrated the unit.
- Let’s begin our discoveries with establishing effective thermocouple placement diagrams in helping to identify potential hot and cold spot areas that may prove detrimental to your samples. By show of hands, how many of you have ultra-low storage units at your facility? Do you have the luxury of space to purchase chest freezers or are constrained by space and need to purchase uprights? This diagram is of a typical upright, ultra-low freezer used in our OQ/PQ protocols. We utilize twelve thermocouples; eleven internal, nine of which are airborne while two (as seen in blue) are placed in glycol solution to simulate product temperatures, while a twelfth thermocouple is placed by the filter to record the ambient temperature of the warehouse as external ambient plays a significant role in the unit’s performance. Where would one find the hotspot (warmest overall) location on a standard upright ultra-low freezer? If you had suspended all your thermocouples in air then the bottom shelf would not have been identified as the hot spot but the top front. However, the material that you are storing is not levitated but rather is in contact with the storage unit’s surface or other product’s surface. I cannot recall the total number of makes and models of upright ultra-low units we have mapped but, if I were to hazard a guess, I would say that it would be over two dozen and I do not remember seeing any other spot but the bottom shelf being the hot spot. The difference between the digital display and this hot spot area typically averages about 10°C with a temperature control set point of -85°C. However, the warmer that set point is, the wider the spread becomes, which also affects the pull down time of the unit following personnel entry. Typically, for upright ultra-low freezers, the time to return below -70°C from a starting temperature of -40°C is about two hours. Recovery time will vary based upon brand, control set point, load, age of unit, ambient temperature, and duration door is left open. This emphasizes the need to have a well thought out data logger placement diagram, which leads to data logger placement diagrams for walk-in refrigerators and freezers.
- I have seen protocols where thermocouple placement diagram captures the top and bottom corners-sometimes the middle plane of the corners-and the geometric center. The unit is mapped and demonstrates conformance to the acceptance criteria. However, the protocol is slightly flawed in the aspect that sources of potential cold or heat generation are not accounted for. Often times, the shelving units in front of the evaporator fans are not probed. For walk-in refrigerators, this is your area of potential cold spikes as the temperature coming out, depending on your temperature control set point, is either close to, at, or below freezing. So, if you have a vaccine that cannot freeze, you certainly want to ensure that material is not stored in the immediate vicinity of the air current of these fans. Conversely, these areas are potential hotspots for walk-in freezers. These units regularly go into defrost to de-ice the lines to prevent mechanical failure either through hot gas or heating up the coils electrically. If there isn’t a time delay in kicking the fans on following defrost then material in close proximity are being regularly blasted with hot air. Let’s say you are storing plasma, which needs to maintain temperatures at or below -18°C (as stated in 21 CFR 600.15, Temperatures during shipment since storage units and shippers serve the same function; one is simply better controlled than the other) and you have the unit going into defrost every four hours. That is six occurrences a day where your material is potentially blasted with hot air. If you say that duration of high temperature excursion is five minutes then that is thirty minutes a day, 183 hours a year, which equates to roughly 8 days cumulative time above the specified high temperature limit. Could be significant or acceptable, it all depends upon your product and it’s stability data. But why take the chance of unnecessary exposure? I recommend an adequate time delay from end of defrost to start of fans kicking on and not storing material in those areas that are susceptible high temperature exposure. So, thermocouple placement diagram is key in identifying potential areas that may adversely affect the quality and efficacy of samples. We’ve looked at an upright ultra-low freezer, walk-in refrigerator, and walk-in freezer. Now, let’s add another element into the equation, which is driven by Operations or Finance. If you qualify one unit then why do I need you need to qualify other units of the same model?
- The unit on the left is the newer model and was at approximately 90% capacity whereas the unit on the right was two years older an at 70% capacity.
- Four units; same model, same set point, similar TC placement and load configuration but four separate outcomes.
- Brand X maintains temperature by supply LN2 directly into the cavity while Brand Y feeds the LN2 into the jacket. Greater storage capacity, which equates to maximum utilization of revenue stream. Less LN2 consumption
- Looking at the temperature gage, which is rarely at the top slot, personnel see a potential or actual problem. Being proactive but unwittingly counterproductive, they make a quick change to the fill level to remedy the situation. Personnel incorrectly assume that by increasing the fill level that they are meeting temperature requirements. This rarely solves the issue but simply shifts the unusable slots from the top to the bottom. Without a thorough temperature mapping then this would not be detected. This is where a comprehensive thermocouple placement diagram comes in handy. On a somewhat similar vane. Over the course of time, units begin to wear, and performance suffers. What follows are intermittent “nuisance” alarms, which drive Operations and/or Facilities personnel nuts. So, they tweak the control set points or alarm parameters. The unit is no longer in a state of control and the validation is rendered useless.
- Case and point. This is why critical parameters are documented in either the protocol or final report without which personnel can make changes and no one is the wiser unless an alarm triggers, someone performs a trend analysis, or performs a revalidation and discovers something amiss.
- How come I received a low temperature alarm from my external monitoring system when the local alarm registered a high alarm? This makes no sense to me. Location, location, location of the controller and associated external alarm/monitoring devices are key.
- It’s to your family, your friends; past, present, and future. It’s to strangers on the street. It’s not your company or to the client. It is to ensure the quality, safety, efficacy, and purity of pharmaceuticals/agents to treat and, in many cases, save the lives of those sick or injured while advancing the success of the healthcare industry. If you put that first and foremost in your thoughts then, by extension, your company and/or client is happy. Sappy but true. As Rob Yaffe can attest, I’m clearly not a rocket scientist and being in perpetual fear of my mortality, I want to contribute as much as I can in assisting the geniuses in eradicating debilitating diseases and not only prolonging but increasing the quality of life.