Guidelines for Validation &Qualification, including Change Control
Contents
1. Short description of equipment or process being validated Testing of Automated grouping analyser using xxx operating software on Windows 2003 platform with a range of challenges to ensure system operability Security Level and clot detection Probe failure rescue Barcodes interpretation Reagent Identification Serology resolution and interpretation Page 38 of 50 Details of equipment used in the validation Automated grouping analyser using xxx operating software on Windows 2003 platform Automated grouping analyser using xxx operating software on Windows 2000 platform Name of IT system data interface and host system ABD ABD ref 5005 grouping cards ABDDAB ref 5009 grouping cards Rh K ref 5011 phenotyping cards LISS IAT ref TAT cards Details of testing levels methods SOP s used in validation x24 samples tested to ensure correct serological and sample barcode interpretations x2 ISBT donation barcode check x1 well verification check xl reagent reversal check x2 test card error check x1 clot replication See 309cval doc xl probe failure replication See 309cval doc x1 sensitivity check using antibody titration x1 well verification check x2 test edit check Sample tube size capability check Password security check lt File Name and CCR Reference Number gt Page 39 of 50 Validation Ti2. 10 9 Please state whether on line manuals are available 10 10 Modem links for remote access for problem solving should be available 10 11 Please provide details of the locality of engineers and spare parts relative to the Authority s normal place of business 10 12 A guarantee must be provided that the proposed equipment will be supported and spares available for the period Page 21 of 50 11 Training 11 3 11 4 Provide details of the initial on site training for staff during the set up period Proposals must include details of the training courses included with the supply of automation including the number of places available and the duration and location of the courses Please provide an example of a training prospectus for the system State whether additional courses are available at a later date and whether any on site training is included Details of any user groups in the UK and the frequency of meetings should be provided proposal of support should be included 12 Health and Safety 12 1 12 2 12 3 12 4 The proposed equipment must comply with relevant regulations for electrical mechanical and biological safety All reagents and cells proposed must confirm comply with relevant regulations regarding shipping labelling and information on hazardous substances COSHH data must be confirmed as available and must be supplied in advance of installation Provide details of waste disposal requirements including
3. Details of guaranteed uptime and its definition must be provided details on how uptime is measured how this will be attained and remedies to the Authority if the uptime is not maintained are required to be submitted Page 17 of 50 4 1 5 Guaranteed uptime must be 24 hours a day seven days a week provided over a calendar month tenderer s must provide details of how this will be achieved 4 2 The range of tests that must be available on the machine are but not limited to the following 4 2 1 ABO and Rh D grouping both full ABO group 4 2 2 3 cell antibody screens by IAT 4 2 3 DAT s including monospecific typing 4 2 4 Antibody identification panel with enzyme treated and IAT cells 4 2 5 Secondary antibody identification panel with enzyme treated and IAT cells 4 2 6 Miscellaneous red cell phenotyping 4 2 7 The analyser must be capable of running without continual operator presence 4 2 8 The proposed system must allow customer definable password protection levels and users 4 2 9 The system must be user friendly and safe operation is expected 4 2 10 The following must be supported 4 2 10 1 Start up 4 2 10 2 Shut down 4 2 10 3 Calibration 4 2 10 4 QC 4 2 11 Local maintenance and general cleaning procedures must be stated and the length of time involved and required frequency of these procedures 4 2 10 6 Requirements and consumption rates for power water saline drainage and air conditioning must be stated and installation costs
4. Title of Validation VALIDATION PLAN Validation Plan Reference number Page x of y 4 4 1 5 5 1 6 6 1 6 2 6 2 1 6 2 2 6 2 3 6 2 4 6 3 6 3 1 6 4 6 4 1 6 4 2 6 4 3 6 4 3 1 6 4 3 2 6 4 3 3 6 4 3 4 System description System maintenance and support strategy Validation approach Schedule Resource summary Staffing Facilities Equipment Finance Responsibilities Method of validation Tools Techniques Method Design Qualification Installation Qualification Operational Qualification Performance Qualification Page 27 of 50 Department of Blood Transfusion Insert Title of Validation VALIDATION PLAN Validation Plan Reference number Page x of y 7 Implementation strategy 7 1 8 Training requirements related to responsibilities 8 1 9 Appendices 9 1 Appendix l System hardware configurations if applicable 9 2 Appendix Il Software Components if applicable 9 3 Appendix Ill Documents that Form the Validation Record and their Approval Requirements e g checklists Page 28 of 50 Appendix 8 Installation Qualification IQ Operational Qualification OQ and Performance Qualification PQ Specification Area Process Practical Aspects Personnel Installation Hardware Electrical checks additional wiring Instrument CE certification Hospital Transfusion staff Qualification requirements Quality Manager IQ Calibration of all measuring
5. and antibody screen must be completed in less than 40 minutes 6 8 Samples should be able to be removed from the proposed equipment either prior or post sampling in case urgent testing is required Varying length of time in which samples can be removed must be stated 6 9 The equipment should be able to display time until the results of test s will be reportable 6 10 The system must validate that appropriate volumes of red cells plasma or reagent have been added to the test 6 11 Any deficiencies must be highlighted to the operator Please state how the system reports such occurrences 6 12 The sampling system should have 6 12 1 level sensing 6 12 2 clot detection 6 12 3 bubble sensing 6 12 4 short sample alerts both audible and visual 6 12 5 Warnings should be given when there is an error 6 13 Known interferences including icterus lipaemia and haemolysis must be stated and how any compensation if any is made 6 14 Details of reagent and sample carry over must be provided 6 15 The tests should be accurate on fresh samples for up to 72 hours and normally observed storage temperatures must not affect them 6 16 It should not be necessary to equilibrate refrigerated samples to room temperature 6 17 The equipment should be able to process plasma serum that has already been separated from the red cells for antibody screening 6 18 The equipment should be able to process different tests within the 1 batch i e adult gro
6. any special precautions for handling High Risk samples or waste A decontamination procedure for the equipment must be provided with recommendations including recommended cleaning products of when it should be used 13 Additional Information 13 1 13 2 Tenderers are invited to include any other information which they deem relevant in support of their proposal Tenderers are invited to include any significant advances that are under development and provide details of when these are scheduled to be released If advances are identified please state how these would be provided and any related costs 14 Location of Equipment 14 1 The Tenderer must review the proposed location of the equipment and confirm that it is suitable for installation and operation If any works are required to the area facilities plant network or utilities it must identify and cost these in its bid Page 22 of 50 Appendix 6 Specifications for inclusion in FDS Section Introduction Detail to include e Who produced the document their authority and for what purpose e The contractual status of the document Relationship to other documents Overview Background departmental strategy previous studies etc Key objectives and benefits Main functions and interfaces Applicable GxP requirements e g CE mark BSQR BS standards e Other applicable regulations and guidelines BCSH guidelines Operational requirements Sys
7. devices PUMN IdONIRY Supplier Requirements for UPS Electrical safety emergency Hospital Estates Compliance with environmental power supply department requirements temperature humidity _ Adequate waste etc Installation by supplier Manufacturers documentation Safety features e g electrical safety _ User manual Asset register CE marking Instruction Manual Software Version control Software operates on current Hospital Transfusion staff Description manual hardware Quality Manager IT links to LIMS Supplier Server requirements i Aste inanaee solwals Hospital Pathology IT versions department Establish and check password security settings Reagents CE marking Ensure the package inserts are Hospital Transfusion staff Certificate of analysis present Quality Manager Environmental requirements Supplier temperature humidity etc Page 29 of 50 Operational Qualification Equipment Continuous running Well verification Hospital Transfusion Self checks Reagent reversal staff Equipment report Test card error Quality Manager Configuration and settings Clot replication probe failure Supplier Verification of sample volumes replication Sequencing Sample tube size capability Identity check critical setting check Alarms safety features Mixed field Establishment of maintenance Representation of patient programme Temperature mapping of incubators cold rooms etc Soft
8. e g required 24 7 or 23 hrs per day e Procedural constraints these include external but inter related factors e g specimen tube type workforce skill mix e Cost Glossary e Definitions of any terms that may be unfamiliar to the readers of the document Page 23 of 50 Appendix 7 Example of a Validation Plan Department of Blood Transfusion Insert Title of Validation VALIDATION PLAN Validation Plan Reference number Insert title of Validation Validation Plan Prepared by Insert details Date Insert date of plan preparation Page 24 of 50 Department of Blood Transfusion VALIDATION PLAN Insert Title of Validation Validation Plan Reference number Page x of y recommend approval insert title Insert name Insert position of this validation plan Date Page 25 of 50 Department of Blood Transfusion Insert Title of Validation VALIDATION PLAN Validation Plan Reference number Page x of y 1 Purpose and scope 1 1 Introduction 1 1 1 1 2 Goals 1 2 1 1 3 Scope 1 3 1 1 4 Specific procedures and processes covered 1 4 1 1 5 Assumptions 1 5 1 2 Background References 2 1 References to legal documents 2 2 References to Guidelines 2 2 1 2 3 References to other documents 2 3 1 3 Definitions and acronyms 3 1 Page 26 of 50 Depa rtment of Blood Transfusion Insert
9. included 4 2 12 Details of any additional consumables special waste containers must be provided and full costs provided 4 3 Proposed system must conform to current blood transfusion guidelines as defined by the British Committee for Standards in Haematology BCSH Blood Transfusion Task Force or equivalent 4 4 Proposed system must conform to current EC directives for in vitro diagnostics IVD electrical safety CE and CPA guidelines or equivalent 4 5 The tendered should state whether they have a software package to assist in the identification of atypical antibodies and whether this attracts an additional cost 4 6 Fully detailed operator manual must be provided Such manuals must be renewed as and when the instrument software or hardware is updated and must be supplied in English 4 7 The User will expect all safety upgrades or enhancements to the equipment to be undertaken free of charge 5 Interfacing 5 1 Proposed equipment must be compatible with the laboratory s LIMS currently insert system Tenderers should state how many installations of the proposed system are interfaced with this LIMS giving location and contact information for each 5 2 Interfaces must be operable before go live and noted in a project plan or key stage document with the submission Tenderer s must also advise of any remedies if the proposed project plan is delayed 5 3 Tenderer s must state details of any Laboratory information systems the
10. or project systems as changes are proposed and implemented management e This section of the VMP can be used to either describe the change control process or to refer to separate change control procedures within the quality system e It should show how validation process fits into the overall change control process e The implementation of entirely new laboratory process equipment facilities or systems may be managed through change control but these and possibly more extensive changes may be large in scope involving significant business risks It may therefore be necessary to use formal project management arrangements available to or imposed upon the laboratory e This section should make it clear how any formal project management arrangements ensure that the validation requirements are identified and met The project management methodology should require individual VMPs to be produced See Above Page 5 of 50 Links to other Quality System Processes Procurement Training amp Document Control Facilities amp Equipment management These links may be shown diagrammatically Validation is usually focussed on validating operational processes and systems and qualifying the facilities equipment and materials used in the process or by the system Clearly the facilities equipment and materials are usually supplied by third parties Therefore e The laboratory quality system should control the pro
11. proposed system is interfaced with providing relevant contact information 5 4 The Tenderer must state how it will achieve the interface to the LIMS and timescales to complete the interface 5 5 Data transfer must be automatic and on line but must also be able to cope with LIMS downtime and must provide details that this is possible within the proposed equipment Page 18 of 50 5 6 The cost of interface development installation licence and maintenance must be included in the system cost and set out in the pricing schedule The pricing must include both sides of the interface 6 Sampling requirements 6 1 6 2 6 3 6 4 6 5 6 6 6 7 Cap piercing facility is desirable proposals must state if cap piercing is available by the proposed equipment The system must be capable of reading and sampling from bar coded primary tubes The system must be compatible with Codabar and ISBT 128 bar codes Please state all other bar code configurations that are readable by the proposed equipment Small volume paediatric samples must be accommodated The minimum volume requirements for all sample tube sizes must be stated The system must have the capability to accept a wide variety of sample tubes Sample tube sizes and types that are not compatible with the proposed equipment must be clearly stated STAT Urgent facility should be available 6 7 1 A rapid ABO and Rh D group should be available in less than 10 minutes 6 7 2 A full group
12. speed response times e Data security and integrity Data handling requirements System interfaces e Define staff groups in terms of roles or functions e g Biomedical Scientist Biomedical Support Worker porter e Interface with other systems e g LIMS e Interface with equipment e g blood issue fridges blood group analysers Environment e Physical layout of the working environment e Physical conditions e g dusty sterile air conditioned Page 15 of 50 Constraints Timescales and milestones e g speed of delivery commissioning time etc Compatibility e g will the software work on your current server IT system Availability e g required 24 7 or 23 hrs per day Procedural constraints these include external but inter related factors e g specimen tube type workforce skill mix Cost Glossary Definitions of any terms that may be unfamiliar to the readers of the document Page 16 of 50 Appendix 5 Example of a User Requirement Specification Provision of Blood Grouping analysers and reagents 1 The proposed equipment must be able to meet the current workloads with capacity to increase these by xx 1 1 The current annual blood transfusion workload is approximately e Blood Groups and screens enter number DAGT enter number Neonatal grouping with DAGT enter number Antibody panel s approx enter number Full crossmatch on cards enter number 2 Proposals are re
13. 11 Blood Transfusion Department Validation sign off report form Date printed Title of Validation Date of validation problems found Resolved Yes No Decision to release Yes No Conditions on release Yes No SOP changes needed and done Yes No Released by Quality Manager or Laboratory Manager Date of release Page 49 of 50 Appendix 12 Acknowledgement and declaration of interest None of the authors have declared a conflict of interest The Transfusion Task Force membership at the time of writing this guideline was Derek Norfolk Andrea Harris Shubha Allard Sarah Alford Hafiz Qureshi Joan Jones Clare Taylor Jenny White These appendices are an accompaniment to the BCSH Guidelines on Validation and Qualification including change control for hospital transfusion laboratories which can be downloaded from the BCSH website at www bcshguidelines com Page 50 of 50
14. 11 3 date of placing on the equipment 7 11 4 warn of expiring reagents State storage requirements for one month and six weekly supply of red cells reagents and consumables including space required at room temperature refrigerated or deep frozen 7 13 State guaranteed minimum shelf life of products provided 7 14 Provide details of standard and emergency orders for red cells or reagents and the 7 15 lead time and cost Details of any third party consumables that are compatible with the proposed systems must be provided Quality Control QC 8 1 The system must have monitoring of all aspects of instrument performance 8 2 8 3 8 4 8 5 8 6 8 7 8 8 8 9 8 10 8 11 incubation temperature centrifuge speed pipette volumes etc Submissions must include details of the quality control material QC proposed and any associated cost Proposals must specify the recommended frequency of QC All QC material must be bar coded and must not require any preparation QC results should be clearly indicated with appropriate status tags against defined results The system should not normally allow testing to proceed where the calibration and QC data are outside the prescribed limits or where the calibration and or QC has not been performed in accordance with the system configuration There should be a security protected override for this Any results generated with the override activated should be flagged to show this Detai
15. Appendices to the Guidelines for Validation amp Qualification including Change Control for Hospital Transfusion Laboratories This document contains the appendices to the BCSH guidelines on validation and qualification which is available to download from www bcshqguidelines com British Committee for Standards in Haematology Transfusion Task Force Address for correspondence BCSH Secretary British Society for Haematology 100 White Lion Street London N1 9PF e mail bcsh b s h org uk Writing group S Allard G Burgess B Cuthbertson C Elliott R Haggas J Jones B Robertson D Sadani K Smith Guidance and Recommendations as per the BCSH web site Disclaimer While the advice and information in these guidelines is believed to be true and accurate at the time of going to press neither the authors the British Society for Haematology nor the publishers accept any legal responsibility for the content of these guidelines Date for guideline review July 2014 1 Barts and the London NHS Trust amp NHSBT Royal London Hospital 80 Newark Street London E1 2ES NHSBT Long Road Cambridge CB2 2PT SNBTS Ellens Glen Rd Edinburgh 4 James Cook University Hospital Middlesborough Blood Transfusion Dept Leeds General Infirmary Great George Street Leeds LS1 3EX WBS Ely Valley Rd Cardiff CF72 9WB Guys amp St Thomas Hospital NHS Trust Westminster Bridge Road London SE1 7EH Leeds Bloo
16. X 10 RH PHENOTYPES Consistent with existing Download from v3 11 instrument instrument and compare printouts from v3 07 3 09 manual and APEX CHECK DOWNLOAD OF ALL RESULTS APEX result flags set to F Use WFE module to print test status and check Page 46 of 50 T7 POSITIVE NEGATIVE AB SCREENS FOR 20 WORKING DAYS RECORD NUMBER OF GROUP FAILURES FOR 20 WORKING DAYS RECORD NUMBER OF FALSE Record and review Express results as and provide summary Validation Completed essessosseseosossesoossesoossesessoesesoossesoesseseesossessossesoessesoesoesessossesoossesossse QA Manager lt File Name and CCR Reference Number gt Page 47 of 50 THIS PAGE TO BE REPLACED WITH ZZZZ IMPLEMENTATION SIGN OFF FORM FOR IMPLEMENTATION PHASE OF VALIDATIONS Recommendations Comments Validation Team Leader Name cirri GeO Solent Signature 5 6 6 5 a Rs Re Date a EA ee oan aie Recommendations Comments Change Manager NAME eere ona renaisse Signature 1 c4 1 05 asec dastaptnbedtariecsaass PAGE os ons enii nin Recommendations Comments on behalf of Review Board lt Title of Process Owner gt ccssccssssccsssrccsssscesssscesseccesees DN AUG sti ecia N A ee Signature 0 00 ee eeeeeeee QA Representative Name 6035s a diswenin Signat tei nonu Aedes ias Dat cena kite na Page 48 of 50 Appendix
17. above Decision Finally a decision is required by the independent expert See above as to whether the process equipment facilities or systems Under validation is acceptable Normally if any of the acceptance criteria are not met then the process is rejected It is possible to accept a process or system where validation outcomes are not as expected or are borderline or ambiguous This would be a Qualified Acceptance and may be acceptable if e On the basis of further analysis and quality risk assessment it is deemed safe to accept e Acomment is recorded giving the rationale for the decision Certain additional constraints or conditions are applied to the process equipment facilities or systems and these are stipulated and recorded Validation e Template consistency In order to ensure a consistent House Documentation Style and more importantly that all requirements are met the format for the Validation Protocol and for Validation Records Reports should be specified in a controlled manner as an integral part of the Quality Management System e This section should describe these or refer to the relevant quality system documents It is common practice to produce validation records as scripts See Appendix 10 using a controlled pro forma Validation e The purpose of Change Control See Section 4 is to maintain the change control amp valid state of critical laboratory process equipment facilities
18. atient samples tested on v3 11 new instrument using ABD ABD cards and results compared against v3 07 v3 09 existing instrument 48 patient samples tested on v3 11 new instrument using LISSIAT cards and results compared against v3 07 v3 09 existing instrument 10 examples of significant antibodies tested on v3 11 new instrument using LISSIAT cards and results compared against v3 07 v3 09 existing instrument 10 patient tests samples tested on v3 11 new instrument using Rh K cards and results compared against v3 07 v3 09 existing instrument and manual results lt File Name and CCR Reference Number gt Page 45 of 50 Validation Title National Validation of Insert equipment using v3 11 software No Description URS FDS Acceptance Criteria Pass Fail Ref Re test 12 ABO D GROUPS USING Consistent with existing Download from v3 11 instrument ABDDAB CARDS instrument and compare printouts from v3 07 v3 09 and APEX 24 ABO D GROUPS USING Consistent with existing Download from v3 11 instrument ABD ABD CARDS instrument and compare printouts from v3 07 3 09 and APEX 48 2 CELL ANTIBODY SCREEN Consistent with existing Download from v3 11 instrument instrument and compare printouts from v3 07 3 09 and APEX 10 EXAMPLES OF SIGNIFICANT Consistent with existing Download from v3 11 instrument ANTIBODIES instrument and compare printouts from INCLUDED IN STEP 3 v3 07 3 09 and APE
19. cal inputs or components are Equipment Facilities and utilities Test kits amp reagents Automation and IT hardware amp software As a minimum these inputs or components need to be qualified See definitions to ensure that the processes and systems are valid and fit Page 3 of 50 for purpose It is useful to identify the key inputs or components to be subject to qualification as part of validation in this section For the laboratory computer system critical inputs will include hardware operating system and application software The amount of validation for computerised systems will depend on complexity and amount of customisation Guidance on this can be found in the Good Automated Manufacturing Practice GAMP guidelines Planning The output from planning is a validation protocol See section 8 2 This section of the VMP should describe or refer to the procedures for planning producing and approving the validation protocol It may also describe the selection and activities of the validation team The protocol should e Describe the risks and rationale for the particular qualification or validation Define the expected outcome s from validation tests e Describe or refer to the validation or qualification procedures to be used In planning the scope extent and methods for validation the following should be considered e The quality risk associated with failure of the process and system See s
20. curement and supply of quality critical goods and services e This should include the qualification of suppliers and possibly trials or evaluation of equipment or materials prior to purchase e tis also possible that an important part of the qualification of new facilities equipment etc known as Design Qualification and will relate to the Functional Design Specification See Section 7 is performed as part of the procurement process Clearly the outcomes from this activity will influence subsequent validation before these goods and services are put into use and therefore this section of the VMP should describe or refer to the supplier control procedures Development of SOPs and training in the use of these SOPs for operating any new system will be crucial before it is finally approved for use This requirement will normally be included in the PQ protocol Once the laboratory process equipment facilities or systems has been approved for use it is essential that documentation is maintained in a current state Therefore part of maintaining processes and systems in a valid state is the qualification of operational staff and of SOPs used As these are usually described in separate training and document control procedures they should simply be referenced in this section It would be appropriate to describe or reference any staff proficiency schemes operated by the laboratory in this section The management and control of facilities a
21. d Centre Bridle Path Leeds Page 1 of 50 Contents 10 11 12 Information to be included in the Validation Master Plan Example of a VMP currently in use in an NHS Hospital Change Control Request Form Specifications of what could be included in a User Requirement Specification Example of a User Requirement Specification Specifications for inclusion in FDS Example of a Validation Plan Installation Qualification Operational Qualification And Process Qualification Example of Validation Protocol Example of a qualification Proforma Validation sign off report Acknowledgements and Declarations of interest page 03 page 07 page 11 page 15 page 17 page 23 page 24 page 29 page 32 page 34 page 49 page 50 Page 2 of 50 Appendix 1 Table 1 Information to be Included in the Validation Master Plan VMP Section Guidance Organisational e Validation requires a structured approach Large organisations Structure and may have a validation department however each laboratory Responsibilities should at least appoint one or more of its managers senior scientists to act as a validation manager s responsible for producing the validation plan which will include a validation protocol and selecting and supervising a validation team to perform and record the validation e There are three distinct functions to be performed planning the validation performing the validation approving the validation
22. e Date Date Signature Signature Signature Page 14 of 50 Appendix 4 Specifications of what could be included in a User Requirement Specification Section Details to include Introduction e Who produced the document their authority and for what purpose e The contractual status of the document e Relationship to other documents Overview e Background departmental strategy previous studies etc e Key objectives and benefits e Main functions and interfaces e Applicable GxP requirements e g CE mark BSQR BS standards e Other applicable regulations and guidelines BCSH guidelines Operational requirements System functions e Functions required including information on the process or existing systems e g perform red cell group and antibody screen e Calculations including all critical algorithms interpret test results to correctly identify a blood group e Modes of operation e g start up shutdown test backup e Quantitative and unambiguous performance and timing requirements e g turn around times for routine or urgent samples QC etc e Back up in case of system failure e g engineer response time e Safety e Security e Maintenance e g planned preventative calibration etc e Definition of data including critical parameters valid data ranges and limits e Capacity requirements e g disk storage capacity archive capacity etc e Access speed requirements network
23. e Planning will require expert input from scientists engineers clinicians Quality Assurance and suppliers of equipment and materials in order to devise appropriate and effective validation protocols See section 8 2 e Staff performing validation work should be experienced operators and will need supervision to ensure that the validation protocol is properly followed and the outcome accurately recorded e Approval that the process or system is valid and fit for purpose is needed at the end of the process and this should be a role for an independent expert i e laboratory QA Manager e All roles and responsibilities should be formally documented in this section Summary of Typically in a transfusion laboratory the following areas will be subject what should be to validation new established critical process equipment facilities validated or systems Sample Blood Component reception booking in Sample transfer and storage Sample handling Particularly robotic dispensing systems Controlled temperature storage of critical reagents and controls Test methods Result reporting and blood component labelling amp tracking Blood Component storage Blood Component Distribution The performance of these process equipment facilities or systems will depend on the quality of critical inputs or components that if they fail to function correctly could adversely affect the quality of samples test results or blood components Criti
24. ection 5 e The need to meet technical quality specifications and regulatory requirements Effective qualification or validation relies on having a good definition of requirements See Section 6 as the acceptance criteria provided in the protocol should be based on meeting these Scheduling This section of the VMP should describe how the validation team undertake performing and recording the validation work and how the validation is signed off and deemed acceptable The typical phases of a validation schedule are e Training in the protocol and new operational techniques This will be required before members of the team are competent to carry out the validation particularly if a new unfamiliar piece of equipment is being used e Performing validation Validation results should be recorded at the time and presented in a validation report See Section 8 3 for comparison with the acceptance criteria in the protocol It is common to summarise the validation method and provide the acceptance criteria in validation scripts and the validation team simply records whether the required outcomes are achieved See examples Appendix 10 e Validation Final Summary Report review and sign off section 9 4 Following validation the validation team should present the Page 4 of 50 validation report for review and sign off The report should at least be reviewed and signed off as an accurate record by the Validation Manager See
25. ening set Sample tube size check Perform sampling No error of probe failures Record tube dimensions 15 with Greiner and Sarstedt tubes representing tube volumes between 4 5ml and 9ml Check password functionality by attempting Edit not available to user access Check with manufacturer 16 step 12 with supervisor and user access level Page 41 of 50 Perform Sample switch check by loading x2 Error or barcode re check Compare with sn 17 samples from step 12 and start run to ensure instrument barcode read Open Machine and reverse sample position 18 19 Validation Completed QA Manager lt File Name and CCR Reference Number gt Page 42 of 50 THIS PAGE TO BE REPLACED WITH YYYY IMPLEMENTATION SIGN OFF FORM FOR IMPLEMENTATION PHASE OF VALIDATIONS Recommendations Comments Validation Team Leader Name 5560s tae Chime Signature 2 55 55 Pa Sess Datei conire ei Oar on RE Recommendations Comments Change Manager N Meisene an autora ateusasies Signature peona in en Dateer Recommendations Comments on behalf of Review Board lt Title of Process Owner gt esssesssecesooescocesoecssccesocesocecooesose Name ea ti ree a tee n aa ae Signature ccccccessceeseseeeeee QA Representative Namee pennan esp Signature 5 ocvoe tne 2 cat ooenaetiuecstecrequsntatenes DALES anena a a l
26. he validation team For large scale changes there may need to be separate validation plans covering each area Performing validation All validations should be performed by staff familiar with the processes being validated The laboratory validations must be performed by a Health Professions Council Registered Biomedical Scientist or above and overseen by an Advanced Biomedical Scientist or above Approving validation Normally all validations will be approved by the Quality Manager Occasionally validations may be approved Department Manager or appropriate Site Coordinator in the absence of the Quality Manager Final validation summary report There should be a document to indicate whether approval for release has been given this should include any conditions on release Final sign off of the validation must be by the Department Manager Quality Manager or appropriate Site Coordinator Summary of the laboratory process equipment facilities or systems to be validated Any changes to the systems or processes in the following areas need to be validated e Sample labelling reception and booking in e Sample storage and transport e Automated Sample handling systems o Insert machines Page 8 of 50 e Controlled temperature storage of critical reagents and controls e Critical Test methods including result reporting o Electronic issue o Crossmatching o Grouping and antibody screening o Phenotyping o DAT testing o Antibody invest
27. igation o Transfusion Reaction investigation o MAJAX procedures o Ante natal Testing Blood component processing labelling amp tracking o Secondary processing systems Plasma thawers Platelet agitators o Labelling procedures o Release procedures e Blood Component cold storage o Receipt procedures o Storage procedures o Monitoring o Alarms e Blood Component Distribution o Blood Track procedures o Traceability procedures 4 Documentation format 4 1 All validation documentation should take the same format this will be 4 2 Validation plan 4 2 1 Approval sheet 4 2 2 Document change control sheet 4 2 3 Purpose and scope 4 2 4 Background References 4 2 5 Definitions and acronyms 4 2 6 System definition and description 4 2 7 System maintenance and support strategy 4 2 8 Validation approach 4 2 9 Implementation strategy 4 2 10 Training requirements related to responsibilities 4 2 11 Appendices 4 3 Validation summary report see template in Appendix 11 4 3 1 Introduction to include e Validation plan details 4 3 2 Validation results 4 3 3 Unexpected results problems 4 3 4 Recommendations Further action 4 3 5 Continuing Validation 4 3 6 References to include e Validation master plan Page 9 of 50 5 1 5 2 7 2 7 3 7 4 e Validation Plan e Change control Planning and scheduling All validations should be planned The validation plan should incorporate any planning and a timescale for
28. ilities of the system including inputting of any additional tests and storage facilities capacity for patient records If the equipment proposed has several linked analysers it must be possible for the other analysers to continue operating if one or more of the analysers are in operable for whatever reason Stored data must be easily retrievable A full audit trail must be available of all tests performed including QC Please state what information is stored and is retrievable A pictorial representation of all tests performed must be stored Please state the format that the audit trail information and pictures will be stored and what capacity of data pictures can be stored 9 15 There should be a facility to operate and monitor the analysers remotely using a handheld Wi Fi device Maintenance 10 1 Routine maintenance must be able to be performed by the BMS staff 10 2 The daily weekly and yearly maintenance procedures must be described 10 3 The quantity frequency and duration of preventative maintenance visits per annum must be stated 10 4 Maintenance contracts available must be described along with the guaranteed response times for callouts 10 5 State the support available at night at weekends and public holidays 10 6 The times during which technical support is available must be stated 10 7 Fully detailed operator manual must be provided in English 10 8 Please state the level of self help available from the manuals
29. implementation The decisions on timescale will be down to the validation team Change control For any proposed change to anything which could affect the quality or reproducibility of test results or components is completed Change control is needed for changes to Starting material e g reagents consumables Procedure method Environment Equipment Changes are assessed by the Quality Manager and any other appropriate officers The result of this assessment can be either Change approved no validation needed Change approved validation required Change not approved References Policies Procedures Forms Add templates Page 10 of 50 Appendix 3 CHANGE CONTROL REQUEST FORM Title of Change Change to new panel cell supplier 2 Reason for Change 2 1 Investigation of a failure to identify a combination of antibodies in a NEQAS exercise suggested that one of the contributory factors in this identification was the poor antigen profile of the panel cells currently used 2 2 Examples of supplier B panel cell antigen profiles were sought and these would have produced unequivocal results and would have aided identification 2 3 The department would like to source its antibody identification panels from supplier B 3 Description of Change 3 1 Change of panel cell supplier from Supplier A to supplier B 3 2 Cells from supplier B will be provided in modified Alsevers solution at 3 In order to use these cells by the c
30. istent with existing instrument 9 Set Configuration settings for Consistent with existing instrument 10 Presence verification OFF BC reading OFF Volumes verification ON Control of expiration ON Validation Completed QA Manager Page 36 of 50 THIS PAGE TO BE REPLACED WITH XXXX IMPLEMENTATION SIGN OFF FORM FOR IMPLEMENTATION PHASE OF VALIDATIONS Recommendations Comments Validation Team Leader Name 6S re ee Signature 5 6 6 5 a Rs Re Date eC Ae ee ee Recommendations Comments Change Manager N Meisene an autora ateusasies Signature peona in en Dateer Recommendations Comments on behalf of Review Board lt Title of Process OWE gt ccsccccsssccsssccsssrccsssccessscesees IN GATING 53 5 6 ol Gach cuenta syne tee n aa ae Signature ccccccessceeseseeeeee QA Representative Namee pennan esp Signature 5 ocvoe tne 2 cat ooenaetiuecstecrequsntatenes DALES anena a a lt File Name and CCR Reference Number gt Page 37 of 50 Validation Title Validation of Automated grouping analyser using xxx software Validation Operational Phase Qualification Change Control Ref No CC 05 133 Hospital Trust Change Manager Validation Team lt 1 gt Manager lt 2 gt Manager PE S QA Manager Manager Name Validation Start Date Validation Finish Date
31. l Description of tests required May be detailed in IQ OQ PQ Validation report pro formas The validation protocol must be cross referenced to the URS Documentation Documentation This section will define the quality system requirements for logging the validation as to whether the validation is part of a wider change control process or if the validation plan is stand alone This section must define which documentation is required for final sign off and where the validation documentation is stored and archived Page 33 of 50 Example of a Qualification Proformas Appendix 10 Validation Title Validation of automated grouping analyser using Validation Installation Phase Qualification Change Control Ref No Hosp Trust Change Manager Validation Team lt 1 gt Manager lt 2 gt Manager D oars QA Manager Manager Name Validation Start Date Validation Finish Date Short description of equipment or process being validated Automated grouping analyser using xxx operating software on Windows 2003 platform Verification of software version Automated grouping analyser using xxx operating software on Windows 2003 platform Verification of electrical mechanical safety Automated grouping analyser using xxx operating software on Windows 2003 platform Verification and confirmation of critical settings Automated grouping analyser using xxx opera
32. ls of QC handling programmes on the equipment must be given The onboard storage capacity of QC data must be given The QC batch numbers targets and results should be available for storage suitable for accreditation purposes Details of onboard validation approval and checking of patient results must be given Automatic validation of results within user defined limits should be available Page 20 of 50 9 Data Processing and Storage 10 9 1 9 2 9 3 9 4 9 5 9 6 9 7 9 8 9 9 9 10 9 13 9 14 The equipment must be capable of interfacing with the laboratory computer system i e insert system The interface must be bi directional The Tenderer should provide details of when the proposed interface will be operational and what functionality will be available for go live Where necessary it must be possible to use the equipment in a stand alone mode Automatic reconnection to the host computer should be available and transmission of results from stand alone running State the capability of the equipment to continue to process samples and generate reports during periods of unavailability of the computer host system and the mechanism for doing this The requirement for a data manager either supplied as original equipment or as an adjunct to the equipment must be stated The precise specification and functionality of such a data manager must be clearly stated Provide details of the data handling and management capab
33. ncorrect tubing out of cells can be mitigated by the production of a robust standard operating procedure which ensures that cells are prepared and labelled in the same way each time Failure to provide an inadequate antigen profile this is mitigated by ensuring that the cells meet the Red Book Guidelines Deterioration of red cell antigens on storage This can be mitigated by validation of the activity of a prepared panel from date of preparation as soon after receipt as possible until its expiry Activity of Panel cells The panel cells should be quality controlled after preparation to demonstrated that they are working correctly Validation requirements A validation plan must be prepared and validation performed to demonstrate that supplier B s panel cells do not deteriorate when prepared in diluent and subsequently stored The validation should involve the use of CE marked weak antisera anti D anti c and anti Fy Page 13 of 50 N Documentation The following documentation will be needed A validation plan protocol Validation results sheets A validation report A validation sign off report NNNNN ea yoe et Rw 7 2 The following documents will need checking updating 7 2 1 BBSOP Preparation and QC of panel cells BBSOP0174 this is the SOP the validation will be performed against 8 References Change Approval YESANO delete as appropriate Name Name Name Position Position Position Dat
34. nd equipment is critical to maintaining the valid state In particular servicing calibration of instrumentation and re qualification should be planned and managed within the laboratory quality system These arrangements may be described in this section or reference made to the appropriate procedures Automated test systems may be subject to proficiency or EQA Schemes and these should be mentioned here Page 6 of 50 Appendix 2 Example of a VMP currently in use at an NHS Hospital Department of Blood Transfusion Code enter details Page Insert numbers Title Validation Master Plan VMP Area of application Blood Transfusion Hospital A Blood Transfusion Hospital B Blood Transfusion Hospital C Index code Implementation date This copy issued to Related CPA standard key words This document is under the department document control system To comply with CPA standard A8 the document control system records the reason for change current revision status of documents dates of review document owner and approver and locations of printed copies It is forbidden to photocopy from authorised printed copies which have been issued to locations as recorded in the software Authorised printed copies can be identified by the authorisation signature and stamp present in the space below SIGNATURE LIST OF CONTENTS Section Page N Validation Policy Organisa
35. on Qualifying with real samples stressing with low frequency weak antigens antibodies Sensitivity tests False positives false negatives Consistency Repeatability tested in duplicate with current system e g 2 weeks or 250 samples whichever occurs first staff Quality Manager Page 31 of 50 Appendix 9 Example of Validation Protocol NAME OF LABORATORY INSTITUTION DIRECTORATE FUNCTION VALIDATION PROTOCOL FOR Enter title of validation Change Control Ref No Document approved by NAMES sicsck esate ett E A A Gb E T AA Quality Representative Date Page 32 of 50 1 Introduction Introduction This section must define such details as why the validation is required who are the relevant stakeholders of the change where this change will operate and in what timescale the changes will become effective Aims e Aims This section will define the outcome of the validation for example ensure that the particular piece of equipment is fit for purpose or that a particular process gives the required output or functionality Applicable Documents Applicable Documents The scope of documentation will be defined and will comprise of at least a simple listing of the validation documents used i e Controlled document references any supporting manufacturers documentation instruction manuals e mails SOP s used for the validation e Change Control e Validation Testing Protoco
36. on functionality by replicating a clotted sample failure in a minimum of x1 sample Clot detection error message Track and verify sequence See 309cval doc Page 40 of 50 Check Barcode interpretation using current Consistent with instrument Compare printouts from 8 RCI labells and x2 Donation testing tubes ff o and Download interface file host pIn Replicate probe malfunction event by Barcodes re read Check with manufacturer 9 processing an empty tube and ensuring the See 309cval doc reset probe re reads all sample tube barcodes before resume Perform test cycle with ABO reverse cell set Error before proceeding Check reagent verification in 10 swapped download file Perform test cycle with 2 cell screening set Error before proceeding Check reagent verification in 11 reversed download file Test result edit on Group A to A edit Data integrity audit must feature edit Check printouts 12 using ABD ABD and ABDDAB test cards event Test Reagent Error Detection by testing x2 Error before proceeding Check reagent verification in 13 group A samples programmed for download file ABD ABD run Replace ABD ABD cards with ABDDAB cards prior to startup Perform Antibody sensitivity check by Greater than 0 01 IU ml sensitivity Compare with 14 testing RhD control plasma in titration using instrument LISSIAT cards and 2 cell scre
37. quired for processing of the current workload as stated The requirement must address but not be limited to e Delivery Installation Commissioning Consumables Reagents Quality Control Maintenance of the equipment Bi directional interface to the laboratory computer system Enter system Training Disposal of equipment at the end of the life 3 The Tenderer must detail how they will comply with the requirement 3 1 It is a requirement that the current laboratory output must be maintained during installation acceptance testing and qualification of the automation 3 2 Proposals must be able to show from current users a high level of satisfaction regarding the automation product and technical support and customer care 3 3 The supplier and their automated users must have a proven track record with regards to NEQAS returns 3 4 The supplier must have adequate support facilities 4 Analyser Specification 4 1 General properties 4 1 1 Proposals must specify the proposed equipment hardware uninterruptible power supply etc 4 1 2 All equipment proposed must be automated and capable of meeting the volumes provide in this document with the ability to increase by at least xx 4 1 3 Due to the nature of the work the User requires equipment to be operable 24 hours a day seven days a week Currently the User has four analysers installed to manage any inoperable time and must state how they will ensure equipment will be operable 24 7 4 1 4
38. t File Name and CCR Reference Number gt Page 43 of 50 Validation Title Validation of insert equipment using v3 11 software Validation Process Phase Qualification Change Control Ref No Hospital Trust Change Manager Validation Team lt 1 gt Manager lt 2 gt Manager lt a QA Manager Manager Name Validation Start Date 13 4 05 Validation Finish Date 22 4 05 Short description of equipment or process being validated Testing of patient samples and comparison of results obtained using Cambridge Insert equipment using v3 11 operating software on Windows 2000 platform compared with results obtained with existing Cambridge Insert equipment using previous v3 07 or v3 09 operating software on Windows 95 or 2000 platform Page 44 of 50 Details of equipment used in the validation Insert equipment using v3 11 operating software on Windows 2000 platform Insert equipment using v3 07 v3 09 operating software on Windows 95 2000 platform APEX data interface and host system ABD ABD ref 5005 grouping cards ABDDAB ref 5009 grouping cards Rh K ref 5011 phenotyping cards LISS IAT ref JAT cards Details of testing levels methods SOP s used in validation 12 patient samples tested on v3 11 new instrument using ABDDAB cards and results compared against v3 07 v3 09 existing instrument 24 p
39. tem functions Data handling requirements System interfaces Environment e Functions required including information on the process or existing systems e g perform red cell group and antibody screen e Calculations including all critical algorithms interpret test results to correctly identify a blood group e Modes of operation e g start up shutdown test backup e Quantitative and unambiguous performance and timing requirements e g turn around times for routine or urgent samples QC etc e Back up in case of system failure e g engineer response time e Safety e Security e Maintenance e g planned preventative calibration etc e Definition of data including critical parameters valid data ranges and limits e Capacity requirements e g disk storage capacity archive capacity etc e Access speed requirements network speed response times e Data security and integrity e Define staff groups in terms of roles or functions e g Biomedical Scientist Biomedical Support Worker porter e Interface with other systems e g LIMS e Interface with equipment e g blood issue fridges blood group analysers e Physical layout of the working environment e Physical conditions e g dusty sterile air conditioned Constraints e Timescales and milestones e g speed of delivery commissioning time etc e Compatibility e g will the software work on your current server IT system e Availability
40. ting software on Windows 2003 platform Verification of statutory certification Details of equipment used in the validation Automated grouping analyser using xxx operating software on Windows 2003 platform Page 34 of 50 Details of testing levels methods SOP s used in validation Check certification Check critical settings Check manufacturer supplied support documentation Validation Title Validation of Automated grouping analyser using xxx software No Description URS FDS Acceptance Criteria Pass Fail Ref Re test Check instrument CE certification Record on receipt 1 Check instrument Identity Record on receipt 2 Check manufacturer support documentation Record on receipt 3 Check instrument for electrical safety Sign off by Facilities check 4 Check and record Windows operating Windows 2003 service pack 4 5 system version and Automated grouping Operating software xxx analyser operating system version Check and record interface software Advised by manufacturer 6 versions Page 35 of 50 Establish and check password security Consistent with existing instrument a settings Check installation of critical settings Consistent with existing instrument 8 software and establish settings Configuration of Dispense verification ON Cons
41. tional structure of validation activities Summary of the facilities systems equipment and processes to be validated Documentation format Planning and scheduling Change control References oS om p NO Oh ook A Page 7 of 50 1 Validation Policy 1 1 2 2 1 2 3 2 3 1 2 3 2 2 4 2 4 1 2 4 2 3 1 1 The validation policy of the Insert name Hospitals blood Transfusion Department is set out in the policy document insert number link This policy applies when a change is proposed to a starting material product component process equipment process environment or site method of production or testing or any other change that may affect product quality or result quality or reproducibility of the process Organisational structure of validation activities Planning validation All validation planning is the responsibility of the Blood Transfusion Quality Manager who liaises with the appropriate Site Coordinator or his designated deputy to ensure that appropriate validation takes place The validation planning should also involve experts in the area being validated e Major IT validation should involve the IT coordinator e Validation in Ante Natal Testing should involve the Ante Natal coordinator For each validation there will be a validation team comprising e The Quality Manager e A Site Coordinator or designated deputy e Other experts as appropriate The quality Manager will be responsible for assembling t
42. tle Validation of Automated grouping analyser using v3 11 software No Description URS FDS Acceptance Criteria Pass Fail Ref Re test Test samples representing 8 commonly Consistent with instrument Compare printouts from encountered ABO D combinations le and Download interface file A B 0 AB A B O AB with each host pln test card Test samples representing a range of RhD Consistent with instrument Compare printouts from expression X10 Including x CatVI With fe and Download each test card interface file host pln Test x2 samples with 50 dual population Consistent with instrument Dp flag recorded for each expression if forward typing tests Ie 50 No Download test well Compare printouts O and 50 AB with each test card from and Download interface file host pln Test group A B and O samples x2 off Consistent with instrument Compare printouts from where plasma is replaced with inert material No Download Jue and Download with each test card interface file host pIn Test x2 samples simulating a DAT case Consistent with instrument Compare printouts from where the control well result is POSITIVE No Download J a and Download with each test card interface file host pIn Check Sample test volume verification functionality by replicating a sample aspiration failure in a minimum of x1 well Check with manufacturer Check Sample clot detecti
43. uce risk 4 2 Antibody Identification has a number of potential risks associated with it 4 2 1 Failure to detect clinically significant antibody can result from e An inadequately prepared panel o Incorrect cell suspensions o Incorrect tubing out of panel cells o Failure to add patient s plasma e Deterioration of red cell antigens through storage e Failure to provide all relevant clinically significant antigens on the profile particularly those with homozygous expression 4 2 2 Failure to identify antibody can result from e Deterioration of red cell antigens through storage e Failure to provide all relevant clinically significant antigens on the profile particularly those with homozygous expression e Antigen profiles on panels providing insufficient antigen negative cells making distinguishing of antibody mixtures particularly difficult Page 12 of 50 4 2 3 5 1 5 2 5 3 5 4 5 5 6 1 All of the above risks can cause potential serious problems to patients including e Failure to provide compatible blood e Failure to provide compatible blood in a timely fashion caused by additional testing or need to refer samples where the panels cannot provide antibody identification REEE Mitigation of risks Incorrect Cell Suspensions can be mitigated by the production of a robust standard operating procedure which ensures that the cell suspensions are prepared by the same method as indicated on the diluent product insert I
44. up DAT Rh phenotype 7 Reagent Cell Requirements 7 1 7 2 The red cells provided for antibody screening must always conform to the BCSH published guidelines regarding required antigen phenotypes and homozygozity Please state whether the proposed solution can provide a Cw and a Kpa positive cell on your standard screening cells If so please state the number of screening cells used to provide this guaranteed expression Page 19 of 50 7 3 7 4 7 5 7 6 7 7 7 8 7 9 7 10 Please state the number of cells in the primary and secondary antibody identification panel and the medium the cells are suspended in Please state whether an antibody identification software package is provided with each panel Please provide specifics of the package The equipment must have level detection and be able to calculate if there are any shortfalls in either regents or consumables to complete a batch of work and alert the Biomedical Scientist BMS immediately The alert must be both audible and visual No reagent or cell preparation must be required All reagents or cells must have load and run facility All reagents containing red cells must be agitated by such methods as required to prevent settling out All reagents must be bar coded The equipment must be capable of reading bar coded information from reagent packs 7 11 As a minimum the following must be re ordered 7 12 7 11 1 batch number 7 11 2 expiry date 7
45. urrent technique the cells will need to be washed and prepared to 0 8 in supplier A s diluent 3 3 The diluent product insert indicates a method for preparing cells to 0 8 The insert indicates that fresh cells from patient s or donor blood prepared in this manner will remain stable for 7 days The insert indicated that commercial panel cells prepared in this manner are only guaranteed to be stable for 24 hours Cells used in this manner do not need any validation 3 4 Daily preparation and use is not practical within the department The department would like to demonstrate that supplier B s cells can be prepared using the method on the diluent product insert and remain suitable for use for 7 days or longer Page 11 of 50 4 Impact Quality Risk Assessment 4 1 Risk matrix used in assessment Risk score Impact x Likelihood Impact Description Likelihood Description Risk Score Risk Level Treatment Timeframe 1 Insignificant 5 Almost Certain Score Risk Rating 2 Low 4 Likely These risks are considered acceptable no action over and above existing procedures 3 Moderate 3 Possible Monitoring of risks with view to effort being made to reduce these within a 12 month period 4 Severe 2 Unlikely Management consideration of risks and reduction of these within 6 month period 5 Catastrophic 1 Rare Senior management attention immediately with view to action being taken to red
46. ware Connectivity with other IT systems Password security check Hospital Transfusion Data sharing Sample barcode interpretations staff Communication between systems Quality Manager Barcode reading sample identification Supplier Acceptance testing IT personnel Alarm testing Reagents Controls positive and negative Examples of all ABO and D Hospital Transfusion Red book requirements groups Weak D and D Samples with negative antibody screen Samples with positive antibody screens to include weakly reacting antibodies Specificity to be confirmed using samples containing anti D c e K Fya Jka and S Sensitivity check using antibody titration staff Quality Manager Page 30 of 50 Performance Qualification PQ Equipment Parallel running with current system by Hospital Transfusion all methods Reliability staff Maximum specification tested Quality Manager Meaningful run time Operation under worst case conditions Tests under various load conditions The level and areas to be qualified should be determined from a risk assessment Software Right interpretation Record all false negatives and Hospital Transfusion Back up false positives staff Interfaces Check download of all results Quality Manager Consistency IT staff Repeatability Failures Data archiving systems Reagents Test all reagents Predetermined number of samples Hospital Transfusi
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