Best Practices For V&V - Cdn.ymaws

CASSS, CMC Strategy ForumSteven W. Badelt, PhDManaging PartnerSuttons Creek, Inc. 2014 Suttons Creek, IncSolving the problem of Complexity.SUTTONSCREEK.COMV&V Best Practices

2014 Suttons Creek, IncSolving the problem of Complexity.SUTTONSCREEK.COM

INCOSE System EngineeringHandbookSolving the problem of Complexity.SUTTONSCREEK.COM21CFR820.30 &FDA Guidance 2014 Suttons Creek, Inc

Solving the problem of Complexity.SUTTONSCREEK.COMCombination Product System 2014 Suttons Creek, Inc

Setup your document tree during the planning designphase Review deliverables with regulatory before proceeding The process that produces a document is what matters,but without the document, what really happened? Assurance cases (i.e. for infusion pumps) are anexample of how engineering failed to deliver sufficientartifacts and follow good engineering practice.SystemsEngineering 2014 Suttons Creek, IncCommunicationRegulatoryAffairsSolving the problem of Complexity.SUTTONSCREEK.COM“Good” Engineering andRegulatory go hand-in-hand

VendorSpecifications 2014 Suttons Creek, IncUnstructuredBrainstormingRequirementsSolving the problem of Complexity.SUTTONSCREEK.COMMany V&V Issues start withRequirements Issues

820.3(z) Validation means confirmation by examination andprovision of objective evidence that the particular requirementsfor a specific intended use can be consistently fulfilled. (1) Process Validation means establishing by objective evidencethat a process consistently produces a result or product meeting itspredetermined specifications. (2) Design Validation means establishing by objective evidencethat device specifications conform with user needs and intendeduse(s). 820.3(aa) Verification means confirmation by examination andprovision of objective evidence that specified requirementshave been fulfilled. Source: Design Control Guidance for Medical DeviceManufacturers - FDA 21 CFR 820.30 and Sub-clause 4.4 ofISO 9001 2014 Suttons Creek, IncSolving the problem of Complexity.SUTTONSCREEK.COMVerification vs Validation

Solving the problem of Complexity.SUTTONSCREEK.COMVerification vs Validation 2014 Suttons Creek, Inc

Solving the problem of Complexity.SUTTONSCREEK.COMV-model in Lifecycle Context 2014 Suttons Creek, IncR. Beasly, Rolls-Royce Aero

Each manufacturer shall establish and maintainprocedures for verifying the device design. Design verification shall confirm that the design outputmeets the design input requirements. The result of the design verification, includingidentification of the design, method(s), the date, and theindividual(s) performing the verification, shall bedocumented in the DHF. 2014 Suttons Creek, IncSolving the problem of Complexity.SUTTONSCREEK.COM820.30(f) – Design Verification

Solving the problem of Complexity.SUTTONSCREEK.COMSystem Level 2014 Suttons Creek, Inc

Typical document tree: Plan Protocols Reports Summary Suitable methods: Inspection Demonstration Test Analysis Keep up with trace matrices in real-time with theproject phase 2014 Suttons Creek, IncSolving the problem of Complexity.SUTTONSCREEK.COMVerification

Content Acceptance criteria Sample Size Materials Traceability Pre and post-conditions Procedure Requirement tags (GENSYS-0034) Standards references (ISO11608-1 5.4g) Best Practices and Challenges: Reliability Create methods and templates – Stop repeating work Integration testing Placebo versus Drug Product Testing with vendors and materials limitations 2014 Suttons Creek, IncSolving the problem of Complexity.SUTTONSCREEK.COMVerification Protocols

Data analysis plans Content Requirement tags (GENSYS-0034)Standards references (ISO11608-1 5.4g)Pass/FailDeviations and DiscrepanciesDo not disposition Create templates RA Engineering - Avoid re-writing forfiling 2014 Suttons Creek, IncSolving the problem of Complexity.SUTTONSCREEK.COMVerification Reports

Injection TimeDosage AccuracyInjection DepthAtmospheric pressuresTemperature TestingDrop testingTransportation testing – including atmospheric conditionsAccelerated AgingReal-time AgingStandards-based testing 2014 Suttons Creek, IncSolving the problem of Complexity.SUTTONSCREEK.COMCommon VerificationEvidence

Solving the problem of Complexity.SUTTONSCREEK.COMDriving Standards Through the ComboProduct Process 2014 Suttons Creek, IncBadelt, Atherton, 2014

Standards Driven Verification Sets requirements Sets test methods Define test limits – k values 2014 Suttons Creek, IncSolving the problem of Complexity.SUTTONSCREEK.COM ISO11608

Pros and Cons: In-house versus Certified Test Labs Within the system requirements - List of what applies: ISO 11608-1ISO 11608-5ISO 23908ASTM D4169ISO 10993-1 - Evaluation and Testing ISO 10993-5 - Cytotoxicity ISO 10993-10 – Sensitivity and Irritation IEC60601-1 – Electromedical devices Caveat – Follow standards, but take a risk-driven approach 2014 Suttons Creek, IncSolving the problem of Complexity.SUTTONSCREEK.COMStandards Driven Verification

Each manufacturer shall establish and maintain procedures forvalidating the device design. Design validation shall be performed under defined operatingconditions on initial production units, lots, or batches, of theirequivalents. Design validation shall ensure that devices conform to defineduser needs and intended uses and shall include testing ofproduction units under actual or simulated use conditions. Design validation shall include software validation and riskanalysis, where appropriate. The results of the design validation, including identification ofthe design, method(s), the date, and the individuals9s)performing the validation, shall be documented in the DHF. 2014 Suttons Creek, IncSolving the problem of Complexity.SUTTONSCREEK.COM820.30(g) – Design Validation

Solving the problem of Complexity.SUTTONSCREEK.COMUser Needs (Outcomes) Level 2014 Suttons Creek, Inc

Clinical Trials Human factors analysis Be careful adding onto your summative 2014 Suttons Creek, IncSolving the problem of Complexity.SUTTONSCREEK.COMSources of ValidationEvidence

PlansRequirementsRisk Management FileSpecificationsVerification ReportsVerification ProtocolsValidation ProtocolsValidation ReportsUsability Engineering Summary FileChange Control Records 2014 Suttons Creek, IncSolving the problem of Complexity.SUTTONSCREEK.COMDHF

Common problems in the verification “story” come frompoor requirements. Assuming a vendor specification as your requirementcan lead to problems Appropriate identification of the correct requirementallows for assessment of the design change against thatrequirement 2014 Suttons Creek, IncSolving the problem of Complexity.SUTTONSCREEK.COMPost-Approval Changes

ASTM D4169 ISO 10993-1 - Evaluation and Testing ISO 10993-5 - Cytotoxicity ISO 10993-10 – Sensitivity and Irritation IEC60601-1 – Electromedical devices C