process validation for bme 512

BME 512BME 512Process ValidationProcess Validation

Copyright GCI, Inc. 2006

Process Validation Process Validation RoadmapRoadmap

MVP

OQChallenge

Process PQ

MVR

Risk

IQ

OQ Limit

Product PQ


Process Validation StepsProcess Validation Steps

1. Determine Risk from FMEA/FTA2. Create a Master Validation Plan3. Perform Installation Qualification4. Identify Acceptable Defect Rate5. Select Reduced Sampling Plan for OQ6. Perform Operational Qualification7. Select Optimal Sampling Plan for PQ8. Execute Performance Qualifications9. Assure Appropriateness of Sampling

Plan 10. Generate a Master Validation Report


Step 1: Determine RiskStep 1: Determine Risk(from process FMEA)(from process FMEA)

RPN Validation Action

1 - 5 Verification

6 - 10 Moderate LTPD

11 - 15 Minimal LTPD

16 Needs Improvement


Step 2: MVPStep 2: MVP

Process Rationale

IQ OQProcess PQ

Product PQ Software

Weld Required Required Required Required RequiredAll elements will be performed

Bond Required Required Required RequiredNot Required

Software validation not required because there is no software associated with this bonding process

Seal Required Complete Required Required Required

OQ from similar impulse sealer will be leveraged, see report # 12345 rev B

Requirement


Step 3: Perform IQStep 3: Perform IQ

Verify Proper Installation

Verify Proper Operation

Verify Equipment Controls


Equipment IssuesEquipment Issues

Mobile and Non-Mobile Equipment

Multiple Machines


IQ Validation ToolsIQ Validation Tools

Poka-yokeVerification & Challenge Factory Acceptance Testing

Control PlanProcess FMEA


IQ DocumentationIQ Documentation

IQ Protocol IQ ChecklistIQ ReportControl PlanFunctional SpecsUser Specs


Step 4: Determine Acceptable Step 4: Determine Acceptable Defect RateDefect Rate

Based on clinical risk

FDA mandates

SOP documentation


Step 5: Select a Reduced Step 5: Select a Reduced Sampling Plan for OQSampling Plan for OQ

Why a reduced plan is acceptable at this point

What is a reasonable sample size?

SOP documentation


Step 6: Perform OQStep 6: Perform OQ

Characterize the process

Establish controls on inputs to ensure quality of output

Alert and action limits

Test the limits

Ensure control plan is effective


Characterize the ProcessCharacterize the Process

Test Method Validation Use experimental design to identify

key process inputs Determine relationships among

inputs (interactions) Understand relationship between

inputs and outputs Establish controls to ensure stability

and capability


Challenge vs. Limit TestingChallenge vs. Limit Testing

Challenge Testing results in product that may not meet acceptance criteria

Limit Testing results in product that meets acceptance criteria, but just barely


Spotlight on OQ:Spotlight on OQ:Taguchi Designed ExperimentTaguchi Designed Experiment Factor Level Response Trial Combined Effect Interaction Confounding


OQ: Taguchi TechniqueOQ: Taguchi Technique

State the problem State desired results Determine quality characteristics Determine measurement methods Select factors Identify noise and control factors Select orthogonal array


Taguchi Technique, cont’d.Taguchi Technique, cont’d.

Select levels for factors Select interactions Design the matrix (assign F/L to

columns) Conduct trials Analyze and interpret results Confirm experiment


Limit Testing In OQLimit Testing In OQ

Using challenge test results, set limits for acceptable product

Poke-yokeManufacturing proceduresOperator trainingCpkReduced sample size is OK


Regulatory Regulatory ExpectationsExpectations

21 CFR Part 820.75(b) : Each manufacturer shall establish and maintain procedures for monitoring and control of process parameters for validated processes to ensure that the specified requirements continue to be met.


FDA Warning LetterFDA Warning Letter

“You have not demonstrated that the process parameters used, under worst case conditions, assure all the products that you manufacture meet specifications and are appropriate for their intended use…”


Contents of an OQ ProtocolContents of an OQ Protocol

Purpose/Scope

Reference Documents

Process Inputs

Process Outputs & Specifications

Process Parameters for Each Run

Operator Training Requirements

Procedure for Conducting Validation


Step 7: Select an Optimal Step 7: Select an Optimal Sampling Plan for PQSampling Plan for PQ

Balancing AQL and LTPD

What is a reasonable sample size?

SOP documentation


Step 8: Process and Product Step 8: Process and Product Performance QualificationsPerformance Qualifications

Process PQ (Performance Qualification) Demonstrate that product meets acceptance criteria Determine Ppk / Pp Minimum of three lots Nominal process settings Performance Levels tied to Process FMEA

Product PQ (Performance Qualification) Demonstrate that entire manufacturing process

produces product that meets product specification Minimum of three lots Nominal process settings Performance Levels tied to Design FMEA


Stability and Stability and CapabilityCapability

Stable: Consistently dependable; resistant to change of position or condition; not easily moved or disturbed (American Heritage Dictionary)

Capable: Having capacity or ability; efficient and able; implies that output of process meets requirements (American Heritage Dictionary)


What are Cpk and What are Cpk and Ppk?Ppk?

Cpk: capability of the process at a point in time (present)

Ppk: capability of the process over time (future)


How Many Lots?How Many Lots?

Should represent multiple:SetupsRaw materialsEquipmentShiftsOperatorsTooling

Make samples representative of future production


Process PQ ProtocolProcess PQ Protocol

Purpose/Scope

Reference Documents

Process Inputs

Process Outputs & Specifications

Process Parameters For Each Run

Operator Training Requirements

Procedure for Conducting Validation


Product PQ ProtocolProduct PQ Protocol

Purpose/Scope Reference Documents Models/Units Product Characteristics Manufacturing Variability Test Method Sample Size Acceptance Criteria



“The process validation report does not document that the welding process itself results in a consistent, predictable weld based upon specific operational process parameters. The process validation protocol is inadequate in that it does not specify:

all data to be collected; test procedures to be used to measure

predetermined success criteria; or statistical rationale for the number of devices

per lot or number of lots…”


PQ ReportPQ Report Cover Page Reference Documents Deviations to Protocol Results

Data summary; Non-conformances & Investigation Results; Errors & how addressed

Additional Process Controls/Monitoring Conclusions



Records documenting the procedure show inconsistencies from the protocol. The protocol stated that the validation would make use of three lots of finished devices. However, the summary page indicates that four lots were used to complete testing. Documentation is inadequate to indicate which lots were used for validation and testing or a rationale for why an additional lot was tested.


Step 9: Verify Step 9: Verify Appropriateness of Sampling Appropriateness of Sampling

PlanPlanAttribute vs. Variable

Distribution Fitting

Distribution-Free


Step 10: Generate a Master Step 10: Generate a Master Validation ReportValidation Report

Cover Page

Deviations to Plan

Conclusions

MVR Matrix


MVR MatrixMVR Matrix

Process Comments

IQ OQ Process PQProduct PQ Software

Weld 2345 rev A 1234 rev A 3456 rev A 4567 rev A S-789 n/a

Bond 5678 rev A 6789 rev A 789 rev A 8910 rev ANot Required

Software validation not required because there is no software associated with this bonding process

Seal 9101 rev B XYZ report 1011 rev B 1112 rev A 1213 rev A

OQ from similar impulse sealer was leveraged, see report # XYZ

Validations Completed

process validation for bme 512

Documents

effectivecopyright gci

capabilitycopyright

barelycopyright gci

mvpcopyright gci

needs improvementcopyright

reduced plan

reduced sampling plan

limitsensure control