site validation master plan
TRANSCRIPT
SITE VALIDATION MASTER PLAN
RELEASING ITS FULL POTENTIAL
ASQ Definitions- Assurance: The act of giving confidence, the state of being certain or the act of making certain.
Quality assurance: The planned and systematic activities implemented in a quality system so that quality requirements for a product or service will be fulfilled.
FDA Definition-FDA Definition-
ValidationValidation: Establishing documented evidence, : Establishing documented evidence, which provides a high degree of assurance that a which provides a high degree of assurance that a specific process will consistently produce a product specific process will consistently produce a product meeting its predetermined specifications.meeting its predetermined specifications.
Validation Master Validation Master PlanPlan
The company’s overall policy, The company’s overall policy, intentions and approach to intentions and approach to validation, including the validation, including the validation of production validation of production processes, cleaning methods, processes, cleaning methods, analytical test methods and analytical test methods and computerized systems, computerized systems, should be established in the should be established in the Validation Master Plan.Validation Master Plan.
Site Validation Master Site Validation Master Plan versus:Plan versus:
Project Master PlanProject Master Plan Cleaning Validation Master Cleaning Validation Master
PlanPlan Process Validation Master Process Validation Master
PlanPlan Computer System Validation Computer System Validation
Master PlanMaster Plan
What PurposeWhat Purpose Where Scope Where Scope Why Policy & RationaleWhy Policy & Rationale Who ResponsibilitiesWho Responsibilities How Doc. Content & How Doc. Content &
FormatFormat When Prioritization & When Prioritization &
Sched.Sched.
Site Validation Master Site Validation Master PlanPlan
Site Validation Master Site Validation Master Plan- ScopePlan- Scope
FacilitiesFacilities Lab EquipmentLab Equipment Laboratory Laboratory
MethodsMethods Water & SteamWater & Steam HVACHVAC Gas SystemsGas Systems
Mfg. EquipmentMfg. Equipment ProcessProcess CleaningCleaning Computer Computer
SystemsSystems
Equipment Equipment QualificationQualification GeneralGeneral Pre-Qualification ActivitiesPre-Qualification Activities Qualification ActivitiesQualification Activities Protocol PreparationProtocol Preparation Installation, Operational & Installation, Operational &
Performance QualificationPerformance Qualification Acceptance CriteriaAcceptance Criteria Summary ReportSummary Report Re-qualificationRe-qualification
ExclusionsExclusions
Employs commonly used technology. Is easily installed. Is routinely (minimum daily) checked for
accuracy prior to use. Does not require specialized operating
skills and expertise.
Test instrumentation and simple equipment (pH meters, viscometers, scales) will be qualified via a procedure instead of a protocol. The procedure approach is applicable to equipment that:
Re-qualificationRe-qualification
The definition of what constitutes a change The definition of what constitutes a change to lab equipment that may require re-to lab equipment that may require re-qualification includes the following:qualification includes the following:
•Failure of test results •Relocation- equipment unplugged and moved within a room, between rooms, between buildings•Major component changes or modifications, including software changes
Planning Step # 1: Planning Step # 1: Inventory Existing WorkInventory Existing Work
ID Equipment Target Qualification
Completion Date
Qualification Status
1-01 Water HPLC 1Q-2008 --
1-02 Shimadzu Spectrophotometer
3Q-2008 --
L 19 Temp. Recorder N/A Calibrated
L 19 Viscosimeter Completed Qualified
Equipment List & Schedule:
Product Contact ListProduct Contact List
Product Description: Alpha A Suspension.doc
IDEquip.
DescriptionCapacity Location
MIXING TANKS
MT-1 Lee Tank 100 L Rm. 21
MT-2 Lee Tank 400 L Rm. 21
PORTABLE MIXERS
PM-1 Hobart NA Portable
FDA 483 ObservationsFDA 483 Observations
Not all manufacturing ISO Class Not all manufacturing ISO Class [removed] rooms, Biological [removed] rooms, Biological Safety Cabinets and Safety Cabinets and manufacturing equipment have manufacturing equipment have documentation of cleaning documentation of cleaning validations.validations.
No validation studies were No validation studies were conducted to support cleaning of conducted to support cleaning of the [removed].the [removed].
Product/Equipment Product/Equipment MatrixMatrixEquip. ID
3001 3002 3003 3004 3005
Name Tank-1 Tank-2 Pump-1 Pump-2 Mixer-1
Prod. Name
Prod. Code
Batch Size
Apha 1 DMEO 290L X X
Apha 2 DFEE 400L X X X X
Beta R YHHJ 350L X X
Beta S YHKP 700L X X X
Planning Step # 2: Planning Step # 2: PrioritizationPrioritization
Product Name
CodeMfg.
on Site
Pkg. on
Site
Lab. Tests
Targeted Completion
Date
Apha 1 DDGH X 1,2 R/S 2Q 2008
Apha 2 GANN X 1,2 R/S 3Q 2008
Beta R KKLV X 1,2 R/S 1Q 2009
Beta S KKLC X 1,2 R/S 4Q 2009
Priority 1 Products:
Planning Steps 3 & 4:Planning Steps 3 & 4:Establish a Timeline & Establish a Timeline & Estimate ResourcesEstimate Resources
Category Totals No. Req. Val.
(A)Pers. Req.
(B)Time Req. (Yrs.)
(A) X (B) =Total Time Required
(Man-years)
Lab Equip. 111 89 2 2.5 5
Methods 124 60 1 9.0 9.0
Mfg. & Pkg. Equip.
195 178 4 3.5 14.0
Process 65 65 2.25 8.0 18.0
Cleaning 65 65 1 7.25 7.25
Sub-Totals: 836 630 -- 9 77.5
SITE VALIDATION MASTER PLANSITE VALIDATION MASTER PLAN
2009
.
Gas6 mo.
MENSZAK
2Q 2008
2010 201520122011
HVAC & LFUs
2.0 yrs.
Lab Equip. Qual.
1.5 yrs.
All Other Process Validation 5.0 yrs.
Cleaning Methods yr.
All Other Equipment 2.0 yrs.
20172013 2014 2016
LOC Transfer Project
All Other Validation
All Other Cleaning Validation4.25 yrs.
LOC Equipment 1.5 yrs.
LOC Process Validation
3.0 yrs.
Total Process Validation
8.0 yrs.
LOC Cleaning Validation3.75 yrs.
Total Cleaning Validation
8.0 yrs.
LOC Methods Validation3.0 yrs.
Total Methods Validation
9.0 yrs.
All Other Methods6.0 yrs.
Total Equipment Qualification
3.5 yrs.
Site Validation Master Site Validation Master Plan ValuePlan Value
The Site Validation Master The Site Validation Master Plan provides clarity, and it Plan provides clarity, and it enables the validation enables the validation manager to communicate the manager to communicate the workload, capacity constraints workload, capacity constraints and justify the need for and justify the need for resources. It facilitates resources. It facilitates effective management and the effective management and the best performance.best performance.
Planning Step # 6: Planning Step # 6: Repeat Steps 1-5 Repeat Steps 1-5
The firm has a protocol for the qualification of solutions used in Manufacturing. This protocol has been effective since 21 Dec 2004. To date only 2 of the approximately 50 materials used in either the manufacture of products or for cleaning/disinfection have been qualified.
FDA 483 Observation:
Six Steps to Planning:Six Steps to Planning:
1. Inventory all existing and upcoming work.
2. Prioritize.3. Establish a timeline.4. Estimate the resources needed.5. Communicate to upper management
for involvement, commitment and resources.
6. Repeat Steps 1-5 on a routine basis.
Process OptimizationProcess Optimization
How?How?
KIWI2.mpeg
1. Identify the Task1. Identify the Task
Document ChangesDocument Changes
Protocol Approval(Signed)
Protocol Execution(Signed)
Summary Report Approval
(Signed)
Draft Revision Amendment Addendum
2. Concentrate the 2. Concentrate the WorkWork
3. Form Partnerships3. Form Partnerships
4. Define Performance4. Define Performance
Activity Val. User / Owner
QA
Planning
Define Priorities:
1) Analytical Methods
2) Laboratory Equipment
3) Facilities / Utilities
4) Production Equipment
5) Process
Responsibilities Matrix:
5. Training5. Training
The greatest benefit of The greatest benefit of training comes not from training comes not from learning something new, learning something new, but from doing better but from doing better what we what we alreadyalready know. know.
Five Steps to Five Steps to OptimizationOptimization
1.1. Identify the tasks.Identify the tasks.
2.2. Concentrate the work.Concentrate the work.
3.3. Define performance.Define performance.
4.4. Form partnerships. Form partnerships.
5.5. Build continuous learning Build continuous learning and teaching. and teaching.
Constraints vs. Constraints vs. PerformancePerformance
Quality
Cost Time
Scope
Look at the Big PictureLook at the Big Picture
Periodic review applying an Periodic review applying an holistic approach to quality holistic approach to quality systems.systems.
Process OptimizationProcess Optimization
Incorporate steps to optimize Incorporate steps to optimize individual processes (quality individual processes (quality system).system).
Look at the constraints.Look at the constraints. Periodically review applying Periodically review applying
an holistic approach to quality an holistic approach to quality systems.systems.
Why?Why?
Regulatory Regulatory RequirementRequirement
Assures QualityAssures Quality Good EconomicsGood Economics
ReferencesReferences
1.1. ASTM E 2500-07 Standard Guide for Specification, ASTM E 2500-07 Standard Guide for Specification, Design, and Verification of Pharmaceutical and Design, and Verification of Pharmaceutical and Biopharmaceutical Manufacturing Systems and Biopharmaceutical Manufacturing Systems and EquipmentEquipment
2.2. ICH Q9 Quality Risk HandbookICH Q9 Quality Risk Handbook
3.3. Pharmaceutical cGMPs for the 21Pharmaceutical cGMPs for the 21stst Century—A Risk- Century—A Risk-Based ApproachBased Approach
4.4. FDA Guide to Inspections of Quality Systems- August FDA Guide to Inspections of Quality Systems- August 19991999
5.5. The Gold Sheet- January 2008: “Quality Systems No The Gold Sheet- January 2008: “Quality Systems No Longer Theoretical as Industry Begins Implementing Longer Theoretical as Industry Begins Implementing Concepts”Concepts”
Lee Menszak Lee Menszak Consulting, Inc.Consulting, Inc.
[email protected]@earthlink.net
845-300-1730845-300-1730