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1、Validation of Pharmaceutical Packaging,S.P.Manek Ph.D(Tech)08-10-2011,1,Validation:Regulatory Compliance,Validation a Key requirement of all GMP GuidelinesProcess ValidationCleaning ValidationAnalytical Methods ValidationComputer systems validationFacility/Equipments Validation/Qualification(IQ/OQ/P
2、Q)Packaging Validation:to confirm that the resulting product from a specified packaging process consistently conforms to product attributes&requirements.A risk-based approach-focusing on processes that have the greatest potential risk to product quality provides a rational framework for developing a
3、n appropriate scope for validation activities.,2,Validation:Packaging Operations,US-FDA and EMEA Regulatory complianceequipment must be suitable for its intended use.need to validate packaging machines/their various componentValidation process:technically complex,time consuming,costly Key Elements:Q
4、ualification of equipments:all relevant sub-systems are thoroughly tested and documented to provide the information that is essential for successful validation.Validation of a Product Packaging operation PQ:verification of facility,utilities,equipment performance,components,trained personnel and pro
5、cessesEvaluation of variance&Assessment of impact on Critical Product Quality attributesCleaning validation:Part of Packaging Validation,3,Validation,Qualification or Validation?Qualification and validation are essentially components of the same conceptThe term qualification is normally used for equ
6、ipment,utilities and systems:A system must be qualified to operate in a validated processThe term validation is normally used for processes In this sense,qualification is part of validation,e.g.you qualify an autoclave,whereas you validate a sterilization processQualification should be completed bef
7、ore process validation is performed,4,Validation:Packaging Operations,A validated process:enables consistent packaging of products to meet the product/market requirements-Quality attributes/consumer needs-in a cost effective&an efficient process with minimum down time,rejects and errors.Consistency&
8、Cost effectiveness-key business considerations,a validation activity should be seen not as a regulatory requirement but as a business necessityMulti-disciplinary effort:equipment engineers,packaging technologists and quality teams must plan and work through a validation program together in order to
9、create a robust operation&ensure consistent Quality packaging,5,Packaging,Packaging:“the art,science and technology of preparing goods for sale in a cost effective manner.”Filling,Sealing,Inspection,Labeling,Final PackagingIn the context of pharmaceuticals,the packaging must:preserve the product-fro
10、m degradation or contamination contain the product-to avoid leakageidentify the product-providing traceability,security-against tampering and counterfeitinginformation on use-an“aide memoir”for complianceconvenience in use-for medical staff or patient All this must be ensured for the life of the pro
11、duct and achieved within a complex regulatory environment.,6,Packaging Validation:Pre-requisites,Key areas impacting the robustness of a packaging process-should be considered in validation:Packaging equipment&Line Layout/Facility spacePackaging materialsSOPs:Equipment Operation,Maintenance,Cleaning
12、Calibration ProgramOperator TrainingMaster Validation PlanPackaging Equipment IQ/OQ/PQ&Validation Protocols,7,Validation:Packaging Line Layout,The design and layout of equipment has major impact on the efficiency of the packaging line.Line Layout:Design for a line layout should include the ability t
13、o manage quick change-over,perform line clearance between batches of product and clean the line in an easy and controlled manner.The majority of problems on packaging lines are related in some way to poor line clearance-important to design these problems out.Devices will normally be located in criti
14、cal positions on the line to detect presence or otherwise of the materials.The layout should provide easy access for operators and the engineers for adjustments and or maintenance,8,Validation:Packaging Line Equipment,Well designed equipment will lend itself to efficient packaging of a consistent st
15、andard,ensuring that the machine,as supplied and installed:Meets Product Packaging expectations.Performs according to Packaging design intentionsComplies with GMP standardsIs provided with a record of key features and components as initially installed.Is provided with information to enable safe,effe
16、ctive and consistent operation and maintenance.Has it systems tested and verified as being in correct working order,to enable validation to be performed.,9,Validation:Packaging Line Equipment,Validation strategy 1st step:important to define the topology of the system-defines the scope of the project
17、.Detail the packaging line system within the validation protocol Identify and list the system functionality,the Software and Hardware of the system Identify the critical measuring devices that need calibration e.g.pressure gauges,thermocouples,hygrometers etc.Assess the GMP risk:define if the system
18、 has the capability to impact on the Product in terms of Quality,Strength,Identity or Purity,leading to product withdrawal/recall.,10,Validation:Packaging Lines,GMP riskIncorrect or contaminated pharmaceutical productIncorrect assembly of the unit of dose carrier(blister,bottle,vial.)Incorrect packa
19、ging component in the final assembly(incorrect carton,missing/incorrect label/leaflet)Incorrect or illegible lot or batch identificationBusiness and operational riskPoor packaging quality(cosmetic defects)Excessive machine down timeMachine damage or wearExcessive change-over times/Slow speed of oper
20、ation,11,Packaging Materials,Variety of Packaging Materials Moisture-impermeable containers(Vials/bottles-glass/plastic,Alu-Alu blisters,Blister strips(multi layered foils)Moisture-permeable containers(PVC blisters,LD/HDPE containers)Multiple suppliers for same packaging itemAn efficient production
21、line needs consistent materials The storage and handling of components is as vital in this respect as their specification to maintain consistency.Fiber-based materials,such as leaflets(inserts),cartons and labels can be adversely affected by temp/RH changes.Supplier/Material qualification,audits,rig
22、orous packaging material specifications Specifications-should include thickness and permeability coefficient,12,Packaging Validation:SOPs,To manage a packaging line,adequate standard operating procedures(SOPs)will be required.Vital to ensure SOPs provide clear and unambiguous instructions on how to
23、operate,adjust,and maintain each piece of equipment detail how a batch is packaged,explains how each material is received on the line and checked for correctness,quantity,Details of In Process Control(IPC)testsProcedure for Line clearance/change-over,including details of cleaning operations to avoid
24、 cross-contamination,13,Packaging Validation:Training,The supplier should identify training needs and provide appropriate training.Consider the specific packaging methods,Machine operating techniques,hardware/software to be used,Selection/identification of packaging materials Product packaging requi
25、rementsRecords of relevant training and experience should be maintained&available as part of the project documentation.The requirement is for classroom training with notes and a test to be made at the end,in both theory and practice.Training Module for retraining/training new operators,14,Validation
26、 Master Plan(VMP),Any validation exercise must start with a detailed Validation Master Plan,will include key elements of the validation program.Companys validation policyorganizational structure of validation activitiessummary of facilities,systems,equipment and processes validated/to be validated.A
27、ll critical equipment,systems,devices,software must be identified and listedDefines nature&extent of testing,test procedures documentation format(e.g.protocol and report)planning and schedulingchange control process-Any validation activity is only as good as the change control process used,15,Qualif
28、ication Protocols,A classical approach to validation:prepare protocols for DQ,IQ,OQ and PQ.test each piece of equipment in the line and to test the interaction between different pieces of equipment/systems.designed to test all the critical steps,providing a list of tests which are to be performed an
29、d the acceptance limits for each test.Tests must demonstrate that the system is able to:do what is expected within the operating range required for the process.Test beyond the normal operating range to provide information on the system behaviour,which can be used to finalize operational limits.,16,V
30、alidation Protocols,Short description of the process with a summary of the critical processing steps or critical parameters to be monitored during validation.Additional testing intended to be carried out(e.g.with proposed acceptance criteria and analytical validation as appropriate).Sampling plan wh
31、ere,when,how and how many samples are taken(more sampling than normal IPC).Details for recording and evaluation of results.,17,Performance Qualification,PQ,the last stage in validation,should reflect the real production environment,using production materials in a normal daily operation.The exercise
32、should extend over a time period sufficient to ensure that shift working patterns and normal lunch breaks etc.are included and to certify that the systems are challenged for stop/start,batch changes etc.It is important to document the rationale for a matrix approach in the VMP-what and why it will b
33、e done.,18,Validation:Change Control,Changes that require revalidationSoftware changes;ControllersSite changes;Operational changesChange of source of materialChange in the processSignificant equipment changeProduction area changesSupport system changes,19,PQ-Examples,Blister Packing:Speed&Temperatur
34、e settings/rangeDifferent materialsDifferent suppliersDifferent productsNeed to package at extreme temps&evaluate its impact on QualitySealing QualityPack appearance(Aesthetics)Product Quality(Stability,purity,assay etc),20,Illustrative variables of tablet packaging,21,PQ-Examples,Ampoule/Vial Filli
35、ng&Packing:Filling:Fill volume variation:fill accuracy Splashing,spillage,container damage deoxygenate,if required(assay)Seal quality:aesthetics,seal test(leak test)Labeling/information overprintingInspection:manual,automatic,bar code readingLine speedProduct viscosity,22,Common Issues,Packaging pro
36、cess validation is often supplemented by 100%inspection online-firms take the approach that it is the way to go&have inspectors set up offline to sort out/rework unacceptably packaged product.Cause:Packaging process variables are not adequately identified,studied/not observed to“nail it”through the
37、validation.Solution:Validate packaging process by optimizing the packaging process variables and making three runs.A statistically valid sampling plan implemented&samples tested per the finished product specifications.Critical variables impacting quality identified&controlled,23,Tips&Hints,Understan
38、d thoroughly the packaging system and its critical steps.Never under estimate the amount of time needed to develop plans-more time you spend in design of the protocols,the less you will waste in resolving issues and investigating failures.Develop a good sound sampling plan-IPC tests are meaningful a
39、nd provide useful data on the line performance(samples should reflect the normal operating conditions).Detect,understand sources°ree of variation,its impact on product attributes and control variationsFinally,any validated system is as good as the associated change control process.make sure all c
40、hanges are fully assessed and documented.the impact of the change on the validation status of the system must be fully assessed before any changes are made.,24,Summary,IndustryConstantly challenged to reduce costsNew markets and new packs add complexity to the operationAn ever changing regulatory en
41、vironment demands compliance.To ensure pack integrity,manage complexity,maximize efficiency and minimize costs;appropriately designed packs,running in validated packaging lines,are a business necessity rather than a regulatory requirement.If validation is well planned and documented,then GMP complia
42、nce will naturally follow.,25,Quality is designed and built into the process/method/equipments/premisesFunctionality,consistency and repeatability is confirmed by Validation,26,Importance of Validation:Cost of Quality,Visible costs,e.g.,waste,returned/recalled goods.Invisible/Hidden costs,e.g.,wrong decisions(machine,change part),non-trained workers,Non-standardized process,low yield,maintenance/idle machine time,unsuitable packaging material etc.,27,Thank you for your attention.,28,
