Post on 01-Sep-2014
description
Quality System ExpectationsQuality System Expectations
Disposables (Single-UseMaterials) use in the Manufactureof Drugs and Biologics
Bill HoldenGlobal Quality LeaderW. L. Gore & Associates, Inc.Gore PharmBIO products
AgendaAgenda
Single-Use Technologies MovementcGMP CFR 820 Applicable PracticesSupplier QualificationsMaterial QualificationsMinimal Quality System Standards
SingleSingle--Use inUse in PharmaPharma & Biotech& Biotech
Single-Use technologies supply materialsto the biomanufacturing process thatreplace the need for stainless steel andtraditional manufacturing processes whichrequire extensive validation and processdevelopment.
What is the Movement?What is the Movement?
Increased availability of Single-Usematerials are replacing traditional stainlesssteel processes.– Use in Single batch or limited campaigns– Reduced process validations– Validations allow for re-usable elements
AdvantagesAdvantages
Decreased Cycle times (Batch to Batch)Decrease Overall Captial InvestmentDecreased LaborDecreased New Product Introductions timeIncreased FlexibilityIncreased Potential CapacityDecreased In Process Waste
DisadvantagesDisadvantages
New Extractables/ Leachables must be determinedfor productIncreased cost of consummablesIncreased need for Vendor AuditsQualified Supply Sources are limitedIncreased potential for scrap of unusedcomponentsMore Solid Waste
The Path to SingleThe Path to Single--Use ProcessUse ProcessSystemsSystems
Single-useBioProcessContainer Systems
Less capitalNo SIPNo CIP
validation
Traditionalstainlesssteel
Large capitalSIPCIP
validation
Ameican Pharmaceutical Review ( See web links References and Resources)
Extractable
Supplier Qualification (Expectations)Supplier Qualification (Expectations)
Limited Validated SuppliersExpectations of Minimal Quality StandardsApplicable cGMP standards
AuditCARS/PARS
RobustQualitySystem
SupplyControlTraceability
21 CFR 820
cGMPISO
Training
Applicable cGMP 21 CFR 820Applicable cGMP 21 CFR 820Applicability 820.1 (a)– Current good manufacturing practice (CGMP)
requirements are set forth in this quality systemregulation. The requirements in this part govern themethods used in, and the facilities and controls usedfor, the design, manufacture, packaging, labeling,storage, installation, and servicing of all finisheddevices intended for human use.
– If a manufacturer engages in only some operationssubject to the requirements in this part, and not inothers, that manufacturer need only comply with thoserequirements applicable to the operations in which itis engaged.
Suggested Applicable RequirementsSuggested Applicable Requirementsfor tubing Molded Manifoldsfor tubing Molded Manifolds
Subpart B--Quality System Requirements§ 820.20 - Management responsibility.§ 820.22 - Quality audit.§ 820.25 - Personnel.
Subpart C--Design Controls§ 820.30 - Design controls.
Subpart D--Document Controls§ 820.40 - Document controls.
Subpart E--Purchasing Controls§ 820.50 - Purchasing controls.
Subpart F--Identification and Traceability§ 820.60 - Identification.§ 820.65 - Traceability.
Subpart G--Production and Process Controls§ 820.70 - Production and process controls.§ 820.72 - Inspection, measuring, and test equipment.§ 820.75 - Process validation.
Subpart H--Acceptance Activities§ 820.80 - Receiving, in-process, and finished device acceptance.§ 820.86 - Acceptance status.
Suggested Applicable RequirementsSuggested Applicable Requirementsfor tubing Molded Manifoldsfor tubing Molded Manifolds
Subpart I--Nonconforming Product§ 820.90 - Nonconforming product.
Subpart J--Corrective and Preventive Action§ 820.100 - Corrective and preventive action.
Subpart K--Labeling and Packaging Control§ 820.120 - Device labeling.§ 820.130 - Device packaging.
Subpart L--Handling, Storage, Distribution, and Installation§ 820.140 - Handling.§ 820.150 - Storage.§ 820.160 - Distribution.§ 820.170 - Installation.
Subpart M--Records§ 820.180 - General requirements.§ 820.181 - Device master record.§ 820.184 - Device history record.§ 820.186 - Quality system record.§ 820.198 - Complaint files.
Subpart N--Servicing§ 820.200 - Servicing.
Subpart O--Statistical Techniques§ 820.250 - Statistical techniques.
Basic Requirements (Manufacturing)Basic Requirements (Manufacturing)
ISO 9001:2008 3rd Party certificationDemonstrable Quality System– Responsible Quality Unit/Team– Trained, responsible production team
members– Appropriate Document Management System
Controlled DocumentsDemonstrable Procedures, Work Instructions, etc.
Basic Requirements (Manufacturing)Basic Requirements (Manufacturing)
Viable Preventative and Corrective ActionSystemsControlled and verified suppliers– Approved supplier list– Verified materials (TSE/BSE Policy)
Identification and Traceability Systems– Manual or Electronic
Basic Requirements (Manufacturing)Basic Requirements (Manufacturing)
Appropriate Production Controls– In Process Assurance of Intermediate Assembly– In Process Traceability– In Process Acceptance Standards– Equipment Validations/ Calibrations/ Preventative
MaintenanceAppropriate isolation and identification of non-conforming product– Segregation/ labeling, and disposition
Basic Requirements (Manufacturing)Basic Requirements (Manufacturing)
Organized Handling Operations– Controlled labels and identification of parts
and components– Assurance of packaging integrity of parts and
components– Assurance of cleanliness of parts and
components– Viable location traceability (manual or
electronic)
Basic Requirements (Manufacturing)Basic Requirements (Manufacturing)
Records– DMF/DHF- Batch History Record
Includes the Bill of Materials (BOM, Drawing,additional customer specifications)Assures traceability of part manufacture and rawcomponentsAssures any linkage from customer complaint canbe made.
Basic Requirements (Manufacturing)Basic Requirements (Manufacturing)
Internal Audits– Yearly Internal Evaluations
Facilities– Clean and Organized– Bioburden/ Particulate readings– Appropriate environmental and disposal
controls for the parts manufactured.– Pest control program and maintenance
Basic Requirements (Materials)Basic Requirements (Materials)
Sterilization method /validations (GAMMA/ STEAM, etc. )
Chemical CompatibilityPhysical PropertiesExtractables Test DataBiocompatibility (USP VI Test Data)Applicable Materials Testing– Application specific testing
EndotoxinBioburdenFFU (Fitness for Use) specific testing
Methods of EvaluationMethods of Evaluation
Desktop AuditSupplier Visit/AuditData ReviewSupplier Performance Data– Delivery– Corrective Actions– Collaborations
Desktop SurveyDesktop Survey
Frequent Topics:
Additional ResourcesAdditional Resources
References– Froimson, Joshua. American Pharmaceutical
Review. 2009. 12, 2 20-27.– Sinclair, Andrew, Monge, Miram.
International BioPharm. 2008. 21, 12 27-29.– Strahlendorf, Kirsten A. Kevin Harper.
American Pharmaceutical Review. 2009. 12, 428-37.
Additional ResourcesAdditional ResourcesWeb Resources
– http://www.futurepharmaus.com/?mc=disposable&page=mt-viewarticle– http://www.pharmamanufacturing.com/articles/2007/164.html– http://www.pharmpro.com/ShowPR.aspx?PUBCODE=021&ACCT=0000100&ISSUE=0604
&RELTYPE=PR&ORIGRELTYPE=ATO&PRODCODE=0000&PRODLETT=A&CommonCount=0
– http://biopharminternational.findpharma.com/biopharm/Disposables/Final-Word-Disposable-Systems-Meet-Todays-Manufact/ArticleStandard/Article/detail/146352
– http://www.bioplanassociates.com/publications/articles/Bp0607_DisposablesAsDisruptive_Jun07.pdf
– http://www.pharmamanufacturing.com/articles/2004/27.html?page=fullAdditional Meetings
– http://www2.ispe.org/annualmeeting2009/education/402.cfm– http://www.pharmpro.com/singleuse/– http://www.advantagemedia.com/ims/scripts/RegisterEventLink.asp?ID=79– http://www.ispe.org/cs/2009_strasbourg_conference/disposables_and_containment_technolo
gy– http://biopharminternational.findpharma.com/biopharm/Disposables+Advisor/User-
Viewpoints-on-Disposables-Implementation/ArticleStandard/Article/detail/601411?contextCategoryId=35801
Additional ResourcesAdditional Resourceshttp://biopharminternational.findpharma.com/biopharm/servlet/ContentRatingServlet#rating_anchorhttp://biopharminternational.findpharma.com/biopharm//article/articleDetail.jsp?ts=081709022143&id=608683http://biopharminternational.findpharma.com/biopharm/article/articleDetail.jsp?id=608683&pageID=1&sk=&date=http://www.in-pharmatechnologist.com/Processing-QC/GE-Healthcare-and-Novavax-collaborate-on-pandemic-flu-solution