Quality System Expectations : Single-Use Materials

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