FOCUS ON.OUTSOURCINGEffective Management ofContract OrganizationsKeeping the Product Pipeline Moving,Compliant, and Availableby Anthony Mire-Sluis, Julia Edwards, Jeffrey Staecker, Qiao Bobo, Patricia Hughes,Stephen Liewbowitz, Shawn Novick, Siddharth J. Advant, and Bernard HuygheBoth small and largebiopharmaceutical companiesare increasingly pursuing theoutsourcing of manufacturingand testing throughout the productlifecycle. The growing use of contractmanufacturing organizations (CMOs)and contract testing organizations(CTOs) has led to increasingcomplexity within thebiopharmaceutical industry as morethird-party sites are leveraged tosupport global markets.To address those issues, a CASSSChemistry, Manufacturing, andControls (CMC) Strategy Forum washeld in Washington, DC, 27–28 July2014. The title was “EffectiveManagement of ContractOrganizations: Sponsors, ContractOrganizations, Health Authoritiesand Patients — Keeping the ProductPipeline Moving, Compliant, andAvailable.” The CMC Strategy Forumis a series of meetings that focus onemerging and relevant CMC issuesthroughout a product’s life cycle. Theforums foster collaborative sharing ofinformation among industryparticipants and regulatory agencies.Their goal is the convergence oftechnical and regulatory best practices.This CMC Strategy Forum onCMO and CTO oversight focused ontrends and challenges associated withoutsourcing. The goal was to identify12BioProcess International13(9)O ctober 2015Regulatory representations wereprovided by the US Food and DrugAdministration (FDA) (both theCenter for Drug Evaluation andResearch (CDER) and the Center forBiologics Evaluation and Research(CBER)) and Health Canada. Productreviewers and current goodmanufacturing practice (CGMP)inspectors expressed their viewpointsthroughout this two-day meeting.KEMWELL BIOPHARMA (WWW.KEMWELLBIOPHARMA.COM)best practices to ensure the safety,efficacy, and quality of productsproduced and tested by CMOs andCTOs. The meeting was divided intofour sessions: Building Quality into theRelationship Manufacturing at the CMO Contracting Analytical Testing atthe CMO and CTO Most of the World Experience(Outside the European Union andUnited States).To converge upon best practices,each session opened with case-studypresentations from a number ofregulators and industryrepresentatives. An interactive paneldiscussion followed case-studypresentations. Both small and largecompanies as well as sponsors andcontractors were represented in thepresentations and panel discussions.Session 1: Building Qualityinto a RelationshipThe forum opened with a session onregulatory and quality issues. JuliaEdwards (Biogen) and StephenLiebowitz (NPS Pharmaceuticals)were session chairs. Speakers andpanelists were Qiao Bobo (FDA),Susan Kalk (NPS), Margit Olson(Tunnell Consulting), Patricia Hughes(FDA), Christian Lynch (FDA),Tracey McKennon (Seattle Genetics),and Tony Mire-Sluis (Amgen).Building a relationship betweencontractor and sponsor is fundamentalto success. Both regulatory andindustry representatives provided theirperspectives on the quality technicalagreement (QTA) and FDA’s newdraft guidance on QTAs (1).Regulators, panelists, and the audienceemphasized the importance of clearlydefining roles and responsibilities in aQTA.

CMC Forum SeriesThe CMC Strategy Forum series providesa venue for biotechnology andbiological product discussion. Thesemeetings focus on relevant chemistry,manufacturing, and controls (CMC)issues throughout the lifecycle of suchproducts and thereby fostercollaborative technical and regulatoryinteraction. The forum strives to shareinformation with regulatory agencies toassist them in merging good scientificand regulatory practices. Outcomes ofthe Forum meetings are published inthis peer-reviewed journal to helpassure that biopharmaceutical productsmanufactured in a regulatedenvironment will continue to be safeand efficacious. The CMC StrategyForum is organized by CASSS, anInternational Separation Science Society(formerly the California SeparationScience Society), and is supported bythe US Food and Drug Administration(FDA).Regardless of role, adherence toCGMP requirements is important toall involved parties. CMOs andsponsors alike can suffer theconsequences of an inspectionalfinding that identifies substantialshortcomings in a quality system.However, the FDA places ultimateresponsibility upon product sponsors.Significant deficiencies observedduring inspections at contractingfacilities imply a deficient level ofoversight by sponsors.During the session, participantsstressed that the QTA (created byappropriate quality and technicaloperations representatives) should be aseparate and complementarydocument from business agreements(e.g., a supply agreement). Together —and with equal weight — the businessagreement and QTA establish a coreframework for sponsor–contractorinteractions. Many items must beconsidered when establishing QTAs.However, session participantsdiscussed the importance of phaseappropriate CGMP in the context ofQTAs. Special care should be takenwith clinical CMOs and CTOsplanning to transition to commercialphases of development. And it shouldbe understood that CMOs and CTOs14BioProcess International13(9)O ctober 2015CMC Strategy Forum NorthAmerica Program CommitteeSiddharth J. Advant (KemwellBiopharma), Yves Aubin (HealthCanada), John Bishop (CBER, FDA),Barry Cherney (Amgen Inc.), JR Dobbins(Eli Lilly and Company), Julia Edwards(Biogen), Sarah Kennett (CDER, FDA),Joseph Kutza (MedImmune, A memberof the AstraZeneca Group), KimberlyMay (Merck & Co., Inc.), Anthony MireSluis (Amgen Inc.), Stefanie Pluschkell(Pfizer, Inc), Nadine Ritter (GlobalBiotech Experts, LLC), Reb Russell(Bristol-Myers Squibb Company), OscarSalas-Solano (Seattle Genetics, Inc.),Dieter Schmalzing (Genentech, aMember of the Roche Group), TimothySchofield (MedImmune, A member ofthe Astra Zeneca Group), ZahraShahrokh (STC Biologics, Inc. and ZDevConsulting), Jeffrey Staecker (BioPhiaConsulting, Inc.), and Andrew Weiskopf(Biogen)are subject to preapproval inspections(PAIs).But formalized agreements are justa piece of the puzzle. For smooth andeffective operations, the importance ofa good relationship founded ontransparent communication betweensponsor and contractor cannot beunderestimated. One participant notedthat there is a limit to what can becovered in a QTA or businessagreement. As a result, the focus canshift to aspects of a relationship thatare not necessarily covered by a formalagreement, such as open and honestcommunication. That is important aspriorities shift (e.g., business focus,problems, and situations that are notspecifically addressed in a QTA).Participants representing contractorganizations stressed the importanceof partnership with sponsors.However, although a contractor mustmeet CGMP requirements, thesponsor holds the ultimateresponsibility to release or rejectproduct. So that relationship is notnecessarily weighted equally and canbecome strained by practicalities of lotrelease and the business. Regulatorsand industry alike stressed that aQTA and business agreements begiven equal weight given the nature ofsponsor–contractor relationships.Session 2: Manufacturingat the CMOSession chairs were Bernard Huyghe(Pfizer) and Ben Locwin (LonzaBiopharmaceuticals). Speakers andpanelists were Bo Chi (FDA), FirelliAlonso-Caplen (Pfizer), Jesus Zordo(Lonza), Nance Green (HealthCanada), Zahra Shahrokh (ZDevConsulting), and Aria Tavana(Alnylam).Manufacturing multiple lots ofproduct at a CMO is a significantfinancial commitment for both aCMO and sponsor. Smallbiopharmaceutical companies dependon CMOs for their continuedexistence, and use of CMOs has amajor impact on financial performancefor larger companies. Problemsbetween a CMO and sponsor canaffect financial performance,especially in issues related to drugquality, drug supply, and introductionof novel drugs.A significant challenge to workingrelationships is the number of productsproduced by a single CMO. Ofparticular concern are high-risk andhigh-potency products, as Chidiscussed in her session presentation.She emphasized the importance ofrisk-based evaluations and crosscontamination controls at contractfacilities. CMOs must be able toconduct such risk analyses on the basisof an understanding of productcharacteristics from multiple sponsors.CMOs can use drug master files(DMFs) for specific site/facilityinformation that may cross overmultiple products. A sponsor shouldinclude product-specific information,(e.g., process validation data) in arelevant drug application (e.g., newdrug application (NDA) or biologicslicense application (BLA)).Alonso-Caplen’s presentation wastitled “Case Study: How to Succeed inVaccine Externalization andTechnology Transfer.” He describedhow outsourcing allows nearly anybiopharmaceutical company toconduct vaccine clinical trials quicklyand without having to deal with thestaggering capital expendituresassociated with building amanufacturing facility. Successful

US Regulations and Guidance onContract Manufacturing and Quality AgreementsFDA Guidance for Industry: Cooperative Manufacturing Arrangements for LicensedBiologics (November 2008) describes different contractual relationships: Shared manufacturing means that two or more manufacturers are licensed andresponsible for specific aspects of manufacturing a product, but none is licensed forall aspects of the manufacture of the product. Contract manufacturing occurs when a licensed manufacturer establishes a contractwith another entity to perform some or all of the manufacture of a product as aservice to the licensed manufacturer. Divided manufacturing (also see 21CFR 610.63) means that two or moremanufacturers (each registered with the FDA and licensed to manufacture a specificbiological product in its entirety) participate jointly in the manufacture of thatproduct.In addition, below are regulations that address contract manufacturing: Contract Manufacturing Facilities (21 CFR 200.10) Procedure in place for receiving information from the contract facility on alldeviations, complaints, and adverse events (21 CFR 600.14(a)). Final approval or rejection of drug product to the market (21 CFR 211.22(a)).The FDA regards contract manufacturers as an extension of the pharmaceuticalmanufacturer’s own facility (21 CFR 200.10). Pharmaceutical manufacturers cannot outsource the responsibility of the qualityunit (QU) to approve and release drug components and finished pharmaceuticals(21CFR 211.22(a)).Contract Manufacturing Arrangements for Drugs: Quality Agreements (Draft Guidance).US Food and Drug Administration: Rockville, MD, May 2013.externalization cannot occur without acareful selection process for the rightCMO and execution of awell‑designed technology transferplan. The company in the case studyhad concluded a major vaccinecontract at a CMO, producing phase 3clinical supplies and conductingprocess validation. Alonso-Caplenrecounted the selection process, theestablishment of service and qualityagreements, and (more important) thecomplex technology transfer ofproduction processes and analyticaltest methods. He discussed whichapproaches worked and did not workand why.Session speakers emphasized theintegration of a CMO’s quality system(QS) with a sponsor’s QS. Effectivequality oversight is a key componentof a supplier management program. Itensures that a quality unit (QU) isinvolved in all phases of an outsourcedproject’s life cycle, from due diligencethrough contract termination. A QUbrings a unique focus to CMOselection, such as identifying thecapabilities and leadership of a CMOand understanding a CMO’sregulatory experience in a sponsor’sintended jurisdictions.16BioProcess International13(9)O ctober 2015The discussion circled back to themain topic of conversation in the firstsession: the QTA. Session participantsnoted that a QTA is the culminationof integrating different quality systemsand must be established to clearlyoutline both sponsor and CMOresponsibilities. That ensures thattheir respective quality systemsinterface effectively. However, thisobjective presents its challenges.A CMO may not be willing toreadily share internal standardoperating procedures (SOPs) andprocesses, and a sponsor is frequentlybound by corporate quality standards.Most CMOs are limited in theirability to allow exceptions from theirestablished QS to alwaysaccommodate different sponsors. A“joint” QS should be established thatworks within the confines of both asponsor’s and a CMO’s existingquality systems, and it must still meetregulatory requirements. Developingthis way of working often takes quite abit of flexibility for both sponsors andcontractors. In addition, joint qualitymetrics should be established thatclearly define CMO and sponsorcontributions as well as shared metricsfor the overall success of a project.Presenters also discussed thecomplexity of multiparty supplychains. Some products aremanufactured at different sitesthroughout their production (e.g.,drug substance, drug product, device,testing, and labeling). Panelists notedthat it is very rare that a sponsorbrings all of those supply-chainelements into a single discussion withthe many parties involved in thoseagreements.Sponsors are responsible foroverseeing end-to-end supply chainsand ensuring that communicationbetween each CMO is working. Jointquality agreements and/or multipartyconfidentiality agreements should beimplemented where relevant. One ofthe authors of this article experiencedan example of potential complexitywhen addressing out-of-specification(OOS) events affecting productsupply: The case involved twosponsors, three CMOs, and testresults from two organizations.Although not every contingency canbe included in a QTA or confidentialdisclosure agreement (CDA),documents should not be limited tosituations in which everything isrunning smoothly. Foresight inpreparing a QTA, the businessagreement, and CDAs along withdeveloping an effective workingrelationship is the benchmark ofeffective collaborations.Regulatory requirements also play arole in establishing relationshipsbetween a sponsor and a CMO. Forexample, the FDA expects that asponsor has scaled-up the manufactureof a product in a planned productionfacility at the time of the prelicense/preapproval inspection (PLI/PAI).That can be a challenging task whenworking with CMOs that arebalancing the needs of manycustomers. It is worth considering a“review date” within the original QTAand business agreement to preventconflict if changes that are requiredhave financial impact.Session 3: Contracting AnalyticalTesting at the CMO and CTOThis session focused discussion oncontracting analytical testing. Session

Best Practices: Navigating Sponsor–Contractor RelationshipsMultiple unanticipated changes stress people. The QTA and business contract are bestaddressed when good relationships and contracts have been created.Both parties should appropriately develop and agree to timelines.Contractors should adhere to QTA requirements (e.g., notifications and cycle times).Plan ahead for life-cycle management for transition from phase 3 to commercialmaterial.Leverage CMO knowledge in developing and maintaining relationships.Establish effective relationships at all levels — junior staff through executives.Don’t finger-point if issues arise. Solve the problem!Have mutual respect between CMO and sponsor.Establish an effective governance procedure that might include a joint steeringcommittee as well as committees for quality, supply, and business.Ensure that teams meet face to face as well as on the phone.Best Practices: Handling ContractorSponsor Audits and Regulatory InspectionsSome CTOs may be testing a wide variety of products and at different stages ofdevelopment. How a CTO incorporates phase-appropriate CGMP into its QS should bewell understood, and compliance should be ensured when performing a GMP audit/inspection.Sample handling and chain of custody and process validation are also audited/inspected. During an audit/inspection, auditors/inspectors may review QTAs tounderstand who is responsible for what.Communication with sponsors can be a source of issues during inspection at acontracting site. Sponsors may request/require communication of certain inspectionalitems even when not part of an inspection directly affecting their product.Data auditing at the contractor by the sponsor is an important aspect of theirrelationship. 100% data verification may refer to every data point or just a subset ofevery study that depends on the CTO.Data integrity is essential and is often an observational issue on inspection. Dataanalysis is getting more complex, and sponsors should involve appropriate experts toensure that data are being handled appropriately by their CTO.Quality audits should include investigations, documentation of investigations, andfollow-up on corrective action.Investigations may lead to retesting, and such procedures must comply with CGMP.For example, inappropriate retesting resulting in a passing result may be inconsistentwith CGMP. If not, modifications should be made to ensure that the CTO’s process is asrigorous as the sponsor’s.chairs were Hal Hopkins (AbbVieInc.) and Shawn Novick (SeattleGenetics). Speakers and panelists wereAnne Kowal (Takeda), MelissaClague (Eli Lilly), Eric Nottingham(CMC Biologics), Dean Clodfelter(Covance), Chana Fuchs (FDA), andEd Moore (University of Illionois,retired from Baxter).Presenters stressed that both sidesof a sponsor–contractor relationshipmust work together to ensurecompliance, business continuity, andtechnical ability at a CTO. Similar tothe discussion from the second sessionon CMOs, the discussion here focused18BioProcess International13(9)O ctober 2015on choosing a CTO and ensuring thateffective communication tools are inplace for all phases — from methoddevelopment/transfer throughcommercial testing. A CTO and asponsor provided case studies thathighlighted both the challenges andsolutions associated with methodtransfer and control of methodperformance through a product’s lifecycle. They noted that many of thediscussion points detailed below alsocan be applied to CMOs.Again, the importance ofcommunication was stressed. However,some discussion in this session alsocentered on the importance of a projectplan as a communication tool. Effectiveproject planning can provide rapidflexibility when planning results inrequiring fewer approvers to movethrough project milestones. However,this approach should be aligned withthe business agreement and QTA.Sponsors frequently have specificpeople dealing with a CTO/CMO whoare familiar with the intricacies ofworking with a contract organization.Usually there is a project team thatdeals with each CTO/CMO or a groupof CTOs/CMOs associated with aparticular product. There may be asingle point of contact devoted to aCMO or CTO, depending on theamount of work.Participants also discussed the leveland extent of sponsor involvement.Representatives from both contractorsand sponsors noted that the routinepresence of a sponsor at a testing site(beyond the occasional face-to-facemeeting or teleconference) often isneeded. It is best to outline inagreements items such as requirementsfor on-site presence during actual testingand deviation management, for example.Especially for investigations anddeviations, effective collaboration isrequired between sponsors andcontractors. It is critical for a CTO tocommunicate an issue to a sponsor as ithappens and then follow the predefinedprocess for working through deviationsand OOS results. A well-definedprocess must be described in the QTAand should include deviations, OOS,investigations, and time allowances fordifferent parts of the process (e.g.,communication to sponsor and initialinvestigation). Additional languagewithin QTAs should cover the numberof audits, size of audit team, andprenotification. Allowing the CTOaccess to method developers (if theCTO hasn’t developed the method)can be important when addressingissues. For complex issues, sending anassay expert to a CTO can bebeneficial. It is important to ensurethat there isn’t something in the QTAthat impedes communication.This session included substantialdiscussion on the handling of sponsoraudits, regulatory inspections, and

Choose the Right ContractorSeveral key elements should beevaluated when choosing a CTO:finances, regulatory history, QMS, andtechnology need to be assessed. Thinkcarefully about Experience of the quality staff Willingness to share information Method transfer capabilities Proximity to manufacturing (especiallyfor validation samples) Short- and long-term costs Change control, deviation, andinvestigation systems Which compendia are leveraged forcompendial test methods andmonographs.contract facilities. Regulators look atvalidation and transfer in regulatorysubmissions and during audits,regardless of whether such activitiesare executed by a sponsor or a CTO.Having a sponsor on site is very usefulfor a preapproval inspection. Manypoints raised are also applicable tocontract manufacturing.A regulator noted in the paneldiscussion that fraud can be hard todetect if you don’t know what you arelooking for. Even CTOs need to haveinternal checks to ensure that analystsdon’t create fraudulent data. Sponsorsshould have a periodic review of rawdata during their audits. Sendingblinded samples and those out ofexpected range (perhaps reporting anOOS result) can be a way ofmonitoring for possible fraud. Anotherway is to look at trends and assayvariability over time to determinewhether those issues are expected.Session 4: Most of theWorld ExperienceThe final session of the meeting wastitled “Most of the World Experience(Outside the EU and US).” Sessionchairs were Patricia Hughes (FDA)and Troy Wright (Amgen). Speakersand panelists were Carmelo Rosa(FDA), Simon Hsu (BMS), JohnMcShane (Genentech), Siddharth J.Advant (Kemwell Biopharma), PankajAmin (FDA), Chana Fuchs (FDA)91030High Flow Check Valvewith Barbed EndSpeakers presented somechallenges in managing CMOs andCTOs worldwide while ensuringglobal quality oversight. One primarydriver for taking manufacturingoverseas is cost. Companies canreduce product cost by 20–30% whenmanufacturing in certain countriesoutside of the United States.Presenters described specificchallenges related to managingdifferent expectations by globalregulatory agencies, including specificin-country import testingrequirements and manufacturingpractices.Data integrity during overseasinspections in Asia is increasingly anissue. Carmelo Rosa, (CDER, FDA)provided examples during hispresentation, “Global RegulatoryOversight for Better or Worse? ARegulatory Perspective on EmergingTrends.” Rosa presented examples ofdata integrity failures that requiredextensive investigation to unearth. Ofparticular concern was findingmultiple sets of data or examples of882173-Way Stopcock2 FLLSwivel MLL51623Sanitary Flangewith Barb11543MLL to BarbConnector11023Slide Clamp11542FLL to BarbConnector14062Pinch Clamp80147Needleless Injection SiteMLL, SwabbableAll trademarks and registered trademarks are property of their respective ownersVisit Qosina at BioProcess International Booth 905, October 27-29, Boston, MAQosina stocks thousands of single-use Bioprocessing components and offers excellent customer service including free samples,low minimums, and immediate delivery. Visit to see over 5000 stock components, place orders and request a [email protected] 1 631-242-3000qosina.com2002-Q Orville Drive North, Ronkonkoma, NY 11779

data where confirmation of actualtesting was questioned. During thediscussion, participants mentioned thatunannounced audits by sponsors maybe a good means of detecting problems.Sponsors need to be mindful of CMOresources and QTA contentspecifications in establishing anapproach to auditing a CMO.Presenters from Bristol-MyersSquibb (BMS) and Genentech (amember of the Roche Group) notedsome best-practices for sponsors wheninteracting with contractors based inemerging markets such as Korea.Challenges associated with distance,time zone, language, and culture weremet with dedicated extensive in-houseexperience and resources. In one casestudy, BMS had a third-partymanufacturing department that was100% dedicated to oversight ofbiologics manufacturing outsourcing.In addition, full-time quality andtechnical person-in-the-plant (PIP)coverage was used during initialtechnology transfer, qualificationcampaign, and regulatory inspections.Offices in Asia and Europe staffedwith quality and technicalprofessionals were an integral part ofworldwide contract manufacturingoversight by BMS.The session closed with apresentation from Siddharth J. Advant(Kemwell Biopharma). He providedinsight into the complexity ofoutsourcing to CMOs in global andemerging markets.As companies (especially largepharmaceutical organizations) continueto find ways to lower costs forbiopharmaceutical development andmanufacturing, India is emerging as adestination for outsourcing biologics.Several factors such as an educatedtalent pool, low cost of infrastructureand resources, local presence of globalvendors, and already existingpartnerships in drug discovery makeIndia an ideal choice for outsourcingbiologics. Although the cost to producemedicines in India is significantlylower than in Western countries,concerns about quality and intellectualproperty (IP) issues could posepotential challenges as companiesconsider outsourcing to India. Thepresentation addressed these andadditional factors that should beevaluated when consideringoutsourcing biologics development andmanufacturing to India. Such issuesalso are discussed in a 2014 BPI article(2).Session discussion includedconsiderations related to in-countrytesting requirements and import/export. For example, certain geographiclocations require in-country testing atvarious stages of drug developmentand/or at release. Shipping drugs andgetting them through customs intogeographic locations such as India andChina can be challenging. Indiarequires a license to be put in placebefore a company can receive materials,and China allows minimum shipmentof materials for testing purposes andpreapproval licenses for commercialproduct development. Some CTOshave established special customs zonesto expedite clearance. Clearing UScustoms depends on the port of entry;

DisclaimerThe content of this manuscript reflectsdiscussions that occurred during theCMC Strategy Forum. This documentdoes not represent officially sanctionedFDA policy or opinions and should notbe used in lieu of published FDAguidance documents, points-to considerdocuments, or direct discussions withthe agency.some ports are faster and easier thanothers. Customs and rules must beunderstood because significant delayscan occur before obtaining licenses andcustom approvals (e.g., India andChina). For example, if a material hasbeen imported previously, then theoriginal approval letter can be attachedto importation documents to speed theprocess.Participants also discusseddifficulties associated withmaintaining complex manufacturingnetworks of many facilities.Maintaining oversight over each site isdifficult, particularly when differentlocal requirements must be met. Somecompanies have “base-case qualitystandards” to which production in allcountries must comply to meet patientsafety and quality criteria. A productcan’t be good for one country and notanother. Some CMOs have twosystems: one domestic, one foreign.Pricing can influence howinvestigations are carried out, or drugsfailing foreign quality standards canget diverted to domestic systems.Rosa described the internationalinspection program and collaborationswith other global regulatoryauthorities. Progress has been made inbuilding confidence with thoseregulators. Inspection reports havebeen exchanged between the FDAand other global regulatory agencies.FDA evaluates and monitors actionstaken in foreign jurisdictions, and insome cases, the agency has takenaction against companies based onthose inspections. The FDA looks forgeneral CGMP failure issues ratherthan country-specific regulatoryissues. The agency has consideredshared inspection results before goingback for secondary inspections. Inaddition, other agencies might have22BioProcess International13(9)O ctober 2015covered areas that the FDA did nothave time to do. That allows theagency to focus on high-riskcompanies rather than on ones thathave passed other agency inspections.The Pharmaceutical InspectionCooperation Scheme (PIC/S) isworking across regulatory agencieswith training and joint inspections toensure consistency. However, sessionparticipants noted that redundantinspections provide for greatercoverage over time because eachinspection is only a snapshot in time.At the FDA, CMC reviewers workwith inspectors to cover productspecific aspects when possible.However, CMC reviewers do notalways go on inspections with FDAinspectors. Standards are the sameregardless of where a product is madeand tested. That is true from both aregulator and industry viewpoint.After a joint inspection withregulatory authorities from regionsoutside the FDA, each authority isstill required to write separate reportsbased on current regulations. Anotherlimitation on joint inspections is asponsor’s unwillingness to shareinformation for confidentialityreasons. There has been openness toexchange reports during thecollaboration process. The FDA hasnoted that it has an “activepharmaceutical ingredient program”that shares inspection details amongdifferent countries.Strategy Forum SummaryMany relevant topics and themes werediscussed over the course of thistwo-day CMC Strategy Forum. Beloware the primary themes of the forum.A sponsor–contractor relationshipis managed through multiplecontracts: e.g., a master serviceagreement (MSA), businessagreement, QTA, and specific projectcontracts. Effective and integratedcontracts must address both routineoperation and challenges such asinvestigatio

Controls (CMC) Strategy Forum was held in Washington, DC, 27–28 July 2014. The title was “Effective Management of Contract Organizations: Sponsors, Contract Organizations, Health Authorities and Patients — Keeping the Product Pipeline Moving, Compliant, and Available.” The CMC