From the Publishers of

www.medicaldesignbriefs.com June 2014

Protecting PrecisionManufacturing of Devices

Thoroughly Cleaning ElectronicAssemblies Ensures Reliability

Eliminating Plasticizer in Medical-Grade PVC

INSIDE: 2014 Outsourcing Guide & Directory page 23

Technology Leaders: Outsourcing

Ensuring Precision Manufacturing in the

Medical Device Industrypage 24

Laser Surface Texturing Strengthens

Bonds, Reduces Variability in Medical Devices

page 28

Directory of Outsourcing Servicespage 64

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2014 Outsourcing Guide & Directory

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Outsourcing

Ensuring Precision Manufacturing in the Medical Device Industry

The English (North America) dic-tionary definition of the word“precision” is accuracy (noun) or

relating to accuracy (adjective). You willfind the word “precision” takes on all thesynonyms of the word “accuracy” in themanufacturing world. This rings espe-cially true in the medical device industry.Let’s examine some synonyms of theword “precision” to see how they relateto device industry regulations and goodmanufacturing practices.Care: Think about and attention todetail (planning)Meticulousness: Thoroughness anddiligence (standards and regulatorycompliance)Correctness: Rightness and truth(process validation/objective evidence)Exactitude: State of being exact, pre-cise or accurate (maintaining the vali-dation state)

Care (Planning)For any medical device program, plan-

ning is the most important aspect. Theprogram’s success depends not only on agood and thorough plan, but also theplan’s well done execution. Therefore, itis essential that thoughtful care andattention be taken in defining therequirements upfront in the devicedevelopment life cycle. The planningteam for any device program shouldconsist of representatives from all func-tional areas of the organization.However, at a minimum, the teamshould have representation from engi-neering, manufacturing, quality assur-ance, and regulatory functions. A mastervalidation plan needs to be developedfor every program. Although the mastervalidation plan is not required to complywith medical device industry regula-tions, it is one of the most sought afterdocuments by auditors and investigators.The contents of a typical master valida-tion plan in clude, but are not limited to:• Purpose and Scope• Responsibilities• Reference Documents• Product/Process Specifications

• Process Overview• Validation Approach• Risk Analysis• Project TimelineThis master validation plan will act as

a roadmap for the validation team andalso as a reference document for themanagement team to make sure enoughresources are available to develop adevice. A typical process validation flow-chart is shown in Figure 1.

Meticulousness (Quality andRegulatory Compliance)Organizations that develop medical

devices for distribution in the UnitedStates have to comply with federal regu-lations. Following are some of the stan-dards and guidance documents that areuseful in setting up the quality systemsfor a manufacturer to comply with themedical device industry’s regulatoryrequirements.21 CFR Part 820 – Medical Devices;Current Good Manufacturing Practice(CGMP) Final Rule; Quality SystemRegulation21 CFR Part 11 – Electronic Records;Electronic SignaturesISO 13485:2003 – Medical Devices-Quality Management Systems –Requirements for Regulatory PurposesISO 14971:2007 – Medical Devices-Application of Risk Management to Medical DevicesQSIT – Guide to Inspections of QualitySystemsGHTF/SG3/N99-10:2004 – FinalDocument, Process Validation GuidanceGeneral Principles of Software

Validation; Final Guidance for Industryand FDA Staff

Correctness (Process Validation/Objective Evidence)Process validation is defined as “estab-

lishing by objective evidence that theprocess consistently produces a result ora product meeting its predeterminedrequirements.” Any manufacturingprocess in which the output cannot beverified should be validated according to

Fig. 1 – Process Validation Flowchart (Credit:Donatelle Plastics Incorporated)

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the regulations. Typical examples ofprocesses that should be validated areinjection molding, welding, sterile pack-aging, sterilization, and manufacturingenvironment (clean room conditions,utilities, and facilities).

Process validation will be successfulonly when it is used as a confirmationtool, not as a fact finding tool. Processvalidation should be considered as anexercise of documenting the perform-ance of an already developed manufac-turing process that is under control toshow evidence that under a productionenvironment and challenged or antici-pated conditions, it will produce anacceptable product.Process validation activities include:• Assigning a multi-functional team• Defining requirements• Developing process flow diagrams• Performing risk analysis• Deciding on validation or verification• Creating a master validation plan• Developing validation protocols• Executing validation protocols• Developing validation reports• Determining process controlsManufacturing processes are much

more sophisticated now. The evolutionin technology demands new require-ments, such as equipment operationalqualifications and software validationsalong with the process validations.Process validations become much easierif an emphasis is placed on understand-ing process input and output variables,

along with product characteristics. Asthe definition of process validation sug-gests, its success depends on the use ofstatistical tools during the validation. As described by the International

Medical Device Regulators Forum,

Global Harmonization Task Force,www.imdr f .org/documents/doc -ght f -sg3.asp, typical statistical tools that canbe used during manufacturing processdevelopment and validation are:• Failure Modes and Effects Analysis(FMEA)• Tolerance Analysis• Measurement System Analysis (MSA)• Design of Experiments• Analysis of Variance• Control Charts• Histograms• Capability StudiesEvery statistical tool mentioned above

includes evaluation of data. The datacomes from a wide variety of sources.These sources are in the form of enduser requirements, material data, similarproduct data, and measurement data.Now, we will examine the source of datafor each tool and what you can glean outof that data to help you make the deci-sions needed during the medical devicemanufacturing process.

Failure Modes and Effects Analysis(FMEA): FMEA includes identifying thedevice critical characteristics and devel-oping the data pools for failure modes,causes, and their effects. Performingboth design FMEA and process FMEA is

critical to improve product and processreliability and quality. Analysis of thisdata will not only help in preventing fail-ures in the future, but also in developinga better product.

Tolerance Analysis: The toleranceanalysis tools will help in studying thedimensional relationships within theassembly and to determine individualpart tolerances.

Measurement System Analysis (MSA):MSA is one of the most important toolsto use during product and/or processdevelopment because the measurementsystem variations alone can influencethe decisions made for making thingsbetter or worse during the early stages ofdevelopment. The measurement systemneeds to be characterized by its accuracy,linearity, stability, repeatability, andreproducibility.

Design of Experiments and Analysisof Variance: Design of Experiments,which is also called ExperimentalDesign, can be used to understand theeffect of process variables on the prod-uct features. This analysis will help indetermining whether the process vari-able has any effect on the product fea-ture or not, and also help to establishcontrol limits on the same to mini-mize variation.

Capability Studies: Process capabili-ty studies are performed to analyzethe extent that the processes are capa-ble to meet the predeterminedrequirements when the processes areunder control. The process capabilitystudies compare the process output tothe specification limits.

Histograms and Control Charts:Histograms are used to understand thedata distribution and frequencies in acontinuous data. Control charts arehelpful in monitoring the behavior ofthe process over a time period. The con-trol charts can also be used to differenti-ate between common cause variationsand special cause variations. Over theyears, the manufacturing industry reliedup on the monitoring of process outputsto ensure that the processes are undercontrol. With the advent of technology,it has become much easier to monitorthe process itself to make sure no defec-tive product is produced. To accommo-date this, the relationship between theprocess variables and the product fea-

Fig. 2 – Process Capability Analysis (Credit: Donatelle Plastics Incorporated)

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tures needs to be established.Some of the statistical software prod-

ucts available in the market are capableof performing all the above mentionedanalyses. Figure 2 shows a graphical rep-resentation of process capability analysis.Device manufacturers need to pre-

pare and maintain a device masterrecord that contains product specifica-tions, process specifications, accept-ance activities, packaging, and labelingspecifications.

Exactitude (Maintaining theValidation State)Maintaining the validation state for

any manufacturing process used in theproduction of medical devices is animportant device life cycle activity. This

can be achieved by instituting processcontrols and continuous monitoring ofprocess parameters, as well as productfeatures. Monitoring process parametersthat affect product features will help inminimizing the product nonconfor-mance and costs associated with it.Validated manufacturing processes needto be performed by qualified individualstrained in device defects.

ConclusionPrecision manufacturing is not a

chance event, but a process developedusing scientific methodology. Decisionswill be made based upon the data,backed by sound statistical principles.Understanding the requirements, com-munication, and cooperation between

the functional areas, and training arethe foundations of an organization thatis striving for manufacturing excellence.Recent trends show medical device

manufacturing is being outsourced tocontract manufacturers. These trendsnecessitate due diligence on the devicedeveloper or manufacturer’s part tomake sure the contract manufacturersnot only comply with quality system reg-ulations, but also have appropriate per-sonnel with the necessary skills, experi-ence, and knowledge in medical devicemanufacturing.

This article was written by RaghuVadlamudi, Chief Research & TechnicalDirector, at Donatelle Plastics Inc., NewBrighton, MN. For more information, visithttp://info.hotims.com/49746-162.

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Eprinted and posted with permission to Donatelle from Medical Design Briefs

June © 2014 Associated Business Publications

Donatelle Plastics Incorporated

501 County Road E2 ExtensionNew Brighton, Minnesota 55112 USA

www.DonatelleMedical.com

Phone: (651) 633-420 0Email: info@Donatelle.net

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