US FDA System Regulation Vs. ISO 13485:2016 Quality .
US FDA QUALITYSYSTEM REGULATIONVERSUS ISO 13485:2016QUALITY MANAGEMENTSYSTEM REQUIREMENTS
NSF INTERNATIONAL 21 CFR § 820 &ISO 13485:2016 ALIGNMENT CHARTAuthor: Robert Ruff, Executive Director, NSF InternationalResearcher: Samuel Brown, Research Associate, NSF InternationalThis tool clarifies the corresponding relationships between the US FDA Quality System Regulation and ISO 13485:2016– Medical devices – Quality management systems – Requirements for regulatory purposes clauses. Use this tool toensure your quality management system meets applicable requirements of both US FDA and ISO 13485:201621 CFR § 820US FDA QUALITY SYSTEM REGULATION ISO 13485:2016820.1 Scope1 Scope820.5 QualitySystemEach manufacturer shall establish andmaintain a quality system that is appropriatefor the specific medical device(s) designedor manufactured, and that meets therequirements of this part.820.20(a)Quality PolicyManagement with executive responsibilityshall establish its policy and objectives for,and commitment to, quality. Managementwith executive responsibility shall ensurethat the quality policy is understood,implemented, and maintained at all levels ofthe organization.820.20(b)OrganizationEach manufacturer shall establish andmaintain an adequate organizational structureto ensure that devices are designed andproduced in accordance with the requirementsof this part.5.5.1Responsibility andAuthorityNo significant difference in requirements.820.20(b)(1)Responsibilityand AuthorityEach manufacturer shall establish theappropriate responsibility, authority, andinterrelation of all personnel who manage,perform, and assess work affecting quality,and provide the independence and authoritynecessary to perform these tasks.5.5.1Responsibility andAuthorityNo significant difference in requirements.820.20(b)(2)ResourcesEach manufacturer shall provide adequateresources, including the assignment of trainedpersonnel, for management, performanceof work, and assessment activities, includinginternal quality audits, to meet therequirements of this part.6.1 Provision ofResourcesNo significant difference in requirements.5.5.2ManagementRepresentativeISO 13485:2016 specifies the managementrepresentative has responsibility and authorityto ensure the promotion of awareness ofapplicable regulatory requirements andquality management system requirementsthroughout the anagement with executive responsibilityshall appoint, and document suchappointment of, a member of managementwho, irrespective of other responsibilities,shall have established authority over andresponsibility for:(i) Ensuring that quality system requirementsare effectively established and effectivelymaintained in accordance with this part;and(ii) Reporting on the performance of thequality system to management withexecutive responsibility for review.2SPECIFIC DIFFERENCES4.1.1 Qualitymanagementsystem, Generalrequirements5.3 Quality Policy5.4.1 QualityObjectivesNo significant difference in requirements.ISO 13485:2016 specifies additional detailrelative to quality policy. For example: 5.3 b),5.3 e). ISO 13485:2016 specifically requiresthe quality objectives to be measurable.
21 CFR § 820US FDA QUALITY SYSTEM REGULATION ISO 13485:2016820.20(c)ManagementReviewManagement with executive responsibilityshall review the suitability and effectivenessof the quality system at defined intervalsand with sufficient frequency according toestablished procedures to ensure that thequality system satisfies the requirements ofthis part and the manufacturer’s establishedquality policy and objectives. The dates andresults of quality system reviews shall bedocumented.820.20(d)Quality PlanningEach manufacturer shall establish a qualityplan which defines the quality practices,resources, and activities relevant to devicesthat are designed and manufactured.The manufacturer shall establish how therequirements for quality will be met.820.20(e)Quality SystemProceduresEach manufacturer shall establish qualitysystem procedures and instructions. Anoutline of the structure of the documentationused in the quality system shall be establishedwhere appropriate.820.22 QualityAuditEach manufacturer shall establish proceduresfor quality audits and conduct such auditsto assure that the quality system is incompliance with the established qualitysystem requirements and to determine theeffectiveness of the quality system. Qualityaudits shall be conducted by individualswho do not have direct responsibility for thematters being audited. Corrective action(s),including a reaudit of deficient matters, shallbe taken when necessary. A report of theresults of each quality audit, and reaudit(s)where taken, shall be made and such reportsshall be reviewed by management havingresponsibility for the matters audited. Thedates and results of quality audits andreaudits shall be documented.820.25(a)Personnel,GeneralEach manufacturer shall have sufficientpersonnel with the necessary education,background, training, and experience toassure that all activities required by this partare correctly performedEach manufacturer shall establish proceduresfor identifying training needs and ensurethat all personnel are trained to adequatelyperform their assigned responsibilities.Training shall be documented.820.25(b)Personnel,Training(1) As part of their training, personnelshall be made aware of device defectswhich may occur from the improperperformance of their specific jobs.(2) Personnel who perform verificationand validation activities shall be madeaware of defects and errors that may beencountered as part of their job functions.5.6 ManagementReview5.6.1 General5.6.2 ReviewInput5.6.3 ReviewOutput5.4.2 QualityManagementSystem Planning4.2 DocumentationRequirements4.2.1 General4.2.2 QualityManualSPECIFIC DIFFERENCESISO 13485:2016 specifies: (1) assessingopportunities for improvement and the needfor changes to the QMS; and (2) specificrequirements for management review inputand output.ISO 13485:2016 specifies 5.4.2 Topmanagement shall ensure that: b) Theintegrity of the quality managementsystem is maintained when changes to thequality management system are plannedand implemented.21 CFR § 820 specifies an outline of thestructure of the documentation used in thequality system; and ISO 13485:2016 specifiesa Quality Manual.21 CFR § 820 specifies the date of theaudit be documented and the audit reportsmust be reviewed by management havingresponsibility for the matters audited.8.2.4 InternalAuditISO 13485:2016 specifies requirements forthe management responsible for the areabeing audited to ensure that correctionsand corrective actions are taken withoutundue delay;ISO 13485:2016 also specifies theverification of the actions taken andreports of the verification results.6.1 Provision ofResources6.2 HumanResources6.2 HumanResources6.4.1(b) WorkEnvironmentNo significant difference in requirements.ISO 13485:2016 specifies more detailthan 21 CFR § 820 and addresses“competence” as opposed to training(e.g. competence via education, skills,experience).21 CFR § 820 specifies requirements for:(1) personnel performing verification andvalidation activities, and (2) 21 CFR § 820states that personnel shall be made awareof device defects which may occur fromimproper performance of their jobs.3
21 CFR § 820US FDA QUALITY SYSTEM REGULATION ISO 13485:2016SPECIFIC DIFFERENCES(1) Each manufacturer of any class III orclass II device, and the class I deviceslisted in paragraph (a)(2) of this section,shall establish and maintain proceduresto control the design of the device inorder to ensure that specified designrequirements are met.(2) The following class I devices are subjectto design controls:820.30(a)Design Controls,General(i) Devices automated with computersoftware; and(ii) The devices listed in the followingchart.Section7.3.1 General21 CFR § 820 specifies exclusions fromdesign control requirements based on therisk of the device (i.e. class I devices otherthan those cited).Device868.6810 Catheter, TracheobronchialSuction.878.4460 Glove, Surgeon’s.880.6760 Restraint, Protective.892.5650 System, Applicator, Radionuclide,Manual.892.5740 Source, Radionuclide Teletherapy.4820.30(b)Design andDevelopmentPlanningEach manufacturer shall establish and maintainplans that describe or reference the design anddevelopment activities and define responsibilityfor implementation. The plans shall identifyand describe the interfaces with differentgroups or activities that provide, or result in,input to the design and development process.The plans shall be reviewed, updated, andapproved as design and development evolves.820.30(c)Design InputEach manufacturer shall establish andmaintain procedures to ensure that thedesign requirements relating to a device areappropriate and address the intended use ofthe device, including the needs of the userand patient. The procedures shall includea mechanism for addressing incomplete,ambiguous, or conflicting requirements.The design input requirements shall bedocumented and shall be reviewed andapproved by a designated individual(s). Theapproval, including the date and signature ofthe individual(s) approving the requirements,shall be documented.7.3.3 Design anddevelopmentinputs820.30(d)Design OutputEach manufacturer shall establish and maintainprocedures for defining and documentingdesign output in terms that allow an adequateevaluation of conformance to design inputrequirements. Design output procedures shallcontain or make reference to acceptancecriteria and shall ensure that those designoutputs that are essential for the properfunctioning of the device are identified.Design output shall be documented, reviewed,and approved before release. The approval,including the date and signature of theindividual(s) approving the output, shall bedocumented.7.3.4 Design anddevelopmentoutputs21 CFR § 820 requires documented designplans.7.3.2 Design anddevelopmentplanningISO 13485:2016 does not require adocumented design and development plan,but does require the documentation ofinformation specified in 7.3.2 a) - f) duringdesign and development planning.21 CFR § 820 specifies the documentationof the date and signature of the individual(s)approving the design inputs.ISO 13485:2016 specifies specific inputs;including applicable output(s) of riskmanagement.ISO 13485:2016 specifies "b) provideappropriate information for purchasing,production and service provision."
21 CFR § 820US FDA QUALITY SYSTEM REGULATION ISO 13485:2016820.30(e)Design ReviewEach manufacturer shall establish and maintainprocedures to ensure that formal documentedreviews of the design results are plannedand conducted at appropriate stages of thedevice's design development. The proceduresshall ensure that participants at each designreview include representatives of all functionsconcerned with the design stage beingreviewed and an individual(s) who does nothave direct responsibility for the design stagebeing reviewed, as well as any specialistsneeded. The results of a design review,including identification of the design, the date,and the individual(s) performing the review,shall be documented in the design history file(the DHF).7.3.5 Design anddevelopmentreview820.30(f) DesignVerificationEach manufacturer shall establish and maintainprocedures for verifying the device design.Design verification shall confirm that the designoutput meets the design input requirements.The results of the design verification, includingidentification of the design, method(s), thedate, and the individual(s) performing theverification, shall be documented in the DHF.820.30(g)DesignValidationEach manufacturer shall establish andmaintain procedures for validating the devicedesign. Design validation shall be performedunder defined operating conditions on initialproduction units, lots, or batches, or theirequivalents. Design validation shall ensurethat devices conform to defined user needs7.3.7 Design andand intended uses A1:D91 shall includedevelopmenttesting of production units under actual orvalidationsimulated use conditions. Design validation shallinclude software validation and risk analysis,where appropriate. The results of the designvalidation, including identification of the design,method(s), the date, and the individual(s)performing the validation, shall be documentedin the DHF.820.30(h)Design TransferEach manufacturer shall establish andmaintain procedures to ensure that the devicedesign is correctly translated into productionspecifications.7.3.6 Design anddevelopmentverification7.3.8 Design anddevelopmenttransferSPECIFIC DIFFERENCES21 CFR § 820 specifies design reviewsinclude "individual(s) who does not havedirect responsibility for the design stagebeing reviewed".ISO 13485:2016 specifies that reviews will"identify and propose necessary actions".ISO 13485:2016 specifies requirements forverification of connectivity or interfaces withother medical devices as applicable.21 CFR § 820 specifies that the individual(s)performing the verification and the date ofthe activity be documented.ISO 13485:2016 specifies requirementsfor validation of the device while connectedto or interfaced with other medical devicesas applicable.ISO 13485:2016 specifies “the organizationshall perform clinical evaluations orperformance evaluations of the medicaldevice in accordance with applicableregulatory requirements” - which is notexplicit to 21 CFR § 820 - but is expected asdiscussed in the preamble comment 65.21 CFR § 820 specifies additionaldocumentation requirements such as thedocumentation (within the DHF) of the dateand individuals performing the validation.ISO 13485:2016 specifies "that design anddevelopment outputs are verified as suitablefor manufacturing before becoming finalproduction specifications and that productioncapability can meet product requirements".While this is not explicitly stated in 21CFR § 820, it is the expectation of designverification activities as well as design transferactivities. Comment 86 of the QSR Preamblestates "The intent of the requirement was toensure that all design specifications releasedto production have been approved, verified,and validated before they are implementedas part of the production process."5
21 CFR § 8206US FDA QUALITY SYSTEM REGULATION ISO 13485:2016SPECIFIC DIFFERENCES820.30(i) DesignChangesEach manufacturer shall establish andmaintain procedures for the identification,documentation, validation or where appropriateverification, review, and approval of designchanges before their implementation.7.3.9Control of designand developmentchangesISO 13485:2016 specifies additionalrequirements. For example: ISO 13485:2016specifies (1) "The review of design anddevelopment changes shall includeevaluation of the effect of the changes onconstituent parts and product in processor already delivered, inputs or outputs ofrisk management and product realizationprocesses" and (2) "The organization shalldetermine the significance of the change tofunction, performance, usability, safety andapplicable regulatory requirements for themedical device."820.30(j) DesignHistory FileEach manufacturer shall establish and maintaina DHF for each type of device. The DHF shallcontain or reference the records necessary todemonstrate that the design was developed inaccordance with the approved design plan andthe requirements of this part.7.3.10 Design anddevelopment filesNo significant difference in requirements.820.40DocumentControlsEach manufacturer shall establish and maintainprocedures to control all documents that arerequired by this part. The procedures shallprovide for the following:820.40(a)Documentapproval anddistributionEach manufacturer shall designate anindividual(s) to review for adequacy andapprove prior to issuance all documentsestablished to meet the requirements of thispart. The approval, including the date andsignature of the individual(s) approving thedocument, shall be documented. Documentsestablished to meet the requirements of thispart shall be available at all locations forwhich they are designated, used, or otherwisenecessary, and all obsolete documents shallbe promptly removed from all points of use orotherwise prevented from unintended use.820.40(b)DocumentChangesChanges to documents shall be reviewedand approved by an individual(s) in the samefunction or organization that performed theoriginal review and approval, unless specificallydesignated otherwise. Approved changes shallbe communicated to the appropriate personnelin a timely manner. Each manufacturer shallmaintain records of changes to documents.Change records shall include a descriptionof the change, identification of the affecteddocuments, the signature of the approvingindividual(s), the approval date, and when thechange becomes effective.4.2.4 Control ofdocuments4.2.5 Control ofrecords4.2.4 Control ofdocuments4.2.5 Control ofrecordsNo significant difference in requirements.21 CFR § 820 specifies the documentationof the date and signature of the individual(s)approving the document.ISO 13485:2016 specifies documentedprocedures to “ensure that documentsof external origin, determined by theorganization to be necessary for the planningand operation of the quality managementsystem, are identified and their distributioncontrolled.”21 CFR § 820 specifies that approvedchanges be communicated to appropriatepersonnel in a timely manner.4.2.4 Control ofdocuments21 CFR § 820 specifies “Change recordsshall include a description of the change,identification of the affected documents,the signature of the approving individual(s),the approval date, and when the changebecomes effective.”
21 CFR § 820820.50PurchasingControlsUS FDA QUALITY SYSTEM REGULATION ISO 13485:2016Each manufacturer shall establish andmaintain procedures to ensure that allpurchased or otherwise received productand services conform to specifiedrequirements.4.1.5 QMS GeneralRequirements7.4.1 Purchasingprocess820.50(a)Evaluationof Suppliers,Contractors,and ConsultantsISO 13485:2016 specifies written qualityagreements between the organization andsuppliers.21 CFR § 820 requires “. purchased orotherwise received product” to be includedin the Purchasing Controls procedures.ISO 13485:2016 limits its requirement topurchased product.Each manufacturer shall establish andmaintain the requirements, includingquality requirements, that must be metby suppliers, contractors, and consultants.Each manufacturer shall:(1) Evaluate and select potential suppliers,contractors, and consultants on thebasis of their ability to meet specifiedrequirements, including qualityrequirements. The evaluation shall bedocumented.SPECIFIC DIFFERENCES7.4.1Purchasingprocess(2) Define the type and extent of control tobe exercised over the product, services,suppliers, contractors, and consultants,based on the evaluation results.ISO 13485:2016 specifies purchasingcriteria to be "d) proportionate to therisk associated with the medical device."Although not explicitly stated in 21 CFR §820, comment 115 of the QSR Preamblediscusses this requirement.ISO 13485:2016 specifies requirementsrelative to the re-evaluation of suppliers.Although not explicitly stated in 21 CFR§ 820, comment 105 of the preamblediscusses this requirement.(3) Establish and maintain records ofacceptable suppliers, contractors, andconsultants.820.50(b)Purchasing DataEach manufacturer shall establish andmaintain data that clearly describe orreference the specified requirements,including quality requirements, forpurchased or otherwise received productand services. Purchasing documents shallinclude, where possible, an agreement thatthe suppliers, contractors, and consultantsagree to notify the manufacturer ofchanges in the product or service so thatmanufacturers may determine whether thechanges may affect the quality of a finisheddevice. Purchasing data shall be approved inaccordance with 820.40.820.60IdentificationEach manufacturer shall establish andmaintain procedures for identifying productduring all stage
include software validation and risk analysis, where appropriate. The results of the design validation, including identification of the design, method(s), the date, and the individual(s) performing the validation, shall be documented in the DHF. 7.3.7 Design and development validation ISO 13485:2016 specifies requirements
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