fda medical device enforcement and quality system update

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FDA Medical FDA Medical Device Device Enforcement and Enforcement and Quality System Quality System UpdateUpdateKimberly TrautmanKimberly TrautmanFDA’s Medical Device Quality Systems FDA’s Medical Device Quality Systems ExpertExpertOffice of Compliance, CDRHOffice of Compliance, CDRH

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FDA Enforcement UpdateFDA Enforcement Update

Remarks by: Remarks by:

Margaret Hamburg, M.D.Margaret Hamburg, M.D.Commissioner of Food and DrugsCommissioner of Food and Drugs

"Effective Enforcement and Benefits to Public Health“ "Effective Enforcement and Benefits to Public Health“ August 6, 2009 August 6, 2009

FDA must be vigilant, strategic, quick and visibleFDA must be vigilant, strategic, quick and visible

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Post Inspection deadlines – 15 day Post Inspection deadlines – 15 day Warning Letter Response deadlineWarning Letter Response deadline

Decrease time between the inspection Decrease time between the inspection and issuance of a Warning Letterand issuance of a Warning Letter

Increase collaboration with regulatory Increase collaboration with regulatory partners such as local, state and partners such as local, state and international partnersinternational partners

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Prioritize enforcement follow-upPrioritize enforcement follow-up

Act swiftly and aggressively to Act swiftly and aggressively to protect the public healthprotect the public health

Warning Letter “Close Out” processWarning Letter “Close Out” process

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QS Regulation Cites by SubsystemQS Regulation Cites by Subsystem

P&PCP&PC CAPACAPA MGMTMGMT DCDC DOCDOC

820.50 820.50 820.120820.120

820.60 820.60 820.130820.130

820.70 820.70 820.140820.140

820.72 820.72 820.150820.150

820.75 820.75 820.160820.160

820.80 820.80 820.170820.170

820.86 820.86 820.200 820.200

820.250 820.250

820.90820.90

820.10820.1000

820.19820.1988

820.5820.5

820.20820.20

820.22820.22

820.25820.25

820.30820.30 820.40820.40

820.180820.180

820.181820.181

820.184820.184

820.186820.186

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Warning Letter Cites by QS Subsystem - 2008Warning Letter Cites by QS Subsystem - 2008

P&PCP&PC == 241241

CAPACAPA == 237237

DESIGNDESIGN == 155155

MGMTMGMT == 130130

DOCDOC == 82 82

------------------------------------------------------------------

TotalTotal == 845845

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Warning Letter Cites by QS Subsystem - 2008Warning Letter Cites by QS Subsystem - 2008

845

241 237155 130

82

0

100

200

300

400

500

600

700

800

900

TOTAL P&PC CAPA DESIGN MGMT DOC

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Top Ten Warning Letter Cites - 2008Top Ten Warning Letter Cites - 2008

21 CFR 820.2221 CFR 820.22 41 41

21 CFR 820.30(g)21 CFR 820.30(g) 28 28

21 CFR 820.198(a)21 CFR 820.198(a) 28 28

21 CFR 820.75(a)21 CFR 820.75(a) 27 27

21 CFR 820.100(a)21 CFR 820.100(a) 25 25

21 CFR 820.30(i)21 CFR 820.30(i) 21 21

21 CFR 820.18421 CFR 820.184 21 21

21 CFR 820.30(a)21 CFR 820.30(a) 20 20

21 CFR 820.80(d)21 CFR 820.80(d) 19 19

21 CFR 820.198(c)21 CFR 820.198(c) 19 19

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Warning Letters with CAPA Subsystem Warning Letters with CAPA Subsystem Cites 2008Cites 2008

January – December 2008January – December 2008

FDA issued 98 Warning FDA issued 98 Warning Letters to medical device Letters to medical device firms for QS/GMP firms for QS/GMP deficienciesdeficiencies

86/98 or 88% contained cites 86/98 or 88% contained cites for CAPA system deficiencies for CAPA system deficiencies

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Warning Letters CAPA Subsystem DataWarning Letters CAPA Subsystem Data

YearYear # WLs# WLs # w/ CAPA # w/ CAPA citecite

%%

20082008 9898 8686 8888

20072007 7474 6262 8484

20062006 7979 6969 8787

20052005 9797 8585 8888

20042004 113113 8989 7979

20032003 6969 6161 8888

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Warning Letters with P&PC Subsystem Warning Letters with P&PC Subsystem Cites 2008Cites 2008


FDA issued 98 Warning FDA issued 98 Warning Letters to medical device Letters to medical device firms for QS/GMP deficienciesfirms for QS/GMP deficiencies

80/98 or 82% contained cites 80/98 or 82% contained cites for P&PC subsystem for P&PC subsystem deficienciesdeficiencies

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Warning Letters with Design Control Warning Letters with Design Control Cites 2008Cites 2008


FDA issued 98 Warning Letters FDA issued 98 Warning Letters to medical device firms for to medical device firms for QS/GMP deficienciesQS/GMP deficiencies

54/98 or 55% contained cites 54/98 or 55% contained cites for Design Control deficienciesfor Design Control deficiencies

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Warning Letters Design Control Warning Letters Design Control Subsystem DataSubsystem Data

YearYear # WLs# WLs # w/ DC cite# w/ DC cite %%

20082008 9898 5454 5555

20072007 7474 4242 5757

20062006 7979 4747 6060

20052005 9797 4949 5151

20042004 113113 5757 5050

20032003 6969 3939 5757

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Quality System Hot Quality System Hot TopicsTopics

Supplier ControlsSupplier Controls

Corrective and Preventive ActionsCorrective and Preventive Actions

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What is unique about What is unique about medical devices?medical devices?

Medical Devices utilize a wide range of supplied Medical Devices utilize a wide range of supplied products and servicesproducts and services

Supplied products:Supplied products:

Finished medical devices or Finished medical devices or accessories in the case of kits or accessories in the case of kits or device systemsdevice systems

Electronic parts to include anything Electronic parts to include anything from individual resistors, capacitors, from individual resistors, capacitors, etc. to completed hybrid boardsetc. to completed hybrid boards

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Supplied products:Supplied products:

Raw materials such as Raw materials such as chemicals, polymers, metals, chemicals, polymers, metals, etc.etc.Software packagesSoftware packagesAntibodies, antigens, etc. for in-Antibodies, antigens, etc. for in-vitro diagnostic productsvitro diagnostic productsFinished drugs or APIs in the Finished drugs or APIs in the case of combination productscase of combination products

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Supplied services:Supplied services:

Contract manufacturersContract manufacturers

Contract laboratoriesContract laboratories

Contract sterilizersContract sterilizers

Calibration test housesCalibration test houses

Contract installers and service Contract installers and service providersproviders

AuditorsAuditors

ConsultantsConsultants

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Further the supplied products and Further the supplied products and services cover the entire range services cover the entire range from a risk perspective.from a risk perspective.

Same supplied product or service Same supplied product or service for one manufacturer may not have for one manufacturer may not have the same risks depending upon the same risks depending upon multiple factors.multiple factors.

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Same supplier for one product or Same supplier for one product or service may have different risks for service may have different risks for a different supplied product or a different supplied product or service.service.

Be wary of utilization of supplier Be wary of utilization of supplier audits without understanding the audits without understanding the scope of the previous supplier scope of the previous supplier audit.audit.

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Quality System (QS) Quality System (QS) RegulationRegulation21 CFR 820.50 21 CFR 820.50 Purchasing ControlsPurchasing Controls

Each manufacturer shall establish Each manufacturer shall establish and maintain procedures to ensure and maintain procedures to ensure that all purchased or otherwise that all purchased or otherwise received product and services received product and services conform to specified requirements.conform to specified requirements.

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Quality System (QS) Quality System (QS) RegulationRegulation21 CFR 820.50(a)21 CFR 820.50(a)

(a) Evaluation of suppliers, (a) Evaluation of suppliers, contractors, and consultants. Each contractors, and consultants. Each manufacturer shall establish and manufacturer shall establish and maintain the requirements, maintain the requirements, including quality requirementsincluding quality requirements, that , that must be met by suppliers, must be met by suppliers, contractors, and consultants. Each contractors, and consultants. Each manufacturer shall:manufacturer shall:

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21 CFR 820.50(a) 21 CFR 820.50(a) Purchasing ControlsPurchasing Controls

(1) Evaluate and select potential (1) Evaluate and select potential suppliers, contractors, and suppliers, contractors, and consultants on the basis of their consultants on the basis of their ability to meet specified ability to meet specified requirements, including quality requirements, including quality requirements. The evaluation shall requirements. The evaluation shall be documented.be documented.

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21 CFR 820.50(a) 21 CFR 820.50(a) Purchasing ControlsPurchasing Controls

(2) (2) Define the type and extent of control Define the type and extent of control to be exercisedto be exercised over the product, over the product, services, suppliers, contractors, services, suppliers, contractors, and consultants, based on the and consultants, based on the evaluation results.evaluation results.

(3) Establish and maintain records of (3) Establish and maintain records of acceptable suppliers, contractors, acceptable suppliers, contractors, and consultants.and consultants.

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21 CFR 820.50(b) 21 CFR 820.50(b) Purchasing DataPurchasing Data

(b) Purchasing data. Each (b) Purchasing data. Each manufacturer shall establish and manufacturer shall establish and maintain data that clearly describe maintain data that clearly describe or reference the specified or reference the specified requirements, requirements, including quality including quality requirementsrequirements, for purchased , for purchased

or otherwise received product and or otherwise received product and services.services.

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21 CFR 820.50(b) 21 CFR 820.50(b) Purchasing DataPurchasing Data

Purchasing documents shall include, Purchasing documents shall include, where possible, an agreement that where possible, an agreement that the suppliers, contractors, and the suppliers, contractors, and consultants agree to notify the consultants agree to notify the manufacturer of changes in the manufacturer of changes in the product or service so that product or service so that manufacturers may determine manufacturers may determine whether the changes may affect the whether the changes may affect the quality of a finished device. quality of a finished device. Purchasing data shall be approved in Purchasing data shall be approved in accordance with Sec. 820.40.accordance with Sec. 820.40.

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Preamble to the 1996 QS Preamble to the 1996 QS RegulationRegulationComment #99Comment #99

Since FDA is not regulating Since FDA is not regulating component suppliers, FDA believes component suppliers, FDA believes that the explicit addition to CGMP that the explicit addition to CGMP requirements of the purchasing requirements of the purchasing controls of ISO 9001:1994 is controls of ISO 9001:1994 is necessary…necessary…

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To ensure purchased or otherwise To ensure purchased or otherwise received product or services conform received product or services conform to specifications, purchasing must be to specifications, purchasing must be carried out under adequate controls, carried out under adequate controls, including the including the assessment and selectionassessment and selection of suppliers, contractors, and of suppliers, contractors, and consultants, consultants,

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the the clear and unambiguous specification clear and unambiguous specification of requirementsof requirements, and the , and the performance of performance of suitable acceptance activitiessuitable acceptance activities. Each . Each manufacturer must establish an manufacturer must establish an appropriate mix of assessment and appropriate mix of assessment and receiving acceptance to ensure receiving acceptance to ensure products and services are acceptable products and services are acceptable for their intended uses. ..for their intended uses. ..

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FDA generally believes that an appropriate FDA generally believes that an appropriate mix of supplier and manufacturer quality mix of supplier and manufacturer quality controls are necessary. However, finished controls are necessary. However, finished device manufacturers who conduct product device manufacturers who conduct product quality control solely in-house must also quality control solely in-house must also assess the capability of suppliers to assess the capability of suppliers to provide acceptable product. Where audits provide acceptable product. Where audits are not practical, this may be done are not practical, this may be done through, among other means, reviewing through, among other means, reviewing historical data, monitoring and trending, historical data, monitoring and trending, and inspection and testing.and inspection and testing.

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Thus the degree of supplier control Thus the degree of supplier control necessary to establish compliance may necessary to establish compliance may vary with the type and significance of vary with the type and significance of the product or service purchased and the product or service purchased and the impact of that product or service on the impact of that product or service on the quality of the finished device.the quality of the finished device.

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Thus, a manufacturer must comply Thus, a manufacturer must comply with these provisions when it receives with these provisions when it receives product or services from its ``sister product or services from its ``sister facility'' or some other corporate or facility'' or some other corporate or financial affiliate. ``Otherwise financial affiliate. ``Otherwise received product'' would include received product'' would include ``customer supplied product'' as in ``customer supplied product'' as in ISO 9001:1994, section 4.7, but would ISO 9001:1994, section 4.7, but would not apply to ``returned product'' from not apply to ``returned product'' from the customer.the customer.

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……FDA believes that all suppliers of FDA believes that all suppliers of such services must be assessed and such services must be assessed and evaluated, just like a supplier of a evaluated, just like a supplier of a product. As always, the degree of product. As always, the degree of control necessary is related to the control necessary is related to the product or service purchased…product or service purchased…

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……certification may play a role in certification may play a role in evaluating suppliers, but cautions evaluating suppliers, but cautions manufacturers against relying solely on manufacturers against relying solely on certification by third parties as evidence certification by third parties as evidence that suppliers have the capability to that suppliers have the capability to provide quality products or services. FDA provide quality products or services. FDA has found during inspections that some has found during inspections that some manufacturers who have been certified to manufacturers who have been certified to the ISO standards have not had the ISO standards have not had acceptable problem identification and acceptable problem identification and corrective action programs. corrective action programs.

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Therefore, the initial assessment or Therefore, the initial assessment or evaluation, depending on the type evaluation, depending on the type and potential effect on device quality and potential effect on device quality of the product or service, should be a of the product or service, should be a combination of assessment methods, combination of assessment methods, to possibly include third party or to possibly include third party or product certification. product certification.

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However, third party certification However, third party certification should not be relied on exclusively in should not be relied on exclusively in initially evaluating a supplier. If a initially evaluating a supplier. If a device manufacturer has established device manufacturer has established confidence in the supplier's ability to confidence in the supplier's ability to provide acceptable products or provide acceptable products or services, certification with test data services, certification with test data may be acceptable.may be acceptable.

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The intent of Sec. 820.50 is to The intent of Sec. 820.50 is to ensure that device manufacturers ensure that device manufacturers select only those suppliers, select only those suppliers, contractors, and consultants who contractors, and consultants who have the capability to provide have the capability to provide quality product and services. As quality product and services. As with finished devices, quality with finished devices, quality cannot be inspected or tested into cannot be inspected or tested into products or services. products or services.

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Rather, the quality of a product or Rather, the quality of a product or service is established service is established during the designduring the design of that product or service, and of that product or service, and achieved through proper control of achieved through proper control of the manufacture of that product or the manufacture of that product or the performance of that service…the performance of that service…

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Quality System (QS) Quality System (QS) RegulationRegulation21 CFR 820.30 Design 21 CFR 820.30 Design ControlsControls

820.30(c) Design Input820.30(c) Design Input

……ensure that the design requirements ensure that the design requirements relating to a device are appropriate and relating to a device are appropriate and address the intended use of the device, address the intended use of the device, including the needs of the user and including the needs of the user and patient…patient…

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820.30(d) Design Output820.30(d) Design Output

……shall contain or make reference to shall contain or make reference to acceptance criteria and shall ensure acceptance criteria and shall ensure that those design outputs that are that those design outputs that are essential for the proper functioning essential for the proper functioning of the device are identified…of the device are identified…

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820.30(g) Design Validation820.30(g) Design Validation

Design validation shall ensure that Design validation shall ensure that devices conform to defined user needs devices conform to defined user needs and intended uses and shall include and intended uses and shall include testing of production units under testing of production units under actual or simulated use conditions. actual or simulated use conditions. Design validation shall include Design validation shall include software validation and software validation and risk analysisrisk analysis......

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……Section 820.80 is specific to a device Section 820.80 is specific to a device manufacturer's acceptance program. manufacturer's acceptance program. While finished device manufacturers While finished device manufacturers are required to assess the capability of are required to assess the capability of suppliers, contractors, and consultants suppliers, contractors, and consultants to provide quality products and to provide quality products and services, inspections and tests, and services, inspections and tests, and other verification tools, are also an other verification tools, are also an important part of ensuring that important part of ensuring that components and finished devices components and finished devices conform to approved specifications.conform to approved specifications.

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Quality System (QS) Quality System (QS) RegulationRegulation21 CFR 820.80 21 CFR 820.80 Acceptance ActivitiesAcceptance Activities

820.80(a) General820.80(a) General

Each manufacturer shall establish Each manufacturer shall establish and maintain procedures for and maintain procedures for acceptance activities. Acceptance acceptance activities. Acceptance activities include inspections, tests, activities include inspections, tests, or other verification activities….or other verification activities….

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The extent of incoming acceptance The extent of incoming acceptance activities can be based, in part, on the activities can be based, in part, on the degree to which the supplier has degree to which the supplier has demonstrated a capability to provide demonstrated a capability to provide quality products or services. An quality products or services. An appropriate product and services appropriate product and services quality assurance program includes a quality assurance program includes a combination of assessment combination of assessment techniques, including inspection and techniques, including inspection and test.test.

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Purchasing Controls and Purchasing Controls and Acceptance Activities Acceptance Activities Commensurate to the Commensurate to the RiskRisk

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Global Harmonization Global Harmonization Task Force (GHTF) Task Force (GHTF) Guidance documentGuidance document

GHTF Study Group 3 Final Guidance:GHTF Study Group 3 Final Guidance:

Quality Management System – Quality Management System – Medical Devices – Guidance on the Medical Devices – Guidance on the Control of Products and Services Control of Products and Services Obtained from Suppliers Obtained from Suppliers

Posted Feb. 5, 2009Posted Feb. 5, 2009http://www.ghtf.org/documents/sg3/sg3final-N17.pdf

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Global Harmonization Task Global Harmonization Task Force (GHTF) Study Group 3Force (GHTF) Study Group 3

Drafting a guidance document:Drafting a guidance document:

Proposed Document for Comment estimated Proposed Document for Comment estimated to be published in Dec 2009.to be published in Dec 2009.

““Quality Management System –Medical Quality Management System –Medical Devices – Guidance on corrective action and Devices – Guidance on corrective action and preventive action and related QMS preventive action and related QMS processes”processes”

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Key TermsKey Terms

Correction:Correction: repair, rework, or adjustment and relates repair, rework, or adjustment and relates to the disposition of an to the disposition of an existingexisting nonconformity. nonconformity.

Corrective Action:Corrective Action: the action taken to eliminate the the action taken to eliminate the causes of an causes of an existingexisting nonconformity, defect or other nonconformity, defect or other undesirable situation in order to prevent recurrence.undesirable situation in order to prevent recurrence.

Preventative Action:Preventative Action: action taken to eliminate the action taken to eliminate the cause of a cause of a potentialpotential nonconformity, defect, or other nonconformity, defect, or other undesirable situation in order to prevent occurrence.undesirable situation in order to prevent occurrence.

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CAPA SummaryCAPA Summary

Coordination / linkage of data / data sources (review and analysis of data sources)

Planning for Measurement, Monitoring, Analysis & Improvement processes

Management Review

Improvement

InvestigationsRoot Cause

Specific & System

Identify Actions

Verify future Action before Implementation

Implement

Determine Effectiveness(Measuring & Monitoring)

Establish Data Sources and Criteria

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Providing Industry Providing Industry AssistanceAssistanceCDRH ResourcesCDRH Resources

CDRH Learn CDRH Learn [New][New]Modules include various premarket and post-market informationModules include various premarket and post-market informationAvailable 24/7Available 24/7Certificate generated per topic upon passing post-testsCertificate generated per topic upon passing post-testsSuggest Future topicsSuggest Future topicshttp://www.fda.gov/cdrh/cdrhlearn/

Device AdviceDevice AdviceSelf-service website Self-service website Searchable by topicSearchable by topichttp://www.fda.gov/cdrh/devadvice/

Division of Small Manufacturers, International, and Consumer Division of Small Manufacturers, International, and Consumer Assistance (DSMICA)Assistance (DSMICA)

Technical Assistance for the Medical Device IndustryTechnical Assistance for the Medical Device Industry800-638-2041 or 240-276-3150800-638-2041 or [email protected]

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Providing Industry Providing Industry AssistanceAssistanceCDRH LearnCDRH Learn

What is CDRH Learn?What is CDRH Learn?NewNew Online Training tool Online Training tool Multi-Media Presentation Multi-Media Presentation Available 24/7Available 24/7Certificate generated per topic upon passing post-testsCertificate generated per topic upon passing post-testsSuggest Future topicsSuggest Future topics

Examples of ModulesExamples of ModulesOverview of Regulatory Requirements: Medical Devices Overview of Regulatory Requirements: Medical Devices Quality System Regulation 21 CFR 820 Basic IntroductionQuality System Regulation 21 CFR 820 Basic IntroductionOverview of the Premarket Notification Process – 510(k)Overview of the Premarket Notification Process – 510(k)How to Get Your Electronic Product on the U.S. Market. How to Get Your Electronic Product on the U.S. Market. BIMO BIMO (under development)(under development)Registration & Listing Registration & Listing (under development)(under development)

http://www.fda.gov/cdrh/cdrhlearn/

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Thank you!Thank you!

Kimberly TrautmanKimberly Trautman

FDA’s Medical Device Quality FDA’s Medical Device Quality Systems Expert Systems Expert

Office of ComplianceOffice of Compliance

[email protected]@fda.hhs.gov

fda medical device enforcement and quality system update

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