MEDICAL DEVICE COMPLIANCE The Who, What and How

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MEDICAL DEVICE COMPLIANCEThe Who, What and How
Carolyn Algar
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What is Compliance?

• A state of being in accordance with established
  guidelines, specifications, or legislation
• or
• The process of becoming so.

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Medical Device Definition

• A medical device is an instrument, apparatus,
  appliance, implement, machine, contrivance,
  implant, in vitro reagent, software, material, or
  other similar or related article, including a
  component part, or accessory which is
• intended for use in the diagnosis of disease or
  other conditions, or in the cure, alleviation,
  mitigation, treatment, or prevention of disease,
  in man or other animals (US) or
• intended to affect the structure or any function
  of the body of man or other animals, but which
  does not achieve its principal intended action in
  or on the human body by pharmacological,
  immunological or metabolic means, but which may
  be assisted in its function by such means

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Is Software a Medical Device?

• Software can be a device by itself (standalone),
  or it can be incorporated into another device,
  either as a component or part, or distributed
  separately for use as an accessory to another
  device.

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Medical Device Classification

• Class I. (low risk)
• subjected to minimal regulation
• Not intended to be
• For use in supporting or sustaining life.
• Of importance in preventing impairment to human
  life.
• And may not present a potential unreasonable risk
  of illness or injury.
• E.g. elastic bandages, tongue depressors, enema
  kits, band aids, gauze
• Class II (medium risk)
• general controls not sufficient to provide
  reasonable assurances of their safety and
  effectiveness.
• Must meet performance standards.
• E.g. powered wheelchairs, infusion pumps,
  surgical drapes, syringes, catheters,
  electrocardiographs
• Class III (highest risk)
• Most rigidly controlled.
• General controls judged insufficient to provide
  reasonable assurances of their safety and
  effectiveness and sufficient information does not
  exist to establish performance standards.
• Usually used to support or sustain human life,
  or substantial importance in preventing
  impairment of human health.
• E.g. replacement heart valves, implanted
  cerebella stimulators, cardiac pacemakers,
  angioplasty balloons

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Medical Device Classification

• Class I General Controls
• Most with exemptions 1
• Few without exemptions
• Class II General Controls and Special Controls
• Few with exemptions 1
• Most without exemptions
• Class III General Controls and Premarket
  Approval

• The higher the class, the greater the level of
  assessment

1 Except from Pre-market Notification
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Why formalize my system?

• Process and product/service control to ensure
  that customer specifications are consistently met
• Legislative requirements have been met
• Procedures are in place in the event of a product
  recall, withdrawal or a customer complaint or in
  the event that product/service non-conformance is
  identified during the production phase
• Training procedures are established, documented
  and implemented
• Processes and procedures are regularly reviewed
  and enhanced or improved where necessary

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CE Marking
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Where and What?

• The CE Marking applies only to products placed in
  the market or put into service in the European
  Economic Area (currently 27 countries)
• The CE Marking is required only for the following
  types of products-Toys-Machinery-Electrical
  and electronic equipment-Personal protective
  equipment-Pressure equipment-Medical
  devices-Active implantable medical devices-In
  vitro diagnostica-Simple pressure vessels
• -Radio and Telecommunications
• terminal equipment
• The CE Marking is NOT required for the following
  products-Chemicals, Pharmaceuticals, Cosmetics,
  Foodstuffs

-Gas appliances-Lifts-Recreational
craft-Equipment and protective systems for use
in explosive atmospheres-Non-automatic weighing
instruments-Cableways-Construction
products-Explosives for civil use-New hot water
boilers-Measuring Equipment
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Directives

• CE Marking product requirements and certification
  procedures
• Currently almost 25 CE Marking directives for
  different product groups (e.g. machinery, toys,
  medical devices) or product aspects (e.g.
  electromagnetic compatibility).
• More than one directive can apply to a single
  product.
• General Product Safety Directive (2001/95/EC)
  applies.

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European Harmonized Standards

• Product standards developed, adopted and
  published by one of the three European standards
  bodies CEN, CENELEC or ETSI
• Content of these standards are harmonized with
  the content of the essential requirements of the
  directives to which they pertain. For every CE
  Marking directive there is a list of European
  harmonized standards.

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Conformity assessment/Certification

• BASICALLY there are only two types of procedures
  
• 'self-certification' by the manufacturer, or
• obligatory certification by a third party
  certification body (called 'Notified Body' or
  'Competent Body').
• Conformity assessment may involve product
  testing, visual inspection, risk analysis, as
  well as a review of the product label and
  instructions

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How?The Process in a Nutshell
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Technical File

• Every CE Marking directive requires the
  manufacturer or importer to compile and keep
  available for inspection a so-called Technical
  File.
• The purpose of the Technical File is to provide
  documented evidence of the product's compliance.
• The Technical File must be kept available for at
  least 10 years after the date of the last
  manufacture of the product.

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Technical File

• Which documentation exactly needs to be provided
  in the Technical File is stipulated in the text
  of the directives. However, mostly general
  descriptions of documents are given, and the
  directives do not specifically list the documents
  that need to be provided.
• As a rule, the Technical File should cover the
  design, manufacture and operation of the product.
  

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Technical File

• The Technical File should contain at least all
  information about the product which allow the
  authorities to
• identify the product
• determine the configuration of the product that
  was approved
• determine which standards were applied
• determine which directives were applied
• determine how the product meets the requirements
  of the relevant directives and standards
• identify the manufacturer and manufacturing
  process
• determine how the manufacturer ensures consistent
  quality of production and continuous product
  compliance

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Technical File

• Most CE Marking directives require a full copy of
  the Technical File to be kept in Europe.
• A good solution is to appoint an 'Authorized
  Representative' that keeps the Technical File.
• An Authorized Representative is strictly a
  regulatory representative, and not involved in
  the design, manufacture or sale of the products.

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Declaration of Conformity

• Manufacturer states the fulfillment of the
  requirements of the relevant directives and
  standards.
• Contain the references to the directives and
  standards that have been applied, a product
  specification and the contact details of the
  manufacturer.
• The Declaration of Conformity must be signed by a
  person authorized to legally bind the company.
• The Declaration of Conformity is kept available
  in the Technical File.

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• Affixing the CE Marking to a product may only be
  done by the manufacturer or his authorized
  representative.
• Confirms that the product meets the applicable CE
  requirements.
• Criminal offense that may be prosecuted.
• The CE Marking must be affixed to the product
  visibly, legibly and indelibly.

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ISO 134852003
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What is ISO

• ISO is the International Organization for
  Standardization.
• Set up in 1947 and is located in Geneva,
  Switzerland.
• Its purpose is to facilitate and support
  international trade by developing standards that
  people everywhere would recognize.

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Why not 90012000?

• ISO 13485 is a stand alone standard
• It is based on ISO 90012000.
• The Medical Device Industry did not agree with
  all the changes to ISO 90012000
• Lacked process orientation
• Primary objective of ISO13485 is to facilitate
  harmonized medical device regulatory requirements

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ISO 134852003

• A process standard not a product standard.
• Establish a quality management system that
  is oriented towards the design, development,
  production, and installation of medical
  devices and related services.
• Demonstrate the ability to supply medical devices
  and related services that meet customer
  expectations and comply with regulatory
  requirements.
• Evaluate how well your organization is able
  to meet customer expectations and comply
  with regulatory requirements.

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How do you do this?

• In order to become certified, you need to develop
  a Quality Management System (QMS) that complies
  with the ISO 13485 2003 standard

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Quality Management System

• ISO 134852003 requires a minimum of 19
  procedures!
• Quality Manual
• 4.2.3 Control of Documents
• 4.2.4 Control of Records
• 6.2.2 Competence, awareness and training
• 7.3 Design and Development
• 7.4.1 Purchasing Process
• 7.5.1.2 Installation activities (if applicable)
• 7.5.1.3 Servicing activities (when required)
• 7.5.3.1 Identification
• 7.5.3.2 Traceability
• 7.5.5 Preservation of Product
• 7.6 Control of Measuring and Monitoring Devices
• 8.1 Statistical Techniques (if used)
• 8.2.2 Internal Audits
• 8.3 Control of nonconforming product
• 8.4 Analysis of Data
• 8.5 Improvement
• 8.5.2 Corrective Action

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Establish, Demonstrate, Evaluate
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FDA and the QSR21 CFR 820
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FDA Organization
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General Controls

• Apply to all medical devices.
• Considered to be the minimum requirements.
• Register each manufacturing location
• List all marketed devices
• Label devices in accordance with applicable
  regulations
• Submit a premarket notification 510(k), unless
  the device is exempt from premarket notification
  or if it identified as being subject to other
  requirements.
• Manufacture devices in accordance with cGMP
  regulations (Current Good Manufacturing Practice)

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Special Controls

• Apply to Class II devices.
• Assume that General Controls not sufficient to
  assure the safety and effectiveness of the
  device.
• Vary from product to product. May include
• Special labeling requirements
• Conformance with certain FDA guidelines
• Mandatory performance standards
• Human clinical trials
• Post market surveillance

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510(k) Premarket Notification

• Most Class II devices are cleared for commercial
  distribution or marketing through this.
• 510(k) clearance (not approval) is based on the
  being substantially equivalent to a predicate
  device
• Usually a device marketed before MDA of 1976
  (preamendment device) or a postamendement device
  that was found to be substantially equivalent to
  a preamendment device.
• FDA must be convinced that
• Device performs the same function and falls
  within an established type of predicate device
• The technological characteristics of the new
  device are comparable to the predicate device
• Whatever differences in characteristics that do
  exist between the new and predicate device will
  not raise any new safety and effectiveness
  questions.

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When is a 510(k) Required?

• The device is introduced into commercial
  distribution for the first time
• The device is in commercial distribution but is
  about to be significantly changed or modified
• A change that could significantly affect the
  safety or effectiveness of the device
• A major change or modification in the intended
  use of the device

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What is required for a 510(k)?

• General information
• Definition of intended use in accordance with
  established product categories
• Comparison to substantially equivalent device
• Drawings
• Product overview
• Labeling
• Truth and accuracy statement
• Safety and effectiveness summary

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What is required for a 510(k)? (cont.)

• Supporting materials (attachments)
• Design specifications (safety risk analysis,
  requirements specification, design description,
  test procedures, )
• Conformance to recognized standards (general
  safety standards such as UL, IEC, etc.)
• Clinical data to show performance or adherence to
  established Guidance requirements to
  demonstrate performance
• Reference materials if a not widely recognized
  method

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PMA Premarket Approval

• A required process of scientific review to ensure
  the safety and effectiveness of most Class III
  devices
• for which insufficient information exists to
  assure safety and effectiveness solely through
  general or special controls.
• An approved PMA application is a private license
  granted to the applicant to market a particular
  medical device.
• Submission-to-Decision time averaged 411 days in
  2001.

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FDA Fees
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When can You Market a Medical Device?

• The device is exempt from premarket
  notification and has been listed with the FDA.
• Applies to most Class I devices and a few Class
  II devices
• The device has a clearance under the 510(k)
  program
• Applies to most Class II devices
• - or - the device has a pending clearance
  (FDAs Compliance guide section 300.600)
• Although a firm may advertise a device that is
  the subject of a pending 510(k) a firm may not
  take orders that might result in contracts for
  sale unless limited to research or
  investigational use
• The device has an approval under the PMA
  program
• Applies to Class III devices

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Quality System Regulations

• 21 CFR 820

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21 CFR Part 820
Quality System Regulations Consists of 15
subparts and 31 sections.

• Subpart A General Provisions
• Subpart B Quality Systems Requirements
• Subpart C Design Controls
• Subpart D Document Controls
• Subpart E Purchasing Controls
• Subpart F Identification and Traceability
• Subpart G Production and Process Controls
• Subpart H Acceptance Activities
• Subpart I Nonconforming Product
• Subpart J Corrective and Preventive Action
• Subpart K Labeling and Packaging Control
• Subpart L Handling, Storage, Distribution and
  Installation
• Subpart M Records
• Subpart N Servicing
• Subpart O Statistical Techniques

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The same but different
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Setting up a Quality System

• Plan, Document, Implement, Maintain
• Documentation drives the whole Quality Management
  System
• The document system is a highly controlled system

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Document Levels
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Examples

• Quality Manual
• Standard Operating Procedures
• Document Control
• Design Control
• Purchasing Control
• Equipment Control
• Work Instructions
• Test Reports
• Equipment Usage
• Forms
• Document Change Form
• Internal Audit Plan
• DMRs and DHRs/batch records

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Design Control
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Customer Requirements, Business Requirements and
Product Requirements
DESIGN TRANSFER
Risk AnalysisTraceability Matrix
Development Project Plan
DESIGN
Plan and ProtocolInterim/Final ReportReview
Minutes and Approval
Patent DisclosuresCommercialization Plan (draft)
3lots
Design Output
Transfer ChecklistManufacturing ProceduresPilot
BuildProduct labeling MSDS
VERIFICATION
Plan and ProtocolFinal ReportReview Minutes and
Approval
VALIDATION
If requiredClinical Evaluation CE
Marking 510(k) Submission/ ClearanceCommercializ
ation Plan
Plan and ProtocolFinal ReportReview Minutes and
Approval
Final Design Review
MARKET RELEASE
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The 1-10-100 Rule
Cost of preventing a defect before it occurs
1
Cost of correcting a defect before it reaches a
customer
10
Cost of correcting a defect after it reaches a
customer
100