Risk Management

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Risk Management For Multilingual Labeling
Marc H. Miller, President Crimson Life Sciences

October 19, 2007
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Outline

• Introduction
• Crimson
• Background demographics
• The Evolving Regulatory Environment
• Multilingual Labeling Risk Sources Mitigations

3
Crimson Background

• Founded in Boston, 1992
• Opened Silicon Valley office (San Francisco),
  1998
• Merged with TransPerfect, 2005
• TransPerfect is worlds largest privately held
  language service provider
• Crimson is specialist medical device practice
  group

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Crimson Credentials

• First company registered to ISO 14971
• Only translation company certified to ISO
  134852003 (and ISO 90012000)
• Worlds only language services practice devoted
  exclusively to Class II and Class III devices,
  List A and List B IVDs

5
Hip to Risk
Stryker Titanium/Ceramic

• Medical devices an empirical reality for growing
  percentage of population in
• US
• Europe
• Asia

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The Graying of America

• US Dept. of Health Human Services
• US population 65 and older due to increase
• 12.4 (34.9 million) in 2000
• 20 (71.5 million) in 2030
• Harvard University, Trends in Medical Spending by
  Age 1963-1999
• Per capita healthcare spending vs. baseline (35
  to 44)
• 65 to 74 300
• Over 75 500

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Paradox of Success

• Success is more dangerous than failure, the
  ripples break over a wider coastline.
• Graham Greene

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Device Risk A Loaded Topic
Q What do airline security and the medical
device industry have in common?
A A similar perspective on device risk.
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Paradox of Success

• Each implanted device is a loaded gun for
  industry raises liability visibility
• Larger installed base increased
  awareness/perception of risk
• Awareness/perception drives regulatory change

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Outline

• Introduction
• The Evolving Regulatory Environment
• Risk perception prompts regulatory caution
• Evidence
• Examples
• Multilingual Labeling Risk Sources Mitigations

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The Doors of Perception

• Importance of awareness/perception reflected in
  ISO 14971
• All stakeholders need to understand that the use
  of a medical device entails some degree of risk.
  Factors affecting each stakeholders perception
  of the risks include the socio-economic and
  educational background of the society concerned
  and the actual and perceived state of health of
  the patient. The way a risk is perceived also
  takes into account, for example, whether exposure
  to the risk seems to be involuntary, avoidable,
  from a man-made source, due to negligence,
  arising from a poorly understood cause, or
  directed at a vulnerable group within society.
• When awareness/perception of risk is elevated,
  stakeholders grow more cautious especially
  regulators

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Evidence of Increased Regulatory Caution

• Products
• EU up-classification of hip and shoulder implants
• EU up-classification of AAA stents and x-ray
  recording devices
• Health Canada five-year plan for the Medical
  Devices Program (MDP) includes new measures to
  increase risk management
• Standards
• Informative reference in ISO 13485
• Normative reference in IEC 60601
• 2005 10 references to ISO 14971
• 2007 over 100 references to ISO 14971

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Further Evidence ISO 14971 Development

• ISO 14971 recognized by FDA Health Canada
• EU harmonized standard Japan Industrial Standard
  
• First registration service introduced by UL,
  developed by Dr. Harvey Rudolph, original
  co-author
• Crimson first registration numerous desk audits
  completed, additional registration audits
  scheduled
• Other registrars developing audit services

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Case in Point Supplier Risk Management

• Broadening application of risk management
  (outside design development)
• Supplier RM an important area of focus for 14971
• Manufacturer natural or legal person with
  responsibility for the design, manufacture,
  packaging or labelling of a medical
  deviceregardless of whether these operations are
  carried out by that person himself or on his
  behalf by a third party.
• 25 of ISO 14971, Annex A (Questions that can be
  used to identify medical device characteristics
  that could impact on safety) are potentially
  supplier-related
• GHTF Guidance
• Processesperformed by suppliers to the
  manufacturer are the responsibility of the
  manufacturer.
• MDD revision
• Manufacturer responsible for outsourced processes
• OK to outsource processes, but cant outsource
  risk

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Supplier Risk Management Labeling Translation

• Coherence between risk analysis and labeling is
  area of increased focus for EU
• 50 are unacceptable (Dr. Kraus, Dutch CA)
• Regulation
• ISO 14971 Annex D (related hazards) specifies
  inadequate instructions and labeling as primary
  use-related hazard
• ISO 13485 The organization shall plan and carry
  out production and service provision under
  controlled conditions. Controlled conditions
  shall include, as applicablethe implementation
  of defined operations for labeling and
  packaging.
• GHTF SG3/N15R8 Specifies labeling as risk
  management requirement
• Increased awareness/perception of supplier risk
  prompts stricter regulatory interpretation
• Heightened awareness from other sources China,
  Inc.

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Labeling TranslationRegulatory Statements

• Due to compliance implications for the essential
  requirements of the MDD and the IVDD, Notified
  Bodies consider translation to be an important
  outsourced serviceThis makes translation
  providers subject to the outsourced vendor risk
  management considerations of ISO 134852003 and
  ISO 14971.
• KEMA Notified Body
• Medical device labeling must convey to users
  critical safety information about the product
  while taking into account the language of both
  the user and the device documentation, it is an
  issue of great importance to the medical
  community.
• Steve McRoberts, Principal Engineer, Medical
  Regulatory Proprietary Compliance, UL
• Generating accurate translations for native
  language users helps to assure that devices are
  operated safely. This is especially true for
  those portions of the labeling that are
  themselves risk controls established by the
  manufacturer (information for safety)efforts to
  improve and perfect the translation of labeling
  should be an integral part of any
  manufacturers risk management system.
• Dr. Harvey Rudolph, ISO 14971 co-author
• Inaccurate translation of device labeling may
  jeopardize ISO 14971 compliance in overseas
  markets.
• Oliver Christ, CEO, PROSYSTEMS (RAPS Conference
  Panelist)

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Outline

• Introduction
• The Evolving Regulatory Environment
• Multilingual Labeling Risk Sources Mitigations
• Sources of risk
• Quality system parity
• Audit
• Process validation

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Sources of Multilingual Labeling Risk

• Resource Risk
• In a professional services setting such as
  commercial translation, risk is directly tied to
  the professional resource who delivers each
  specified service... Effective risk management,
  therefore, is based upon rigorous resource
  selection, training, and evaluation/audit.
• Process Risk
• Project Management/Handoff
• Scheduling
• Technical
• Linguistic
• Product
• Source A Method for Analyzing and Managing
  Risk Within the Translation Activity, pending
  business method patent, filed by Crimson Life
  Sciences

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Methods for Mitigating Multilingual Labeling Risk

• QS Parity
• Recommended by Notified Bodies as least
  burdensome approach
• Audit
• Not full inspection
• Establish a measurement methodology
• Process Validation
• Requires most under the hood insight

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Quality System Parity

• Definition Equivalent levels of quality system
  certification between manufacturer and supplier,
  e.g., ISO 13485
• First survey of US device suppliers, April 2007
• Methodology primary and secondary research
• Total suppliers surveyed 429
• Supplier types contract manufacturers component
  manufacturers packaging suppliers sterilization
  suppliers

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QS Parity Survey Results

• Since latest revision of ISO 13485
• 36 of total US supplier base certified to ISO
  13485
• 55 of ISO 13485 certified suppliers Non-Exempt
  (i.e., voluntary certification)
• 20 of ISO 9001 certified suppliers planning
  additional ISO 13485 certification

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QS Parity Survey Results

• Regulations and regulators favor quality system
  parity as one means for demonstrating appropriate
  risk management and supplier control
• Manufacturer purchasing practices indicate the
  value of quality system parity
• Current and projected rates of ISO 13485
  certification across all supplier types indicate
  value of quality system parity

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Not All ISOs Created Equal

• All animals are equal, but some animals are more
  equal than others.
• George Orwell
• Does the suppliers registrar appear on the FDA
  list of accredited third parties?
  http//www.accessdata.fda.gov/scripts/cdrh/cfdocs/
  cfthirdparty/accredit.cfm
• Is the suppliers registrar associated with a
  Notified Body?

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The Shape of Things to Come

• ISO 14971 registration from UL other registrars
  following suit
• Economic factors
• Supplier management
• Potentially lower insurance premiums
• UL clients have demonstrated savings
• Regulatory factors
• Global acceptance of ISO 14971
• Cross reference (other standards)

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Audit for Verification

• Problem
• Labeling verification (especially in US)
• Full inspection (e.g., distributor/third party
  review) is common solution
• A cure worse than the disease
• Often, reviewers do not have the requisite
  knowledge of the source/target languages nor do
  they have the required timeto adequately review.
  Because the review process itself is typically
  ill-defined, review comments can be stylistic in
  nature and rather low-value. Finally, since
  translation review is not a specified part of the
  reviewers job descriptionmaterials are simply
  returned with no feedback at all
• Notified Body endorsed labeling guidance
• Solution
• Eliminate full document review substitute
  appropriate RM processes
• Structured review or audit

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Audit for Verification

• Inherent problems / limitations
• Subjective nature of language (no adequate
  measures for all applicable criteria)
• Translation is a Professional Service
  (limitations in buyers ability to determine
  quality)
• Complete incoming inspection not economically
  feasible
• Inspection methods subject to same limitations as
  activity itself
• No universally accepted methodology
• Approaches
• Adopt a common framework and methodology to
  enforce objectivity
• Crimson approach to translation audit reviewed
  and approved by KEMA Notified Body

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Overview SAE J2450

• Developed in 1997 by the automotive/aerospace
  industries as a translation quality metric
  (elevated to Standard in 2005)
• Provides classification of translation errors in
  predefined linguistic categories exclusion of
  stylistic criteria
• Adapted to medical industry requirements
  (approved by KEMA)
• Serious Error designation are issues, e.g., that
  potentially cause patient harm
• Value of practical application

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A Closer Look SAE J2450
Examples
Wrong Term, serious
Omission, serious
a 112 dilution of liquid household bleach or
equivalent eine 112-Verdünnung flüssiger
Haushaltsbleiche
Punctuation, serious
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Other Applications

• Legacy translation audits

• Can serve as translation risk management evidence
  in technical file

Process validation audits

• Determine process effectiveness by measuring
  error rates at various process steps

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Process Validation

• Requires understanding of translation processes,
  tools, and quality systems
• Focus on key items for least burdensome
  approach
• For guidance, see ISO 14971-Based Risk
  Management Guidance for Multilingual Labeling

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Process Validation

• Resource Audit
• Qualifications
• Testing/screening
• Evaluation/audit/trending
• Standardized methodology (e.g., J2450)

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Process Validation

• Process Audit
• ISO 9001 Doing-Checking
• Closed loop linguistic QA
• Linguistic Risk Analysis
• Effectiveness check
• Project risk evaluation
• Project hazard list
• Effectiveness check (FPA)

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Summary

• Demographics create success paradox for medical
  devices
• Increased visibility prompts increased
  awareness/perception of risk and regulatory
  scrutiny
• Supplier risk management is important area of
  concern follow-on affects for multilingual
  labeling
• Coherence between risk analysis and labeling
• CAs fed up with poor translation quality Was
  this done with an Internet tool?
• Strategies for effective multilingual labeling
  risk management include
• QS Parity
• Labeling Audit
• Process Audit

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Risk Management For Multilingual Labeling
Thank You! Questions?
Marc H. Miller 617.731.6920 mmiller_at_crimsonlanguag
e.com

October 19, 2007