Risk Management
For Multilingual Labeling
Marc H. Miller, President
Crimson Life Sciences
October 19, 2007
• Introduction
– Crimson
– Background demographics
• The Evolving Regulatory Environment
• Multilingual Labeling Risk: Sources &
Crimson Background
• Founded in Boston, 1992
• Opened Silicon Valley office (San
Francisco), 1998
• Merged with TransPerfect, 2005
– TransPerfect is world’s largest privately
held language service provider
– Crimson is specialist medical device
practice group
Crimson Credentials
• First company registered to ISO 14971
• Only translation company certified to ISO
13485:2003 (and ISO 9001:2000)
• World’s only language services practice
devoted exclusively to Class II and Class
III devices, List A and List B IVDs
Hip to Risk
Stryker Titanium/Ceramic
• Medical devices
an empirical reality
for growing
percentage of
population in:
– US
– Europe
– Asia
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%
Paradox of Success
• “Success is more dangerous than
failure, the ripples break over a wider
– Graham Greene
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.
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
• Introduction
• The Evolving Regulatory Environment
– Risk perception prompts regulatory
– Evidence
– Examples
• Multilingual Labeling Risk: Sources &
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 stakeholder’s perception of the risks include the socioeconomic 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
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
Further Evidence :
ISO 14971 Development
• ISO 14971 recognized by FDA & Health
• EU harmonized standard; Japan Industrial
• First registration service introduced by UL,
developed by Dr. Harvey Rudolph, original
• Crimson first registration – numerous desk
audits completed, additional registration
audits scheduled
• Other registrars developing audit services
Case in Point: Supplier Risk Management
Broadening application of risk management (outside design &
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
device…regardless 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
– Processes…performed by suppliers to the manufacturer are the
responsibility of the manufacturer.
MDD revision
– Manufacturer responsible for outsourced processes
OK to outsource processes, but can’t outsource risk
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 applicable…the
implementation of defined operations for labeling and
– GHTF SG3/N15R8: Specifies labeling as risk management
• Increased awareness/perception of supplier risk
prompts stricter regulatory interpretation
– Heightened awareness from other sources: China, Inc.
Labeling Translation:
Regulatory Statements
“Due to compliance implications for the essential requirements of the
MDD and the IVDD, Notified Bodies consider translation to be an
‘important outsourced service’…This makes translation providers
subject to the outsourced vendor risk management considerations of
ISO 13485:2003 and ISO 14971.”
“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
[manufacturer’s] risk management system.”
KEMA Notified Body
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)
• Introduction
• The Evolving Regulatory Environment
• Multilingual Labeling Risk: Sources
& Mitigations
– Sources of risk
– Quality system parity
– Audit
– Process validation
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
* Source: “A Method for Analyzing and Managing Risk Within the Translation Activity,” pending business
method patent, filed by Crimson Life Sciences
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
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
– Methodology: primary and secondary research
– Total suppliers surveyed: 429
– Supplier types: contract manufacturers;
component manufacturers; packaging suppliers;
sterilization suppliers
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 “NonExempt” (i.e., voluntary certification)
– 20% of ISO 9001 certified suppliers
planning additional ISO 13485 certification
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
Not All ISOs Created Equal
“All animals are equal, but some animals
are more equal than others.”
George Orwell
Does the supplier’s registrar appear on the
FDA list of accredited third parties?
Is the supplier’s registrar associated with a
Notified Body?
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)
Audit for Verification
– 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 time…to 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
reviewer’s job description…materials are simply returned
with no feedback at all”
• Notified Body endorsed labeling guidance
– Eliminate full document review – substitute appropriate
RM processes
– Structured review or audit
Audit for Verification
Inherent problems / limitations
– Subjective nature of language (no adequate
measures for all applicable criteria)
– Translation is a Professional Service (limitations in
buyer’s ability to determine quality)
– Complete incoming inspection not economically
– Inspection methods subject to same limitations as
activity itself
– No universally accepted methodology
– Adopt a common framework and methodology to
enforce objectivity
– Crimson approach to translation audit reviewed and
approved by KEMA Notified Body
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
A Closer Look: SAE J2450
Slide the block down over the top of the tube.
Den Block nach unten über die Spitze des Rohres
Wrong Term, serious
Do not pipette by mouth.
Mit dem Mund pipettieren.
Omission, serious
a 1:12 dilution of liquid household
bleach or equivalent
eine 11:2-Verdünnung flüssiger
Punctuation, serious
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
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”
Process Validation
• Resource Audit
– Qualifications
– Testing/screening
– Evaluation/audit/trending
– Standardized methodology (e.g., J2450)
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”)
• Demographics create “success paradox” for medical
• 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
– CA’s “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
Risk Management
For Multilingual Labeling
Thank You!
Marc H. Miller
October 19, 2007