Risk ManagementFor Multilingual Labeling

October 19, 2007

Marc H. Miller, President

Crimson Life Sciences

• Introduction– Crimson– Background demographics

• The Evolving Regulatory Environment

• Multilingual Labeling Risk: Sources & Mitigations

Outline

• 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 Background

• 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

Crimson Credentials

Hip to Risk

Stryker Titanium/Ceramic

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

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%

The Graying of America

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

Paradox of Success

Q: What do airline security and the medical device industry have in common?

Device Risk: A Loaded Topic

A: A similar perspective on device risk.

• 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

Paradox of Success

• Introduction• The Evolving Regulatory Environment

– Risk perception prompts regulatory caution

– Evidence– Examples

• Multilingual Labeling Risk: Sources & Mitigations

Outline

• 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 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

The Doors of Perception

• 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

Evidence of Increased Regulatory Caution

• 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

Further Evidence :ISO 14971 Development

• 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 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

Case in Point: Supplier Risk Management

• 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 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.

Supplier Risk Management: Labeling Translation

• “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.”

– 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 [manufacturer’s] 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)

Labeling Translation:Regulatory Statements

• Introduction• The Evolving Regulatory Environment• Multilingual Labeling Risk: Sources

& Mitigations– Sources of risk– Quality system parity– Audit– Process validation

Outline

• 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

Sources of 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

Methods for Mitigating Multilingual Labeling Risk

• 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

Quality System Parity

• 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

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

QS Parity Survey Results

• “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? http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfthirdparty/accredit.cfm

• Is the supplier’s registrar associated with a Notified Body?

Not All ISOs Created Equal

• 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)

The Shape of Things to Come

• 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 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

• Solution– 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

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

Audit for Verification

• 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

Overview: SAE J2450

a 1:12 dilution of liquid household bleach or equivalent

eine 11:2-Verdünnung flüssiger Haushaltsbleiche

Slide the block down over the top of the tube.

Den Block nach unten über die Spitze des Rohres schieben.

Examples

Wrong Term, serious

Do not pipette by mouth.

Mit dem Mund pipettieren.

Omission, serious

Punctuation, serious

A Closer Look: SAE J2450

Legacy translation audits

Process validation audits Determine process effectiveness by

measuring error rates at various process steps

Can serve as translation risk management evidence in technical file

Other Applications

• 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”)

Process Validation

• 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– 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

Summary

Risk ManagementFor Multilingual Labeling

October 19, 2007

Marc H. Miller

617.731.6920

mmiller@crimsonlanguage.com

Thank You! Questions?