ISO 10993-18 in the MDR - Nelson Labs · 2020. 3. 10. · MDR: 10.4.2. Justification R A T isk...
Transcript of ISO 10993-18 in the MDR - Nelson Labs · 2020. 3. 10. · MDR: 10.4.2. Justification R A T isk...
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Understanding the restrictions and risk assessment for substances which are
Carcinogenic, Mutagenic, toxic to Reproduction (CMR) or have Endocrine-
Disrupting (ED) properties (section 10.4, Annex I MDR)
Annelies Vertommen, PhD
4 MARCH 2020
ISO 10993-18 in the MDR :
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Introduction
2020: The Year Of Change for the Medical Device Industry
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Introduction
2020: The Year Of Change for the Medical Device Industry
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Introduction
2020: The Year Of Change for the Medical Device Industry
R
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Outline
• MDR: section 10.4, Annex I, Chapter II
• ISO 10993-18:
o a screening vs a targeted analytical approach
o three levels of quantification
• ISO 10993-18 in the MDR
• Conclusion: proposed workflow
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Section 10.4 in the MDR
MDR Annex I (GSPR)
Design and manufacture of devices to reduce risks posed by substances or particles that may be released from the device
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MDR Annex I, Chapter II, Section 10.4.
Risk justification and labelling for substances
• 10.4.1: when? Design and manufacture of devices
• 10.4.2: how justification?
o Section 10.4.3: guideline on phthalates
o Section 10.4.4: guideline on other CMR & ED substances
• 10.4.5: how labelling?
Section 10.4 in the MDR
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10.4.1 When?
1. What type of test items?
Device, part or material
• Invasive & direct contact with human body
• (Re)administering medicines or other substances to/from body
• Transport or storing medicines or other substances
MDR: 10.4.1 Design and manufacture of devices
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10.4.1 When?
2. Cannot contain CMR 1A, CMR 1B or ED substance > 0.1 % weight/weight unless justification & labelling o CMR: Carcinogenic, mutagenic, or reprotoxic
CMR 1A: Known human CMR
CMR 1B: Presumed human CMR
CMR 1A/1B: As per Annex VI CLP Regulation
o ED substance: Endocrine disruptor (human health) Article 59, EC 1907/2006 (REACH)
Article 5(3) EC 528/2012 (biocidal)
MDR: 10.4.1 Design and manufacture of devices
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• Analysis of (patient & user) exposure
MDR: 10.4.2. Justification
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• Analysis of (patient & user) exposure
MDR: 10.4.2. Justification
R
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ISO 10993-18
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• Analysis of (patient & user) exposure
= risk assessment : ISO 10993-18
• Analysis of alternative substances, materials, designs
• Benefit-risk assessment
MDR: 10.4.2. Justification
Terephthalate No endocrine-disruptor
Isophthalate Endocrine-disruptor
DEHP DEHT
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• 10.4.3: Guideline on phthalates (Scheer, 2019)
• 10.4.4: Guideline on other CMR and endocrine-disrupting substances
MDR: 10.4.2. Justification
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Where?
• on the device itself and/or
• on the packaging for each unit or,
• on the sales packaging
MDR: 10.4.5: labelling
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The missing link?
MDR: missing link
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> 0.1 % weight/weight: HOW?
ISO 10993-18?
MDR: missing link
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Test my device for all substances?? 0.1 % w/w = a lot !
MDR: missing link
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Test my device for all substances??
MDR: missing link
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Test for all substances??
Supplier: intentionally added
Polycarbonate – Bisphenol A (BPA)
PVC - Phthtalates
Only those substances that can be present > 0.1% w/w
MDR: missing link
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Test for all substances??
Supplier: intentionally added
Polycarbonate – Bisphenol A (BPA)
PVC - Phthtalates
Only those substances that can be present > 0.1% w/w
MDR: missing link
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ISO 10993-18: - Answer for > 0.1 % w/w?
- Tool for risk assessment/justification
ISO 10993-18
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ISO 10993-18: - Answer for > 0.1 % w/w?
- Tool for risk assessment/justification
ISO 10993-18
a screening versus a targeted approach
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• No predefined target: screen for all • General techniques:
• HS-GC/MS: volatile organic compounds (VOC) • GC/MS: semi-volatile organic compounds (SVOC) • LC/MS: non-volatile organic compounds (NVOC)
• No LOD, LOQ for each compound
Screening
ISO 10993-18: screening vs targeted
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• A limited number of known targets • Selective technique:
• ICP/OES: elements • IC: anions • Validated method: specific organic compound, e.g. Bisphenol A: GC/MS method
• LOD, LOQ for each compound
Targeted
ISO 10993-18: screening vs targeted
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• A screening versus a targeted analytical approach :
three levels of quantification in ISO 10993-18
ISO 10993-18: three levels of quantification
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• A screening versus a targeted analytical approach :
three levels of quantification in ISO 10993-18:
1. Estimated quantification
2. Semi-quantification
3. Full quantification Targeted approach
ISO 10993-18: three levels of quantification
Screening approach
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ISO 10993-18: three levels of quantification
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I.S. [I.S.]known = 10 mg/L AreaIS = 100
Area[EXT] = 100 [EXT]Estimated = 10 mg/L
Assuming RFIS = RF [EXT]
I.S. Bisphenol A
ESTIMATED QUANTITATIVE ANALYSIS
Bisphenol A
ISO 10993-18: three levels of quantification
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Internal Standard (IS) Bisphenol A
=
ISO 10993-18: three levels of quantification
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a. Semi-quantitative analysis via surrogate compound b. Semi-quantitative analysis via individual RRF correction
ISO 10993-18: three levels of quantification
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a. SEMI-QUANTITATIVE ANALYSIS VIA SURROGATE RRF CORRECTION
ISO 10993-18: three levels of quantification
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[SUR] = 10 mg/L Area [SUR] = 50 [I.S.] = 10 mg/L Area [I.S.] = 100
RRFSUR = 0.5
Bisphenol A
SURROGATE
Surrogate compound: compound similar to target compound BUT: many variation, e.g. Bisphenol A_d16, Naphthalene_d4
a. SEMI-QUANTITATIVE ANALYSIS VIA SURROGATE RRF CORRECTION
Area EXT = 100 [EXT] = 20 mg/L
ISO 10993-18: three levels of quantification
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IS
>>>
Surrogate compound
ISO 10993-18: three levels of quantification
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IS
=
Bisphenol A
=
Surrogate compound
>>>
ISO 10993-18: three levels of quantification
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[SUR] = 10 mg/L Area [SUR] = 50 [I.S.] = 10 mg/L Area [I.S.] = 100
RRFSUR = 0.5
Bisphenol A
SURROGATE
a. SEMI-QUANTITATIVE ANALYSIS VIA SURROGATE RRF CORRECTION
Area EXT = 100 [EXT] = 20 mg/L
ISO 10993-18: three levels of quantification
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b. SEMI-QUANTITATIVE ANALYSIS VIA INDIVIDUAL RRF CORRECTION
ISO 10993-18: three levels of quantification
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b. SEMI-QUANTITATIVE ANALYSIS VIA INDIVIDUAL RRF CORRECTION
Bisphenol A
Bisphenol A
ISO 10993-18: three levels of quantification
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IS
>>>>>>
Bisphenol A
ISO 10993-18: three levels of quantification
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0
100
200
300
400
500
600
0 2 4 6 8 10 12
Rel
ativ
e ab
un
dan
ce
Relative concentration
RRF, Bisphenol A
ISO 10993-18: three levels of quantification
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b. SEMI-QUANTITATIVE ANALYSIS VIA INDIVIDUAL RRF CORRECTION
Bisphenol A Bisphenol A
Bisphenol A
ISO 10993-18: three levels of quantification
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ISO 10993-18: three levels of quantification
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0
200
400
600
800
1000
1200
0 5 10 15 20 25
Res
po
nse
concentration
Multiple point calibration curve, Bisphenol A
ISO 10993-18: three levels of quantification
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1. Estimated 2.1 Semi-quantitative through surrogate
2.2 Semi-quantitative through RRF
3. Fully quantitative
ISO 10993-18: three levels of quantification
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1. Estimated 2.1 Semi-quantitative through surrogate
2.2 Semi-quantitative through RRF
3. Fully quantitative
Assuming RFIS = RF [EXT]
[EXT]Estimated = 10 mg/L
Assuming RFSur = RF [EXT]
[EXT]semi-quant = 20 mg/L
RF [EXT]
AT 1 CONC LEVEL
[EXT]semi-quant = 30 mg/L
[EXT]quant = 35 mg/L
RF [EXT] AT MULTIPLE CONC LEVELS
ISO 10993-18: three levels of quantification
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1. Estimated 2.1 Semi-quantitative through surrogate
2.2 Semi-quantitative through RRF
3. Fully quantitative
Assuming RFIS = RF [EXT]
[EXT]Estimated = 10 mg/L
Assuming RFSur = RF [EXT]
[EXT]semi-quant = 20 mg/L
RF [EXT]
AT 1 CONC LEVEL
[EXT]semi-quant = 30 mg/L
[EXT]quant = 35 mg/L
RF [EXT] AT MULTIPLE CONC LEVELS
High uncertainty Low uncertainty
ISO 10993-18: three levels of quantification
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1. Estimated 2.1 Semi-quantitative through surrogate
2.2 Semi-quantitative through RRF
3. Fully quantitative
High uncertainty Low uncertainty
Screening
ISO 10993-18: three levels of quantification
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1. Estimated 2.1 Semi-quantitative through surrogate
2.2 Semi-quantitative through RRF
3. Fully quantitative
High uncertainty Low uncertainty
Screening Targeted
ISO 10993-18: three levels of quantification
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ISO 10993-18: - Answer for 0.1 % w/w?
- Tool for risk assessment
a screening versus a targeted approach: three levels of quantification
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Test for all substances??
Supplier: intentionally added
Polycarbonate – Bisphenol A (BPA)
PVC - Phthtalates
Only those substances that can be present > 0.1% w/w
ISO 10993-18 in the MDR
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> 0.1 % weight/weight: HOW?
ISO 10993-18?
ISO 10993-18 in the MDR
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• Target the substance that is expected : BPA
ISO 10993-18 in the MDR
![Page 52: ISO 10993-18 in the MDR - Nelson Labs · 2020. 3. 10. · MDR: 10.4.2. Justification R A T isk ssessment ool ISO 10993-18 •Analysis of (patient & user) exposure = risk assessment](https://reader035.fdocuments.us/reader035/viewer/2022062318/5fdeae50d27ae15b3706ebd9/html5/thumbnails/52.jpg)
• Target the substance that is expected : BPA • Knowledge on total amount BPA needed
ISO 10993-18 in the MDR
![Page 53: ISO 10993-18 in the MDR - Nelson Labs · 2020. 3. 10. · MDR: 10.4.2. Justification R A T isk ssessment ool ISO 10993-18 •Analysis of (patient & user) exposure = risk assessment](https://reader035.fdocuments.us/reader035/viewer/2022062318/5fdeae50d27ae15b3706ebd9/html5/thumbnails/53.jpg)
• Extract the total amount BPA: “digest the material”: Use solvent that best solubilizes the target substance
ISO 10993-18 in the MDR
![Page 54: ISO 10993-18 in the MDR - Nelson Labs · 2020. 3. 10. · MDR: 10.4.2. Justification R A T isk ssessment ool ISO 10993-18 •Analysis of (patient & user) exposure = risk assessment](https://reader035.fdocuments.us/reader035/viewer/2022062318/5fdeae50d27ae15b3706ebd9/html5/thumbnails/54.jpg)
• Extract the total amount BPA: “digest the material”: Use solvent that best solubilizes the target substance
ISO 10993-18 in the MDR
![Page 55: ISO 10993-18 in the MDR - Nelson Labs · 2020. 3. 10. · MDR: 10.4.2. Justification R A T isk ssessment ool ISO 10993-18 •Analysis of (patient & user) exposure = risk assessment](https://reader035.fdocuments.us/reader035/viewer/2022062318/5fdeae50d27ae15b3706ebd9/html5/thumbnails/55.jpg)
• Extract the total amount BPA: “digest the material”: Use solvent that best solubilizes the target substance • Use 1 analytical technique (GC/MS)
ISO 10993-18 in the MDR
![Page 56: ISO 10993-18 in the MDR - Nelson Labs · 2020. 3. 10. · MDR: 10.4.2. Justification R A T isk ssessment ool ISO 10993-18 •Analysis of (patient & user) exposure = risk assessment](https://reader035.fdocuments.us/reader035/viewer/2022062318/5fdeae50d27ae15b3706ebd9/html5/thumbnails/56.jpg)
• Extract the total amount BPA: “digest the material”: Use solvent that best solubilizes the target substance • Use 1 analytical technique (GC/MS) • Include calibration curve: quantitative result
ISO 10993-18 in the MDR
![Page 57: ISO 10993-18 in the MDR - Nelson Labs · 2020. 3. 10. · MDR: 10.4.2. Justification R A T isk ssessment ool ISO 10993-18 •Analysis of (patient & user) exposure = risk assessment](https://reader035.fdocuments.us/reader035/viewer/2022062318/5fdeae50d27ae15b3706ebd9/html5/thumbnails/57.jpg)
ISO 10993-18: Answer for 0.1 % w/w (= Material characterization)
ISO 10993-18 in the MDR
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ISO 10993-18 in the MDR
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Screen for all possible target substances
ISO 10993-18 in the MDR
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Keep device/material/part intact during extraction: • Extraction conditions: ISO 10993-18
ISO 10993-18 in the MDR
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• CMR/ED substance: different sizes, different nature Different extraction solvents, different analytical techniques • CMR/ED not known: no calibration curve of target substance
Screening: estimated/semi-quantitative concentration
ISO 10993-18 in the MDR
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ISO 10993-18 in the MDR
525 95
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CMR/ED substance detected?
Lists in MDR (> 2000 compounds)
Reduced lists (MedTech Europe, proprietary, < 200)
ISO 10993-18 in the MDR
525 95
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CMR/ED substance detected?
DEHP: CMR 1B (toxic for reproduction), ED properties
Ziram: potential ED (under evaluation)
525 95
ISO 10993-18 in the MDR
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No calibration curve! ESTIMATED (semi-quantitative) concentration close to 0.1 w/w %? (1000 µg/g)
525 95
ISO 10993-18 in the MDR
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• No calibration curve! • ESTIMATED (semi-quantitative) concentration • close to 0.1 w/w %? (1000 µg/g)
Include second step
ISO 10993-18 in the MDR
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• No calibration curve! • ESTIMATED (semi-quantitative) concentration • close to 0.1 w/w %? (1000 µg/g)
Include second step
• Run same extract with calibration curve for detected CMR/ED (DEHP, Ziram) Quantitative result!!!
ISO 10993-18 in the MDR
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• calibration curve • QUANTITATIVE concentration • close to 0.1 w/w %? (1000 µg/g)
No
ISO 10993-18 in the MDR
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• calibration curve • QUANTITATIVE concentration • close to 0.1 w/w %? (1000 µg/g)
No
ISO 10993-18 in the MDR
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• calibration curve • QUANTITATIVE concentration • close to 0.1 w/w %? (1000 µg/g)
No
Yes
• Extract the total amount: “digest the material”: Use solvent that best solubilizes the target substance
• Use 1 analytical technique • Include calibration curve:
quantitative result
ISO 10993-18 in the MDR
ISO 10993-17
![Page 71: ISO 10993-18 in the MDR - Nelson Labs · 2020. 3. 10. · MDR: 10.4.2. Justification R A T isk ssessment ool ISO 10993-18 •Analysis of (patient & user) exposure = risk assessment](https://reader035.fdocuments.us/reader035/viewer/2022062318/5fdeae50d27ae15b3706ebd9/html5/thumbnails/71.jpg)
Using chemical characterization for CMR/ED substances in lack of information? - Information on all substances that can be released from the device: Estimate overall risk to the patient (not only CMR/ED) Evaluation results: ISO 10993-17 - Justification in case conc CMR/ED substances > 0.1 % (w/w)
ISO 10993-18 in the MDR
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Conclusion: proposed workflow
![Page 73: ISO 10993-18 in the MDR - Nelson Labs · 2020. 3. 10. · MDR: 10.4.2. Justification R A T isk ssessment ool ISO 10993-18 •Analysis of (patient & user) exposure = risk assessment](https://reader035.fdocuments.us/reader035/viewer/2022062318/5fdeae50d27ae15b3706ebd9/html5/thumbnails/73.jpg)
Information on concentration present (e.g. conc. CMR/ED = 0.5% w/w)?
YES
STEP 1: ASK INFORMATION FROM SUPPLIERS Information on nature of CMR/ED present (e.g. contains BPA)
Conclusion: proposed workflow
![Page 74: ISO 10993-18 in the MDR - Nelson Labs · 2020. 3. 10. · MDR: 10.4.2. Justification R A T isk ssessment ool ISO 10993-18 •Analysis of (patient & user) exposure = risk assessment](https://reader035.fdocuments.us/reader035/viewer/2022062318/5fdeae50d27ae15b3706ebd9/html5/thumbnails/74.jpg)
Information on concentration present (e.g. conc. CMR/ED = 0.5% w/w)?
YES
STEP 1: ASK INFORMATION FROM SUPPLIERS Information on nature of CMR/ED present (e.g. contains BPA)
YES NO
CMR/ED > 0.1 % w/w ? Full digestion of material Targeted analysis Fully quantitative
Conclusion: proposed workflow
![Page 75: ISO 10993-18 in the MDR - Nelson Labs · 2020. 3. 10. · MDR: 10.4.2. Justification R A T isk ssessment ool ISO 10993-18 •Analysis of (patient & user) exposure = risk assessment](https://reader035.fdocuments.us/reader035/viewer/2022062318/5fdeae50d27ae15b3706ebd9/html5/thumbnails/75.jpg)
Information on concentration present (e.g. conc. CMR/ED = 0.5% w/w)?
YES
STEP 1: ASK INFORMATION FROM SUPPLIERS Information on nature of CMR/ED present (e.g. contains BPA)
YES NO
CMR/ED > 0.1 % w/w ? Full digestion Targeted analysis Fully quantitative
Conclusion: proposed workflow
![Page 76: ISO 10993-18 in the MDR - Nelson Labs · 2020. 3. 10. · MDR: 10.4.2. Justification R A T isk ssessment ool ISO 10993-18 •Analysis of (patient & user) exposure = risk assessment](https://reader035.fdocuments.us/reader035/viewer/2022062318/5fdeae50d27ae15b3706ebd9/html5/thumbnails/76.jpg)
Information on concentration present (e.g. conc. CMR/ED = 0.5% w/w)?
YES
STEP 1: ASK INFORMATION FROM SUPPLIERS Information on nature of CMR/ED present (e.g. contains BPA)
YES NO
CMR/ED > 0.1 % w/w ? Full digestion Targeted analysis Fully quantitative
YES
JUSTIFICATION LABEL
Conclusion: proposed workflow
![Page 77: ISO 10993-18 in the MDR - Nelson Labs · 2020. 3. 10. · MDR: 10.4.2. Justification R A T isk ssessment ool ISO 10993-18 •Analysis of (patient & user) exposure = risk assessment](https://reader035.fdocuments.us/reader035/viewer/2022062318/5fdeae50d27ae15b3706ebd9/html5/thumbnails/77.jpg)
Information on concentration present (e.g. conc. CMR/ED = 0.5% w/w)?
YES
STEP 1: ASK INFORMATION FROM SUPPLIERS Information on nature of CMR/ED present (e.g. contains BPA)
YES NO
CMR/ED > 0.1 % w/w ? Full digestion Targeted analysis Fully quantitative
JUSTIFICATION LABEL
YES NO
NO LABEL
Conclusion: proposed workflow
![Page 78: ISO 10993-18 in the MDR - Nelson Labs · 2020. 3. 10. · MDR: 10.4.2. Justification R A T isk ssessment ool ISO 10993-18 •Analysis of (patient & user) exposure = risk assessment](https://reader035.fdocuments.us/reader035/viewer/2022062318/5fdeae50d27ae15b3706ebd9/html5/thumbnails/78.jpg)
Information on concentration present (e.g. conc. CMR/ED = 0.5% w/w)?
YES
STEP 1: ASK INFORMATION FROM SUPPLIERS Information on nature of CMR/ED present (e.g. contains BPA)
YES NO
CMR/ED > 0.1 % w/w ? Full digestion Targeted analysis Fully quantitative
NO LABEL JUSTIFICATION LABEL
NO
Chemical characterization ISO 10993-18: Screen for all Semi-quantitative
NO
YES
Conclusion: proposed workflow
![Page 79: ISO 10993-18 in the MDR - Nelson Labs · 2020. 3. 10. · MDR: 10.4.2. Justification R A T isk ssessment ool ISO 10993-18 •Analysis of (patient & user) exposure = risk assessment](https://reader035.fdocuments.us/reader035/viewer/2022062318/5fdeae50d27ae15b3706ebd9/html5/thumbnails/79.jpg)
Set-up chemical characterization for safety risk assessment
1. Make extract 72h -50°C, shaking incubation polar & non-polar solvent
2. Analytical techniques:
VOC: HS-GC/MS screening SVOC: GC/MS screening NVOC: LC/MS screening Elements: ICP/OES
Estimated/ Semi-quantitative results
Fully quantitative results
STEP 1. Gather all results
Conclusion: proposed workflow
![Page 80: ISO 10993-18 in the MDR - Nelson Labs · 2020. 3. 10. · MDR: 10.4.2. Justification R A T isk ssessment ool ISO 10993-18 •Analysis of (patient & user) exposure = risk assessment](https://reader035.fdocuments.us/reader035/viewer/2022062318/5fdeae50d27ae15b3706ebd9/html5/thumbnails/80.jpg)
Set-up chemical characterization for safety risk assessment
1. Make extract 72h -50°C, shaking incubation polar & non-polar solvent
2. Analytical techniques:
VOC: HS-GC/MS screening SVOC: GC/MS screening NVOC: LC/MS screening Elements: ICP/OES
Estimated/ Semi-quantitative results
Fully quantitative results
STEP 1. Gather all results
Compare with published CMR/ED substances lists
Conclusion: proposed workflow
![Page 81: ISO 10993-18 in the MDR - Nelson Labs · 2020. 3. 10. · MDR: 10.4.2. Justification R A T isk ssessment ool ISO 10993-18 •Analysis of (patient & user) exposure = risk assessment](https://reader035.fdocuments.us/reader035/viewer/2022062318/5fdeae50d27ae15b3706ebd9/html5/thumbnails/81.jpg)
Set-up chemical characterization for safety risk assessment
Estimated/ Semi-quantitative results
Fully quantitative results
STEP 2. CALIBRATION CURVE: more QUANTITATIVE results for CMR/ED
STEP 1. Gather all results
Compare with published CMR/ED substances lists
Conclusion: proposed workflow
![Page 82: ISO 10993-18 in the MDR - Nelson Labs · 2020. 3. 10. · MDR: 10.4.2. Justification R A T isk ssessment ool ISO 10993-18 •Analysis of (patient & user) exposure = risk assessment](https://reader035.fdocuments.us/reader035/viewer/2022062318/5fdeae50d27ae15b3706ebd9/html5/thumbnails/82.jpg)
Information on concentration present ?
YES NO
STEP 1: ASK INFORMATION FROM SUPPLIERS Information on nature of CMR/ED present (e.g. contains BPA)
Chemical characterization: ISO 10993-18 RISK TO PATIENT SCREEN for all, SEMI-QUANT Compare with CMR/ED lists CMR/ED IN LIST (2-step): QUANT
RESULTS: ISO 10993-17
Conclusion: proposed workflow
![Page 83: ISO 10993-18 in the MDR - Nelson Labs · 2020. 3. 10. · MDR: 10.4.2. Justification R A T isk ssessment ool ISO 10993-18 •Analysis of (patient & user) exposure = risk assessment](https://reader035.fdocuments.us/reader035/viewer/2022062318/5fdeae50d27ae15b3706ebd9/html5/thumbnails/83.jpg)
CONC close to 0.1 % (w/w)
Information on concentration present ?
YES NO
STEP 1: ASK INFORMATION FROM SUPPLIERS Information on nature of CMR/ED present (e.g. contains BPA)
Chemical characterization: ISO 10993-18 RISK TO PATIENT SCREEN for all, SEMI-QUANT Compare with CMR/ED lists CMR/ED IN LIST (2-step): QUANT
RESULTS: ISO 10993-17
Conclusion: proposed workflow
![Page 84: ISO 10993-18 in the MDR - Nelson Labs · 2020. 3. 10. · MDR: 10.4.2. Justification R A T isk ssessment ool ISO 10993-18 •Analysis of (patient & user) exposure = risk assessment](https://reader035.fdocuments.us/reader035/viewer/2022062318/5fdeae50d27ae15b3706ebd9/html5/thumbnails/84.jpg)
CONC close to 0.1 % (w/w)
Information on concentration present ?
YES NO
STEP 1: ASK INFORMATION FROM SUPPLIERS Information on nature of CMR/ED present (e.g. contains BPA)
Chemical characterization: ISO 10993-18 RISK TO PATIENT SCREEN for all, SEMI-QUANT Compare with CMR/ED lists CMR/ED IN LIST (2-step): QUANT
RESULTS: ISO 10993-17
Full digestion Targeted analysis Fully quantitative
Conclusion: proposed workflow
![Page 85: ISO 10993-18 in the MDR - Nelson Labs · 2020. 3. 10. · MDR: 10.4.2. Justification R A T isk ssessment ool ISO 10993-18 •Analysis of (patient & user) exposure = risk assessment](https://reader035.fdocuments.us/reader035/viewer/2022062318/5fdeae50d27ae15b3706ebd9/html5/thumbnails/85.jpg)
CONC close to 0.1 % (w/w)
NO
STEP 1: ASK INFORMATION FROM SUPPLIERS Information on nature of CMR/ED present (e.g. contains BPA)
Chemical characterization: ISO 10993-18 RISK TO PATIENT SCREEN for all, SEMI-QUANT Compare with CMR/ED lists CMR/ED IN LIST (2-step): QUANT
RESULTS: ISO 10993-17
Full digestion Targeted analysis Fully quantitative
CMR/ED > 0.1 % w/w ?
Information on concentration present ?
Conclusion: proposed workflow
YES
![Page 86: ISO 10993-18 in the MDR - Nelson Labs · 2020. 3. 10. · MDR: 10.4.2. Justification R A T isk ssessment ool ISO 10993-18 •Analysis of (patient & user) exposure = risk assessment](https://reader035.fdocuments.us/reader035/viewer/2022062318/5fdeae50d27ae15b3706ebd9/html5/thumbnails/86.jpg)
CONC close to 0.1 % (w/w)
NO
STEP 1: ASK INFORMATION FROM SUPPLIERS Information on nature of CMR/ED present (e.g. contains BPA)
Chemical characterization: ISO 10993-18 RISK TO PATIENT SCREEN for all, SEMI-QUANT Compare with CMR/ED lists CMR/ED IN LIST (2-step): QUANT
RESULTS: ISO 10993-17
Full digestion Targeted analysis Fully quantitative
YES
JUSTIFICATION LABEL
Information on concentration present ?
yes
Conclusion: proposed workflow
YES NO
CMR/ED > 0.1 % w/w ?
![Page 87: ISO 10993-18 in the MDR - Nelson Labs · 2020. 3. 10. · MDR: 10.4.2. Justification R A T isk ssessment ool ISO 10993-18 •Analysis of (patient & user) exposure = risk assessment](https://reader035.fdocuments.us/reader035/viewer/2022062318/5fdeae50d27ae15b3706ebd9/html5/thumbnails/87.jpg)
CONC close to 0.1 % (w/w)
NO
STEP 1: ASK INFORMATION FROM SUPPLIERS Information on nature of CMR/ED present (e.g. contains BPA)
Chemical characterization: ISO 10993-18 RISK TO PATIENT SCREEN for all, SEMI-QUANT Compare with CMR/ED lists CMR/ED IN LIST (2-step): QUANT
RESULTS: ISO 10993-17
Full digestion Targeted analysis Fully quantitative
YES
JUSTIFICATION LABEL
Information on concentration present ?
yes
Conclusion: proposed workflow
YES NO
CMR/ED > 0.1 % w/w ?
![Page 88: ISO 10993-18 in the MDR - Nelson Labs · 2020. 3. 10. · MDR: 10.4.2. Justification R A T isk ssessment ool ISO 10993-18 •Analysis of (patient & user) exposure = risk assessment](https://reader035.fdocuments.us/reader035/viewer/2022062318/5fdeae50d27ae15b3706ebd9/html5/thumbnails/88.jpg)
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2020: The Year Of Change for the Medical Device Industry
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