Regulatory Open Forum

[...] Devices, or those parts thereof or those materials used therein that:

• are invasive and come into direct contact with the human body,
• (re)administer medicines, body liquids or other substances, including gases, to/from the body, or
• transport or store such medicines, body fluids or substances, including gases, to be (re)administered to the body,

[...] Devices, or those parts thereof or those materials used therein that:

• are invasive and come into direct contact with the human body,
• (re)administer medicines, body liquids or other substances, including gases, to/from the body, or
• transport or store such medicines, body fluids or substances, including gases, to be (re)administered to the body,

Good Morning,

in my opinion the principle of this requirement from patient point of use is as follows:  

Devices shall be designed and manufactured in such a way as to reduce as far as possible the risks posed by substances or particles, including wear debris, degradation products and processing residues, that may be released from the device.

So, I would consider a bench test at least, that provides information about the load of inhaled particles or substances, that may be sourced from the spirometer and/or the gas tank.

In case the finished product release procedure (including specifications) of the spirometer and the gas product ensure, that neither the particle contamination, nor the substance contamination of the inhaled gas is possible, probably there will be no need for bench test, I guess.

regards

[...] Devices, or those parts thereof or those materials used therein that:

• are invasive and come into direct contact with the human body,
• (re)administer medicines, body liquids or other substances, including gases, to/from the body, or
• transport or store such medicines, body fluids or substances, including gases, to be (re)administered to the body,

Good Morning,

in my opinion the principle of this requirement from patient point of use is as follows:  

Devices shall be designed and manufactured in such a way as to reduce as far as possible the risks posed by substances or particles, including wear debris, degradation products and processing residues, that may be released from the device.

So, I would consider a bench test at least, that provides information about the load of inhaled particles or substances, that may be sourced from the spirometer and/or the gas tank.

In case the finished product release procedure (including specifications) of the spirometer and the gas product ensure, that neither the particle contamination, nor the substance contamination of the inhaled gas is possible, probably there will be no need for bench test, I guess.

regards

[...] Devices, or those parts thereof or those materials used therein that:

• are invasive and come into direct contact with the human body,
• (re)administer medicines, body liquids or other substances, including gases, to/from the body, or
• transport or store such medicines, body fluids or substances, including gases, to be (re)administered to the body,

Dear Colleague,

this is my quickly formed opinion. If I were an auditor, I may raise the following questions:

• is the spirometer for personal use only or applied in a health care facility and used for repeated daily testing of a high number of patients?
• what is the average use of the spirometer device for one patient per periods, like week, month or year, consequently, what is the frequency of exposure per patient?
• may any part of spirometer be contaminated with bacteria, fungi (overgrowth) or viruses?
• cross-contamination of patients is possible?
• are there effective and validated tools of cleaning/sterilisation if these are needed?
• are all of these described properly in the IFU?
• is this practice properly applied by patients and/or HCPs?
• may vapour or any other material (or combination of these), including carbon monoxide, in the incoming airflow chemically react with any part of the spirometer on the long run (use of the device for months/years)?
• if yes, may this lead to exposure of the users/patients to toxic materials or particles?
• does the manufacturer of the spirometer have control over the quality of the CO gas?
• does the quality of this CO gas match definite standards/specifications (sufficiently controlled, regularly tested and reported in certificate of analysis)?
• does the manufacturer have the results of (at least simulation) tests or sufficient clinical evidence to prove compliance of the device used according to the IFU, with MDR, requirement #10.4.1 of Annex I ?

regards

Good Morning,

in my opinion the principle of this requirement from patient point of use is as follows:  

Devices shall be designed and manufactured in such a way as to reduce as far as possible the risks posed by substances or particles, including wear debris, degradation products and processing residues, that may be released from the device.

So, I would consider a bench test at least, that provides information about the load of inhaled particles or substances, that may be sourced from the spirometer and/or the gas tank.

In case the finished product release procedure (including specifications) of the spirometer and the gas product ensure, that neither the particle contamination, nor the substance contamination of the inhaled gas is possible, probably there will be no need for bench test, I guess.

regards

[...] Devices, or those parts thereof or those materials used therein that:

• are invasive and come into direct contact with the human body,
• (re)administer medicines, body liquids or other substances, including gases, to/from the body, or
• transport or store such medicines, body fluids or substances, including gases, to be (re)administered to the body,

I'd like to add to add to Peter's answer.

I'm a logician by education, so I often write these requirements in a logic-based format.

IF the device administers a gas to the body, THEN the concentration of certain substances should be below 0.1% w/w.

IF the concentration of certain substances is above 0.1% w/w THEN justify it following 10.4.2 AND label it following 10.4.5.

Since this applies to your device (the first IF) you must determine the concentration of the substances. There are multiple ways to do this. One is to collect CoAs from your supplies and add up the weighted concentrations. Another method is to send a representative product to a test house. Presumably you will be below 0.1% w/w.

IF the second IF applies, then you need to either justify the situation or design out the problem components.

Notice that the ISO 18562 family of standards does not enter into the requirements. While valuable, they don't directly apply to this EU-MDR requirement.

Dear Colleague,

this is my quickly formed opinion. If I were an auditor, I may raise the following questions:

• is the spirometer for personal use only or applied in a health care facility and used for repeated daily testing of a high number of patients?
• what is the average use of the spirometer device for one patient per periods, like week, month or year, consequently, what is the frequency of exposure per patient?
• may any part of spirometer be contaminated with bacteria, fungi (overgrowth) or viruses?
• cross-contamination of patients is possible?
• are there effective and validated tools of cleaning/sterilisation if these are needed?
• are all of these described properly in the IFU?
• is this practice properly applied by patients and/or HCPs?
• may vapour or any other material (or combination of these), including carbon monoxide, in the incoming airflow chemically react with any part of the spirometer on the long run (use of the device for months/years)?
• if yes, may this lead to exposure of the users/patients to toxic materials or particles?
• does the manufacturer of the spirometer have control over the quality of the CO gas?
• does the quality of this CO gas match definite standards/specifications (sufficiently controlled, regularly tested and reported in certificate of analysis)?
• does the manufacturer have the results of (at least simulation) tests or sufficient clinical evidence to prove compliance of the device used according to the IFU, with MDR, requirement #10.4.1 of Annex I ?

regards

Good Morning,

in my opinion the principle of this requirement from patient point of use is as follows:  

Devices shall be designed and manufactured in such a way as to reduce as far as possible the risks posed by substances or particles, including wear debris, degradation products and processing residues, that may be released from the device.

So, I would consider a bench test at least, that provides information about the load of inhaled particles or substances, that may be sourced from the spirometer and/or the gas tank.

In case the finished product release procedure (including specifications) of the spirometer and the gas product ensure, that neither the particle contamination, nor the substance contamination of the inhaled gas is possible, probably there will be no need for bench test, I guess.

regards

[...] Devices, or those parts thereof or those materials used therein that:

• are invasive and come into direct contact with the human body,
• (re)administer medicines, body liquids or other substances, including gases, to/from the body, or
• transport or store such medicines, body fluids or substances, including gases, to be (re)administered to the body,

I'd like to add to add to Peter's answer.

I'm a logician by education, so I often write these requirements in a logic-based format.

IF the device administers a gas to the body, THEN the concentration of certain substances should be below 0.1% w/w.

IF the concentration of certain substances is above 0.1% w/w THEN justify it following 10.4.2 AND label it following 10.4.5.

Since this applies to your device (the first IF) you must determine the concentration of the substances. There are multiple ways to do this. One is to collect CoAs from your supplies and add up the weighted concentrations. Another method is to send a representative product to a test house. Presumably you will be below 0.1% w/w.

IF the second IF applies, then you need to either justify the situation or design out the problem components.

Notice that the ISO 18562 family of standards does not enter into the requirements. While valuable, they don't directly apply to this EU-MDR requirement.

Dear Colleague,

this is my quickly formed opinion. If I were an auditor, I may raise the following questions:

• is the spirometer for personal use only or applied in a health care facility and used for repeated daily testing of a high number of patients?
• what is the average use of the spirometer device for one patient per periods, like week, month or year, consequently, what is the frequency of exposure per patient?
• may any part of spirometer be contaminated with bacteria, fungi (overgrowth) or viruses?
• cross-contamination of patients is possible?
• are there effective and validated tools of cleaning/sterilisation if these are needed?
• are all of these described properly in the IFU?
• is this practice properly applied by patients and/or HCPs?
• may vapour or any other material (or combination of these), including carbon monoxide, in the incoming airflow chemically react with any part of the spirometer on the long run (use of the device for months/years)?
• if yes, may this lead to exposure of the users/patients to toxic materials or particles?
• does the manufacturer of the spirometer have control over the quality of the CO gas?
• does the quality of this CO gas match definite standards/specifications (sufficiently controlled, regularly tested and reported in certificate of analysis)?
• does the manufacturer have the results of (at least simulation) tests or sufficient clinical evidence to prove compliance of the device used according to the IFU, with MDR, requirement #10.4.1 of Annex I ?

regards

Good Morning,

in my opinion the principle of this requirement from patient point of use is as follows:  

Devices shall be designed and manufactured in such a way as to reduce as far as possible the risks posed by substances or particles, including wear debris, degradation products and processing residues, that may be released from the device.

So, I would consider a bench test at least, that provides information about the load of inhaled particles or substances, that may be sourced from the spirometer and/or the gas tank.

In case the finished product release procedure (including specifications) of the spirometer and the gas product ensure, that neither the particle contamination, nor the substance contamination of the inhaled gas is possible, probably there will be no need for bench test, I guess.

regards

[...] Devices, or those parts thereof or those materials used therein that:

• are invasive and come into direct contact with the human body,
• (re)administer medicines, body liquids or other substances, including gases, to/from the body, or
• transport or store such medicines, body fluids or substances, including gases, to be (re)administered to the body,

[...] Devices, or those parts thereof or those materials used therein that:

• are invasive and come into direct contact with the human body,
• (re)administer medicines, body liquids or other substances, including gases, to/from the body, or
• transport or store such medicines, body fluids or substances, including gases, to be (re)administered to the body,

The requirement applies to your device because it administers a gas to the patient. You need to demonstrate that your device, particularly all elements of the path the gas follows, meets the requirements for the substances in the (a) part and in the (b) part. If you don't meet the requirement, then you need to justify, from the patient's point of view, why this is acceptable.

I infer that when the patient exhales the gas is gone. By that I mean you don't capture it and use it again on the same patient. If so, then you also readminister the gas: administer it once, collect it, and administer the gas again.

[...] Devices, or those parts thereof or those materials used therein that:

• are invasive and come into direct contact with the human body,
• (re)administer medicines, body liquids or other substances, including gases, to/from the body, or
• transport or store such medicines, body fluids or substances, including gases, to be (re)administered to the body,

[...] Devices, or those parts thereof or those materials used therein that:

• are invasive and come into direct contact with the human body,
• (re)administer medicines, body liquids or other substances, including gases, to/from the body, or
• transport or store such medicines, body fluids or substances, including gases, to be (re)administered to the body,

[...] Devices, or those parts thereof or those materials used therein that:

• are invasive and come into direct contact with the human body,
• (re)administer medicines, body liquids or other substances, including gases, to/from the body, or
• transport or store such medicines, body fluids or substances, including gases, to be (re)administered to the body,

• Regarding 10.4.1(b), it appears that an act has in fact been delegated.  See Regulation (EU) 2017/2100.

• From my education in chemistry, 10.4.1's wording regarding the 0.1% w/w concentration limit appears to apply to any of the substances individually rather than collectively.  In other words, if any single listed substance exceeds the 0.1% w/w threshold, then the justification (i.e., the risk/benefit analysis) prescribed by 10.4.2 and labeling requirements of 10.4.5 is needed for that substance.

• To identify the CMR chemicals list, filter the Regulation (EC) No 1272/2008 Annex VI Tables 3.1 and 3.2 chemicals lists to identify those named in MDR Annex I.II.10.4.1 second paragraph, indent (a).  Specifically, those are the category 1A and 1B carcinogens, mutagens, and reproductive toxicants.  They are identified in these tables by the labels "Muta. 1A", "Muta. 1B", "Carc. 1A", "Carc. 1B", "Repr. 1A", and "Repr. 1B" which can be used as search terms when filtering the Table 3.1 and 3.2 lists.

• To identify the ED chemicals lists, the safest bet seems to be a twofold approach due to 10.4.1 indent (b)'s ambiguity (in my opinion) regarding application of two alternative approaches:

1. Filter the Regulation 1907/2006 (REACH) Annex XIV chemicals list to identify the ED chemicals named by the first part of MDR Annex I.II.10.4.1 second paragraph, indent (b) with human health risk (they will be annotated "Human Health" or similar).   Note that based on the basic premises of REACH regulation Article 57, such endocrine disrupting chemicals essentially mean any endocrine disrupting chemicals listed in REACH's Annex XIV.  In the current consolidated version of that Regulation's Annex XIV, it does not appear that any endocrine disrupters affecting human health are listed.  For emerging ED substances with reasonable potential to be added to REACH Annex XIV, see the latest updated lists at https://echa.europa.eu/authorisation-list and https://echa.europa.eu/candidate-list-table and filter them for ED substances with human health risk.  I also recommend looking at the preliminary assessment list at https://echa.europa.eu/ed-assessment for early warning and strategic planning in the event the envisaged device materials include any on this list.  I recommend that these lists be regularly monitored and/or used during medical device product development considerations and/or EU MDR gap work.
2. Identify the ED chemicals indicated via the criteria in Section A of the sole Annex of Regulation (EU) 2017/2100 [which is the delegated Act that has, since 2017/745's entry into force, been subsequently adopted pursuant to Article 5(3) of Regulation 528/2012].  At https://echa.europa.eu/-/guidance-on-identifying-endocrine-disruptors-published , there is a guidance document and other resources to help with this part of the ED identification process.  It appears that Europe as a community may already be collaboratively working on generating an ED list via this approach at https://echa.europa.eu/ed-assessment.  That collaborative community list may or may not suffice as the one to be generated by each manufacturer for its devices.  I'm hoping we can just rely on the community list, as doing such a derivation on one's own will be daunting.

• Regarding 10.4.3 and Phthalates, look at the guidance document at https://ec.europa.eu/health/sites/health/files/scientific_committees/scheer/docs/scheer_o_015.pdf to determine what adjustments (if any) are needed regarding the aforementioned lists. Note also that this guidance document has some good general CMR / ED guidance in it.

[...] Devices, or those parts thereof or those materials used therein that:

• are invasive and come into direct contact with the human body,
• (re)administer medicines, body liquids or other substances, including gases, to/from the body, or
• transport or store such medicines, body fluids or substances, including gases, to be (re)administered to the body,

• Regarding 10.4.1(b), it appears that an act has in fact been delegated.  See Regulation (EU) 2017/2100.

• From my education in chemistry, 10.4.1's wording regarding the 0.1% w/w concentration limit appears to apply to any of the substances individually rather than collectively.  In other words, if any single listed substance exceeds the 0.1% w/w threshold, then the justification (i.e., the risk/benefit analysis) prescribed by 10.4.2 and labeling requirements of 10.4.5 is needed for that substance.

• To identify the CMR chemicals list, filter the Regulation (EC) No 1272/2008 Annex VI Tables 3.1 and 3.2 chemicals lists to identify those named in MDR Annex I.II.10.4.1 second paragraph, indent (a).  Specifically, those are the category 1A and 1B carcinogens, mutagens, and reproductive toxicants.  They are identified in these tables by the labels "Muta. 1A", "Muta. 1B", "Carc. 1A", "Carc. 1B", "Repr. 1A", and "Repr. 1B" which can be used as search terms when filtering the Table 3.1 and 3.2 lists.

• To identify the ED chemicals lists, the safest bet seems to be a twofold approach due to 10.4.1 indent (b)'s ambiguity (in my opinion) regarding application of two alternative approaches:

1. Filter the Regulation 1907/2006 (REACH) Annex XIV chemicals list to identify the ED chemicals named by the first part of MDR Annex I.II.10.4.1 second paragraph, indent (b) with human health risk (they will be annotated "Human Health" or similar).   Note that based on the basic premises of REACH regulation Article 57, such endocrine disrupting chemicals essentially mean any endocrine disrupting chemicals listed in REACH's Annex XIV.  In the current consolidated version of that Regulation's Annex XIV, it does not appear that any endocrine disrupters affecting human health are listed.  For emerging ED substances with reasonable potential to be added to REACH Annex XIV, see the latest updated lists at https://echa.europa.eu/authorisation-list and https://echa.europa.eu/candidate-list-table and filter them for ED substances with human health risk.  I also recommend looking at the preliminary assessment list at https://echa.europa.eu/ed-assessment for early warning and strategic planning in the event the envisaged device materials include any on this list.  I recommend that these lists be regularly monitored and/or used during medical device product development considerations and/or EU MDR gap work.
2. Identify the ED chemicals indicated via the criteria in Section A of the sole Annex of Regulation (EU) 2017/2100 [which is the delegated Act that has, since 2017/745's entry into force, been subsequently adopted pursuant to Article 5(3) of Regulation 528/2012].  At https://echa.europa.eu/-/guidance-on-identifying-endocrine-disruptors-published , there is a guidance document and other resources to help with this part of the ED identification process.  It appears that Europe as a community may already be collaboratively working on generating an ED list via this approach at https://echa.europa.eu/ed-assessment.  That collaborative community list may or may not suffice as the one to be generated by each manufacturer for its devices.  I'm hoping we can just rely on the community list, as doing such a derivation on one's own will be daunting.

• Regarding 10.4.3 and Phthalates, look at the guidance document at https://ec.europa.eu/health/sites/health/files/scientific_committees/scheer/docs/scheer_o_015.pdf to determine what adjustments (if any) are needed regarding the aforementioned lists. Note also that this guidance document has some good general CMR / ED guidance in it.

[...] Devices, or those parts thereof or those materials used therein that:

• are invasive and come into direct contact with the human body,
• (re)administer medicines, body liquids or other substances, including gases, to/from the body, or
• transport or store such medicines, body fluids or substances, including gases, to be (re)administered to the body,

• Regarding 10.4.1(b), it appears that an act has in fact been delegated.  See Regulation (EU) 2017/2100.

• From my education in chemistry, 10.4.1's wording regarding the 0.1% w/w concentration limit appears to apply to any of the substances individually rather than collectively.  In other words, if any single listed substance exceeds the 0.1% w/w threshold, then the justification (i.e., the risk/benefit analysis) prescribed by 10.4.2 and labeling requirements of 10.4.5 is needed for that substance.

• To identify the CMR chemicals list, filter the Regulation (EC) No 1272/2008 Annex VI Tables 3.1 and 3.2 chemicals lists to identify those named in MDR Annex I.II.10.4.1 second paragraph, indent (a).  Specifically, those are the category 1A and 1B carcinogens, mutagens, and reproductive toxicants.  They are identified in these tables by the labels "Muta. 1A", "Muta. 1B", "Carc. 1A", "Carc. 1B", "Repr. 1A", and "Repr. 1B" which can be used as search terms when filtering the Table 3.1 and 3.2 lists.

• To identify the ED chemicals lists, the safest bet seems to be a twofold approach due to 10.4.1 indent (b)'s ambiguity (in my opinion) regarding application of two alternative approaches:

1. Filter the Regulation 1907/2006 (REACH) Annex XIV chemicals list to identify the ED chemicals named by the first part of MDR Annex I.II.10.4.1 second paragraph, indent (b) with human health risk (they will be annotated "Human Health" or similar).   Note that based on the basic premises of REACH regulation Article 57, such endocrine disrupting chemicals essentially mean any endocrine disrupting chemicals listed in REACH's Annex XIV.  In the current consolidated version of that Regulation's Annex XIV, it does not appear that any endocrine disrupters affecting human health are listed.  For emerging ED substances with reasonable potential to be added to REACH Annex XIV, see the latest updated lists at https://echa.europa.eu/authorisation-list and https://echa.europa.eu/candidate-list-table and filter them for ED substances with human health risk.  I also recommend looking at the preliminary assessment list at https://echa.europa.eu/ed-assessment for early warning and strategic planning in the event the envisaged device materials include any on this list.  I recommend that these lists be regularly monitored and/or used during medical device product development considerations and/or EU MDR gap work.
2. Identify the ED chemicals indicated via the criteria in Section A of the sole Annex of Regulation (EU) 2017/2100 [which is the delegated Act that has, since 2017/745's entry into force, been subsequently adopted pursuant to Article 5(3) of Regulation 528/2012].  At https://echa.europa.eu/-/guidance-on-identifying-endocrine-disruptors-published , there is a guidance document and other resources to help with this part of the ED identification process.  It appears that Europe as a community may already be collaboratively working on generating an ED list via this approach at https://echa.europa.eu/ed-assessment.  That collaborative community list may or may not suffice as the one to be generated by each manufacturer for its devices.  I'm hoping we can just rely on the community list, as doing such a derivation on one's own will be daunting.

• Regarding 10.4.3 and Phthalates, look at the guidance document at https://ec.europa.eu/health/sites/health/files/scientific_committees/scheer/docs/scheer_o_015.pdf to determine what adjustments (if any) are needed regarding the aforementioned lists. Note also that this guidance document has some good general CMR / ED guidance in it.

[...] Devices, or those parts thereof or those materials used therein that:

• are invasive and come into direct contact with the human body,
• (re)administer medicines, body liquids or other substances, including gases, to/from the body, or
• transport or store such medicines, body fluids or substances, including gases, to be (re)administered to the body,

• Regarding 10.4.1(b), it appears that an act has in fact been delegated.  See Regulation (EU) 2017/2100.

• From my education in chemistry, 10.4.1's wording regarding the 0.1% w/w concentration limit appears to apply to any of the substances individually rather than collectively.  In other words, if any single listed substance exceeds the 0.1% w/w threshold, then the justification (i.e., the risk/benefit analysis) prescribed by 10.4.2 and labeling requirements of 10.4.5 is needed for that substance.

• To identify the CMR chemicals list, filter the Regulation (EC) No 1272/2008 Annex VI Tables 3.1 and 3.2 chemicals lists to identify those named in MDR Annex I.II.10.4.1 second paragraph, indent (a).  Specifically, those are the category 1A and 1B carcinogens, mutagens, and reproductive toxicants.  They are identified in these tables by the labels "Muta. 1A", "Muta. 1B", "Carc. 1A", "Carc. 1B", "Repr. 1A", and "Repr. 1B" which can be used as search terms when filtering the Table 3.1 and 3.2 lists.

• To identify the ED chemicals lists, the safest bet seems to be a twofold approach due to 10.4.1 indent (b)'s ambiguity (in my opinion) regarding application of two alternative approaches:

1. Filter the Regulation 1907/2006 (REACH) Annex XIV chemicals list to identify the ED chemicals named by the first part of MDR Annex I.II.10.4.1 second paragraph, indent (b) with human health risk (they will be annotated "Human Health" or similar).   Note that based on the basic premises of REACH regulation Article 57, such endocrine disrupting chemicals essentially mean any endocrine disrupting chemicals listed in REACH's Annex XIV.  In the current consolidated version of that Regulation's Annex XIV, it does not appear that any endocrine disrupters affecting human health are listed.  For emerging ED substances with reasonable potential to be added to REACH Annex XIV, see the latest updated lists at https://echa.europa.eu/authorisation-list and https://echa.europa.eu/candidate-list-table and filter them for ED substances with human health risk.  I also recommend looking at the preliminary assessment list at https://echa.europa.eu/ed-assessment for early warning and strategic planning in the event the envisaged device materials include any on this list.  I recommend that these lists be regularly monitored and/or used during medical device product development considerations and/or EU MDR gap work.
2. Identify the ED chemicals indicated via the criteria in Section A of the sole Annex of Regulation (EU) 2017/2100 [which is the delegated Act that has, since 2017/745's entry into force, been subsequently adopted pursuant to Article 5(3) of Regulation 528/2012].  At https://echa.europa.eu/-/guidance-on-identifying-endocrine-disruptors-published , there is a guidance document and other resources to help with this part of the ED identification process.  It appears that Europe as a community may already be collaboratively working on generating an ED list via this approach at https://echa.europa.eu/ed-assessment.  That collaborative community list may or may not suffice as the one to be generated by each manufacturer for its devices.  I'm hoping we can just rely on the community list, as doing such a derivation on one's own will be daunting.

• Regarding 10.4.3 and Phthalates, look at the guidance document at https://ec.europa.eu/health/sites/health/files/scientific_committees/scheer/docs/scheer_o_015.pdf to determine what adjustments (if any) are needed regarding the aforementioned lists. Note also that this guidance document has some good general CMR / ED guidance in it.

[...] Devices, or those parts thereof or those materials used therein that:

• are invasive and come into direct contact with the human body,
• (re)administer medicines, body liquids or other substances, including gases, to/from the body, or
• transport or store such medicines, body fluids or substances, including gases, to be (re)administered to the body,