Regulatory Open Forum

hi,

I think many EU IVD manufacturers are currently struggling with the question how to be in compliance when they need venous blood collections for analytical performance studies. The 'old' way was to have an internal blood donor program, covered by Ethics Committee. Those blood specimens were used for the performance verification program.

But now IVDR forces any performance study in which surgically invasive sample-taking is done only for the purpose of the performance study into an Annex XIV submission requiring competent authority authorization. Most EU member states will follow (MDR Annex VIII, Chapter 1, 2.2) and concur that venipuncture is a surgically invasive sample-taking procedure. The Annex XIV submission procedure can however be very lengthy.

While waiting on the MDCG Q&A guidance document on performance evaluation studies (where this hopefully will be tackled), any ideas how to approach this? Any experience in being compliant but not having to go for performance evaluation study authorization? EU countries that handle Annex XIV submissions smoothly when prospective venipunctures are clearly used for analytical performance studies only?

Thanks, all feedback welcome!

hi,

I think many EU IVD manufacturers are currently struggling with the question how to be in compliance when they need venous blood collections for analytical performance studies. The 'old' way was to have an internal blood donor program, covered by Ethics Committee. Those blood specimens were used for the performance verification program.

But now IVDR forces any performance study in which surgically invasive sample-taking is done only for the purpose of the performance study into an Annex XIV submission requiring competent authority authorization. Most EU member states will follow (MDR Annex VIII, Chapter 1, 2.2) and concur that venipuncture is a surgically invasive sample-taking procedure. The Annex XIV submission procedure can however be very lengthy.

While waiting on the MDCG Q&A guidance document on performance evaluation studies (where this hopefully will be tackled), any ideas how to approach this? Any experience in being compliant but not having to go for performance evaluation study authorization? EU countries that handle Annex XIV submissions smoothly when prospective venipunctures are clearly used for analytical performance studies only?

Thanks, all feedback welcome!

Hi Anon,

You bring up an interesting challenge. It seems the quickest route would be to determine a study design where you could use leftover specimens for these studies. This would allow you to only require ethics review. You must also still respect data protection requirements for these leftover specimens. 

I will say that you might find where some Member States take a different interpretation on whether venipuncture is considered invasive. Part of your due diligence might include specifically asking each MS CA where you're considering collecting specimens their interpretation of this.

Best of luck!

hi,

I think many EU IVD manufacturers are currently struggling with the question how to be in compliance when they need venous blood collections for analytical performance studies. The 'old' way was to have an internal blood donor program, covered by Ethics Committee. Those blood specimens were used for the performance verification program.

But now IVDR forces any performance study in which surgically invasive sample-taking is done only for the purpose of the performance study into an Annex XIV submission requiring competent authority authorization. Most EU member states will follow (MDR Annex VIII, Chapter 1, 2.2) and concur that venipuncture is a surgically invasive sample-taking procedure. The Annex XIV submission procedure can however be very lengthy.

While waiting on the MDCG Q&A guidance document on performance evaluation studies (where this hopefully will be tackled), any ideas how to approach this? Any experience in being compliant but not having to go for performance evaluation study authorization? EU countries that handle Annex XIV submissions smoothly when prospective venipunctures are clearly used for analytical performance studies only?

Thanks, all feedback welcome!

hi,

I think many EU IVD manufacturers are currently struggling with the question how to be in compliance when they need venous blood collections for analytical performance studies. The 'old' way was to have an internal blood donor program, covered by Ethics Committee. Those blood specimens were used for the performance verification program.

But now IVDR forces any performance study in which surgically invasive sample-taking is done only for the purpose of the performance study into an Annex XIV submission requiring competent authority authorization. Most EU member states will follow (MDR Annex VIII, Chapter 1, 2.2) and concur that venipuncture is a surgically invasive sample-taking procedure. The Annex XIV submission procedure can however be very lengthy.

While waiting on the MDCG Q&A guidance document on performance evaluation studies (where this hopefully will be tackled), any ideas how to approach this? Any experience in being compliant but not having to go for performance evaluation study authorization? EU countries that handle Annex XIV submissions smoothly when prospective venipunctures are clearly used for analytical performance studies only?

Thanks, all feedback welcome!

Hi Anon,

not sure how other member states handled this previously, but as far as I remember the previous German law (MPG) also required authority authorization for performance studies involving invasive sampling performed exclusively (or in the MPG even to a substantial degree) for the study (MPG §24). Given the definition of "surgically invasive device" in Annex VIII MDR that you cite I also assume that it is improbable someone will interpret venipuncture as not surgically invasive.

With respect to submission procedure as far as I can see you will at least be able to go via the Article 66 (7)a route that should allow you to start the study after successful validation date instead of having to waith for the full authorization, but I know currently of no example how well that procedure worked.

Best regards

Christoph

hi,

I think many EU IVD manufacturers are currently struggling with the question how to be in compliance when they need venous blood collections for analytical performance studies. The 'old' way was to have an internal blood donor program, covered by Ethics Committee. Those blood specimens were used for the performance verification program.

But now IVDR forces any performance study in which surgically invasive sample-taking is done only for the purpose of the performance study into an Annex XIV submission requiring competent authority authorization. Most EU member states will follow (MDR Annex VIII, Chapter 1, 2.2) and concur that venipuncture is a surgically invasive sample-taking procedure. The Annex XIV submission procedure can however be very lengthy.

While waiting on the MDCG Q&A guidance document on performance evaluation studies (where this hopefully will be tackled), any ideas how to approach this? Any experience in being compliant but not having to go for performance evaluation study authorization? EU countries that handle Annex XIV submissions smoothly when prospective venipunctures are clearly used for analytical performance studies only?

Thanks, all feedback welcome!

hi,

I think many EU IVD manufacturers are currently struggling with the question how to be in compliance when they need venous blood collections for analytical performance studies. The 'old' way was to have an internal blood donor program, covered by Ethics Committee. Those blood specimens were used for the performance verification program.

But now IVDR forces any performance study in which surgically invasive sample-taking is done only for the purpose of the performance study into an Annex XIV submission requiring competent authority authorization. Most EU member states will follow (MDR Annex VIII, Chapter 1, 2.2) and concur that venipuncture is a surgically invasive sample-taking procedure. The Annex XIV submission procedure can however be very lengthy.

While waiting on the MDCG Q&A guidance document on performance evaluation studies (where this hopefully will be tackled), any ideas how to approach this? Any experience in being compliant but not having to go for performance evaluation study authorization? EU countries that handle Annex XIV submissions smoothly when prospective venipunctures are clearly used for analytical performance studies only?

Thanks, all feedback welcome!

Hi Anon,
Based on our experience, few EU countries including Italy will not necessarily consider blood collection by venipuncture as a "surgically invasive" sampling technique, in line with FDA approach on this (see In Vitro Diagnostic (IVD) Device Studies - Frequently Asked Questions, FDA guidance June 2010).  It is true, however, that the procedure could be considered either invasive or generating "other risk" for study subjects, in which case IVDR Annex XIV procedures would still apply. I think a good approach would be to provide a rationale in the clinical performance study plan as to why the manufacturer believes that blood collection by venipuncture would not represent a risk for study subjects. Such rationale should take into account different aspects such as subjects involved in the study, quantity of blood to be collected, collection frequency etc. If the rationale is sufficiently strong, the manufacturer should submit the study only to the Ethics Committee (EC) and rely on its judgement. It would remain in the EC authority to determine if the study would also require CA authorization. This approach was successful for a study we recently followed requiring repeated blood collection from transplanted patients in Italy. 

Regards

hi,

I think many EU IVD manufacturers are currently struggling with the question how to be in compliance when they need venous blood collections for analytical performance studies. The 'old' way was to have an internal blood donor program, covered by Ethics Committee. Those blood specimens were used for the performance verification program.

But now IVDR forces any performance study in which surgically invasive sample-taking is done only for the purpose of the performance study into an Annex XIV submission requiring competent authority authorization. Most EU member states will follow (MDR Annex VIII, Chapter 1, 2.2) and concur that venipuncture is a surgically invasive sample-taking procedure. The Annex XIV submission procedure can however be very lengthy.

While waiting on the MDCG Q&A guidance document on performance evaluation studies (where this hopefully will be tackled), any ideas how to approach this? Any experience in being compliant but not having to go for performance evaluation study authorization? EU countries that handle Annex XIV submissions smoothly when prospective venipunctures are clearly used for analytical performance studies only?

Thanks, all feedback welcome!

hello Daniela,

thank you for your message. But isn't it not up to the EC to decide if the study needs to go to the competent authority? They must of course issue a positive opinion first, but I didn't think they have the regulatory authority to decide whether or not the proposed study requires an 'annex XIV' submission. Am I seeing this wrong?

Best reagrds

Hi Anon,
Based on our experience, few EU countries including Italy will not necessarily consider blood collection by venipuncture as a "surgically invasive" sampling technique, in line with FDA approach on this (see In Vitro Diagnostic (IVD) Device Studies - Frequently Asked Questions, FDA guidance June 2010).  It is true, however, that the procedure could be considered either invasive or generating "other risk" for study subjects, in which case IVDR Annex XIV procedures would still apply. I think a good approach would be to provide a rationale in the clinical performance study plan as to why the manufacturer believes that blood collection by venipuncture would not represent a risk for study subjects. Such rationale should take into account different aspects such as subjects involved in the study, quantity of blood to be collected, collection frequency etc. If the rationale is sufficiently strong, the manufacturer should submit the study only to the Ethics Committee (EC) and rely on its judgement. It would remain in the EC authority to determine if the study would also require CA authorization. This approach was successful for a study we recently followed requiring repeated blood collection from transplanted patients in Italy. 

Regards

hi,

I think many EU IVD manufacturers are currently struggling with the question how to be in compliance when they need venous blood collections for analytical performance studies. The 'old' way was to have an internal blood donor program, covered by Ethics Committee. Those blood specimens were used for the performance verification program.

But now IVDR forces any performance study in which surgically invasive sample-taking is done only for the purpose of the performance study into an Annex XIV submission requiring competent authority authorization. Most EU member states will follow (MDR Annex VIII, Chapter 1, 2.2) and concur that venipuncture is a surgically invasive sample-taking procedure. The Annex XIV submission procedure can however be very lengthy.

While waiting on the MDCG Q&A guidance document on performance evaluation studies (where this hopefully will be tackled), any ideas how to approach this? Any experience in being compliant but not having to go for performance evaluation study authorization? EU countries that handle Annex XIV submissions smoothly when prospective venipunctures are clearly used for analytical performance studies only?

Thanks, all feedback welcome!

hello Daniela,

thank you for your message. But isn't it not up to the EC to decide if the study needs to go to the competent authority? They must of course issue a positive opinion first, but I didn't think they have the regulatory authority to decide whether or not the proposed study requires an 'annex XIV' submission. Am I seeing this wrong?

Best reagrds

Hi Anon,
Based on our experience, few EU countries including Italy will not necessarily consider blood collection by venipuncture as a "surgically invasive" sampling technique, in line with FDA approach on this (see In Vitro Diagnostic (IVD) Device Studies - Frequently Asked Questions, FDA guidance June 2010).  It is true, however, that the procedure could be considered either invasive or generating "other risk" for study subjects, in which case IVDR Annex XIV procedures would still apply. I think a good approach would be to provide a rationale in the clinical performance study plan as to why the manufacturer believes that blood collection by venipuncture would not represent a risk for study subjects. Such rationale should take into account different aspects such as subjects involved in the study, quantity of blood to be collected, collection frequency etc. If the rationale is sufficiently strong, the manufacturer should submit the study only to the Ethics Committee (EC) and rely on its judgement. It would remain in the EC authority to determine if the study would also require CA authorization. This approach was successful for a study we recently followed requiring repeated blood collection from transplanted patients in Italy. 

Regards

hi,

I think many EU IVD manufacturers are currently struggling with the question how to be in compliance when they need venous blood collections for analytical performance studies. The 'old' way was to have an internal blood donor program, covered by Ethics Committee. Those blood specimens were used for the performance verification program.

But now IVDR forces any performance study in which surgically invasive sample-taking is done only for the purpose of the performance study into an Annex XIV submission requiring competent authority authorization. Most EU member states will follow (MDR Annex VIII, Chapter 1, 2.2) and concur that venipuncture is a surgically invasive sample-taking procedure. The Annex XIV submission procedure can however be very lengthy.

While waiting on the MDCG Q&A guidance document on performance evaluation studies (where this hopefully will be tackled), any ideas how to approach this? Any experience in being compliant but not having to go for performance evaluation study authorization? EU countries that handle Annex XIV submissions smoothly when prospective venipunctures are clearly used for analytical performance studies only?

Thanks, all feedback welcome!