ISO 10993 Requirements For 510k - Substantial Equivalence

[kiwi.kczt]

Hello everybody, thanks for stopping by!

A little background:

I am a research engineer working for a medical device company, and my colleagues and I are in the midst of preparing a 510k submission for a new medical device. The predicate device we have chosen for substantial equivalence has been cleared for both ISO10993-5 and ISO10993-10.

My questions:

1. Am I correct to say that our device would also have to pass ISO10993-5 and ISO10993-10 (amongst other things) to claim substantial equivalence?

2. An adhesive that we will most likely be using in the assembly of the device has cleared for only ISO10993-5, and not ISO10993-10. Would this be a problem if the adhesive would not come into contact with body tissue / fluids under normal (non-failure) use?

3. Would it be a reasonable assumption to say that ISO10993-5 (cytotoxicity) is a "higher bar" to clear as compared to ISO10993-10 (irritation and sensitisation)? If so, would having passed ISO10993-5 suggest that the adhesive should generally be non-irritating and non-sensitising?

Thanks a lot in advance!

Keith

 

[Mark Meer]

1. Am I correct to say that our device would also have to pass ISO10993-5 and ISO10993-10 (amongst other things) to claim substantial equivalence?

Not just for substantial equivalence. The FDA wants to see evidence of biocompatibility for any device submission.

Check out this guidance.

2. An adhesive that we will most likely be using in the assembly of the device has cleared for only ISO10993-5, and not ISO10993-10. Would this be a problem if the adhesive would not come into contact with body tissue / fluids under normal (non-failure) use?

The important thing is to consider patient contact under intended use conditions. ...so no, if the adhesive is not intended to contact patients under normal use, the explicit 10993 testing of this material is not of value (unless, of course, you've identified some other biocompatibility risk). Risk assessment is key.

Also, depending on the type of device, check that there aren't any special guidance documents from the FDA that might give specific biocompatibility guidance for a given type of device.

3. Would it be a reasonable assumption to say that ISO10993-5 (cytotoxicity) is a "higher bar" to clear as compared to ISO10993-10 (irritation and sensitisation)? If so, would having passed ISO10993-5 suggest that the adhesive should generally be non-irritating and non-sensitising?

No. They are completely different tests. You can not conclude anything about the outcomes of one test from the results of the other.

 

[kiwi.kczt]

Not just for substantial equivalence. The FDA wants to see evidence of biocompatibility for any device submission

Understood, thanks.

The important thing is to consider patient contact under intended use conditions. ...so no, if the adhesive is not intended to contact patients under normal use, the explicit 10993 testing of this material is not of value (unless, of course, you've identified some other biocompatibility risk). Risk assessment is key.

Also, depending on the type of device, check that there aren't any special guidance documents from the FDA that might give specific biocompatibility guidance for a given type of device..

That's great news. So it seems that not having 10993 testing for the adhesive is a justifiable position to take. Unfortunately, the FDA does not have specific guidance documents pertaining to the biocompatibility requirements for our device.

No. They are completely different tests. You can not conclude anything about the outcomes of one test from the results of the other.

Got it. I thought that was a long shot to assume so myself. However it seems from your second point that we might not need all the biocomp tests for the adhesive afterall.

 

[Ronen E]

Just a general note - biocompatibility testing, when required, should be done at the finished device form. Biocompatibility testing of specific components may contribute to your confidence level when selecting them, but it's not a substitute for whole-device testing.

 

[kiwi.kczt]

Just a general note - biocompatibility testing, when required, should be done at the finished device form. Biocompatibility testing of specific components may contribute to your confidence level when selecting them, but it's not a substitute for whole-device testing.

Hi Ronen, when you say "finished device form" are you referring to the grinding up (homogenisation) of the entire device prior to biocompatibility testing?

The reason I ask is because only part of the device contacts the body - a good percentage (more than 80%) of the device remains outside of the body during use. In this case would you still say that biocompatibility testing should be done at the finished device form?

 

[Ronen E]

Hi Ronen, when you say "finished device form" are you referring to the grinding up (homogenisation) of the entire device prior to biocompatibility testing?

The reason I ask is because only part of the device contacts the body - a good percentage (more than 80%) of the device remains outside of the body during use. In this case would you still say that biocompatibility testing should be done at the finished device form?

"Finished device form" as opposed to individual components / raw materials, and including all manufacturing processes (e.g. moulded plastics should be tested as-moulded, not in raw material form). Which parts go into actual testing is subject to careful analysis which should be a cooperation between test lab and manufacturer. Intended use matters.

 

[kiwi.kczt]

"Finished device form" as opposed to individual components / raw materials, and including all manufacturing processes (e.g. moulded plastics should be tested as-moulded, not in raw material form). Which parts go into actual testing is subject to careful analysis which should be a cooperation between test lab and manufacturer. Intended use matters.

I see, thanks for the clarification. Could you comment on this in the context of a 510k submission - i.e. would material biocompatibility data be insufficient for a 510k?

 

[Ronen E]

would material biocompatibility data be insufficient for a 510k?

This is typically the case.
The FDA guidance Mark Meer has linked to is the most complete and up to date FDA guidance to all things biocompatibility. I don't have very recent experience that can add upon that. Sorry.

Ronen.

 

[kiwi.kczt]

This is typically the case.
The FDA guidance Mark Meer has linked to is the most complete and up to date FDA guidance to all things biocompatibility. I don't have very recent experience that can add upon that. Sorry.

Ronen.

I chanced upon a page that describes biological evaluation in medical devices in the context of a 510k:

www.fda.gov/MedicalDevices/DeviceRe...s/PremarketNotification510k/ucm134578.htm#bio

I quote, "Evaluation of any new medical device requires information from systematic evaluation of the benefits provided by the final device and the potential risks produced by the device. The analysis should show that contact with the device does not produce unacceptable risk associated with adverse local or systemic effects, either directly or through the release of the device’s material constituents.", emphasis added by me.

It seems to me from that statement that biocompatibility data for the constituent materials (of the parts that come into human contact) is sufficient to demonstrate biocompatibility of the device. However, I'm not entirely sure if I am interpreting the text correctly.

 

[Marcelo]

It seems to me from that statement that biocompatibility data for the constituent materials (of the parts that come into human contact) is sufficient to demonstrate biocompatibility of the device.

Biological evaluation (or biological safety evaluation) is basically a risk management issue. Biocompatibility is one part of biological evaluation.

And, from the mentioned guidance:

A. Risk Assessment of the Medical Device
The risk assessment should evaluate the final finished device. The Agency makes a clearance or approval decision for a medical device as it is supplied in its final finished form. The Agency does not clear or approve individual materials that are used in the fabrication of medical devices. Therefore, the risk assessment should evaluate not only the materials used in the device, but also the processing of the materials, the manufacturing methods (including the sterilization process), and any residuals from manufacturing aids used during the process.

The risk assessment should also consider the proposed clinical use of the device, including the anatomical location, duration of exposure, and intended use population.

For example, for pediatric patients with a limited life expectancy, the tolerance for risk associated with a permanently implanted medical device may be higher than the tolerance for risk from the same device in an otherwise healthy pediatric population. The potential exposure duration should also consider which material components of the device have direct or indirect contact with tissue, and whether exposure would be a one-time exposure, a constant exposure over time, or an intermittent exposure over time that could have a cumulative effect. For example, pacemaker pulse generators commonly contain internal electronic components made from chemicals that could be toxic to the body, but appropriate bench testing can demonstrate that the pulse generator is hermetically sealed and will limit exposure of those chemicals to the surrounding tissues.