ISO 10993 Requirements For 510k - Substantial Equivalence

#1
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
 
Last edited:
Elsmar Forum Sponsor

Mark Meer

Trusted Information Resource
#2
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.
 
Last edited:
#3
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

Problem Solver
Staff member
Moderator
#4
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.
 
#5
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

Problem Solver
Staff member
Moderator
#6
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.
 
#7
"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

Problem Solver
Staff member
Moderator
#8
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.
 
#9
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.
 
Last edited by a moderator:

Marcelo

Inactive Registered Visitor
#10
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.
 
Thread starter Similar threads Forum Replies Date
I ISO 10993 Biocompatibility Requirements - manufacturing process chemicals Other Medical Device Related Standards 8
R Biocompatibility - ISO 10993 and SVHC Requirements Other Medical Device Related Standards 4
S ISO 10993-1: External Communicating Device biocompatibility test requirements Other ISO and International Standards and European Regulations 4
E Meeting ISO 10993-1 2009 Material Risk Assessment Requirements Other Medical Device Related Standards 13
J Biological Evaluation requirements per ISO 10993 - Medical Device Testing ISO 13485:2016 - Medical Device Quality Management Systems 2
T ISO 10993 Tests of End Product vs. Test of Material - Japanese Requirements ISO 13485:2016 - Medical Device Quality Management Systems 6
M FDA News FDA Releases Draft Guidance Clarifying Application of ISO 10993-1 Biocompatibility Standard Medical Device and FDA Regulations and Standards News 0
L Biological Assessment (ISO 10993-1) Other Medical Device Related Standards 1
L Process changes and biocompatibility (ISO 10993-1) Other Medical Device Related Standards 1
S ECG Cable Banana to Snap or Tab electrode Adapters -- ISO 10993 Requirement Other Medical Device Related Standards 0
K Diagnostic X-ray devices - Applicability of Biocompatibility Testing per ISO 10993-1 Manufacturing and Related Processes 7
A ISO 10993-7:2008/ Amd.1:2019 - Classification of special populations Other Medical Device Related Standards 3
P European versions of standards - ISO 10993-1 and ISO 11607-1 EU Medical Device Regulations 6
S ISO 10993 Biocompatibility Evaluation - Electronic thermometer Other Medical Device Related Standards 3
P ISO 10993-1:2018 - When will the European equivalent become a Harmonized Standard? Other Medical Device Related Standards 13
N Technical File Reviewer has requested more testing to ISO 10993 Other Medical Device Related Standards 10
T ISO 10993-7 - Ethylene oxide sterilization residues Other Medical Device Related Standards 1
planB ISO 10993-1:2018 has just been published Other Medical Device Related Standards 2
M Does ISO 10993 Apply to Packaging? (e.g. Travel Case) Other Medical Device Related Standards 4
T Using Risk Management in ISO 10993 - Medical Device Accessory 21 CFR Part 820 - US FDA Quality System Regulations (QSR) 4
P ISO 10993 - Sterile (Irradiation) Polypropylene Syringe Question Other Medical Device Related Standards 6
D Actual Definition of Non-Contact for ISO 10993 Other Medical Device Related Standards 1
S Selecting materials for implants to comply with ISO 10993 biocompatibility Other Medical Device Related Standards 4
T Plastic of an infusion pump enclosure and ISO 10993 ISO 13485:2016 - Medical Device Quality Management Systems 2
E Upcoming changes for ISO 10993 and IEC 60601 in South Korea Other Medical Device Regulations World-Wide 2
M FDA issues draft guidance to replace G95-1 (Application of ISO 10993) 21 CFR Part 820 - US FDA Quality System Regulations (QSR) 0
B Verify GB/T 16886 is the same as ISO 10993 US Food and Drug Administration (FDA) 5
B New ISO 10993-12 - Consistency of Extraction Conditions through different Assays Other ISO and International Standards and European Regulations 1
S Suppliers of ISO 10993 compliant Material for Skin Contact Other ISO and International Standards and European Regulations 3
M ISO 10993 - Repeat tests necessary if colour changes slightly? Other Medical Device Related Standards 11
M Pre-Selecting Materials for ISO 10993-1 Biocompatibility Compliance Other ISO and International Standards and European Regulations 5
F ISO 10993-10 - Removed from List of Harmonized Standards Other Medical Device Related Standards 4
S ISO 10993 Cytotox Testing - Direct Contact rather than Extractables Other Medical Device Related Standards 4
M ISO 10993 Labs which can test Cytotoxicity, Sensitizaton and Irritation Other Medical Device Related Standards 10
M ISO 10993 for Fabric based Electrode - Finding already FDA Approved Materials Other Medical Device Related Standards 11
A Claiming Biocompatibility without ISO 10993-1 Other Medical Device Related Standards 19
J ISO 10993 (Biological Compatibility) Approved Materials US Food and Drug Administration (FDA) 23
T ISO 10993-10: 2002 vs 2010 version - What are the Major Changes? ISO 13485:2016 - Medical Device Quality Management Systems 2
W ISO 10993 (Biological Evaluation of Medical Devices) for Suppliers Other ISO and International Standards and European Regulations 8
I EO (Ethylene Oxide) Residuals - EN ISO 10993-7:2008 EU Medical Device Regulations 5
D Does anyone know of a biocompatible ABS tested & certified to ISO 10993-1 Other Medical Device Related Standards 5
W ISO 10993 - Replacing Sensitization Test with Systemic Toxicity Test? Other Medical Device Related Standards 4
I ISO 10993-10:2010 Guidance Document for Irritation and Sensitization Test - Changes ISO 13485:2016 - Medical Device Quality Management Systems 3
M EO (Ethylene Oxide) and ECH (Ethylene Chlorohydrin) Residual as per ISO 10993-7:2008 ISO 13485:2016 - Medical Device Quality Management Systems 15
I ISO 10993-1:2009 Sensitization (Initial Evaluation Test) vs. USP Other Medical Device Related Standards 3
B What ISO 10993 considers Non-Invasive vs. Invasive MDD 93/42/EEC EU Medical Device Regulations 3
C Differences between the biocompatibility standards ISO 7405 and ISO 10993 Other Medical Device Related Standards 2
R What the difference in ISO 10993-11:2006 and 2009? Other Medical Device Related Standards 17
R Extent of Recognition of ISO 10993-1 US Food and Drug Administration (FDA) 5
M Biocompatibility of Medical Devices (ISO 10993 vs Japan requirement) Japan Medical Device Regulations 1

Similar threads

Top Bottom