Is complete testing required as per ISO 10993 for materials used in orthopedic implants or is literature review route possible

[mpfizer]

Hi,

We are manufacturers of orthopedic implants viz Plates , Screws , Nails etc, made of stainless steel and titanium alloys as per ISO 5832-1 and ISO 5832 -3 .Bothe these grades have been used for a very long time and there does not seem to be bio compatibility issues . Is there an option of doing BER by literature review or doing say only three out of 9 tests as per ISO 10993 standard.

Has anyone taken this approach ? Huge amount of money is spent by manufactures for doing bio compatibility testing for similar types of products with same raw material and process .

Views and comments .

Thanks
michelle

 

[planB]

ISO 10993-1:2018, section 4.1 says

[...] Such an evaluation might result in the conclusion that no testing is needed if the material has a demonstrable safe history of use in a specified role and physical form that is equivalent to that of the medical device under design. The type of information that can be useful to demonstrate equivalence is included in Annex B. Testing is usually not necessary when sufficient information is already available to perform a risk assessment of the material and/or the medical device (see Annex C)

Such route may be feasible if you have adequate information not only for the materials, but also enough detailed information about manufacturing processes for devices of comparable intended use. "Both these grades have been used for a very long time and there does not seem to be bio compatibility issues" is definitely not enough (demonstrated) information to establish equivalency in terms of biological evaluations. The required level of (documented) manufacturing information is typically challenging to retrieve from (competitor) existing devices, unless e.g. you have your predicate device inhouse at hand.

However, "complete" testing of all endpoints-to-consider is typically also not required in case you generated enough (screening) data by material characterisation according to ISO 10993-18, and cytotoxicity testing according to ISO 10993-5. These experimental data could be adequate and sufficient to establish biocompatibility with a risk management process. Some Asian regulators may still insist on "complete" testing, though.

HTH,

 

[Enternationalist]

To add motivation to explanation - just because you use the "same" materials as somebody else doesn't mean your biocompatibility is the same. Imagine you take an existing orthopaedic screw, and then wash it using dirty cleaning solution. Biocompatibility bad, even though the product is "identical".

This is why you have to consider the whole chain.

 

[Ronen E]

Hi,

We are manufacturers of orthopedic implants viz Plates , Screws , Nails etc, made of stainless steel and titanium alloys as per ISO 5832-1 and ISO 5832 -3 .Bothe these grades have been used for a very long time and there does not seem to be bio compatibility issues . Is there an option of doing BER by literature review or doing say only three out of 9 tests as per ISO 10993 standard.

Has anyone taken this approach ? Huge amount of money is spent by manufactures for doing bio compatibility testing for similar types of products with same raw material and process .

Views and comments .

Thanks
michelle

As @planB explained, there are formal routes that, it seems like it, will allow big savings in your case, in both amount of testing and $$ expense. Either way, you will most likely need the services of a qualified and experienced toxicologist to pull any of that off, in reviewing the available information, planning, overseeing the required testing and finally, writing the official report. Since this is a given, I would skip the pondering stage and approach one (shop around first, of course) - they will have the expertise to outline the strategy, and you will need them later anyway.

One option (apparently not cheap) is NAMSA - I'm not affiliated with them in any way.

The current regulatory BE paradigm, in all leading markets, is minimising the amount of animal testing (typically, the more expensive tests) where it can be helped, and there are certainly many more official ways available to promote that goal now than there were 10-15 years ago.

 

[bjwalthall]

You need to run a complete "master" biocompatibility panel on the specific material including processing steps (cleaning, polishing ,etc.). After that, you can reference the "master" results on other products using the same material/processing steps. You will need to a risk assessment on each new iteration, focusing on any risks induced by the particular product envisioned.

At least one major orthopedic company in the early 2000's, changed the processing (cleaning) of some implants and did not effectively address the biocompatibility of the resulting product. The subsequent recalls and lawsuits effectively forced the sale of the company.

 

[Dirk S]

In general I do agree with @planB and @Ronen E . I doubt that for an orthopedic implant chemical analysis and Cytotox. alone would be enough to conclude on biological safety. You might be asked why you did not perfome Sensitization and Irritation, both endpoints which cannot be addressed with chemical analysis.

 

[Chrisx]

I would recommend taking a look at ISO 19227 Cleanliness of Orthopedic Implants. The primary risk is not in the material itself, but rather residues left from manufacturing. This standard provides guidance on establishing that an implant is clean. Clean is not biocompatible, but the information demonstrating cleanliness can be used to develop a risk based rationale for reduced testing. As a minimum a biocompatibility report per ISO 10993-1 must be written by a person of appropriate expertise.