Starts off with Definitions:
A Blank is the extract fluid without test article in it.
A negative control yields a non reactive result.
A positive control yields a reactive result.
A reference material is used for calibration and should be in the same material class as the test material.
A certified reference material is a reference material with a certificate.
A test material is that which is subdivided for testing.
A test sample is the extract of the subdivided sample or the subdivided sample itself.
Experimental Controls are used to validate a procedure. A predicate device may constitute an experimental control.
Test Material: Medical devices should be in final form, being the preferred test sample. Secondary to that is representative pieces present in proportions equivalent to that of the final form. The last choice is materials that have been processed in the same manner as the final form.
Coated products should be tested with the coating on the substrate. If connections, joints or seals are present in the final form they should be included in the test sample.
Materials that cure in situ shall be tested after curing.
Tests such as the implant tests should evaluate materials individually.
Differing materials in one device could have synergies or interactions and this should be considered in choosing the test sample
Test and reference materials should be handled in a manner that minimizes contamination.
If the final form is sterilized it should be tested sterilized and maintained sterile if necessary for the tests.
The effect of exposing internal components from the practice of cutting up the test material should be considered.
Extraction conditions should be appropriate for the nature and use of the final product.
Preparation of extracts.
Containers to be inert and of a size to minimize headspace and precautions taken to prevent contamination.
A Blank is the extract fluid without test article in it.
A negative control yields a non reactive result.
A positive control yields a reactive result.
A reference material is used for calibration and should be in the same material class as the test material.
A certified reference material is a reference material with a certificate.
A test material is that which is subdivided for testing.
A test sample is the extract of the subdivided sample or the subdivided sample itself.
Experimental Controls are used to validate a procedure. A predicate device may constitute an experimental control.
Test Material: Medical devices should be in final form, being the preferred test sample. Secondary to that is representative pieces present in proportions equivalent to that of the final form. The last choice is materials that have been processed in the same manner as the final form.
Coated products should be tested with the coating on the substrate. If connections, joints or seals are present in the final form they should be included in the test sample.
Materials that cure in situ shall be tested after curing.
Tests such as the implant tests should evaluate materials individually.
Differing materials in one device could have synergies or interactions and this should be considered in choosing the test sample
Test and reference materials should be handled in a manner that minimizes contamination.
If the final form is sterilized it should be tested sterilized and maintained sterile if necessary for the tests.
The effect of exposing internal components from the practice of cutting up the test material should be considered.
Extraction conditions should be appropriate for the nature and use of the final product.
Preparation of extracts.
Containers to be inert and of a size to minimize headspace and precautions taken to prevent contamination.
Temperature and times
37oC +/- 1oC for 24 hours +/- 2 hours
37oC +/- 1oC for 72 hours +/- 2 hours
50oC +/- 2oC for 72 hours +/- 2 hours
70oC +/- 2oC for 24 hours +/- 2 hours
121oC +/- 2oC for 1 hour +/- 0.2 hour
A statement that extract conditions that simulate clinical conditions are preferred.
Materials should be cut to enhance submersion in the extract liquid. But, laminates, coated substrates and elastomers should be extracted intact.
Polar vehicle examples are water, physiologic saline, cell culture media without serum.
Non polar vehicle examples are vegetable oils such as cottonseed oil, sesame oil or oleum naturale
Alternate vehicle examples 5% ethanol in saline or water, polyethylene glycol 400 diluted to physiological osmotic pressure, dimethylsulfoxide and cell culture media with serum.
Extract ratios
For a thickness less than half a millimeter a 6 cm2 per 1 ml with a 10% tolerance should be used. For a thickness greater than half a millimeter a 3 cm2 per 1 ml with a 10% tolerance should be used. Examples of materials for both of these ratios are metals, polymers, ceramics, composite films sheets and tubings.
Then there are two more ratios that state for a thickness less than or equal to 1 millimeter a ratio of 3 cm2 per 1 ml and for a thickness greater than 1 millimeter 1.25 cm2 per 1 ml is to be used. But the example for both these is natural elastomer and nothing else is listed.
Finally if there is an irregular thickness ratios of 0.1 gram per 1 ml to 0.2 gram per 1 ml or 6cm2 per 1 ml are to be used for pellets.
A description of how to extract absorbent materials is outlined. The absorbent capacity of a 2 gram sample should be determined and then 2 grams should be extracted in 20 ml past the absorption capacity. This indicates the ratio of absorbent materials is to be 0.1 gram per 1 ml.
The extracts can be performed under static or agitation conditions. Extracts should be used within 24 hours, otherwise stability data is required.
The extract should not by standard practice be centrifuged, filtered or have suspended particulates removed. If these are performed then they should be reported.
