ISO 10993-9:2019 pdf download – Biological evaluation of medicaldevices— Part 9: Framework for identification and quantification of potential degradation products.
The approved study plan for multi-component devices shall take into account each individual component/material and shall consider synergistic effects on the degradation of the different components as well as the possibility of secondary reactions between/among the degradation products.
N0TF Degradation can in most cases he modelled by in vitro tests. During degradation pH needs to be controlled to a clinically relevant range, especially if p11 can affect degradation product composition. Th user needs to be aware that both the degradation rate and amount of generated by-products can be affected if pH Is different from that expected for the service environment.
4.4 Characterization of degradation products from medical devices
The degradation products produced in the study can be particulate or soluble compounds or ions, Appropriate analytical methods to characterize these products shall be used and reported In the study report. These methods shall he adequately qualified for their intended purpose. If particles are generated, they shall be characterized with regard to size, shape, surface area and other relevant characteristics.
Hecause the physical and chemical properties of particulate materials can change at the nanoscale (approximately 1 nm to 100 nm), this can affect their toxicological properties. For those medical devices composed of or containing nanoscale materials, the user is referred to ISO/TR 10993-22 for a thorough consideration of the impact on the risk assessment of nanoscale products.
If biological evaluation of the degradation products is required, then care shall be taken in the design of the degradation study In order to ensure that It does not Interfere with the biological assay.
Considerations for the degradation study are provided in AnnexE. The protocol shall include a) identification and characterization of device and/or material and intended use.
b) Identification and characterization of possible mechanism of degradation, cl identification and characterization of known, probable and potential degradation products, and d) test methodologies.
The extent and rate of release of degradation products depends on variables such as manufacturing processes that alter surface composition and structures; migration to the surface from within the material; soluhility in. and chemical composition of, the physiological milieu; etc.
5 Study report
The study report shall include the following information, where relevant:
a) description of material(s) or device (see B.2). including intended use and nature of body contact;
b) description of proposed degradation mechanism(s) (e.g.. hydrolytic, enzymatic, oxidative, etc.), and how the degradation study is appropriately designed to assess the proposed mechanism(s);
c) description of the degradation study procedures (e.g. test article, sample size, degradation media, ratio of test article vs. degradation media, study conditions, experimental steps and parameters, sampling strategy, monitoring and observation, etc.);
d) description of analytical methods, including quantification limits and controls;
e) statement of compliance to appropriate good laboratory practices and/or to quality management systems for test laboratories (e.g. ISO/LEC 17025);
f) identification and quantification of degradation products (e.g. form and condition of degradation products, their stability and controls used);
g) summary of results;
Degradation studies shall be considered if:
a) the device is designed to be absorbed by the body or
b) the device Is Intended to be implanted for longer than thIrty days or
an informed consideration of the material(s) system indicates that toxic degradation products could be released during body contact.
However, degradation studies might not be needed if sufficient material formulation, and manufacturing process Information arc available and degradation data relevant to degradation products in the intended use already exist.
NOTE Relevant degradation data can Include inFormation on degradation mechanism, degradation rate, identification and quantity of degradation products, and particle shape/size and distribution.
The need for in vivo studies shall be considered in light of results from in vitro studies.
Where appropriate, in vitro experiments shall be considered for investigating theoretically possible degradation processes. In viva studies shall take into consideration ISO 10993-2. In viva and in vitro studies shall also be considered for determining the probability of occurrence of degradation and the identification of probable degradation products and the degradation rate.
The flowchart In FigurcAJ. Illustrates the logic applicable to these considerations. For polymers that are intended to hydrolytically degrade, e.g. polylactide, the user is referred to ISO 13781.