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YY/T 1815-2022 English PDF (YYT1815-2022)

YY/T 1815-2022 English PDF (YYT1815-2022)

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YY/T 1815-2022: Biological evaluation of medical devices - Application of the threshold of toxicological concern (TTC) for assessing biocompatibility of medical device constituents
This document specifies the method that uses threshold of toxicological concern (TTC) to assess the biocompatibility of constituents of a medical device. This document applies to: - Compare with the maximum concentration of identified or unidentified constituents in an extract (see GB/T 16886.18); - Toxicological equivalence studies; - Comparison with the estimated maximum exposure dose for an identified constituent (see GB/T 16886.17).
YY/T 1815-2022
PHARMACEUTICAL INDUSTRY STANDARD
ICS 11.040.01
CCS C 30
Biological evaluation of medical devices - Application of the
threshold of toxicological concern (TTC) for assessing
biocompatibility of medical device constituents
ISSUED ON. MAY 18, 2022
IMPLEMENTED ON. JUNE 01, 2023
Issued by. National Medical Products Administration
Table of Contents
Foreword... 3
Introduction... 4
1 Scope... 5
2 Normative references... 6
3 Terms and definitions... 6
4 Background... 7
4.1 Overview... 7
4.2 Protective effect of TTC value... 7
5 Application of TTC to medical device constituents... 8
5.1 General... 8
5.2 Selection of TTC value based on human exposure period... 8
5.3 Coc... 9
5.3.1 General... 9
5.3.2 Identification of Coc... 10
5.4 Suitability of TTC values for mixtures... 10
Bibliography... 11
Biological evaluation of medical devices - Application of the
threshold of toxicological concern (TTC) for assessing
biocompatibility of medical device constituents
1 Scope
This document specifies the method that uses threshold of toxicological concern (TTC) to assess the biocompatibility of constituents of a medical device.
This document applies to.
- Compare with the maximum concentration of identified or unidentified
constituents in an extract (see GB/T 16886.18);
- Toxicological equivalence studies;
- Comparison with the estimated maximum exposure dose for an identified constituent (see GB/T 16886.17).
This document does not apply to.
- Obtainment of tolerable intake (TI) values for components with sufficient toxicity data (see GB/T 16886.17);
- Safety assessment of biological endpoints other than carcinogenicity, systemic toxicity and reproductive toxicity in the biological evaluation of medical devices in accordance with GB/T 16886.1, such as. cytotoxicity, irritation, sensitization, hemocompatibility, material-mediated pyrogenicity, and local reactions to tissues at the site of contact between a medical device and the human body (for example, observations from implantation studies);
- Safety assessment of medical devices that have indirect contact with the human body through the airway;
NOTE. For the application of TTC of constituents present or released in such devices, see the ISO 18562 series of standards.
- Safety assessment with special concern constituents (cohort of concern constituent, Coc) (see 5.3).
2 Normative references
The following referenced documents are indispensable for the application of this document. For dated references, only the edition cited applies. For undated references, the latest edition of the referenced document (including any amendments) applies. GB/T 16886.1, Biological evaluation of medical devices - Part 1.Evaluation and testing within a risk management process
GB/T 16886.17, Biological evaluation of medical devices - Part 17.Establishment of allowable limits for leachable substances
GB/T 16886.18, Biological evaluation of medical devices - Part 18.Chemical characterization of materials
3 Terms and definitions
For the purposes of this document, the following terms and definitions apply. 3.1 constituent
A chemical or compound present in or on an end product or constituent material of a medical device.
NOTE 1.Constituents may be expected (such as additives and antioxidants), or unexpected (such as impurities).
NOTE 2.When TTC is applied to extractable or leachable, the identified extractable/leachable represent constituents of the medical device that may be exposed to the patient during use. 3.2 extractable
Constituents released when a medical device or constituent material is extracted using laboratory extraction conditions and media.
NOTE. When TTC is applied to extractable, the amount of extractable is assumed to be the amount of potential human exposure to the medical device during clinical use, see GB/T 16886.17. 3.3 identified constituent
A constituent whose chemical structure is known.
3.4 leachable
A constituent released from a medical device during clinical use and potentially in contact with the human body.
5 Application of TTC to medical device constituents
5.1 General
ICH establishes a threshold for mutagenic impurities. This threshold is considered to be suitable for protection against potential carcinogenic and non-carcinogenic effects of patient exposure to constituents released from a medical device. ICH M7TTC values are established for oral or parenteral routes. They are also suitable for adults, children and pregnant women. Therefore, the TTC values in this document are considered to be of general applicability to medical devices.
Before applying TTC to medical device constituents, select the appropriate TTC value based on the medical device exposure classification, see 5.2.TTC does not apply to highly toxic substances (that is, Coc, see 5.3). The application of TTC to the mixture is specified in 5.4.
5.2 Selection of TTC value based on human exposure period
See Table 1 for the TTC values of medical devices selected based on the human exposure cycle. For short-term and long-term exposure of medical devices, the recommended TTC value is 120μg/d. The TTC values (that is, 20μg/d, 10μg/d and 1.5μg/d) are suitable for medical devices with permanent exposure. When a medical device is classified as a persistent exposure medical device, but the actual human exposure time is determined according to uncertain, diverse and specific circumstances, then a TTC value greater than 10 years (1.5μg/d) shall be selected. The TTC value chosen based on the human exposure period shall be justified.
Table 1 contains TTC values for two human exposure periods (that is, greater than 1~12 months and greater than 1~10 years). The two exposure periods are specified in Table A.1 of ISO 10993-1.2018.That is, this is different from conventional biological evaluation of medical devices. TTC values less than 10 years (that is10μg/d or 20μg/d) shall be based on the conditions of use of the medical device to limit the maximum duration of human exposure to less than 12 months or less than 10 years. NOTE 1."Maximum" means that the absolute or estimated total number of days of human exposure is determined by a number of factors (for example, instructions for use). These factors limit (or prevent) prolonged exposure to the human body.
NOTE 2.For medical devices that come into contact with the human body once a week in a lifetime [that is, 9.9 years = (1 time/week × 52 weeks/year × 70 years) ÷ 365 days/year], 10μg/d is selected as its TTC value.
When experimental data or model-derived predictions indicate that an identified constituent is unlikely to be carcinogenic (for example, negative mutagenic data or at - Polycyclic amines;
- Steroid;
- Organophosphorus compounds.
In addition, TTC values are not applicable to the safety assessment of high molecular weight polymers, particles (including nanoparticles), ceramics, proteins and radioactive components. Because these types of substances are not included in the data originally used to establish the TTC method.
Identify the constituents (including Coc, see 5.3.2) by information collection. Such information collection methods include, but are not limited to, the material processing, material composition, process/step or chemical composition (including possible impurities) of the medical device, ingredient or material obtained.
5.3.2 Identification of Coc
When information collection indicates that Coc is contained in material processing or material composition, further evaluation shall be carried out in accordance with GB/T 16886.1, GB/T 16886.17 and GB/T 16886.18.
Examples of Coc reported to be present in the material composition of medical devices include, but are not limited to.
The N-nitroso group is the product of the reaction between a specific organic precursor molecule, a secondary amine, and a "nitroso agent". In rubber compounds, secondary amines may be formed from specific vulcanization accelerators such as thiurams and dithiocarbamates.
5.4 Suitability of TTC values for mixtures
Because multiple components are used in processing, handling, and sterilization of medical devices, medical devices and their constituent materials may contain and release complex mixtures of constituents. The TTC values specified in this document apply to individual constituents, whether they exist alone in the extract or as one of many components in a complex mixture extracted from medical devices. Since no toxicological interactions are expected at low exposure levels corresponding to TTC values, no additional steps need to be taken to evaluate the cumulative effect of multiple constituents in a mixture.
NOTE. Guidelines for toxicological risk assessment of mixtures are given in GB/T 16886.17.
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