GB/T 16886.16-2013 English PDF (GB/T16886.16-2013)

GB/T 16886.16-2013: Biological evaluation of medical devices -- Part 16: Toxicokinetic study design for degradation products and leachables
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GB/T 16886.16-2013
Biological evaluation of medical devices.Part 16. Toxicokinetic study design for degradation products and leachables
ICS 11.100
C30
National Standards of People's Republic of China
Replace GB/T 16886.16-2003
Medical device biology evaluation
Part 16. Degradation products and leachables
Toxicokinetic study design
Part 16. Toxicokineticstudydesignfordegradationproductsandleachables
(ISO 10993-16.2010, IDT)
Released on.2013-12-17
Implementation of.2014-08-01
General Administration of Quality Supervision, Inspection and Quarantine of the People's Republic of China
China National Standardization Administration issued
Foreword
GB/T 16886 "Biological Evaluation of Medical Devices" consists of the following parts.
--- Part 1. Evaluation and testing in the risk management process;
--- Part 2. Animal welfare requirements;
--- Part 3. Genotoxicity, carcinogenicity and reproductive toxicity test;
--- Part 4. Test options for interaction with blood;
---Part 5. In vitro cytotoxicity test;
--- Part 6. Post-implantation local reaction test;
---Part 7. Ethylene oxide sterilization residue;
---Part 9. Qualitative and quantitative frameworks for potential degradation products;
--- Part 10. Stimulation and delayed type hypersensitivity test;
--- Part 11. Systemic toxicity test;
---Part 12. Sample preparation and reference samples;
--- Part 13. Qualitative and quantitative determination of polymer degradation products;
--- Part 14. Qualitative and quantitative determination of ceramic degradation products;
---Part 15. Qualitative and quantitative determination of metal and alloy degradation products;
---Part 16. Design of toxicokinetic studies of degradation products and leachables;
--- Part 17. The establishment of a limitable amount of leachables;
---Part 18. Chemical characterization of materials;
---Part 19. Physical chemistry, morphological and surface characterization of materials;
--- Part 20. Principles and methods for immunological toxicology testing of medical devices.
This part is the 16th part of GB/T 16886.
This part is drafted in accordance with the rules given in GB/T 1.1-2009.
This part replaces GB/T 16886.16-2003 "Biological evaluation of medical devices - Part 16. Degradation products and leachables
Dynamics Research Design, compared with GB/T 16886.16-2003, the main technical changes are as follows.
--- Modified "3 terms and definitions";
--- Revised the "5 Test Method Guide";
--- Revised "Appendix A should be considered in the study of toxicokinetics", introducing ISO 10993-17, ISO 10993-18 and
The content of ISO 14971.
This section uses the translation method equivalent to ISO 10993-16.2010 "Medical Device Biological Evaluation Part 16. Degradation Products and
Design of toxicokinetic studies of leaching materials.
The documents of our country that have a consistent correspondence with the international documents referenced in this part are as follows.
--- GB/T 16886.1-2011 Biological evaluation of medical devices - Part 1. Evaluation and testing in the process of risk management
(ISO 10993-1.2009, IDT);
--- GB/T 16886.2-2011 Biological evaluation of medical devices - Part 2. Animal welfare requirements (ISO 10993-2.2006,
IDT);
--- GB/T 16886.12-2005 Biological evaluation of medical devices - Part 12. Sample preparation and reference samples (ISO 10993-
12.2002, IDT);
--- GB/T 16886.17-2005 Biological evaluation of medical devices - Part 17. Establishment of leaching allowances
(ISO 10993-17.2002, IDT);
--- GB/T 16886.18-2011 Biological evaluation of medical devices - Part 18. Chemical characterization of materials (ISO 10993-18.
2005, IDT);
---YY/T 0316-2008 Medical device risk management for medical devices (ISO 14971.2007, IDT).
Some of the contents of this document may involve patents. The issuing organization of this document is not responsible for identifying these patents.
This part is proposed by the State Food and Drug Administration.
This part is under the jurisdiction of the National Technical Committee for Standardization of Medical Device Biology Evaluation (SAC/TC248).
This section is mainly drafted by. National Food and Drug Administration Jinan Medical Device Quality Supervision and Inspection Center.
Participated in the drafting of this section. Shanghai Biomaterials Research and Testing Center, Peking University Frontier Interdisciplinary Research Institute, Biomedical Materials and
Tissue Engineering Research Center.
The main drafters of this section. Yu Shaohua, Sun Wei, Yan Tingfei, Liu Chenghu, Hua Nan, Feng Keran.
introduction
Toxicokinetics describes the absorption, distribution, metabolism, and excretion of foreign compounds in the body over time. Medical device
The key to a full evaluation is to consider the stability of the material in the body as well as the expected and unanticipated leachables and degradation products. Toxic generation
Kinetic studies are valuable in evaluating the safety of materials used in the development of medical devices or in elucidating the mechanisms of observed adverse reactions.
of. Toxicokinetic studies may also be applicable to medical devices containing active components. Should be based on the nature and time of contact between the device and the human body,
Rethink the necessity and scope of conducting toxicokinetic studies (see Appendix A). Existing toxicological literature and toxicokinetic data can be full
This is a consideration in this regard.
The potential hazard caused by medical devices may be due to interactions between the components of the device or its metabolites and biological systems.
Leachables from medical devices that can be released from their materials (eg residual catalysts, processing aids, residual monomers, fillers, antioxidants, plasticization)
The agent and/or the migrating degradation products may have an adverse effect in the body.
There are many published literatures on the use of toxicokinetic methods to study the in vivo orientation of chemicals (see references), which are used in these studies.
The methodology and technology form the basis of this part of the GB/T 16886 guide. Appendix A gives the use of this part of GB/T 16886
Description.
Medical device biology evaluation
Part 16. Degradation products and leachables
Toxicokinetic study design
1 Scope
This part of GB/T 16886 gives the principles for designing and implementing toxicokinetic studies for medical devices. Appendix A describes the medical device
Mechanical biology evaluates the issues that should be considered in the study of toxicokinetics.
2 Normative references
The following documents are indispensable for the application of this document. For dated references, only the dated version applies to this article.
Pieces. For undated references, the latest edition (including all amendments) applies to this document.
ISO 10993-1 Biological evaluation of medical devices - Part 1. Evaluation and testing in the process of risk management (Biologicalevalua-
tionofmedicaldevices-Part 1.Evaluationandtestingwithinariskmanagementprocess)
ISO 10993-2 Medical Device Biology Evaluation Part 2. Animal welfare requirements (Biologicalevaluationofmedical
devices-Part 2.Animalwelfarerequirements)
ISO 10993-12 Biological evaluation of medical devices - Part 12. Sample preparation and reference samples (Biologicalevaluationof
medicaldevices-Part 12. Samplepreparationandreferencematerials)
ISO 10993-17 Biological evaluation of medical devices - Part 17. Establishment of leaching allowances (Biological
evaluationofmedicaldevices-Part 17.Establishmentofalowablelimitsforleachablesubstances)
ISO 10993-18 Biological evaluation of medical devices - Part 18. Chemical characterization of materials (Biologicalevaluationofmedical
devices-Part 18..Chemical characterizationofmaterials)
ISO 14971 Medical Device Risk Management for Medical Devices (Medicaldevices-Applicationofriskman-
Agementtomedicaldevices)
3 Terms and definitions
The following terms and definitions defined by ISO 10993-1 apply to this document.
3.1
Absorption
The process by which a substance enters the blood and/or lymphatic system.
3.2
Bioavailability
The extent to which a given substance is absorbed by the system.
3.3
Biodegradation biodegradation
Degradation caused by the biological environment.
Note. In vitro tests can be used to simulate biodegradation.
3.4
Bioabsorption
The process by which biological materials undergo degradation in a physiological environment and degradation and/or absorption of degradation products.
3.5
Clearance clearance
The rate at which a particular substance is expelled from the body or parts of the body by metabolism and/or excretion.
3.6
Cmax
The highest concentration of a given substance in plasma, expressed in mass per unit volume.
Note. When referring to the highest concentration in body fluids or tissues, it is advisable to have a suitable label, such as cmax, liver, expressed in mass per unit volume or mass.
3.7
Degradation product
Material product resulting from chemical damage to raw materials.
3.8
Distribution distribution
The process by which absorbed substances and/or their metabolites circulate and disperse in the body.
3.9
Excretion excretion
The process by which the absorbed material and/or its metabolites are discharged from the body.
3.10
Extract extract
The liquid obtained by the leaching process of the test substance or the control substance.
3.11
Half-life half-life
T1/2
The time required for a given substance to fall within 50% of its initial value in the same body fluid or tissue.
3.12
Leachable leachable
A chemical that can migrate from a device or component under storage or use conditions.
Note. Leachables (such as additives, monomers or oligomeric components in polymeric materials) can be impregnated under laboratory conditions that simulate normal contact conditions.
3.13
Average dwell time meanresidencetime
A statistical moment parameter associated with half-life for quantitatively estimating the retention time of a given substance in the body.
3.14
Metabolicism
The process by which an absorbed substance causes a structural change in the body due to an enzymatic reaction and/or a non-enzymatic reaction.
Note. The product of the initial reaction can be altered by enzymatic or non-enzymatic reactions prior to excretion.
3.15
Test substance testsubstance
Degradation products or leachables for toxicokinetic studies.
3.16
Tmax
The time of cmax was observed.
3.17
Apparent distribution volume volumeofdistribution
Vd
The parameters of the single-chamber model, if the test substance is uniformly distributed in the body, this parameter is used to express the apparent content of the test sample in the body.
volume.
4 Design principles for toxicokinetic studies
4.1 The toxicokinetic study should be designed according to the specific situation.
4.2 A research protocol should be written prior to the start of the study, which should identify the study design including the method. 4.3~4.8 and Chapter 5 give
Some specific requirements in the study.
4.3 The results of leaching studies should be considered in order to determine the method used for toxicokinetic studies. Also consider the chemistry and physicochemical properties of the material
Information on energy, surface morphology, and biochemical properties of leachables.
Note. The rate and extent of release of leachables depends on their surface concentration, migration from the interior of the material to the surface, and solubility and flow rate in a physiological environment.
4.4 When conducting toxicokinetic studies, it is recommended to use leachables or degradation products that have been identified as potentially toxic. But poisoning the mixture
Generational dynamics studies may need to be performed under specific conditions. In special cases, extracts of materials or instruments can be used (see
ISO 10993-12), abrasive or powder, and should be demonstrated in the study design.
4.5 Analytical methods should be able to detect and characterize degradation products, leachables and metabolites in biological fluids or tissues. ISO 10993 should be used
The corresponding analytical method in the other sections and the description of the method should be adequately described in the study report (see 5.1.11). Quantitative analysis
The method should be specific, sensitive and reproducible, and the data obtained over the expected analytical concentration range should be linear. Should be described in the research report
Confirmation of the test method.
4.6 The study design shall state the level of analysis to be determined for physiological fluids, tissues or excreta.
Note. Blood is easy to sample, so it is often used for kinetic parameters and absorption studies. It must be clearly analyzed whether whole blood, serum or plasma is used and this option is provided.
Proof of validity. In vitro methods can be used to determine conjugates with circulating blood proteins or red blood cells.
4.7 The study report should include information on the binding (eg, content and affinity) of the analyte within the sample and confirm that the combination is not
This can result in underestimation of the concentration of the analyte.
4.8 To determine the kinetic parameters, it is advisable to measure enough data points and the spacing between the data should be appropriate. In theory, the data points should cover several
Half-life, but actually limited by analytical methods, may not meet this requirement.
5 Test Method Guide
5.1 General considerations
5.1.1 It is advisable to conduct research using an appropriate species and gender. Allow healthy, early-aged animals to acclimate for at least 7 days under laboratory conditions.
Animals should be transferred to a separate metabolic cage for at least 24 h. Environmental conditions should be consistent with the guidelines for the care and use of animals.
Conditions for discussion (see ISO 10993-2). During the study period, animal diet and drinking water should be unrestricted unless otherwise specified in the protocol. At each time
During the study period, animals should be ra...