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YY/T 1292.4-2017: Test for Reproductive and Developmental Toxicity of Medical Devices - Part 4: Two-generation Reproductive Toxicity Test
YY/T 1292.4-2017
Test for reproductive and developmental toxicity of medical devices—Part 4. Two-generation reproductive toxicity test
ICS 11.040.01
C30
People's Republic of China Pharmaceutical Industry Standard
Medical device reproductive and developmental toxicity test
Part 4. Two-generation reproductive toxicity test
Part 4. Two-generationreproductivetoxicitytest
Published on.2017-02-28
2018-01-01 implementation
State Food and Drug Administration issued
Foreword
YY/T 1292 "Medical Device Reproductive and Developmental Toxicity Test" is divided into four parts.
--- Part 1. Screening test;
--- Part 2. Embryo developmental toxicity test;
--- Part 3. Generation reproductive toxicity test;
--- Part 4. Two-generation reproductive toxicity test.
This part is the fourth part of YY/T 1292.
Other aspects of the medical device reproductive and developmental toxicity test will have other parts of the standard.
This part is drafted in accordance with the rules given in GB/T 1.1-2009.
YY/T 1292 This section refers to OECD416-2001 "Two Generations of Reproductive Toxicity Test" combined with medical devices/materials themselves
The characteristics are based on the formulation.
Please note that 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 drafted by. Shandong Province Medical Device Product Quality Inspection Center, Shenzhen Medical Device Testing Center.
Drafters of this section. Qiao Chunxia, Zhu Fuyu, Cao Ping, Xu Wei District.
introduction
The test methods for detecting potential reproductive and developmental toxic substances given in GB/T 16886.3 are the Organization for Economic Cooperation and Development.
(OECD) The methods specified in the Chemical Testing Guide, but these methods are developed for the characteristics of the chemical, without giving details
The test procedure is therefore not suitable for direct use in the detection of medical devices/materials. This part of YY/T 1292 refers to the OECD416 test side.
The basic principles of the law, and the test methods have been appropriately modified according to the characteristics of the medical devices/materials, and detailed test procedures are specified.
As a method standard in the reproductive and developmental toxicity test in GB/T 16886.3.
The reproductive and developmental toxicity potential of medical devices/materials has a significant impact on human health. Especially for absorbable medical care
Instruments or medical devices containing leachables. The following medical devices/materials are recommended in GB/T 16886.3, in the absence of reproductive and developmental toxicity
In the case of evidence of sexual risk, reproductive and developmental toxicity tests should be considered.
a) instruments, absorbable or leaching substances (such as silica gel) that may be in direct or permanent contact with the reproductive system or embryo (fetus)
Gum breast implant);
b) Energy storage medical devices.
This section provides general information on the effects of test samples on the reproductive function and behavior of the reproductive system of female and male animals.
Such as gonadal function, estrus cycle, mating behavior, conception, pregnancy, childbirth, breastfeeding, weaning, and growth and development of offspring, etc.
Preliminary data on disease, death, developmental toxicity before and after birth, and provide reference for the next toxicity test. In addition to studying F1
In addition to the growth and development of this generation, this section can also systematically evaluate the growth and development of F2 progeny and the female and male reproductive systems of F2 progeny.
price. For further comprehensive access to information on developmental toxicity and functional deficits, additional developmental toxicity and/or development may sometimes be required.
These endpoints were studied in a neurotoxicity test or in other trials.
Due to the limitations of the preparation of the test sample and the confirmation of the test method, it should be charged before the determination of this part of the test.
Consider the requirements of GB/T 16886.1 and GB/T 16886.18. Two generations of reproductive toxicity risk should be triggered in the evaluation of medical device use
On the basis of this, the decision to conduct the test is demonstrated.
For absorbable or leaching-containing medical devices, if there is sufficient reliable data on absorption, metabolism and distribution studies, or
Acceptable biological risk assessment of medical devices when all components identified in the medical device extract have no two-generation reproductive toxicity
After the assessment, if the risk of two generations of reproductive toxicity has been ruled out, no further testing is required.
Medical device reproductive and developmental toxicity test
Part 4. Two-generation reproductive toxicity test
1 Scope
This part of YY/T 1292 gives a two-generation reproductive toxicity test method for medical devices/materials.
This section applies to the evaluation of reproductive and developmental toxicity of two generations of medical devices/materials.
2 Normative references
The following documents are indispensable for the application of this document. For dated references, only dated versions apply to this article.
Pieces. For undated references, the latest edition (including all amendments) applies to this document.
GB/T 16886.1 Biological evaluation of medical devices - Part 1. Evaluation and testing in the process of risk management (GB/T 16886.1-
2011, ISO 10993-1..2009, IDT)
GB/T 16886.2 Biological evaluation of medical devices - Part 2. Animal welfare requirements (GB/T 16886.2-2011,
ISO 10993-2.2006, IDT)
GB/T 16886.3 Biological evaluation of medical devices - Part 3. Tests for genotoxicity, carcinogenicity and reproductive toxicity (GB/T 16886.3-
2008, ISO 10993-3.2003, IDT)
GB/T 16886.12 Biological evaluation of medical devices - Part 12. Sample preparation and reference samples (GB/T 16886.12-
2005, ISO 10993-12.2002, IDT)
3 Terms and definitions
The terms and definitions defined in GB/T 16886.1, GB/T 16886.3 and GB/T 16886.12 apply to this document.
4 main equipment
Common equipment in the laboratory, biological microscope, stereo microscope, vernier caliper, animal sperm analyzer (optional), pathological examination instrument.
5 Test principle
Different groups of test animals are given a specific dose of test sample. If the device is intended to be applied to a male, in order to arrive at the test sample pair
Side effects of sperm formation, males should be given test samples during the growing season and include at least one complete spermatogenesis cycle (mouse approximately
56d, rat approximately 70d). In order to obtain the side effect of the test sample on the estrus cycle, the parental female should give the test sample at least for a short time.
Includes several complete estrus cycles and then cages the animals. Animals of both sexes are given test samples during the cage, during pregnancy and feeding
Only female animals are given during the lactation period. The progeny F1 continues to give test samples after weaning, and from the growth stage, maturity, mating, and child of the progeny F1
Generation F2 was born to F2 weaning.
6 experimental animals
6.1 General
All animal testing should be conducted in a laboratory approved by a national accreditation body and in compliance with all applicable regulations for laboratory animal welfare.
And should also meet the requirements of GB/T 16886.2.
6.2 Animal selection
6.2.1 Selection of species
This section recommends the use of healthy, sexually mature rats. If other species are used, appropriate arguments should be made. Low breeding rate should not be used
Or a well-known species with a high rate of developmental defects. It is advisable to use untested healthy animals and record the species, strain and sex of the test animals.
Do not, weight and age. Before the start of the trial, the difference in body weight between the test animals should be as low as possible so that it does not exceed the average weight of the same sex.
20%.
6.2.2 Quantity and gender
Each test group and control group should contain a sufficient number of animals to obtain about 20 pregnant animals. For high doses of poison
This requirement may not apply if the substance is too large or causes infertility. Only a sufficient number of pregnant rats can be fertility, conception, behavior of the mother,
Breastfeeding and progeny F1 are valuable from the growth of the fetus to maturity, the potential impact of the birth of F2 to the weaning
Evaluation.
6.2.3 Feeding conditions
The feeding environment temperature of the test animals should be 20 ° C ~ 26 ° C, and the relative humidity is 40% ~ 70%. When using artificial lighting, it should be
12h illumination and 12h dark cycle. Animals can be raised using suitable feeds without restricting drinking water. Pregnant females should be raised in a single cage and raised
For comfortable bedding.
6.2.4 Animal preparation
It should be adapted to the environment for at least 5 days before the test. The kinship of the animals used should be clarified prior to the test to avoid sibling mating. Should move
The subjects were randomly divided into a control group and a test group (recommended by random weight grouping). Each animal should have a separate and unique label. Parental (P)
The substance should be labeled before the start of the test, and the offspring F1 is weaned in the animal and selected for pre-mating labeling. All selected offspring F1 animals,
Record and save information about the source of the nest. When the pups need to weigh or perform an examination, they should be marked as early as possible after birth.
7 Sample preparation
7.1 Prepare test samples according to the principles of GB/T 16886.12. Whenever possible, medical devices should be tested in a "standby" state.
7.2 For energy-storing medical devices, it is advisable to use systemic contact with animals. The dosage should be the expected dose for contact with human reproductive organs.
multiple.
8 test steps
8.1 General
It is advisable to refer to existing toxicological data as well as all information on the toxicokinetic aspects of the test sample or related substances to select the appropriate
Dosage range to avoid excessive maternal toxicity. This information can also help to determine the frequency of the dose.
8.2 Determination of the maximum dose
The maximum tolerated dose or the physiological limit of the animal model is used as the maximum dose of animal contact, which should be the estimated maximum human body.
The multiple of the dose (expressed in grams per kilogram or square centimeter per kilogram).
Note. Unlike typical chemical reproductive and developmental toxicity tests, most materials may not have a significant dose-effect relationship. For these materials,
The maximum dose test for exposure is considered to determine the presence of a toxic hazard, but appropriate support data should be provided for the dose range used in the test.
8.3 Choice of dose level
If the test sample is considered to produce two generations of reproductive toxicity to the test animal, at least three test groups and one control group should be used. except
Not limited by physical and chemical properties and biological effects, the highest dose selected should cause toxicity but not cause death and severe pain in the parental animal.
bitter. In the trial, if death occurs, the mortality rate of the parental (P) animal should be controlled below 10%. The other two groups should design a decreasing dose of water.
Level, can show any effect related to sample processing and no observable adverse reaction level (NOAEL). Decreasing group spacing is usually selected
Choose 2 times to 4 times. If you want to set the 4th dose group, the group distance of the dose group can be very large (such as more than 10 times). As a test sample
For the medium used, a medium control group is required. The control group should be treated in the same manner as the test group except that the test sample is not given.
8.4 Test process
Parental males and females should be given daily test samples starting from 5 weeks to 9 weeks of age. The offspring F1 female and male rats start from weaning
Test samples were given daily. For female and male rats of parental and progeny F1, sample administration should include at least 10 weeks prior to mating and 2 weeks of mating.
Male rats that no longer need to be evaluated for reproductive function should be humanely sacrificed and anatomically examined. Parental females should continue to give test samples from
During pregnancy, the offspring F1 is weaned. It is advisable to determine the respective dose according to the weight of each animal, but for the third third of pregnancy
The amount adjustment should be cautious.
Parental and progeny F1 female and male rats should be given test samples until the end of the trial. When the parent and offspring F1 female and male are no longer needed, they should
All of them were humanely executed. There are no F1 progeny and all F2 progeny mice that are used for mating after humane weaning.
8.5 Animal mating
8.5.1 Parental mating
At each mating, the female should always be caged with a male in the same dose group but not in the same litter until conception or up to 2 weeks. Every morning
Sperm or scrotum should be checked and the day of the test for sperm or vaginal plug should be defined as day 0 of pregnancy. If the mating is unsuccessful, consider using the same
The other males of the group who have demonstrated successful mating have been re-matted with females. Paired animals should have clear identification and records to avoid near
Pro-matching.
8.5.2 Child F1 mating
When the offspring F1 is mated, at least one female and male mouse are selected from the same litter at the time of weaning, and other animals of the same dose but different litters are
Mating mating to breed offs...