YY/T 1579-2018 English PDF (YYT1579-2018)
YY/T 1579-2018 English PDF (YYT1579-2018)
YY/T 1579-2018: In vitro diagnostic medical devices--Evaluation of stability of in vitro diagnostic reagents
In vitro diagnostic medical devices--Evaluation of stability of in vitro diagnostic reagents ICS 11.100
People's Republic of China Pharmaceutical Industry Standard
In vitro diagnostic medical device
In vitro diagnostic reagent stability evaluation
(ISO 23640.2011, IDT)
State Food and Drug Administration issued
This standard was drafted in accordance with the rules given in GB/T 1.1-2009. This standard uses the translation method equivalent to ISO 23640.2011 "in vitro diagnostic medical device in vitro diagnostic reagent stability evaluation". The documents of our country that have a consistent correspondence with the international documents referenced in this standard are as follows. ---YY/T 0316-2016 Medical device risk management for medical devices (ISO 14971.2007 more genuine, IDT) 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 standard was proposed by the State Food and Drug Administration.
This standard is under the jurisdiction of the National Medical Clinical Laboratory and the In vitro Diagnostic System Standardization Technical Committee (SAC/TC136). This standard was drafted. Beijing Medical Device Inspection Institute, Beijing Medical Supervision Bureau Medical Device Technology Evaluation Center, Chinese food Drug Testing Institute, Shenzhen Mindray Biomedical Electronics Co., Ltd., Asia Energy Biotechnology (Shenzhen) Co., Ltd., Capital Medical University Beijing Tiantan Hospital, Jiangxi Tekang Technology Co., Ltd., Huada Biotechnology (Wuhan) Co., Ltd. The main drafters of this standard. Wang Jun, Dai Leiying, Zheng Yi, Shi Dawei, Li Ke, Ren Wei, Kang Xixiong, Yan Wei, Cheng Lei. introduction
An important aspect of the development and manufacture of in vitro diagnostic reagents is the initial design of the product's stability, and then determine and verify the delivery The expiration date of the products in the market. The manufacturer evaluates to determine shelf life, transport stability, and stability of use. In order to be heavy To provide information to the user, the manufacturer identifies key factors that may affect the stability of the in vitro diagnostic reagent and carefully evaluates these characteristics. body The stability of the external diagnostic reagent affects the performance of the device and thus affects the patient's diagnosis. It is the responsibility of the manufacturer to determine and monitor the stability of the in vitro diagnostic reagent to ensure that the performance characteristics of the product are maintained. In stability Before the information is provided to the user, it is best to complete the establishment of a stability evaluation program, generate valid data, and analyze to establish an appropriate shelf life and transportation limit. System and usage stability information.
In vitro diagnostic medical device
In vitro diagnostic reagent stability evaluation
This standard applies to in vitro diagnostic medical devices (including reagents, calibrators, controls, diluents, buffers, and kits, hereinafter referred to as Stability evaluation of "in vitro diagnostic reagents"). This standard also applies to substances containing sample storage or to initiate reactions to further process samples. A sample collection device for the substance.
This standard specifies the general requirements for stability evaluation when generating data from the following processes, as well as for real-time stability and acceleration stability. Specific requirements for sex.
--- Establish the shelf life of in vitro diagnostic reagents, including the determination of the transport conditions to ensure product performance; --- Establish the stability of the use of in vitro diagnostic reagents after initial opening of the initial packaging, for example, in machine stability, reconstitution stability, opening stability;
---Monitor the stability of in vitro diagnostic reagents that have been placed on the market; --- Verification of the stability of the improved reagent. After the reagent is improved, it may affect the stability and the stability needs to be verified. This standard does not apply to instruments, devices, equipment, systems, specimen containers, and test samples. 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 29791.1-2013 Information provided by in vitro diagnostic medical device manufacturers (labeling) Part 1. Terms, definitions and General requirements (ISO 18113-1.2009, IDT)
ISO 14971 Medical Device Risk Management for Medical Devices (Medicaldevices-Applicationofriskman- Agementtomedicaldevices)
3 Terms and definitions
The following terms and definitions apply to this document.
Accelerated stability evaluation acceleratedstabilityevaluation
Predict the shelf life of in vitro diagnostic reagents by designing severe environmental conditions to increase the rate of chemical and/or physical degradation and change the study.
Note. The design of the accelerated stability evaluation may include extreme conditions of temperature, humidity, light or vibration. 3.2
A mathematical function that describes the approximate relationship between the chemical reaction rate constant and temperature and activation energy. [CLSIEP25-A]
A specified amount of material having consistent characteristics produced by a process or series of processes. [GB/T 29791.1-2013, definition 3.5]
Batch number batchcode; lotnumber
A specific number and/or combination of letters that can clearly identify a batch and make it traceable to manufacturing, packaging, labeling, and shipping history. [GB/T 29791.1-2013, definition 3.6]
Expiration date expirydate;expirationdate
The upper limit of the time interval under which the material properties can be guaranteed by storage under specified conditions. Note. The manufacturer sets the expiration date of in vitro diagnostic reagents, calibrants, controls, and other components based on the stability characteristics determined by the assay. [GB/T 29791.1-2013, definition 3.17]
In vitro diagnostic medical device invitrodiagnosticmedicaldevice
IVD medical device IVDmedicaldevice
Used alone or in combination, the manufacturer is expected to use the device for in vitro testing of human specimens, and the test is pure or mainly to provide diagnosis and monitoring. For the purpose of compatibility information, the device includes reagents, calibrators, controls, sample containers, software, and related instruments or devices or other items. [GB/T 29791.1-2013, definition 3.27]
In vitro diagnostic reagent invitrodiagnosticreagent
IVD Reagent IVDreagent
It is intended by the manufacturer to be used as a chemical, biological or immunological component, solution or preparation for in vitro diagnostic medical devices. [GB/T 29791.1-2013, definition 3.28]
Real-time stability evaluation realtimestabilityevaluation
The in vitro diagnostic reagent is placed under the conditions specified by the manufacturer to establish or verify the reagent shelf life test. Note. Conditions affecting the stability of in vitro diagnostic reagents may include temperature, transport conditions, vibration, light, and humidity. 3.9
The period of time until the expiration date. The in vitro diagnostic reagent is kept in its original packaging under the storage conditions specified by the manufacturer during this time period. Hold its stability.
Note. Stability and expiration dates are related concepts
[GB/T 29791.1-2013, definition 3.66]
The ability of an in vitro diagnostic medical device to maintain its performance characteristics within the limits specified by the manufacturer. Note 1. Stability applies to.
--- when in vitro diagnostic reagents, calibrators or controls are stored, transported and used under the conditions specified by the manufacturer; --- Reconstituted lyophilized material prepared, used and stored in accordance with the manufacturer's instructions, working fluid and materials removed from the closed container. Note 2. The stability of in vitro diagnostic reagents or measurement systems is usually quantified by time. --- the length of the interval in which a certain amount of change occurs in the metrological performance characteristics; or --- Changes in characteristics over a certain time interval.
[GB/T 29791.1-2013, definition 3.68]
Provide objective evidence for a given project to meet regulatory requirements. Example 1. Confirmation of the magnitude of a given reference substance and its uniformity with respect to the measurement procedure. Example 2. Verification of the performance characteristics or requirements of the measurement system that remain throughout the life of the failure. Example 3. Verification of the magnitude and direction of the continuous change of the measurement system over time from the initial determination until the entire stabilization period in accordance with its claimed regulations. Example 4. Confirmation that the target measurement uncertainty can be satisfied. Note 1. A given project can be, for example, a process, a measurement procedure, a substance, a compound, or a measurement system. Note 2. The requirements can be, for example, to meet the manufacturer's declaration or technical specifications. [GB/T 29791.1-2013, definition 3.73].
4 General requirements
Given the risks of using in vitro diagnostic reagents and the instability of reagent components, there should be sufficient data to confirm the stability statement. Data obtained from accelerated stability studies, and/or experience gained from in vitro diagnostic reagents that are expected to be reasonably comparable in stability characteristics, Consider using to establish the initial expiration date. The experience of similar reagents and the risks associated with the use of the device should be used as the basis for establishing the initial expiration date. foundation. When the product is placed on the market, if the stability statement is based on past data, it should be verified by real-time stability study data. statement.
The production conditions of the reagents used for the stability evaluation should be substantially the same as those of the conventional production conditions. If the conditions are different, or the in vitro diagnostic reagent is not The manufacturer shall provide a reasonable explanation of the stability statement in the final configuration. The manufacturer shall establish procedures for the need for stability monitoring and, if necessary, establish. The evaluation at the end of the preservation period is sufficient For this purpose.
The improvement of subsequent products or production processes should be reviewed to determine if a stability change procedure is necessary. 4.2 Scheme
The conclusion of stability should be obtained on the basis of the data generated by the pre-designed scheme. The preset schemes include. ---Responsibility;
--- Clear identification of in vitro diagnostic reagents;
---Conditions of Use;
Example 1. Considering changes in environmental factors, including the worst case scenario. ---The goal and purpose of the evaluation;
---Reagent sample information;
Example 2. batch, quantity, container, source identification, concentration. --- The potential impact of key components;
Note. The “key” is relative to stability.
--- Recommended storage conditions for in vitro diagnostic reagent samples; Example 3. 2 ° C ~ 8 ° C, no more than 20 ° C.
--- Check the interval of time points;
--- Inspection at the end of each interval;
Example 4. Procedure and extent of inspection.
--- The number of tests for in vitro diagnostic reagents depends on the precision of the test method (taking into account the in vitro diagnostic reagents, instrumental variables Sex)
--- The duration of stability in the study protocol, which may include the upper confidence limit for the target stability claim; --- Description of data analysis;
Example 5. Data points are traded off with reference to statistical methods and conditions. --- acceptable standards to be achieved;
--- Interpretation of the data.
The protocol should be part of the in vitro diagnostic reagent technical documentation. 4.3 Stability Report
The stability report should be used to document stability studies.
Examples. intermediate reports and final reports.
The report should contain or mention at least.
---The plan to follow;
--- The batch involved;
---All results obtained;
--- Acceptable criteria for passing/not passing;
--- Stability conclusion.
The report should be maintained as part of the in vitro diagnostic reagent technical documentation. 5 procedures
The procedure should be used to evaluate and validate the stability statement of the in vitro diagnostic reagent. Note. CLSIEP25-A has information on stability evaluation study design, implementation conditions and procedures. 5.1.2 Inspection
The test shall be carried out in accordance with the procedures described in the protocol. In vitro diagnostic reagents representative of storage conditions and time are tested and tested The number depends on the precision of the method used.
The inspection shall be carried out at the time specified in the plan. The selected time interval should cover at least the entire target retention period. Should be properly selected The number of points in order to identify trends from data changes.
The amount of in vitro diagnostic reagent sample used for testing should be sufficient for the entire stationary phase evaluation and retest. If the conditions for the stability evaluation of in vitro diagnostic reagents are different from their final configuration, a risk assessment should be performed (see ISO 14971 as a body). External diagnostic medical device risk management guide).
Example. The reagent loading is different or in a different material than the original reagent container. 5.1.3 Inspection batch
The minimum number of test lots should be determined by the evaluation purposes listed below. --- For the evaluation of the shelf life of a new in vitro diagnostic reagent (ie real-time stability evaluation), three batches are required; --- In vitro diagnostic reagents have a longer shelf life and require 3 batches; ---simulated transportation, 1 batch;
--- In vitro diagnostic reagent use stability, 1 batch;
--- In vitro diagnostic reagent improvement, if the risk assessment according to YY/T 0316 shows that it is necessary to conduct stability evaluation, 1 batch.
If less than the required number of batches is to be used, a risk assessment of the in vitro diagnostic reagents should be performed in accordance with YY/T 0316. 5.2 Real-time stability evaluation
5.2.1 Shelf period
During the shelf life evaluation, the in vitro diagnostic reagents should be stored under the conditions specified by the manufacturer. Note. The conditions specified by the manufacturer are set according to the capabilities of the equipment used for testing or the expected storage conditions of the product. Example. The refrigerator used in the laboratory for storing reagents generally claims that the temperature is controlled between 2 ° C and 8 ° C. The evaluation of the storage period should not include below 2 ° C or 8 ° C. the above.
5.2.2 Transportation stability
The manufacturer shall verify that the specified transport conditions do not affect the expiration date of the in vitro diagnostic agent. If the transport conditions are simulated, the design of the test plan should be based on knowledge of the transport conditions. If it is not known, the actual transportation should be handled. Conditions were investigated as a basis for simulated transportation.
Examples. transport time, expected temperature, humidity.
5.2.3 Stability of use
The stability of use should reflect the daily conditions of use.
Examples. on-machine stability, reconstitution and bottle opening stability. 5.3 Accelerated stability evaluation
Accelerated stability evaluation should be accepted as the basis for establishing the initial expiration date of the product description. Note 1. For some reagents, accelerated stability evaluation may not be applicable. Note 2. Refer to CLSIEP25-A for the acceleration stability evaluation procedure. 5.3.2 Procedure
Prior to the start of the test, the study material should be stored under the storage conditions described in the information provided by the manufacturer. After the test begins, the material should be placed Under the severe conditions specified. Samples should be taken at the specified point in time for inspection or replacement, as described in the information provided by the manufacturer. Under storage conditions, the inspection is carried out in accordance with the established protocol. 5.3.3 Data Analysis
The acceleration stability data is analyzed according to the scheme.
Example. Arrhenius equation, nonlinear model.
5.3.4 Evaluation and conclusion
Establish an expiration date based on data analysis, interpretation, and pre-established acceptance criteria. references
 ISO 18113-1.2009 Invitrodiagnosticmedicaldevices-Informationsuppliedbythemanu- Facturer(labeling)-Part 1.Terms,definitionsandgeneralrequirements
 EN13640 Stabilitytestingofinvitrodiagnosticreagents
 CLSIEP25-A EvaluationofStabilityofInVitroDiagnosticReagents;ApprovedGuideline, SecondEdition