YY/T 1268-2015 English PDF (YYT1268-2015)
YY/T 1268-2015 English PDF (YYT1268-2015)
YY/T 1268-2015: Product adoption and process equivalence for ethylene oxide sterilization
PHARMACEUTICAL INDUSTRY STANDARD
OF THE PEOPLE’S REPUBLIC OF CHINA
Product adoption and process equivalence
for ethylene oxide sterilization
ISSUED ON. MARCH 02, 2015
IMPLEMENTED ON. JANUARY 01, 2016
Issued by. China Food and Drug Administration
Table of Contents
Foreword ... 3
1 Scope ... 4
2 Normative references ... 4
3 Terms and definitions ... 5
4 Product adoption ... 7
5 Process equivalence ... 13
Appendix A (Informative) Evaluation guide for adoption of products to ethylene oxide product family or ethylene oxide processing group ... 19
Product adoption and process equivalence
for ethylene oxide sterilization
This standard specifies the equivalence of the sterilization process when using new equipment in the process of adopting new product or changed product into the originally validated ethylene oxide sterilization process.
This standard applies to medical devices that have been treated by ethylene oxide (EO) sterilization and that use conventional release or parametric release. The ethylene oxide sterilization conditions applicable to this standard include. a) Adding new products to the already validated ethylene oxide sterilization process;
b) Evaluating the changes to validated products;
c) Transferring the validated process to a different site or equipment; d) Evaluating the equivalence of the sterilization process.
Although this standard is intended for use in medical devices, its content also applies to other related products or materials.
2 Normative references
The following documents are essential to the application of this document. For the dated documents, only the versions with the dates indicated are applicable to this document; for the undated documents, only the latest version (including all the amendments) are applicable to this standard.
GB/T 16886.7 Biological evaluation of medical devices - Part 7. Ethylene oxide sterilization residuals
ISO 11135-1.2007 Sterilization of health care products - Ethylene oxide - Part 1. Requirements for development, validation and routine control of a sterilization process of formal devices)
components (e.g., drug-containing kits), manufacturers shall, in addition to considering the impact of the sterilization process on the shelf life of the contained product, also consider the regulatory requirements for the safety and efficacy of the product components.
The ethylene oxide process used for product testing shall include
representative challenges to the product and its packaging system (using the most challenging process parameters). This requirement is detailed in 7.2.1 of ISO 11135-1.2007. The documentation shall state the difference between the challenge process and the routine process. For product acceptance, product qualification shall demonstrate that these parameters are acceptable.
Note. It should evaluate the ethylene oxide residue of the candidate product and its packaging, as well as the effect of any changes in the two on product release. GB/T 16886.7 can be used as a guide for this evaluation.
4.3.3 Determination of product design impact
The design of the candidate product shall be reviewed for difficulty change or difference in the penetration of ethylene oxide, heat or moisture as compared to existing product or process challenge devices. Examples of possible
changes include longer lumens, increased closure or more binding surfaces. Review of product design and initial product’s functional testing are to ensure that these changes do not adversely affect the functionality of the product. Note. This evaluation usually does not include the surface of the instrument that is sealed and not exposed during the intended use, such as. sealed, hollow, molded or closed cavity components.
4.3.4 Determination of the impact of product materials and characteristics It shall check any differences in the characteristics of the candidate product that potentially affect the bioburden of the product, such as manufacturing methods, equipment, locations, and types and sources of raw materials. It shall review the composition of the material, to ensure that the product does not maintain a higher residue level or a residual level that exceeds the specified limits. 4.3.5 Determination of the impact of sterile barrier system
It shall check any factors that create a barrier to ethylene oxide, heat or moisture permeation in the sterile barrier system of the candidate product. These factors can be a reduction in the porosity of the permeable material, a smaller permeable surface area, a closure of the venting surface, or any other feature that makes the candidate product more challenging to the sterilization process than existing product or process challenge devices. In addition, it shall evaluate the effects of changes in the sterile barrier system on the bioburden of the accordance with the requirements of Appendix A or Appendix B of ISO 11135- 1.2007, it shall use the sample of the candidate product as well as the existing product or process challenge device to run at least one short-term period, to perform this study. If the microbial resistance of the candidate product proves to be less than or equal to the resistance of the qualified product or process challenge device, the candidate product may be adopted to the existing
ethylene oxide product family or the ethylene oxide processing group. If the candidate product fails to demonstrate that the resistance is less than or equal to the qualified product, at least the microbiological performance qualification is required to be performed, which does not meet the requirements for being adopted to the existing ethylene oxide product family or ethylene oxide processing group.
Note. Comparative resistance studies related to the candidate product and the process challenge device can be performed in the sterilization chamber for testing purposes. It shall evaluate the candidate product which affects the load mode of the sterilization process, to determine the effectiveness of the sterilization chamber for production and the sterilization chamber for testing purposes.
4.4.3 Study of temperature and humidity distribution
If the technical review indicates that the candidate product may affect the loading thermodynamic response of the sterilization process, it can perform a study of temperature and humidity distribution, to evaluate the candidate product. Distribute the temperature and humidity sensors to the entire
sterilization load based on its initial performance qualification methods, run at least one cycle to implement this study. If the temperature and humidity response of the candidate product is comparable to the temperature and
humidity of the existing product or proves to have no adverse effect on the existing load, the candidate product may be adopted to the existing ethylene oxide product family or ethylene oxide processing group. If the above results are not available during loading, at least microbial performance qualification is required.
The results of the distribution studies may indicate that products that have limitations on temperature or humidity require further product qualification or changes to the sterilization process to meet these limits. Although it does not affect the sterility of the product, it may require performance qualification in this case.
4.4.4 Study of residue
If the technical review indicates that the candidate product is more challenging in removing the biocide residue, it may perform a residue study, to evaluate the candidate product. The study is conducted by performing a complete
a) In accordance with the requirements of ISO 11135-1.2007, implement a complete sterilization process validation in at least one existing system; b) Prove and document that all equipment has been installed in accordance with the equipment specification and run the study on installation
qualification and operational qualification performance in accordance with the corresponding requirements;
c) Include the allowed tolerances and the process definition of documents at various stages of the process;
d) Process data analysis related to the tolerances validated for the candidate equipment and the initial equipment (see 5.3.2).
5.3 Determination of process equivalence
Compare the data obtained by running the same validated process on each equipment, to establish the sterilization process equivalence that is delivered between different equipment. This comparison shall include an evaluation of the reproducibility ability of the equipment to deliver the expected process parameters, during loading sterilization in routine production, it may also use the process data obtained using performance qualification. The parameters and tolerances delivered shall be the data obtained from the performance
qualification of the initial equipment for the sterilization process.
Equivalence evaluation includes implementation of process analysis and
evaluation, as well as microbiological evaluation.
5.3.2 Process analysis and evaluation
Perform data analysis related to the validated process of the candidate equipment and initial equipment. Process data shall be collected from the candidate equipment. These data shall be compared to the range of parameters for a particular sterilization process as well as the data obtained during the initial equipment performance qualification process. Establish a range of parameters for the sterilization process (including all process requirements identified by ISO 11135-1.2007) during initial validation in existing equipment. These
specifications, acceptance criteria, trays or load configurations shall be identical to the requirements as specified by the initial performance qualification. Generally, in the equivalent confirmation, the actual parameters to be evaluated are a subset of the entire process specification. The parameters and the principles selected shall be documented. Statistical methods for evaluating the concentration trend of test data and data dispersion can be used for this 2) The temperature inside the cabinet at the selected time point in the sterilization cycle (for example, the end of the processing or the start of gas residence);
3) Ethylene oxide concentration (if measured) in the sterilizer at the
selected time point during the gas residence phase of the sterilization cycle, or gas pressure increase or gas weight.
Other parameters that can be considered include.
1) The depth and rate of evacuation at selected points during the process of sterilization cycle;
2) The number of times of moisture injection and the rate of moisture
3) The gas injection temperature and rate as well as the gas usage (mass, concentration or pressure);
4) The injection rate of air or nitrogen.
Process data analysis is used to indicate that these processes are equivalent or not equivalent within their capabilities, to meet the existing process parameter ranges and any additional acceptance criteria. It shall use a format analysis and assembly of the resulting data for the determination of future process equivalence.
5.3.3 Microbiological evaluation
During the microbiological evaluation process, run a short cycle or half cycle to demonstrate that in all evaluated equipment, the sterilization process is capable of delivering the specified minimum sterility assurance level.
Note. In the process analysis, if the running period is a short cycle or half cycle and includes microbiological monitoring, these data can also be used for this evaluation.
In addition to evaluating the delivery of the minimum sterility assurance level, other factors including the change of sterilization location or manufacturing sites which affect the bioburden level of the terminally sterilized product shall also be evaluated. Increased distances between production facilities and sterilization sites may result in higher bioburden levels, especially for products that support microbial growth. Even though for products that do not support microbial growth, the difference of the production environment of products may also result in a bioburden of more or stronger resistance of the manufactured products as compared with the qualified products. Another problem to be evaluated is the different transport conditions for transporting products between different can be claimed to be equivalent to the existing sterilization process equipment shall be documented. The document shall at least include.
a) Complete specifications of the candidate equipment. detailed description of the equipment, operating specifications, tolerances and reference
documents or a list of applicable operating procedures, calibration
procedures and maintenance plans. According to the requirements of ISO
11135-1.2007, the specification shall include or refer to the current
b) The equipment provides proof of capability or evaluation of the expected process. According to the requirements of ISO 11135-1.2007, the proof or evaluation shall include or refer to the current operational qualification; c) Results of comparison of the candidate process equipment and the
existing validated process equipment. This comparison shall clearly
demonstrate that all major systems and key parameters have been
evaluated, including statistical analysis (if used);
d) The proof or evaluation of product conditions during the sterilization of the candidate equipment, to demonstrate equivalence with existing processes; e) The evaluation results of other factors which may affect the mortality rate of the sterilization process (if applicable);
f) The candidate equipment is equivalent to the specific equipment
referenced in the current validation study, the conclusion that the specified sterility assurance level is achieved shall be documented and shall include or refer to additional test results to supplement the existing validation study, as well as the validation of the routine release of the product which is sterilized by the use of existing validated cycle or the further test for the implementation of qualification (e.g., residue testing, functional testing for first three batches, etc.);
g) Approval by the sterilization specialist and other personnel as specified within the organization’s regular change control requirements or process document control measures;
h) A list of applicable sterilizer operating procedures as well as a list of approved specifications that have been published or changed for
candidate equipment for routine processing of the product.