YY/T 1302.1-2015 English PDF (YYT1302.1-2015)
YY/T 1302.1-2015 English PDF (YYT1302.1-2015)
YY/T 1302.1-2015: Physical requirements and microbiological performance of ethylene oxide sterilization - Part 1: Physical aspects
PHARMACEUTICAL INDUSTRY STANDARD
OF THE PEOPLE’S REPUBLIC OF CHINA
Physical requirements and microbiological
performance of ethylene oxide sterilization -
Part 1: Physical aspects
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 ... 4
4 Equipment for ethylene oxide sterilization process ... 5
5 Determine the minimum temperature of product before preconditioning ... 12 6 Calculate humidity ... 14
7 Calculation of ethylene oxide concentration ... 17
8 Calculation by the use of flammability curves ... 19
9 Guide to statistical contrast methods for determining process equivalence 20 Appendix A (Informative) An example of a method for determining the
concentration of ethylene oxide gas based on the physical formula of an ideal gas ... 26
Appendix B (Informative) Calculation example using a flammability curve ... 29 Physical requirements and microbiological
performance of ethylene oxide sterilization -
Part 1: Physical aspects
This part of YY/T 1302 specifies the physical requirements for the sterilization of ethylene oxide.
This part is intended to provide guidance for sterilization equipment,
preconditioning, calculation of relative humidity, concentration of ethylene oxide, flammability, statistical applications in process equivalents.
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 3836.1-2010 Explosive atmospheres - Part 1: Equipment - General
GB 3836.14-2014 Explosive atmospheres - Part 14: Classification of areas - Explosive gas atmosphere
GB 50169-2006 Code for construction and acceptance of grounding
connection electric equipment installation engineering
GBZ 2.1-2007 Occupational exposure limits for hazardous agents in the
workplace Part 1: Chemical hazardous agents
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 medical devices
3 Terms and definitions
The terms and definitions as defined in ISO 11135-1:2007 as well as the following terms and definitions apply to this document.
b) The interior of the sterilizing cabinet shall also comply with the
requirements or equivalent requirements of the category T2 electrical
equipment in the zone IIB0 in GB 3836.1-2010 and GB 3836.14-2014;
c) Equipment and piping shall comply with the grounding requirements of GB 50169-2006 or other equivalent requirements;
d) The storage, disposal, use of ethylene oxide shall comply with relevant national regulations;
e) When designing the sterilization cycle, the environment inside the
sterilizing cabinet shall be kept non-flammable.
4.1.2 Under abnormal conditions (such as equipment failure, power interruption, test cycle, etc.), when the product is exposed to an ethylene oxide sealed environment and lack proper ventilation (failure of air exhaust or ventilation equipment, etc.), it shall pay attention to the hazard as caused by the accumulation of the flammable and explosive ethylene oxide. The possibility of this hazard is independent of the mixture used.
4.1.3 Fume hoods or ventilation areas (buildings, rooms) shall be equipped with equipment that removes sterilized gases and restores them to a safe level (see GBZ 2.1-2007).
4.1.4 For electromagnetic interference as caused by the equipment or
environment or both inside the workshop (such as a mobile phone) or outside the workshop, it shall evaluate the impact on the sterilization process. When designing the plant, it shall comprehensively consider the infrastructure (appropriate grounding, shielded cables, circuit isolation, protective building materials, etc.), to avoid interference with the sterilization process. Note: For guidance on electromagnetic interference, see GB/T 17799.
4.2 Preconditioning area (outside sterilizing cabinet)
4.2.1 If the product is heated and humidified in the workshop, there shall be equipment to adequately control and record the room temperature and humidity. In ISO 11135-1:2007, humidity is only expressed in terms of relative humidity. Humidity may also be recorded in other engineering units, such as dew point, absolute humidity, water vapor pressure.
4.2.2 It shall use supporting air circulation to meet the requirements for the temperature and humidity control and its distribution as specified in the available rooms (areas).
4.2.3 During identification of equipment, it shall establish and record the air 4.3.4 It shall select the sensors which are suitable for the ethylene oxide sterilization process (such as pressure, temperature, gas concentration, relative humidity sensors, etc.).
4.3.5 If there is a deviation in the sterilization process, it shall use audible and/or visual alarm to alarm the operator.
4.3.6 Sterilizing cabinets shall be mechanically (interlocked) designed to prevent inadvertent contact loading prior to the completion of the sterilization cycle. If the sterilization cycle fails, it shall be limited only to understanding the fault condition and the employee contact loading which may has risk.
4.3.7 When the sterilizing cabinet is used to condition the product loading (regardless of static or dynamic), it shall be able to adequately control and record the sterilizing cabinet’s temperature, pressure, other parameters to achieve the desired process conditions.
4.3.8 Since the process conditions within the sterilizing cabinet may reach the dew point of the water, it shall evaluate the condensate on products and equipment. In particular, the condensate at cold point will reduce the partial pressure of water vapor in the sterilizing cabinet, resulting in additional steam injection to maintain a constant pressure under static processing conditions. Excessive condensate in the sterilizing cabinet or on the product/package will impede the killing effect of ethylene oxide gas on the microorganism of the product; meanwhile it will adsorb ethylene oxide gas and ethylene oxide derivative. The adsorbed ethylene oxide gas will diffuse when the product loading is ventilated or stored, endangering the health of the staff. In addition, the condensate in the sterilizing cabinet or on the product load will re-evaporate and make the humidity level in the headspace of the sterilizing cabinet exceed the confirmed level.
4.3.9 For equipment designed to heat and humidify, the sterilizing cabinet shall avoid direct humidification of the product loading (such as the use of manifolds or partitions). Generally, it uses steam valves, traps and/or coalescing filters to control the quality of the steam which enters the sterilizing cabinet. Steam water shall not contain contaminants that affect the sterilization process or damage the sterilizing cabinet or sterilized load.
4.3.10 It shall select the equipment that has sufficient control over the parameters as provided and as selected by the monitoring, such as:
a) Pressure control;
b) Rate control (such as exhaust or gas injection);
c) Temperature control;
4.3.14 The distribution of temperature, humidity, sterilization gas shall comply with the requirements of the sterilization process. It shall specify the available sterilizing cabinet’s boundaries and product loading dimensions, to eliminate the adverse effects due to too closeness of sterilized loading of the product and the interior walls of the cabinet. These effects may include gas circulation problems due to product’s obstruction, uneven heating of product loading due to direct contact to cabinet wall as well as the interference of product to the process monitoring instrument.
4.3.15 It shall use the infrastructure and/or engineering controls to ensure the specified steam, appropriate gas, air and/or nitrogen are injected into the cabinet.
4.3.16 It shall configure nitrogen and air injection filters to protect products and equipment. If compressed air is in contact with the product, the air shall be protected or treated, to ensure it is dry, oil-free and filtered.
4.3.17 When sterilizing products that do not contain protective packaging, it shall follow the quality system of the manufacturer to configure sterilizing filter. 4.4 Ventilation system
4.4.1 After gas exposure, if using a room/zone/cabinet to ventilate the product, it shall be equipped with equipment which continuously control and record the air temperature. It shall be equipped with facilities which regularly check the air flow and/or ventilation rate during the ventilation period, to verify compliance with the originally validated performance specifications. If fresh air flows into and out of the room/zone/cabinet changes, the temperature distribution of room/zone/cabinet may exceed the confirmed tolerances. This will affect the proper resolution of the ventilation product and/or the problem of employee exposure to hazards.
4.4.2 The specified limits for the accuracy and reproducibility of measuring instruments used in the ventilation process shall be in accordance with the process requirements.
4.4.3 Ventilation rooms/zones/cabinets shall be easy to clean. The construction materials are adapted to the cleaning process. In accordance with good
hygienic practices and manufacturer-defined procedures, carry out the cleaning process.
4.4.4 It shall be equipped with facilities that identify the loading of different products in the ventilated room/zone/cabinet.
4.4.5 In the event of a deviation, it shall use an audible and/or visual alarm to prompt the operator.
n) Systems that supply steam and heat;
o) Vacuum equipment;
p) Weighing system;
r) Pressure transmitter;
4.7.1 It shall use ethylene oxide gas with caution, because it is toxic, potentially flammable, explosive. When selecting ethylene oxide sterilization and
ventilation equipment, it shall comply with national health and environmental protection regulations.
4.7.2 It shall carry out risk assessment (sch as batteries and capacitors) on any product which contains energy-storing components.
4.7.3 The exposure to ethylene oxide in the workplace shall comply with the occupational exposure levels of GBZ 2.1-2007.
5 Determine the minimum temperature of product
5.1.1 In 9.5.4 a) 2) of ISO 11135-1:2007, it requires determining the minimum temperature of the product before starting preconditioning. The loading temperature before entering the preconditioning shall be determined in the coldest zone. When the product which was too cold after placement enters preconditioning, it shall dispose it with caution. Sudden changes in temperature may cause product damage and/or large amounts of condensed water.
5.2 Simulation of expected process conditions
5.2.1 Process validation shall consider the most difficult sterilizing conditions to be expected for loading. It shall evaluate the effects of loading temperature limits on the sterilization process during transportation, handling, storage. These expected loading temperature limits can be simulated at the time of validation by including, but not limited to, the following methods:
is established during process validation. In monitoring and controlling conventional production, each load shall be temperature probed prior to preconditioning and compared to the value verified at the time of validation. Any loading that does not meet the minimum requirements shall be maintained in the storage area until the coldest load meets the specified requirements. 5.4.2 Hard-to-heat loading
It shall be specified that before entering the preconditioning zone or the sterilizing cabinet, the product loading shall reach the minimum acceptable temperature. This is especially important for loads that are difficult to heat or that enter into the preconditioning zone below the dew point temperature or that are preconditioned by a sterilizing cabinet. In all loads, the zone which shows the lowest temperature will receive sufficient microbial challenges.
6 Calculate humidity
6.1 Static humidification
6.1.1 Process definition
Usually after being loaded in a sterilizing cabinet to subject to the vacuum process, it designs a process to add or replenish the moisture and heat of the load. When statically humidified, steam is injected into the sterilizing cabinet to achieve a desired partial pressure and obtain a desired relative humidity level. In most systems, because the load absorbs a large amount of the injected moisture, in the steam holding stage of the sterilizing process, the control system automatically controls the pressure of the sterilizing cabinet by increasing steam injection. It may control the rate of steam injection to enhance the effect of steam injection. Taking the injection rate control measures will allow sufficient time for the steam to penetrate into the load, thereby resulting in better heating and heat distribution effects.
6.1.2 Design a static humidification process
18.104.22.168 Low-vacuum process
It is used to sterilize loads that may contain pressure sensitive materials or instruments. These processes often employ vacuum levels of about half
atmospheric pressure. In addition, use a lower vacuum rate to minimize the effects of pressure changes on vacuum sensitive materials or instruments. Using a low-vacuum level. During the initial vacuuming stage of the sterilization cycle, most of the heat and moisture inside the product load remains in the load, which requires little replenishment. The moisture level of the load remains stable, because the process pressure is still greater than the steam pressure at 6.2.1 Process definition
Dynamic processing is a process of increasing the thermal energy (heat) of load. It uses steam stream as the heating medium. The available heat depends on the operating pressure during the dynamic processing stage. Pulsed steam injection (PSI) and continuous steam injection (CSI) are two general methods. 6.2.2 Design dynamic processing stage
22.214.171.124 Operating pressure of dynamic processing
126.96.36.199.1 Determine the operating temperature of the sterilizing cabinet which is used in the sterilization process.
188.8.131.52.2 Use the pressure-steam relationship table, to determine the absolute pressure of the steam at the operating temperature of the sterilizing cabinet. 184.108.40.206.3 Use the pressure-steam relationship table, to select the desired dynamic processing steam’s temperature. The corresponding absolute
pressure will be the maximum pressure for the dynamic process.
Note: The temperature of the dynamic steam process shall be lower than the operating temperature of the sterilizing cabinet. Failure to maintain a pressure below the saturated steam pressure at the operating temperature of the
sterilizing cabinet will result in excess condensate during the dynamic process. 220.127.116.11.4 For pulsed steam injection (PSI), in addition to determining the maximum absolute pressure for dynamic processing, it shall also select the minimum absolute pressure (temperature).
18.104.22.168 Description and setting of pulsed steam injection
22.214.171.124.1 With the operation of the vacuum system, steam is injected into the sterilizing cabinet until the maximum value of the pressure setting in the “processing stage” is met. The steam supply is stopped. The vacuum system then reduces the pressure in the sterilizing cabinet, until the minimum value of the pressure setting in the “processing stage” is met. At this point, the steam injection is resumed, until the maximum value of the pressure setting in the “processing stage” is met. The steam injection/vacuuming process continues to meet the requirements for setting value in the “process hold stage”. The change of final pulsed steam injection pressure is similar to the sawtooth pattern between the maximum pressure and the minimum pressure at the “processing stage”.
126.96.36.199.2 Program the setting values of the maximum, minimum, expected
“processing hold time” of determined steam injection pressure into the control system.
K represents a constant for a given mixture of ethylene oxide;
Mavg represents the average molar mass of the gas mixture;
Mdg represents the molar mass of the diluent gas;
Meo represents the molar mass of ethylene oxide;
n represents the number of moles of gas;
p represents the gas pressure;
pEO represents the partial pressure of ethylene oxide gas as injected into the sterilizing cabinet;
R represents a gas constant;
T represents the absolute temperature of the ethylene oxide/diluted mixture in the sterilizing cabinet after the sterilization gas is injected;
V represents the volume.
7.3 Ideal gas equation
Under the conditions of finishing gas injection and the temperature is equalized, calculate the average density of ethylene oxide gas in the sterilization system, based on the ideal gas equation (4):
This equation is based on the following assumptions:
a) The sterilizing cabinet is empty;
b) An ethylene oxide mixture, water steam and air (and diluent gas, if used) are used as an ideal gas;
c) The information indicated on the label on the gas cylinder is accurate. During gas injection, the mass fraction of the mixed gas remains the same; d) The pressure reading for the determination of partial pressure may be absolute pressure or gauge pressure.
The ideal gas equation is transformed and multiplied by a constant K. Either pure ethylene oxide or a mixed gas can be used to calculate the ethylene oxide’s concentration by the use of equation (5).
determining process equivalence
One way to determine equivalence is to perform a statistical comparison of the performance of each device over the required control range. If all devices can operate within the expected control range and meet certain confidence levels, these devices can be said to be equivalent. Note that this statistical contrast does not use the T test, the F test, or other test methods to prove that the process is the same. The content of the evaluation is used to demonstrate that different devices can operate in a given range of predetermined processes with a certain degree of statistical confidence.
One way is to choose a set of parameters that indicate whether the device is capable of running the required process. Parameters include (but are not limited to):
a) The temperature of the sterilizing cabinet at a setting time point within the cycle (for example, the end of the conditioning or the beginning of the gas exposure);
b) The relative humidity of the sterilizing cabinet (for example, the end of the conditioning or the prophase at the beginning of the gas action after the condition is stabilized);
c) The concentration of ethylene oxide in the sterilizing cabinet (if directly measured, after an allowable stabilization cycle);
d) The increase in ethylene oxide pressure or the weight of ethylene oxide injected;
e) The loading temperature at a setting time point during the cycle (if using a loading probe). ...