洁净室验证

Cleanroom Validation Applications

Establishment of quality environment validation plan for manufacturing medical devices/in vitro diagnostic reagents/cosmetics/food

Consignment tests for quality control during manufacturing (EO gas residual test, sterility test, etc.)

Maintenance and repair including expiration date setting, sterilization validation, packaging and cleanroom validation, etc.

Service area

• ① Clean room validation (clean bench, clean booth, etc.)

Clean according to the international standard ISO14644-1 (Cleanrooms and associated controlled environments — Part 1: Classification of air cleanliness by particle concentration) and the requirements for cleanliness in the work environment / product cleanliness and contamination control of medical device manufacturing and quality control standards It refers to verifying that the standards are established and facilities and equipment are equipped to maintain and manage them. In general, in the following cases, the validation document should be prepared by applying the cleanliness management standards of manufacturing facilities.

Sterilized products (including ‘Pyrogen free’ products)

Products that are shipped non-sterile, but are designed to be sterilized by the user before use

Products with expiration date set

Products with special conditions for handling and storage

Products whose electronic circuits or software are affected by static electricity (ESD)

Products that are affected when used by microorganisms, dust particles, or environmental conditions

The following medical devices are also examples.

Products that are sterilized or cleaned by the manufacturer prior to use
(Ex: sterile needle, blood storage container, coronary artery cannula, biomaterial for tissue restoration, after RBM treatment on the surface of dental implant fixture, etc.)

Products supplied in a non-sterile state that require sterilization or a cleaning process prior to use
(Example: reusable lancets, body type universal probes, synthetic polymer materials, drainage tubes or similar products for tubes, etc.)

- Process agents are removed from the product during the manufacturing process.
(Example: Remove acid treatment agent and organic cleaning agent after anodizing on the surface for bone bonding)

The cleanliness class classification standards set by ISO standards are as follows.

ISO classification (N)	The maximum particle concentration limit indicated below is the concentration in an area greater than or equal to the specified particle size (concentration of particles in 1 m3).
	0.1μm	0.2μm	0.3μm	0.5μm	1μm	5μm
ISO 1	10	2
ISO 2	100	24	10	4
ISO 3	1,000	237	102	35	8
ISO 4	10,000	2,370	1,020	352	83
ISO 5	100,000	23,700	10,200	3,520	832	29
ISO 6	1,000,000	237,000	102,000	35,200	8,320	293
ISO 7			10	352,000	83,200	2,930
ISO 8			10	3,520,000	832,000	29,300
ISO 9			10	35,200,000	8,320,000	293,000
Remark When determining the cleanliness level, there is a measurement error, so only 3 significant digits of the measured value are used.

Clean room design/construction

Validation such as installation qualification (IQ), operational qualification (OQ), performance qualification (PQ), etc.

Airflow (wind speed) measurement and ventilation frequency/airflow direction test and visualization

Filter leak test / Confirmation of suspended particles / Confirmation of cleanliness recovery

Noise / Illuminance / Temperature / Humidity / Differential pressure measurement

Microbiological test (float bacteria, drop bacteria, surface bacteria, worker's hand bacteria)

Cleanroom validation monitoring - annually

Clean room re-validation – every 3 years

• ② Process validation

Supporting facilities and equipment such as clean air, manufacturing water, steam, etc. as a method of collecting and evaluating data that is confident that the entire process from the development stage of the manufacturing process to the manufacturing process can be maintained consistently and continuously according to the intended result. In addition to the system, it must be proven through validation that the entire process system, from manufacturing process, sterilization, cleaning, filling, etc. to testing, is continuously maintained under certain conditions. As a verification method such as documentation to ensure that a specific process can continuously manufacture products that meet the specifications and quality/performance set by the company, process control and product testing are minimized to improve safety and quality and reduce costs etc. to maximize the effect.

Packaging validation (ISO11607), cleaning validation, etc.

Validation such as installation qualification (IQ), operational qualification (OQ), performance qualification (PQ), etc.

Validation monitoring for maintenance

Re-Validation to check whether changes in manufacturing process and manufacturing environment affect product quality

• ③ EO Gas Sterilization Validation

Sterilization using Ethylene Oxide gas follows ISO11135 (Sterilization of health care products - Ethylene oxide - Part 1: Requirements for development, validation and routine control of a sterilization process for medical devices) standard. It is a chemical method that kills microorganisms such as viruses, and since sterilization is performed at 37 ~ 60 ℃, it is possible to sterilize rubbers such as syringes and catheters that are difficult to autoclave, surgical instruments for surgical instruments, and medical devices that are weak to heat and moisture such as microscopes. used when However, due to the residual amount of EO gas, it cannot be used until the residual gas is below the allowable value, and an aeration step is required to remove it. Therefore, an EO gas residual test that can confirm whether sterilization is complete should be accompanied, and this is in accordance with ISO10993-7 (Biological evaluation of medical devices - Part 7: Ethylene oxide sterilization residuals).

Validation such as installation qualification (IQ), operational qualification (OQ), performance qualification (PQ), etc.

Bio Indicator (BI) test

Sterility test

EO gas residual amount test, etc.

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• ④ High-pressure steam sterilization

Sterilization using Moist Heat with high-pressure steam conforms to the standard of ISO17665-1 (Sterilization of health care products - Moist heat - Part 1: Requirements for the development, validation and routine control of a sterilization process for medical device) . It is a commonly used sterilization method because it does not remain toxic like EO gas sterilization, so the sterilization time is short (121℃ / 15-20 minutes at 15Psi), and the maintenance cost is not high. It is often used in medical devices that require user sterilization, such as reusable medical devices.

Validation such as installation qualification (IQ), operational qualification (OQ), performance qualification (PQ), etc.

Bio Indicator (BI) test

Sterility test, etc.

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• ⑤ Radiation sterilization

It is a method used for sterilization of medical devices using the strong penetrating power of radiation, and conforms to the ISO11137 (Sterilization of health care products — Radiation — Part 1: Requirements for development, validation and routine control of a sterilization process for medical devices) standard. . It is possible to sterilize efficiently and reliably even the parts that are difficult to process because they are weak to heat, which makes it difficult to sterilize by high pressure steam or because the residual amount has to be checked like the EO gas sterilization method. However, depending on the material, epiphysis or deterioration of strength can be a problem, so it is used for sterilization of needles, syringes, artificial dialysis machines, surgical gloves, etc.

Validation such as installation qualification (IQ), operational qualification (OQ), performance qualification (PQ), etc.

Bio Indicator (BI) test

Sterility test, etc.

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