Sterilization in the pharmaceutical industry is used a as a mechanism to ensure purity. It prevents and remove contamination throughout the entire manufacturing life cycle. It enables the final finished product to provide a patient with a safe, quality product capable of delivering its therapeutic effects.

 There are different ways of sterilization, selection of which depends upon the product’s characteristics, contamination type, and relevant regulatory guidelines.

Steam sterilization

In steam sterilization, steam is used to achieve the desired high temperature and is maintained for a fixed time. 

 Steam sterilization in the pharmaceutical industry is regulated and standardized under various international standards and regulatory guidelines. While fulfilling every other requirement may often become tiring and costly, standardization helps pharmaceutical manufacturers in many ways, such as safe operation, efficient results, customer trust, process reliability, and regulatory accreditation. One such standard is EN 285.

EN 285

EN 285 specifies test methods for large steam sterilizers used for sterilizing medical devices. This standard, which is applicable in Europe and the United Kingdom, requires a minimum capacity of 60 liters for the sterilizer, and cannot be applied to sterilizers below 60-liter capacity. It defines the load configuration & operating cycle, and ensures sterilizer safety.

Scope

The EN 285 standard is not meant for all sterilizers. Instead, it is limited as defined in the following

Steam Sterilizer

The EN 285 standard is only applied when steam is used as a medium to achieve high temperatures

Capacity

 The EN 285 applies to sterilizers that have a large capacity, typically more than 60 Liters. The large size enables them to handle differently sized loads. Alternatively, it should be able to hold at least one sterilization module per cycle.

Load Types

 Loads are the items used to sterilize in the sterilizer. According to the EN 285 standard, the load

• Should be arranged in adequate spacing and orientation.

• Its weight must be equally distributed throughout the sterilizer chamber.

• It is necessary to allow effective steam penetration and distribution. 

• The load must be related to medical devices used in the pharmaceutical and healthcare industry.

• The load selection shall be made to represent the real condition and the majority of components.

• The load can include warped rubber, metal, and porous materials. 

• For testing heavy metal objects and long and/or narrow lumens, a separate arrangement for testing the steam sterilizer shall be made. 

Out of Scope

The EN 285 does not include to test the following. 

• Any steam sterilizer whose chamber is less than 60 liters.

• Less than one sterilization module

• Obtaining guidance about the manufacturing of a steam sterilizer

• Environmental impact of the steam sterilizer during its life cycle

Some Key Requirements

Let’s discuss these briefly.

Design Requirements

Design requirements specify the characteristics and functions of the sterilizer, to achieve the desired product specification and meet user expectations. It includes

Material of Construction 

The material of construction for parts that come in direct contact with the steam will not be affected by the steam & its condensate, nor will the steam be affected by the material. In addition, the contact should not release toxic substances, creating a health or environmental issue.

Chamber

• The external surface of the chamber should be insulated.

• The chamber should comply with the specification EN 13445 - Unfired Pressure Vessels. 

• The door seal should be replaceable.

• The door should be able to open before starting the sterilization cycle, but it should not be able to open during the sterilization cycle.

• For a double-ended design,

• it should not be possible to open both doors simultaneously, except for maintenance purposes.

• The unloading door should not be opened without conducting a Bowie & Dick test and air leakage.

• The sterilization cycle control should be located at the loading side. 

 Framework and paneling 

• If the sides of the sterilizer are visible from the operator area, it must be paneled according to the manufacturer’s instructions.

• The paneling should allow for maintenance and be demountable. If personnel access is required, its dimension should be less than 500mm wide and 15 in height.

Piping and Fittings

• Pipe joints & fillings must be both pressure-tight and vacuum-tight.

• Where temperatures are above 60°C, it must be insulated except where this insulation interferes with the sterilizer’s function.

• All control valves must be adequately marked with their functions.

Steam Source

• The steam source for the sterilizer can be from an external dedicated source, such as a boiler. It can also be part of the sterilizer itself.

• The shell boiler should comply with EN 14222 or EN 12953

• The capacity of the steam generator must be adequate to provide the steam demand for the sterilizer.

• Cleanrooms shall be used for designs, where external air is used inside the chamber, per class H14 and EN 1822.

• The filter shall be accessible from the external side and remain dry to prevent the ingress of steam, water, or moisture from the chamber to the filter.

 Instrumentation and Indicating Devices

• All instruments and indicators must be located & their function identified in an easy-to-access location for the operator. 

• These devices must be easily readable from a distance of 1,00 ± 0,15 m, with a minimum external illumination of (215 ± 15) lx. 

• The maximum and minimum temperature & humidity conditions in the area must not exceed their manufacturer’s recommended specifications.

• The sterilizer shall be provided with the following instruments and indicating devices.

• Chamber temperature indicator and recorder

• Chamber pressure indicator and recorder

• Jacket pressure indicator 

• Chamber pressure gauge

• Visual display indicating

• Door locker

• In progress

• Cycle complete

• Fault

• Cycle selected

• Operating cycle indicator

• Cycle number

• Cycle’s stage indication

• For a double-door sterilizer, the following should be provided at both ends.

• Chamber pressure

• Door locked indicator

• In progress

• Cycle complete

• Fault

Temperature Sensors

• All temperature sensors must be platinum resistance types or a thermocouple of acceptable tolerance Class 1 of EN 60584-2:1993. 

• The sensor to control the sterilization cycle should also be used to record the sterilization cycle.

• The chamber temperature indicator should comply with the following.

• Can be digital or analogue and graded in Celsius

• Must be within 50°C to 150 °C

• accuracy of ± 1% for the range of 50 °C to 150 °C

• Analogous sensors should not be graduated in divisions greater than 2 °C.

• Digital sensors must have a resolution of 0.1 °C or higher.

Pressure Indicating Instrument

The indicator for pressure

• It can be digital or analogue, graduating in kilopascals or bars.

• The pressure scale shall range from 0 kPa to 400 kPa or, 1 bar to 3 bar, with a zero reading at absolute vacuum or ambient pressure.

• Accuracy of f ±1,6 % or above, on a scale for the range of kPa to 400 kPa (- 1 bar to 3 bar)

• The graduation of Analogue instruments shall not be greater than 20 kPa (0,2 bar)

• The resolution of the digital instrument shall be 1 kPa (0,01 bar) or better.

• Time indicating sensors shall be graduated in hours, minutes, and seconds, and the error shall not exceed 1%

Pressure Indicating Instrument

• The recorder can be analogue or digital

• Its value and reading must be separate from the automatic controller

• The records shall be readable when stored in defined conditions for a period not less than 11 years

• Records should be readable at a distance of 250 ± 25 mm in an illumination of 215 ±15 lx

• The time markers shall be in seconds or minutes

Temperature characteristics

For a small and full load, the holding time should be at least 15 minutes for 121°C, 10 minutes for 126°C, and 3 minutes for 134°C, repectively

Bowie and Dick test

The indicator should show a uniform and adequate color change under this test.

Air Detector

The Air Detector should indicate a fault if air or non-condensable gases are retained or introduced into the chamber during the air removal or steam introduction phase.

Safety

The autoclave should include all safety devices per EN 61010-2-040 and EN 13445

Markings

• The sterilizer should be appropriately marked for safety per EN 61010-1, EN 61010-2-040, and EN 13445.

• Other markings should at least include the name and address of the manufacturer

• For manufacturers outside of Europe, the marking should include

• Identification number

• Model identification

• Production year

• Sterilizer description

• Control valve identification

Steam Supply

• The steam sterilizer should be designed to operate with saturated steam, with a 3,5% V/V of non-condensable gases.

• The sterilizer should be designed to operate with dryness values of 0.95 for metal loads and 0.90 for other load types. The steam supply should be free from      contaminants.

• The pressure fluctuations shall be within ± 10 % of the nominal gauge.

Compressed Air

The sterilizer should be able to operate with compressed air, with a pressure of 600 kPa to 800 kPa or 5 bar to 7 bar.

Testing

Document records as evidence should be maintained, indicating that the sterilizer complies with EN 285 specifications.

Calibration

Before conducting any of the tests, all pressure and temperature-related instruments should be calibrated for optimum performance, fault identification, and rectification. 

About the Author

Muhammad Asim Niazi has a vast experience of about 11 years in a Pharmaceutical company. During his tenure he worked in their different departments and had been part of many initiatives within the company. He now uses his experience and skill to write interested content for audiences at PharmaSources.com.