Review of New Aseptic Processing Standards
As of December 31, 2011, EN 13824:2004 (Sterilization of medical devices. Aseptic processing of liquid medical devices. Requirements) can no longer be used to provide a presumption of conformity with Essential Requirements of the Medical Device Directive 93/42/EEC, and the In Vitro Diagnostic Medical Device Directive 98/79/EC. The standard is replaced by the international ISO 13408 series of standards.
Introduction to Aseptic Processing
Have you ever wondered what means? It is the symbol for sterile using aseptic processing techniques. If you are a contact lens wearer you are likely to have seen it on your lens solution packaging. It is also typically used with other ophthalmic medical devices such as drops for dry eyes and certain other medical devices that are similar to pharmaceutical liquids
In Terminal Sterilization devices are packed and sealed under a high level of environmental control ‘clean room’ conditions. Devices in their final product containers are then subjected to a sterilization process:
Sterilized using steam or dry heat
|Sterilized using ethylene oxide|
Sterilized using radiation
Aseptic manufacturing is used if the device cannot be sterilized in its final container for example if the device is heat sensitive and will become unstable. In Europe it is seen as the last resort and should only be used if all other methods of terminal sterilization have been excluded.
In aseptic processing the highest levels of environment control are used. Device containers and closures are first subjected to validated sterilization by a terminal method. Sterility of the device is achieved by filtering bulk solution through a bacteria retaining filter into the final sterile product containers.
The entire process is validated by conducting a media fill where microbiological nutrient media is used instead of the medical device. The filled and sealed containers are incubated and inspected for any microbial growth. The media fill simulates the normal manufacturing process including environment and personnel control, cleaning and sterilization of manufacturing equipment (cleaning in place CIP and sterilization in place SIP); sterilization of containers and closures; device compounding and mixing; sterile filtration and filling.
Lyophilization (freeze drying) is a physical drying process that involves freezing a solution and removing solvent to a level such that the product no longer supports chemical reactions or biological growth - primarily to achieve product stability. If lyophilizaton of sterile solution is required, then controls are required to ensure no contamination of the solution (from microbiological and particulate contamination) between the filling operation and completion of the lyophilization process.
Changes in the Standards
The existing ISO standards for Aseptic processing (e.g. as used in pharmaceutical manufacturing) have become harmonized within Europe and are published as EN ISO standards. Although the principles of Aseptic Processing remain the same, the EN ISO 13408 series of standards specify requirements in much more depth, and have some additional requirements.
So manufacturers who use aseptic processing will need to obtain the latest versions of standards to identify if existing processes and procedures are compliant and to identify any improvement actions. Notified Bodies will start to use the new standards to assess the technical documentation and processes used by manufacturers of CE marked products.
Summary of ISO 13408 Standards
- EN ISO 13408-1:2011 Aseptic processing of health care products - Part 1: General requirements (Equivalent to ISO 13408-1:2008).
The standard specifies the general requirements for, and offers guidance on processes, programs and procedures for development, validation and routine control of the manufacturing process for aseptically-processed health care products. It includes requirements and guidance relative to the overall topic of aseptic processing.
- EN ISO 13408-2:2011 Aseptic processing of health care products - Part 2: Filtration (Equivalent to ISO 13408-2:2003).
The standard specifies requirements for sterilizing filtration as part of aseptic processing of health care products. It also offers guidance to filter users concerning general requirements for set-up, validation and routine operation of a sterilizing filtration process, to be used for aseptic processing of health care products.
- EN ISO 13408-3:2011 Aseptic processing of health care products - Part 3: Lyophilization (Equivalent to ISO 13408-3:2006).
ISO 13408-3 specifies requirements for, and offers guidance on equipment, processes, programs and procedures for the control and validation of lyophilization as an aseptic process. It does not address the physical/chemical objectives of a lyophilization process.
- EN ISO 13408-4:2011 Aseptic processing of health care products - Part 4: Clean-in-place technologies (Equivalent to ISO 13408-4:2005).
ISO 13408-4 specifies the general requirements for clean-in-place (CIP) processes applied to product contact surfaces of equipment used in the manufacture of sterile health care products by aseptic processing and offers guidance on qualification, validation, operation and control. It is applicable to processes where cleaning agents are delivered to the internal surfaces of equipment designed to be compatible with CIP, which may come in contact with the product. It is not applicable to processes where equipment is dismantled and cleaned in a washer.
- EN ISO 13408-5:2011 Aseptic processing of health care products - Part 5: Sterilization in place (Equivalent to ISO 13408-5:2006).
ISO 13408-5 specifies the general requirements for sterilization in place (SIP) applied to product contact surfaces of the equipment used in the manufacture of sterile health care products by aseptic processing and offers guidance on qualification, validation, operation and control. It applies to processes where sterilizing agents are delivered to the internal surfaces of equipment that can come in contact with the product.
- EN ISO 13408-6:2011 Aseptic processing of health care products - Part 6: Isolator systems (Equivalent to ISO 13408-6:2005).
ISO 13408-6 specifies the requirements for isolator systems used for aseptic processing and offers guidance on qualification, bio-decontamination, validation, operation and control of isolator systems used for aseptic processing of health care products. It is focused on the use of isolator systems to maintain aseptic conditions; this may include applications for hazardous materials.
A more detailed review of those parts of the EN ISO 13408 standards that are of most interest to medical device manufacturers and the areas where requirements are more detailed is available from SGS. Please email a request if this will be useful to you.