7.3 Component processing
Component Production areas should satisfy the requirements defined in the current Rules and Guidance for Pharmaceutical Manufacturers and Distributors, 2002.(1) In addition:
the ambient temperature of blood component processing areas should be maintained within a range that would not be expected to adversely affect component viability/shelf life
where appropriate, steps should be taken to ensure that air quality in the blood component processing environment does not increase the bioburden to which blood components are exposed.
The starting material
The starting material for component preparation is whole blood or the products of apheresis collected from donors who satisfy current donor selection criteria. Components must be collected into blood packs/apheresis harness assemblies that are CE-marked.
Before use, packs/apheresis harness assemblies that have not previously been validated, or contain component parts that have not previously been validated should be subject to validation or process qualification as appropriate according to the protocols set out in Chapter 9.
Starting material for component preparation should be transported as described in Section 7.10.
Prevention of microbial contamination
Infections associated with the microbial contamination of blood and blood components still occur. Whilst there is no evidence to suggest that routine, retrospective sterility testing of blood components diminishes or eliminates such instances of infection, the following measures will minimize the risks:
creating and maintaining the highest level of awareness among all personnel of the constant care and attention to detail needed to minimize microbial contamination e.g. validation and periodic monitoring of the effectiveness of venepuncture site preparation
using validated procedures designed to minimize microbial contamination of the environment and prevent microbial contamination of components
diverting the first part of the donation into a sample pouch, to avoid entry into the primary donation. This may be used for mandatory screening tests
monitoring the microbial load in equipment and in the environment of component preparation areas.
It is important that data derived from such monitoring exercises are accumulated and regularly examined with a view to taking appropriate action.
Screening of platelet components for bacterial contamination is being evaluated or implemented by some blood establishments to address concerns over bacterial contamination.
The term 'closed system' refers to a system in which the blood pack assembly is manufactured under clean conditions, sealed to the external environment and sterilised by an approved method.
With the exception of the venepuncture procedure and strict requirements for open processing (see Section 7.3), the blood pack system and its contents must not be vented to the external environment at any stage during blood collection or processing.
Blood pack and apheresis harness fluid pathways must at all times be protected from the external environment by
hermetic seal(s) incorporated during manufacture or Blood Service use
other validated devices for effecting a permanent seal
break seal closure(s)*
port(s) incorporating a tamper proof closure and pierceable membrane*
* These devices must comply with the requirements of relevant standards for medical devices, including ISO 3826 Parts 1 and 3, must be validated by the manufacturer and provided with clear instructions for use.
Before severing any sub-component of the pack assembly, the pack contents must first be protected from the external environment by a minimum of one permanent seal made using a validated hermetic sealer cleaned and maintained according to SOP.
Temporary sealing clamps/clips must be used only to control the flow of fluid within a closed system. They must not be used as the sole means of protection from the external environment.
When a device for making a sterile connection is used the system can be regarded as closed providing that the process of joining and sealing has been validated and shown not to lead to an increased risk of microbial contamination of the component. The procedure for use should ensure that the operator carefully checks the suitability of every weld and also pays particular attention to effective cleaning of the working parts of the equipment.
Cleaning should be by validated procedure with regular checks to ensure conformance to procedures.
Pressure or tensile testing the strength of welds should be performed during the validation or Process Qualification of equipment. Guidance on methods for this are available from the chair of SAC on Blood Components Technical Sub-Committee.
Where a sterile connecting device has been used to add satellite packs, the components must not be issued with the weld in place.
Pre-donation sampling must only be carried out using blood pack assemblies that incorporate a device to prevent the return of blood and or air from the sample pouch towards the donor and donation. The procedure must be validated by the Blood establishment and documented in blood collection SOP.
After filling, the sample pouch must be permanently sealed from the donation before collecting blood samples.
In the event of inadvertent contamination of the donation by blood or air from the sample pouch, the donation must be discarded.
The term 'open system' refers to a system in which the integrity of the closed system must be breached but where every effort is made to prevent microbial contamination by operating in a clean environment, using sterilised materials and aseptic handling techniques. In such circumstances, positive pressure should be exerted on the original container and maintained until the container is sealed. Open system processing should be undertaken in a designated clean environment as defined in the current Rules and Guidance for Pharmaceutical Manufacturers and Distributors 2002.(1)
The sterility of components prepared in an open system should be monitored using validated methods.
Blood components prepared by an open system should be used as soon as possible. If storage is unavoidable, components with a recommended storage temperature of 22°C±2°C should be used within six hours. Components with a recommended storage temperature of 4°C±2°C should be used within 24 hours.
Components are rendered unsuitable for clinical use when breached and the requirements defined for an open system have not been observed, unless issued under medical concession.
Any new development in component preparation by an open procedure must be validated to ensure the maintenance of sterility before the procedure can be used to produce components for therapeutic use.
Procedures for collecting samples for sterility testing must not adversely affect the sterility of components intended for subsequent transfusion.