Update notice: text HIGHLIGHTED has changed following the issue of Change Notification 23 - 2009
A monospecific blood grouping reagent is one containing an antibody or blend of antibodies specific for one antigen, e.g. anti-A, anti-IgG.
A polyspecific blood grouping reagent is one containing a blend of antibodies specific for more than one antigen.
Polyspecific anti-human globulin reagent should be the name for a reagent which contains anti-human IgG and anti-human complement (C3d) activity, and is recommended by the manufacturer for use in both the direct and indirect anti-human globulin techniques, i.e. for the detection of red cell bound human IgG, and C3 complement in the form EiC3b and EC3d irrespective of the presence of other human immunoglobulin or human complement specificities.
Potency titre is a term used to describe the highest dilution of a reagent that effects a grade 2 end-point reaction.
Prozone is the term used to denote the absence or weakening of agglutination with excess of antibody.
A reagent control is a reagent made to the same formulation as a blood grouping reagent but without the specific blood group antibody reactivity. If the reagent control contains serum or plasma, the reagent control should be shown to be free from specific blood group antibody reactivity.
A reference preparation is prepared nationally or locally and contains a known or agreed concentration of the activity being measured. It should be assayed to establish the sensitivity or calibration of a test procedure or reagent.
Sensitivity in relation to these guidelines, is a term defining the limit of detectable specific reactions using reagents or test systems. These guidelines specify levels of sensitivity that should be achieved.
Shelf life is the period until expiry date.
Specificity in relation to these guidelines, is a term defining the ability of a reagent or test system to react selectively. In particular terms, it represents the absence of unwanted or false positive reactions.
Validation is the confirmation, through the provision of objective evidence that the requirements for a specific or intended use have been fulfilled. Validation of a manufacturing method is to ensure that the product will be of the quality required for its intended use and that tests used in monitoring will accurately reflect the quality of the product.
Verification is the confirmation, through the provision of objective evidence that specific requirements have been fulfilled.
Undiluted in these guidelines means the reagent as intended for use by the manufacturer. This term includes a diluted reagent if the reagent is supplied in a form requiring dilution by the user prior to use, as specified in the manufacturer's 'instructions for use'.
An unequivocal reaction in a test system is a reaction that is unambiguous. In the manual tube test, this is defined as a reaction of grade 3 or greater.
12.1.4 General manufacturing considerations
a) Good manufacturing practice
Reagents for blood group serology must be manufactured in accordance with Directive 98/79/EC of the European Parliament and of the Council of 27 October 1998 on in vitro Diagnostic Medical Devices.
Guidance on the principles of Good Manufacturing Practice can be obtained from Rules and Guidance for Pharmaceutical Manufacturers and Distributors (TSO, London).
The method of manufacture should result in a product within an immediate container that is homogeneous and free of properties which adversely affect its intended use throughout its recommended shelf life. The reagent should have no precipitate, particles or fibrin gel.
Each batch or sub-batch should be specifically identified by a distinctive combination of numbers and/or letters (batch reference) which permits its history to be traced.
Reagents should be produced by a validated process, that is one shown to be suitable for the intended purpose, including any methods for preserving red cells prior to their preparation as reagent red cells.
The manufacturer should monitor the batch-to-batch performance of the blood grouping reagent, for example, by the reaction against some internal reference material, in order to provide consistency of performance. This is particularly important when the blood grouping reagent is provided as a test system, kit or kit component, when the performance may be dependent on the characteristics of other system variables or kit components.
b) Risk management
Risk management should be performed in accordance with:
BS EN ISO 14971:2001 Medical Devices – Application of Risk Management to Medical Devices.
BS EN 13641:2002 Elimination or Reduction of Risk of Infection Related to in vitro Diagnostic Reagents.
c) Performance evaluation
Performance evaluation should be performed in accordance with:
BS EN 13612:2002 Performance Evaluation of in vitro Diagnostic Medical Devices.
Reagents listed in Annex II, List A, of the EU in vitro Diagnostic Medical Device Directive must also comply with the Common Technical Specifications for in vitro Diagnostic Medical Devices (2002/364/EC).
d) Stability data
Stability testing should be performed in accordance with:
BS EN 13640:2002 Stability Testing of in vitro Diagnostic Reagents.
e) Date of manufacture
For blood grouping reagents the date of manufacture is the date of commencement of the last potency test on the batch or sub-batch that indicates attainment of the required specification.
For reagent red cells the date of manufacture is the date of collection from the donor. Where reagent red cells are prepared from more than one donor, the date of collection of the first donation should be recorded as the date of manufacture.
Where a freezing process is used to preserve red cells before their preparation for issue as reagent red cells, the date of manufacture is the date of recovery from the frozen state.
f) Colour coding of reagents
No colouring agent should be added to reagents for blood group serology except that:
Polyspecific anti-human globulin reagents may be coloured green, anti-A may be coloured blue, anti-B may be coloured yellow.
The colourant should not interfere with the observation of the test result.
'Bespoke' antisera for use on automation may be coloured providing the information contained in the barcode on each bottle contains sufficient identifiers (specificity and lot number) to provide assurance that the intended test has been performed. The colours used for other specificities should not be coloured blue or yellow to avoid confusion with those for anti-A and anti-B reagents.