Reagents

 

Reagents or laboratory reagents are an integral part of quality control for assessing the quality of APIs and finished products. For this reason, they are generally subject to the same requirements as standards and reference substances, in terms of preparation and documentation. (see chapter 14.C Standards and reference substances)

The EU GMP Guideline (6.19) explicitly requests that particular attention be paid to quality and that preparation must be carried out in accordance with written procedures. In principle, it is irrelevant if the reagents concerned are intended for qualitative or quantitative analyses.

Depending on the field of use, the list of a selection of different reagents may be as shown in figure 14.B-1. The list makes no claim to completeness, and the corresponding reagents are to be used accordingly for further tests.

11 Labelling

Laboratory reagents must be labelled with the date of receipt and date of opening (if purchased) or the date of manufacture (if manufactured in-house). Unlike for standards and reference substances, for reagents the EU GMP Guideline (6.21) recommends an identity test (in certain cases) or a different test after receipt or before use. Experience has shown that a corresponding test is usually indispensable during the examination on receipt of the reagents (factor assignment).

Reagents can be labelled with a code instead of a name. This must be unique and must not lead to confusion, either with other batches of the same reagents or with other reagents.

The EU GMP Guideline (6.20) can be consulted as a minimum requirement for the labelling of reagents (on the label). It stipulates that the information listed in figure 14.B-2 must be present.

12 Usage and stability

In principle, reagents are for the intended use only. If they cannot be purchased, their preparation must be described in as much detail as the instructions for test procedures.

For all reagents used, a reasonable expiration dating period (stability) must be established. This should be based on historical operating data and written in an SOP. The expiration dating periods must be adapted to newly acquired findings, and the maximum permissible period is 5 years. Here, companies have a lot of freedom in stipulating (the deadlines), but not in selecting the reagents. The principle of documenting the stipulation in such a way that it can be understood by a competent professional applies here too. This means that the stipulation must not only be documented, but also scientifically substantiated.

For some reagents and groups of reagents, possible expiration dating periods are listed in figure 14.B-3. If reagents are purchased, the manufacturer's specifications should be used. However, caution is required if, for example, bottled buffer solutions for setting the pH meter are provided with an expiration dating period, but there are no specifications on how long the buffer solution can be used for after the bottle is opened. As experience shows, the user himself is required to set deadlines here. An elegant solution to this problem is the use of pH portion sachets which are all individually provided with a use-by date and are ideal for one-time usage. These are available in the optimal quality for pH meters by different manufacturers. This variant is also cost-effective, as open, half-empty bottles of usual pH solutions do not have to be discarded once the expiration dating period has been exceeded.

It is important to specify the storage conditions (protection from light, refrigerator). It is well known that reagents often have a different expiration dating period to their solutions. If, for example, the resolution check as part of the SST in HPLC determinations is done with a mixture of substances (API and degradation products), then a suitable quantity of this substance mixture can be prepared once as an "SST solution" and used again at a later time. This requires the availability of the stability and storage condition tests/data (e.g. 6 months in a refrigerator protected from light).

13 Documentation

On the one hand, the documentation contains the receipt or preparation of the reagents, and on the other hand, it also contains their usage in quality control testing.

The preparation must be described accurately, preferably in the same format as the company uses for test instructions. The quality of chemicals to be used should also be stipulated. Each preparation process must be documented in such a way that at any time during use of the reagents it is possible to tell the date, manufacturer and chemicals used. In practice, the use of reagent log books has proven very useful. (See figure 14.B-4). In these log books, the preparation of reagents can be documented on templates.

When using reagents, the code, manufacturer's name and date of manufacture are used in the documentation during quality control testing. This ensures traceability. This data is completed with the expiration dating period. (see figure 14.B-5)

The stipulation of the expiration dating period must be documented. If any form of stability testing was carried out to this end, the results must be recorded. If there are new findings from the use of the reagents, the expiration dating period must be corrected accordingly.