Identification

 

„At all times during processing, all materials, bulk containers, major items of equipment and where appropriate rooms used should be labelled or otherwise identified [...]." (5.12 EU GMP Guideline). This can be achieved through the use of labels or other identification. The declaration of materials, containers and rooms is an essential basic principle for the prevention of cross-contamination, misidentification and cross-mixing (see chapter 11.J Prevention of cross-contamination). The labelling must be carried out in such a way that it can be easily identified by the observer, i.e. labels should not be below specific minimum sizes. It is recommended that a uniform layout is used throughout the company. Colours and symbols may be used to achieve a signalling effect - e.g. to provide warnings about entering rooms where sensitive products are manufactured and specific aspects of pharmacology and work safety apply.

"Labels applied to containers, equipment or premises should be clear, unambiguous and in the company's agreed format. [...]". (5.13 EU GMP Guideline). This requirement has implications for the legibility of writing (sufficient size and legible) and the appropriate use of material designations (for complex designations, e.g. when using chemical nomenclatures, abbreviations or number codes).

Labels are often used for identification. It is also possible to use preprinted cards that can be slotted into mounts on the equipment. It would be unacceptable simply to place a batch record or the associated manufacturing instructions on a container.

The labelling must be durable, i.e. sufficient adhesion of the glue on the label on the relevant container or vessel materials must be ensured. Temperature influences must be taken into account depending on the storage area used. At higher temperatures, softening effects have been observed whereas at lower temperatures, solidification and loss of adhesion were noted. These factors must be taken into account when selecting label types. It must also be possible to remove labels without leaving a residue, e.g. if they are to be used in the batch documentation. Also, for cleaning purposes it is important that labels can be completely removed. It may occasionally be beneficial to affix foil to containers beforehand to which labels are subsequently applied. Labels may therefore be easily removed and included in the batch documentation without causing problems. The foil can then be removed during the cleaning process. It is recommended that specific areas be designated as labelling areas for containers, vessels and equipment to make handling more efficient and to minimise the danger of double labelling.

The scope of the labelling depends on the extent of data monitoring or control. The more extensively organised the recording and control of operating data is, the less effort will be required when creating the labels.

11.H.1 Starting materials

Companies normally apply their own form of identification to incoming starting materials, usually in the form of self-adhesive labels affixed to each container. The application of the labels must be durable, i.e. they must be securely affixed. For deliveries of raw materials consisting of a large number of containers, it is difficult to label individual containers separately. The practise of providing the calculated number of labels loose with the pallet for the labelling of individual containers as required is not acceptable.

"[...] When fully computerised storage systems are used, all the above information need not necessarily be in a legible form on the label." (5.29 EU GMP Guideline). Ideally, the expiration date should be included on readable labels, but as the running time is normally only assigned during the approval process this is often not possible. In such cases, the container is labelled anew following approval. If physical approval is carried out by applying status labels (rejected, quarantine, released), it is certainly practicable to declare the expiration date. Status control via a warehouse management system also makes monitoring of running times possible even with a random location storage system - as with the random distribution and subsequent booking of pallet bays.

When starting materials are delivered, order requirements or confirmations are normally compared with the information provided with the goods delivered. Data already stored in the warehouse management system is the master data to be completed and printed on labels. Figure 11.H-1 shows an example for the labelling of starting materials. This information is to be attached if visual checks are to be subsequently carried out.

11.H.2 Labelling in the manufacturing process

Equipment, containers

As a matter of principle, all equipment, containers etc. used must be labelled. While this requirement may seem trivial, it needs precise knowledge to be obtained about the practical implementation of manufacturing processes. It must be possible clearly to identify items, products, partial quantities etc. promptly. It is unacceptable to attach labels following completion of a production step (e.g. to a container once it has been filled). It must be clear to all staff involved that where interruptions take place and these are insufficiently labelled, this could lead to incorrect identification at a later stage. The significance of personnel training in this area must therefore be emphasised. Inconsistent handling in this regard poses a serious risk of misidentification. The labelling of an item of equipment that comes into contact with a product must not be completely removed once the end of the relevant manufacturing step has been reached. It must be ensured that information on the product manufactured is available during cleaning as this may not be carried out by the same staff or at the same location. Otherwise it is hardly feasible to describe this as product-specific cleaning from the point of view of cleaning validation. During cleaning, the labels or identification plates must be removed and information attached to the equipment stating that it has been purified.

Labels can be completed by hand or printed out. In either case they must be authenticated by a date and signature. To improve legibility, the printed option should ideally be chosen. Labels may be printed either directly or in advance. Labels are printed directly either by entering data manually at an input device or by scanning the relevant containers and equipment/machines with a data recording system. As is the case with written entries, manual entries for printing purposes must be carefully checked to ensure conformity. Basic mistakes such as inputting numbers in the reverse order must be avoided.

Labels may be printed in advance in tandem with the compilation of documents (as an integral part of the batch documentation) and then affixed by personnel at the relevant production level. In so doing, it should be ensured that any potential confusion is eliminated. In addition to signing the labels when they are attached, the number of labels produced should be known and the number used documented in the batch record for reconciliation purposes.

"Defective equipment should, if possible, be removed from production and quality control areas, or at least be clearly labelled as defective." (3.44 EU GMP Guideline). Labelling must be carried out in every case to provide a clear visual indication of the equipment's status (see figure 11.H-3). It must be ensured that this is not used due to lack of knowledge for production processes. This labelling must be durable for equipment that cannot be taken away to be repaired due to the way it has been installed or its size. Where such equipment is removed from the production area, its use in the period prior to and during transportation must be prevented.

Cleaning status

The labelling of the cleaning status is an important prerequisite for the use of production equipment and containers. Only cleaned equipment may be used. It must be possible through status declaration to differentiate between cleaned equipment and not yet cleaned equipment (see figure 11.H-4)

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It is not acceptable simply to assign separate rooms (clean/contaminated), e.g. to deposit a used container in a room labelled contaminated. The labelling should show the material and batch designation of the previous product - this ensures that the product history can be traced or compiled. Comprehensive data recording (during the acquisition of operating data) that serves the purposes of a process control system allows information on previous products to be omitted from labels on the containers and equipment itself. When qualifying the system, it should be ensured that all equipment and containers can be correctly recorded. For example, this may be achieved by attaching bar codes. If these are simply glued to the equipment, i.e. there is a possibility that it could go missing or be replaced, a control number should be added as a minimum requirement in addition to the bar code itself as a counter check option when identifying the object manually (e.g. inventory number).

Where the previous batch is to be documented on the label, the following procedure may be applied by way of example (see figure 11.H-5).

Cleaning label no. 1 is on the equipment before the new production process starts. This contains the necessary data for identification of the previous batch. As the facility was cleaned before the new start, this is documented on the label. A visual status check is carried out directly before the facility is reused (condition of the equipment still visually clean, expiry date for purity status not passed). The label is removed and affixed at a defined position in the batch record. The check is documented. A new label (no. 2) is completed using the data provided in the instruction and attached to the equipment. Once manufacturing is complete, the cleaning is documented on label no. 2. This guarantees the possibility of product-specific cleaning as information on the contamination is available and also that for the next product the cleaning of the equipment is testified in the batch record.

11.H.3 Labelling of rooms

Rooms should be labelled in such a way that their status can be easily identified. It should therefore be clear from outside the room what is being manufactured at any given point in time or what the cleaning status is. This can be achieved using room cleaning reports, for example (see chapter 11.C.2 Cleaning). In this case, the product data and cleaning statuses are declared.