11.

H Labelling
Up24 Dr. Christian Gausepohl

Here you will find answers to the following questions:

● What general requirements apply to labelling?

● What needs to be observed when handling labels?
● What features must be considered when labelling starting materials?
● How are containers, equipment and rooms labelled?
● How is the cleaning status of machinery documented in batch records?
● What information has to be included when labelling products?

11.H.1 General requirements

Labelling is used to assign information to an object. A visual mode of communication is generally used to do this, e. g. a
label or sign. The information on the label must be accessible to the addressee to ensure that they can, for example ,
identify the object or check its suitability.

Figure 11.H-1 Labelling: Objects

What needs to be labelled?

● rooms and areas according to function and hygiene zone

● machines, facilities, devices, tools
● materials
● products

The requirements for labelling in the production areas apply to

● materials (see Chapter 11.H.3 Labelling of starting materials),

● devices (see Chapter 11.H.4 Labelling machines, devices and containers),
● containers (see Chapter 11.H.4 Labelling machines, devices and containers),
● rooms (see Chapter 11.H.5 Labelling of rooms),
● products (see Chapter 11.H.6 Labelling of products).

The specific requirements are outlined directly in the GMP Guidelines or stem from other related guidelines. The
general requirements for labelling are summarised in Figure 11.H-2. They are explained briefly below.

Figure 11.H-2 Labelling: General requirements

General requirements for labelling

● required for the entire processing time

● identification of the material name or code, product name or code, batch number, strength, stage of manufacture and
cleaning status
● clarity and unambiguity
● use of signal colours to improve visualisation
● internal specification of the labelling types (SOP)

The type of labelling used depends on the objects to be labelled and the processes concerned. In the case of
manufacturing processes, for example, the cleaning status of rooms or the calibration status of equipment must be
identified. The design of the identification type used (e. g. labels) must prevent errors that can occur when reading or
filling in the label (error prevention). The suitability of the design should be regularly evaluated, e.g. by examining the
batch record review or self-inspection findings. Labels that can be read by electronic devices, e. g. bar code labels, are
also becoming more and more important in pharmaceutical companies. This prevents human reading errors and
incorrect interpretation.

Labelling in manufacturing areas is subject to a number of overlapping requirements. The entire processing time for a
batch must be covered. This means that labels are required for all the processes including the receipt of the starting
material, sampling, storage, internal transport, processing, packaging and preparation for shipping. All departments in a
company must have a system for labelling materials, bulk products, equipment and rooms in place.

With a view to identification, the products or materials are assigned item numbers, codes and batch numbers. If
products or materials are available in different dosages, this must be specified. It is advisable to document the
respective stage of manufacture when labelling to prevent mix-ups and ambiguity during campaign manufacture. A
sample label for starting materials is shown in Figure 11.H-3.

Figure 11.H-3 Sample label for starting materials

The label must be clear and unambiguous and meet the general requirements for documentation (see Chapter 15.B
GMP-compliant documentation). The font should be large and plain enough to read, and the name of the material
should be indicated in a way that makes sense. In the case of complex names, e. g. chemical nomenclatures, the use of
abbreviations or numerical codes is recommended. If labels are to contain handwritten entries, they should contain
fields that make it easy to enter and check data.

It makes sense to use colours on the labels, e. g. red labels for rejected/quarantined materials or green labels for clean
machines. This type of visual aid is particularly important when a difference in status can pose a significant risk. The use
of colour only without text should be avoided to prevent misinterpretation.

The type of identification used, e. g. labels, must be described in an SOP. It should include information on the size,
content, layout and colour of the labels to ensure that only the described labels are used. At the same time, the sources
of information for the individual data fields must be specified, e. g. for batch numbers fields on container labels. This can
be the relevant batch report, for example. If coded data is to be used (e. g. bar codes), the process for creating the
code, i.e. data sources, the type of code used, and the generation and output of the code, must be defined and
validated as a computerised application (see Chapter 9.E Validation of computerised systems). The actions to be taken
in the following situations must be defined and described in advance:
● labels are lost or damaged
● machines or rooms are not labelled
● labels are illegible (e. g. after cleaning using water)

Figure 11.H-4 contains aspects that must be considered when designing and controlling labels.

Figure 11.H-4 Labelling: Relationship between design and control

11.H.2 Handling labels
Labels are frequently used for identification purposes. Two things are important when selecting and using labels:

● the labelling period (permanent or temporary) and

● removability (destructive or non-destructive)

Permanent labelling, for example, is required for the containers of starting materials, while manufacturing equipment
normally only requires temporary labelling for the duration of its use during manufacture of the respective batch.

The removability of the label is determined by whether the information will be required at a later date, e. g. as part of the
batch record (non-destructive removability), or whether the labels are used as an authenticity feature (destructive
removability), e. g. on product containers.

Adhesive labels
The right adhesive must be chosen to ensure that the labels stick properly to the respective container or packaging
materials. Depending on the storage location, temperature can have an impact. Higher temperatures can have a
softening effect and lower temperatures a crystallising effect which leads to a loss of flexibility and adhesive strength.
Alternatively, it must be possible to remove temporary adhesive labels without leaving any residues, e. g. when they
have to be stuck into the batch documentation. Labels must also be completely removed during cleaning. A suitable
attachment process must be chosen that also allows residue-free removal. It can also make sense to stick foil to
containers and then stick the label to the foil. In this way, the label can simply be removed "in one go" and then stuck
into the batch document. The foil is removed during the cleaning process.

Slot-in labels
If temporary identification is required, preprinted cards can be used that slot into holders which are fitted to the
equipment. It would be unacceptable to simply place a document such as a batch record on a container without
attaching it to the container because the risk of error through incorrect identification is too high.

Where should the label be located?

Specific areas on containers, packaging and equipment should be designated as labelling areas to make handling more
efficient and minimise the danger of double labelling.

What must be observed when preparing the labels?

Labels can be filled in manually or printed out. For reasons of legibility, the printed version is preferable. Labels can
be printed when required or in advance. Printing can be carried out directly by entering the data manually using an input
device or by scanning the respective containers and systems or machinery using a data collection system.

Compliancewith the requirements must always be checked, regardless of whether the data is entered manually or
handwritten. Simple mistakes such as mixing up two digits can have serious consequences and must be avoided at all
costs. The compliance check can be documented by the person carrying out the check by signing and dating the label.
The significance of this signature should be emphasised in the respective SOP or in the manufacturing instructions.
Labels that are created manually should be checked for accuracy by two different members of staff (four-eyes principle).

Labels can be printed in advance (e. g. during the creation of the batch documentation) and attached by the members of
staff that carry out the respective manufacturing step. It is important to ensure that mix-ups do not occur. The labels
must be signed when they are attached. Information about the number of labels supplied must be available and the
number of labels used must be documented in the batch record to facilitate a reconciliation. The destruction of labels
must also be documented.

The scope of labelling depends on the degree of data monitoring and/or control. If the production data acquisition and
process control are very well organised, less effort is required when creating labels because the data is already
available.

The most important aspects of handling labels are summarised in Figure 11.H-5.

Figure 11.H-5 Important aspects of handling labels

At a glance: the most important aspects of handling labels

● attachment period (permanent or temporary)

● attachment method (adhesion or slot-in)
● labelling area
● removability (destructive or non-destructive)
● time of creation (as required or in advance)
● reconciliation

11.H.3 Labelling of starting materials

Starting materials are generally labelled on delivery using in-house labels. Self-adhesive labels are normally used that
are attached to each container. The labels must be permanent, i.e. firmly stuck. It is difficult to label a large number of
individual containers in a shipment of raw materials when it arrives. It can be quite helpful if labels for the containers on
a pallet are attached directly to the individual pallet, e. g. using self-adhesive pockets. Placing loose labels on the pallet
does not comply with GMP requirements. If individual containers are removed from the pallet, they must be labelled
immediately. The individual unit (pallet or container) must always be properly labelled. The process must be clearly
described.

The labelling used by the supplier of the containers should be discussed in advance. For example, it can greatly benefit
the internal incoming-goods process if the container label of the supplier includes the item number or order number of
the recipient. In addition to a controlled exchange of information with regard to the tamper-evident seals used, the layout
and content of the container labels should be agreed. This supports the measures used to prevent counterfeiting. The
content of the labels is checked during the incoming-goods process and their layout is also compared with the agreed
version.

How the labels of the supplier are dealt with after the in-house labels are attached must be specified. On the one hand,
they can be invalidated, e. g. by crossing out. On the other hand, it can make sense to leave them unchanged on the
containers in the interests of ensuring complete traceability. In this way, supplier-specific information is retained, e. g.
supplier container numbers or manual changes. This can, for example, be beneficial if a complaint has to be filed about
a starting material or anomalies occur during the subsequent manufacturing process. However, this approach takes it
for granted that the staff involved in processing (e. g. storage and weighing) will only read the in-house labels. This must
be included in an SOP and the staff members must be trained accordingly. Noticeable and standardised in-house labels
(e. g. with a large, colour company logo) are helpful to ensure that the process is adhered to.

The in-house labels must contain the minimum information described in Figure 11.H-6. If a completely computerised
storage system is in place, it is not necessary to have the content in legible plain text on the label. Bar codes or other
codes can then be used.

Figure 11.H-6 Labelling of starting materials in accordance with the EU GMP

Guidelines

Minimum requirement for the labelling of starting materials

● material name, item number or code (5.32 i)

● batch number (5.32 ii)
● documentation of sampling (6.11 vi)
● status, if appropriate (approved, quarantined, rejected) (5.32 iii)
● expiry date, if appropriate, testing date (5.32.iv)

It would be desirable to include the expiry date on legible labels, however, it is generally not possible because the shelf
life is normally assigned during the release. As a result, the containers must be relabelled after the release. If a release
is carried out by attaching status labels (rejected, quarantined, released), the expiry date can be added at the same
time.

Using a storage management system to control the status also facilitates the control of expiry dates in chaotic (dynamic)
warehousing situations, i.e. the random or space-saving distribution of pallet places with subsequent booking
(see Chapter 24.D Incoming goods). During status control, the assignment of expiry dates (e. g. retest dates) can also
be carried out so that this type of container labelling is no longer required.

When an order of starting materials is received, the order requirements or order confirmations are compared with the
documentation on the delivered goods. The data that is already stored in the storage management system forms the
data set that is subsequently printed onto the labels. The actual identification realised by attaching the labels happens
during the incoming goods process and should be checked for accuracy by a second person (see Chapter 24.D
Incoming goods).

Figure 11.H-7 shows the information normally used for the in-house labelling of starting materials. Together with the
aspects contained in Figure 11.H-6, the possibility of assigning a sample to the corresponding container at a later stage
is important. If the storage conditions are included, the need for special storage conditions can be quickly identified, e. g.
cold storage. Safety instructions, filling quantities and the container number with regard to the total number of containers
in the batch is also important and should be included in plain text or as a machine-readable code.

Figure 11.H-7 Standard content of the in-house labelling of starting

materials

Content of the in-house labelling of starting materials

● material name, item number or code

● in-house batch number/supplier batch number
● manufacturer or supplier
● assigned sampling/sample number
● status, if appropriate (rejected, quarantined, released)
● storage conditions (e. g. cold storage)
● safety information
● filling quantity
● container number (x of y)

An example of a label for starting materials is shown in Figure 11.H-8.

Figure 11.H-8 Sample label for starting materials

Rejected or quarantined materials must be clearly labelled and stored separately. The responsibility for labelling must
be clearly specified in an SOP. This generally involves printing the labels indicating the critical status and attaching
them to the containers. Quality Control and storage personnel are normally involved.

11.H.4 Labelling machines, devices and containers

11.H.4.1 General

In principle, all machines, devices, containers, etc. in use must be labelled. Codes or inventory numbers must be used
to ensure unique identifiability. Depending on the type of operational data system, bar codes can also be used on the
machines. A material check that is carried out, for example, can then be documented by scanning the code on the
machine. If a machine or piece of equipment is made up of a number of different parts that can be disassembled, all of
the parts should be labelled. It must be ensured that the lids of containers, for example, are assigned to their respective
containers so that it is possible to retrace in which machines products are manufactured.

These requirements also apply to hosing, filters, etc. Their identity must be clearly indicated, in particular when flexible
hosing or pipe connections are used. This can be done, for example, by using clearly assigned colours as a supporting
feature. The flow direction must also be clearly indicated. For pieces of equipment that are dedicated or single-use only,
suitable labelling is required so the difference is clearly visible.

These labels must be attached permanently and may not be removed during cleaning. This ensures that nothing is
interchanged or mixed up. The batch-specific information is recorded in the manufacturing documents to ensure
traceability of the machines and individual pieces of equipment used. Depending on the degree of automation, this can
also be carried out in an MES system (see Chapter 4.D.4 Process control systems).

Why must labelling be carried out during the process?

It must be possible to clearly identify objects, products, partial quantities, etc. in the manufacturing process at any time.
Placing a label on a container after a manufacturing step is complete (e. g. filling) is unacceptable. It has to be clear to
the operators that every single interruption during the process can lead to incorrect identification if proper labelling is not
in place throughout the process. An inconsistent approach represents a major risk of mix-ups. For this reason, the
importance of immediate labelling during the process should be reinforced time and time again during staff training. The
actual practice of labelling should be checked regularly, e. g. on a day-to-day basis and during self-inspections.

The labelling of a piece of equipment that has been in contact with the product may not be completely removed at the
end of the manufacturing step. It must be ensured during the cleaning process, which is not necessarily carried out by
the same employee or at the same location, that information about the manufactured product is available. This is a
requirement for product-specific cleaning in accordance with the cleaning validation. During cleaning, the labels or
identification signs must be removed and replaced by a label indicating that the device has been cleaned.

The most important requirements for the labelling of devices are summarised in Figure 11.H-9.

Figure 11.H-9 Requirements for the labelling of devices

Requirements for the labelling of devices

● clear identification of the machine and machine parts with a view to preventing errors
● name of material/product (including batch and compound number)
● status information, e. g. manufacturing stage, cleaning status
● permanent
● plain text or machine-readable
● identification of dedicated and single-use parts
● traceability of all parts
● training about the importance of the time of labelling
● regular checks of labelling in practice

Figure 11.H-10 shows an example of the labelling of a machine during the manufacturing process.

Figure 11.H-10 Example of the labelling of a machine during the manufacturing

process

11.H.4.2 Calibration and maintenance

To ensure that only calibrated machinery is used, appropriate labels should be attached to the machines and systems. It
is recommended that labels are attached to the machinery at locations that are clearly visible and, if required, at more
than one calibration location. The use of labels makes it obvious to the operator of a machine whether the calibration is
still valid or whether the calibration date has been exceeded (see Chapter 4.F Calibration).

A similar procedure can also be put in place for maintenance intervals (see Chapter 4.G Maintenance). It makes sense
to use a single universal type of label for indicating the calibration and maintenance status throughout the company
rather than using area-specific labels. This makes it easier to identify the labels.

11.H.4.3 Quarantine

Defective equipment should be removed, whenever possible. If this is not possible, e. g. because the equipment is due
to be repaired, the affected equipment must be clearly labelled to prevent its use. Labels should be colour-coded and
use warning colours (e. g. red) to achieve a better visual impact. This ensures that the equipment will not be used for
production processes due to lack of knowledge. When the equipment is to be removed from the manufacturing area, its
use before or during transport must be ruled out. In the case of equipment that cannot be moved because of the way it
is installed or because of its size, the label must be permanent (example: see Figure 11.H-11).

The location that is selected for attaching the label must be chosen so that it cannot be inadvertently overlooked, e. g. at
the specified location for standard ID labels. It must be clearly specified who is responsible for preparing and attaching
this type of quarantine label. This also applies to the reverse process, the removal of equipment from quarantine when it
has been successfully repaired. It is also advisable to put the quarantine label into the maintenance report when the
work is complete as proof that the requirements were met. This is particularly true for critical processing equipment such
as sterilisers, for example.

Figure 11.H-11 Sample label for quarantining a machine

11.H.4.4 Cleaning

Using labels to indicate the cleaning status of machines, equipment and containers is an important aspect of their use:
only clean devices may be used. The status must be indicated so that it is possible to differentiate between clean
devices and those that are yet to be cleaned. It is not acceptable to separate equipment only by physical measures, e.
g. placing used containers in a room designated as unclean.

The cleaning status has a maximum validity (e. g. n days). This information must be added when labelling takes place,
e. g. by including an expiry date on the cleaning label. Purely manual or complex computerised systems (e. g. MES,
see Chapter 4.D.4 Process control systems) can be used depending on the type of production data acquisition. For
example, the cleaning status (clean/unclean) and the expiry date of a container can be checked by the weighing system
during the weighing of the containers. In order to be able to track the history of a product, the name of the material and
the batch number of the previous product must be documented. In manual systems, this information can be added to
the cleaning label. It is recorded in the system during the acquisition of production data. During the qualification of the
system, it must be ensured that all of the equipment and containers are recorded correctly. This can be done by
attaching bar codes to the machines. If these are simply stuck on, there is the possibility of them being lost or mixed up.
A permanent control number should therefore be placed beside the bar code for manual identification of the object (e. g.
the inventory number) which facilitates a counter-control.

These requirements also apply to disinfection and sterilisation. Differentiation between sterile and non-sterile machine
components is very important. Figure 11.H-12 shows a sample cleaning status label. The most important aspects that
apply to the identification of the cleaning status are summarised in Figure 11.H-13.

Figure 11.H-12 Sample cleaning label and cleaning status label

Figure 11.H-13 Aspects of cleaning status identification

Identification of the cleaning status

● Objectives: status control and traceability

● computerised monitoring, e. g. using MES
● manual documentation of the cleaning process
● systematic or manual documentation of the "cleaned" status validity period
● documentation of the visual control and the validity period of the cleaning status
● documentation of the product manufactured before cleaning
● archiving with the batch documentation of the next product

In the case of a purely manual identification using a label, the following process can be used:

● Cleaning label number 1 is on the device before starting the manufacture of a new product. It contains the necessary
data for identifying the previous batch. The machine was cleaned before the new start and this is also documented on
the label.
● A visual control of status is carried out immediately before the machine is used again (status of device is still visually
clean, specified validity period of the cleaning status has not yet been exceeded).
● The label is removed and stuck into the intended place in the batch record of the next product. The control is
documented on the label.
● A new label (number 2) is filled out using the data in the instructions and attached to the device.
● When manufacture has been completed, the cleaning process carried out is documented on label number 2.

This approach facilitates a product-specific cleaning process because information about the contamination is available.
The actual cleaning of the device is recorded in the batch record of the following product, which ensures
traceability. Figure 11.H-14 shows the described labelling sequence of the cleaning status.

Figure 11.H-14 Sample labelling sequence of the cleaning status

11.H.5 Labelling of rooms
Rooms should be labelled in such a way that their status is immediately recognisable. This means that the following
must be obvious from outside the room:

● the function of the room,

● the product currently being manufactured and
● the room's current status.

This applies, for example, to the labelling of separate areas when the status of rooms is being managed manually in the
storage area. These separate areas can be quarantine areas or areas for recalled or rejected materials (see Chapter
24.B Storage areas).

When production rooms are labelled, the current status of the manufacturing process must be indicated in addition to
the product and batch designations. Coloured room signs can be used for this purpose (example: see Figure 11.H-15).

Figure 11.H-15 Examples of different room

labels
To ensure health and safety in the workplace, room signs can also indicate possible risks or health and safety measures
that must be observed. It is important that a uniform system of signs/labels is used in all areas of the company. Their
proper use must be explained during training and regularly reviewed.

If the product-specific data is included in the cleaning protocols for the rooms and clearly visible, additional signs or
labels indicating the product or batch designation are not required (see Chapter 11.D.2 Documentation).

It is also important to assign functions within the rooms. Floor or wall markings can be used to indicate specific
functional areas. These can include :

● storage spaces for materials

● storage spaces for equipment
● waiting zones before the transfer of materials
● storage areas for auxiliary devices, e. g. suction hoses
● changing zones in locks

The aim is to standardise manufacturing processes, material transport, cleaning, etc. using consistent description and
identification to prevent potential errors and risks. The identification of hygiene zones also helps prevent errors.
Personnel should receive appropriate training, and compliance with the processes should be controlled on a regular
basis.

11.H.6 Labelling of products

Products and intermediates must be labelled clearly and sufficiently. The required information should be provided in the
processing instructions. When using automated system-specific label printers, e. g. when weighing bulk products, the
requirements can be saved in the software. There are normally interfaces to a primary system (e. g. MES or ERP
software) from which order-related data is taken. The handling of this data (entry, verification, transfer) is part of the
system validation.

For reasons of verification and traceability, a sample label should be archived in the batch report. This applies, in
particular, to packaged products. The batch labelling samples containing the expiry date and any other additional
printed information must be archived together with the batch records (EU GMP Guidelines Part I, Chapter 4.21 f).

Labelling that uses variable data is checked for accuracy, completeness, durability and legibility during the packaging
process using manual or automatic testing systems (see Chapter 13.B.6 Labelling).

The respective national regulations must be observed when labelling finished medicinal products. Figure 11.H-16 lists
the requirements for labelling according to the German Medicinal Products Act as an example.

Figure 11.H-16 General requirements for the labelling or finished medicinal products in accordance with Section 10 of
the Medicinal Products Act (AMG)
Requirements for labelling in accordance with Section 10 of the German Medicinal -Products Act (AMG)

How should labelling be carried out?

● in writing that is easily read
● in language that is comprehensible
● it must be permanent
● it must comply with the available expert information.

What information is mandatory?

● the name or company and the address of the pharmaceutical entrepreneur
● the name of the medicinal product (including strength, pharmaceutical form)
● the marketing authorisation number
● the batch identification or date of manufacture
● the pharmaceutical form
● the content by weight, volume or number of units
● the method of administration
● the active substances by type and quantity
● other constituents by type, in so far as this is imposed
● the expiry date (to be used by)
● "prescription only" or "pharmacy only"
● "Keep out of the reach and sight of children"

What information may be required in addition?

● where necessary: "For babies, children and adults"
● when manufactured using genetic engineering: active substances, name of genetically modified microorganism or
cell line
● "sample – not for sale"
● precautions, if necessary
● the intended use in the case of non-prescription medicinal products

11.H Summary
Proper labelling is a basic GMP requirement because it provides unambiguous identification. It can help prevent mix-
ups. The labelling of starting materials, intermediates, finished products, equipment and rooms is mandatory.
Production rooms and machinery must be labelled with the name of the product and the batch number. The cleaning
status must also be clearly indicated.
Labelling should be precise and unambiguous as well as properly attached. Electronic systems for production data
acquisition facilitate the creation of accurate and comprehensive data and help reconcile the labels.