17.09.2014 |

LOGFILE No. 08/2014 - Packaging Medicinal Products

Packaging Medicinal Products

An excerpt from the GMP MANUAL

by Dr. Christian Gausepohl, Ruven Brandes

In the glossary of the EU GMP Guidelines, the term packaging is defined as follows: “All operations, including filling and labelling, which a bulk product has to undergo in order to become a finished product.
Note: Sterile filling would not normally be regarded as part of packaging, the bulk product being the filled, but not finally packaged, primary containers.”

Packaging processes are generally carried out in packaging areas that are physically separate from production, with the exception of on-line packaging. In these areas, various bulk products are packaged in primary and secondary packaging materials that are frequently different. The differences arise, for example, from the various packaging sizes or if packaged for different destination countries.

Packaging processes carry a high level of risk due to the large number of factors that can affect quality and safety. The risk factors include the complex mechanics of the machinery, the range of packaging variants and country-specific designs, the correct application of variable data and the measures required to protect against counterfeiting.

A fundamental requirement of packaging is to minimise the risk of cross-contamination, mix-up and substitutions (EU GMP Guidelines Part I, Section 5.44). This requires, in principle, measures relating to both building structure and organisation (including personnel).

This article focuses mainly on the organisational side of the packaging process and the GMP-relevant aspects of medicinal product safety. A precondition for a smooth and error-free packaging process is, however, perfect coordination of structural and organisational measures. The better the structural conditions, the easier it is to organise the entire packaging process. For example, older premises and equipment in an open-plan environment with very few automatic monitoring devices require greater differentiation in operational organisation and a greater degree of monitoring.

The basic conditions required for packaging are summarised in Figure 1.

Basic requirements for GMP-compliant packaging

Structural Measures Organisational measures
- Suitable premises - Definition of procedures (SOPs)
- Qualified equipment - Assignment of responsibilities

- Qualified air conditioning
and ventilation systems

- Training of personnel
Figure 1: Basic requirements for packaging

 

 

 

 

 

As already explained, the packaging of bulk product is part of the manufacturing process leading to a proprietary medicinal product. There are different types of packaging. Figure 2 provides a basic overview of the different types of packaging.

Overview of the different types of packaging

Dosage
form
Example Packaging Labelling
Solid Tablets,
dragees,
capsules
Blisters Using folding cartons and preprinted foil 
(brand name)
    PE bottles (US market) Using adhesive labels or printed bottles
  Powder Pouches/sachets Printed sachets
    Screw top jar,
PE bottles
Using adhesive labels or printed bottles
Liquid
(non-sterile)
Solutions
(syrup,
drops)
Glass bottles,
drop bottles
Using adhesive labels or printed bottles
Semi-solid Emulsions  Glass bottles,
plastic bottles
Using adhesive labels or printed bottles
  Creams,
ointments
Tubes (plastic or aluminium) Printed tubes
    Tubs, tins or jars with screw 
tops
Using adhesive labels or printed containers

Figure 2: Overview of the different types of packaging

Packaging in blisters

Blister packaging is the most widely used type of packaging for tablets, dragees and cap-sules. It is space-saving, consumer-friendly and economical. Its greatest advantage, however, is that each single dose can be removed individually in a hygienic way. The packaging can also be made child-resistant by using special foils and applying cross perforation.

A plastic foil is heated on a deep draw thermoforming machine to make it malleable. The blister cavities are then formed using pressure or vacuum. The dimensions of the cavities are set to suit the filling product. The tablets or dragees are placed in the cavities using special feeding devices. The filled blisters then undergo a filling inspection. They are subsequently covered with a printed aluminium foil that is sealed by the application of heat. Afterwards, the strips are coded (printing of variable data) and punched out. The individual blisters are auto-matically stacked for further packaging. At the same time, the folding cartons are coded, controlled (code reader) and stacked in a feed chute. The package leaflets are also controlled and stacked. In the next step, the blister and package leaflet are placed in the unfolded folding carton which is then closed. The completely filled folding carton (blister and package leaflet) then moves over a checkweigher. If the folding carton is underweight or overweight, it is ejected.

Other units can be directly connected to the blister packaging line, e.g. batch packaging, heat shrink tunnel and/or cartoner.

Packaging in PE or glass bottles

When solid, liquid and semi-solid dosage forms are packaged in containers, the filled con-tainers are usually labelled immediately after the filling process. In the labeller, the batch number, expiry date and security code (e.g. Data Matrix code) are added to the adhesive labels on the carrier strip and checked. The adhesive label is then transferred from the carrier strip to a label attachment unit. The containers which are round in most cases are moved to the label attachment unit of the labeller. The labels are then attached to the containers in a rotating movement.

After the label has been attached to the container, the presence of the label on the container is controlled again.

The rest of the process, whereby the labelled primary packages and the package leaflets are packed into folding cartons using cartoning machines, is practically identical to the method used when packaging blisters. The folding carton is labelled during the cartoning process on the line with a batch number, expiry date and security code. The package leaflet is identified by a code reader, repeatedly folded automatically and then inserted along with the package goods into the folding carton which was also previously checked and unfolded automatically. The folding carton is then moved across a checkweigher where it is checked for complete-ness.

Other types of packaging (e.g. tubes)

Tubes or jars etc. do not have labels attached. The primary packaging is already preprinted. The label is literally already printed on the primary packaging. Additional packaging in folding cartons with the package leaflet is carried out as described above.

The packaging process

Regardless of the type of packaging, the packaging process is carried out as shown in the flowchart in Figure 4.

In this example, the production and in-process control groups are assigned different functions. Deviating organisational forms are possible.

The actual status of a packaging line must be made evident at all times by attaching clearly visible labels (see Figure 3).

Labelling of packaging lines

  • Setup status
  • Cleaning status
  • Production status
  • Specification of product description, batch number, dosage as applicable, packaging size etc.

Figure 3: Labelling of packaging lines

Image

Figure 4: Packaging process flowchart

This article is an excerpt from update 17 of the GMP MANUAL.

Authors:

Dr. Christian Gausepohl
Rottendorf Pharma GmbH, Germany

Ruven Brandes
WDT eG, Germany

LOGFILE-08-2014_Packaging.pdf

 

 
 

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