This article provides answers to the following questions:
- What are the general requirements that apply to packaging materials and their specifications in a pharmaceutical environment?
- What are the most important primary packaging materials?
- What are the possible effects of interaction between primary packaging materials and the product?
- What is the function of secondary packaging materials?
- What labelling requirements apply?
- What are the advantages of standardised packaging materials?
- How can packaging materials contribute to the safety of medicinal products?
- What are the advantages of standardised packaging?
- What factors have to be considered when drawing up packaging specifications?
- How is the packaging material test process coordinated?
- What must be observed when storing and identifying the status of packaging material?
General requirements for packaging materials
The terms “packaging” and “packaging materials” as used in this article refer to the packaging of industrially manufactured finished pharmaceutical products. These packaging materials must satisfy specific requirements when used both singly and in combination with one another.
The most important function of such packaging is to protect the tested and approved product until it reaches the end user and to ensure that it conforms, within the defined limits, to the product specification until the expiry date.
In addition, the packaging materials must correspond at all times to the specification reported and submitted to the authorities (authorisation). Any deviations from this specification must be reported to the authorities and in serious cases will lead to a recall of the product from the market concerned.
As regards the properties and functionality of the materials, the requirements relate mainly to their processing on high-performance packaging machines and their use along the distribution chain from the manufacturer through the warehouse to the wholesaler and on to the pharmacy. It must also be ensured that the product can easily and safely used by the patient. Over the past few years, further requirements relating to user-friendliness and safety have been added, for example the inclusion of Braille, child resistance, fraud and counterfeit prevention and tamper-evident seals.
Primary packaging materials are packaging materials that have direct contact with the product. They include plastic films, aluminium foils, different glass types and qualities, plastic and elastomer caps, tubes made of aluminium, plastic or composite materials, containers made of plastic, aluminium or sheet metal and the closures used on these.
All other materials used in the packaging of finished pharmaceutical products such as package inserts, brochures, labels, adhesive labels, folding cartons and items such as dose administration aids, applicators, etc. are referred to as secondary packaging materials.
Printed packaging materials are particularly important, as these contain product-specific information and any errors could have far-reaching consequences.
In accordance with the definitions of the EU GMP Guidelines, packaging materials are not starting materials. However, the requirements that apply when handling starting materials should also be applied when handling packaging materials, as stated in Chapter 5.45 of the EU GMP Guidelines (effective from March 1,2015): “The selection, qualification, approval and maintenance of suppliers of primary and printed packaging materials shall be accorded attention similar to that given to starting materials.” This is understandable because the packaging materials, in some cases, have direct contact with the product, and labelling errors and incorrect assignment can lead to serious problems for the user. The responsibilities for handling packaging materials are clearly regulated.
Fig. 1 Responsibilities for handling packaging materials
Different companies take different approaches when defining responsibilities for packaging materials. Depending on the size of the company and the main focus of its business, the individual responsibilities within the packaging process may be weighted differently and therefore organised in different ways. Research-and-development-driven pharmaceutical companies tend to employ specialists to deal with the primary packaging materials right from the development stage. These people are generally also responsible for disposable medical products and devices, as the technology is similar. If such specialist knowledge is not required constantly, companies may consider purchasing the know-how from other departments within the company (production) or from outside.
Primary packaging materials
Task and functions
Primary packaging materials protect the packaged product against external influences and safeguard the product in accordance with its specification until it reaches the end user.
Because the primary packaging comes into direct contact with the product, there must be no interaction between the product and the material used for packaging. Fig. 2 shows the main possible types of interaction: adsorption, absorption, diffusion and migration.
Fig. 2 Types of interaction between medicinal products and the environment
Active ingredients, preservatives, auxiliaries and solvents may be affected by adsorption and absorption. As far as the medicinal product is concerned, this may result in a loss of active ingredient, impaired antimicrobial properties, decomposition due to the loss of stabilising components and a loss of aroma. Possible consequences for the packaging material include swelling, changes in the mechanical properties, stress corrosion, discoloration and changes in permeability.
In the case of diffusion the usual scenario is that solvents diffuse out of the medicinal product, while hydrogen, oxygen and carbon dioxide diffuse into the medicinal product from outside. This can lead to oxidative degradation of the active ingredients, a change in the pH value, hydrolytic degradation, the absorption of external odours and a change in the smell or taste. The appearance of the product may also change.
A further type of undesirable interaction is the migration of low-molecular-weight substances (e.g. plasticisers) to the surface of plastics (in this case the packaging material) or into the surrounding media (in this case the medicinal product). In most cases, additives (such as stabilisers, lubricants, plasticisers, colorants, crosslinking agents, vulcanisation accelerators, fillers, catalysts, antistatic agents, UV adsorbers) migrate out of the packaging materials into the medicinal products. Migration may lead to discoloration of the medicinal product if the packaging material is not colourfast, cloudiness and precipitation, degradation of the active ingredient and changes to the smell and taste. As regards the packaging material, migration may cause discoloration as a result of pigment loss, brittleness due to the loss of plasticiser, ageing as a result of loss of stability and changes in the permeability.
Comprehensive knowledge of the ingredients of both the medicinal product and the packaging material is essential in order to accurately assess the possible interaction between the medicinal product and the packaging.
Selection of suitable primary packaging materials
The primary packaging materials to be used are chosen at an early stage in the development of a medicinal product. The responsible product developer can tell from the product composition and initial stability tests what specific product requirements have to be met. On the basis of this knowledge the appropriate primary packaging material can be selected. The medicinal products may, for example, be sensitive to light or moisture, or they may be known to be incompatible with certain substances. Nevertheless, any changes to the product and/or the primary packaging materials only become apparent after prolonged storage trials under conditions similar to those in the relevant global climate zones.
The risk of changes to the primary packaging as a result of unsatisfactory storage results can be minimised by selecting and using different types of primary packaging during the early pharmaceutical development phase. Late changes to the primary packaging materials are normally very expensive and, in extreme cases, can prevent the early launch of a new medicinal product or the further marketing of a product that has previously been launched.
Any statutory requirements in the target markets, specific requirements relating to the function of the product (e.g. child resistance, suitability for elderly people) and existing production facilities should also be factored into the selection process for the primary packaging at an early stage.
Fig. 3 Gives an overview of the main selection criteria for primary packaging materials
When plastics were first used for packaging around 60 years ago, they opened the way to an entirely new method of packaging solid medicinal products. This involves heating a preformed plastic sheet, moulding it to form cavities or pockets and then allowing it to cool. The tablets or capsules are placed in the cavities and sealed with thin aluminium foil. The resultant strip is then die-cut to give individual blister packs of the appropriate size and shape. Thus each individual unit of the medicinal product remains in its protective wrapping until it is needed. The side of the aluminium foil that is facing away from the product is used to label the medicinal product clearly.
In principle, any formable sheet material is suitable for this type of packaging. When the technology was still new, PVC (polyvinyl chloride) was cheap and widely available. To improve the water vapour barrier, the PVC sheeting was coated with different amounts of PVDC. Other combinations of different plastics that provide a better gas barrier are now available as blister materials. In addition, formable aluminium foils can be used for products that are extremely sensitive to moisture.
In the 1980s, a discussion about environmentally critical products started. Chlorine chemistry fell into disrepute. Due to the threat of a ban on PVC, the industry started to look for alternatives. Polypropylene (PP) proved to be extremely suitable because it can be used to replace both PVC and PVC/PVDC films. From 1992/93 onwards, PP deepdrawn film was used by a number of companies as a new type of blister film. Shortly afterwards, a single-material PP blister was developed. This type of packaging replaces the aluminium sealing foil with a press-through PP film.
When assessing the quality of blister packaging, it is essential to determine the wall thickness distribution of each blister pocket. This can be done using inductive measuring systems, although problems may occur when testing composite plastic film, as it is not possible to measure the different components individually, only the composite material. Consequently, potential defects may not be detected. The quality of the seal must also be determined. The commonly used vacuum leak testing procedure (methylene blue dye bath test) identifies only major defects in the material and/or seal. It is not capable of detecting the potential gas permeability of the material and/or seal. A more effective, though more costly, method of identifying gas permeability is to test each blister pocket for a decrease in pressure or to place the blister pack on a light table to show any damage to the aluminium foil.
In addition to blister packs, plastic containers are widely used for solid medicinal products, especially in the United States, where manufacturers commonly supply tablets and capsules in bulk to pharmacists, who then transfer them to smaller packaging units. The containers used are generally made of HDPE and/or PP, round or rectangular and range in size from 30 cm3 to 1,000 cm3. The containers are sealed with aluminium foil and fitted with a child-resistant closure. The name of the product and other information for use are printed on an adhesive label. The package insert is folded up small and stuck to the container. Outside the United States, this form of packaging is also used for hospital supplies. The packaging machine is equipped with a vacuum testing device which checks that the aluminium seal is intact.
The use of glass containers and aluminium tubes with the appropriate closures for solid medicinal products is becoming increasingly rare.
Injection and infusion containers and accessories
A highly comprehensive set of standards governing primary packaging for parenteral products and the relevant accessories has been in place for many years. Based on the German (DIN) standards, European (EN) and, more importantly, international (ISO) standards were drawn up for packaging materials. These standards, which are continually updated, define the requirements regarding
- Design, dimensions, tolerances and functionality,
- Identification of elastomer components,
- Physical, chemical and biological properties,
- Quality management systems.
It is good practice to refer to the current standards on a day-to-day basis. The standards describe and specify in detail the main packaging materials used for this type of application, such as ampoules, tubular glass, injection vials and infusion bottles made of moulded glass including the corresponding rubber stoppers and crimping caps, prefilled syringes and pens.
Some special applications may require solutions that are not covered by these standards. In such cases it is always advisable to collaborate with the market leaders in this segment and jointly develop suitable products.
Tubes made of aluminium, plastic and composite materials
Ointments and gels – generally for topical application – are packaged in aluminium tubes and sealed with plastic closures. The tubes are cold-formed out of circular blank sheet prefabricated at the aluminium foundry. Depending on the type of blank sheet used, tubes with or without a membrane closure are obtained. The inside of the tube is provided with a protective, preferably pore-free, coating. An elastic rubber coating is applied to the open filling end to ensure a tight seal inside the crimp once the tube has been filled and closed. The outside of the tube is printed. The cold-formed tubes can be widened to a conical shape, which saves space during transport and storage and also facilitates handling on the packaging line.
Tubes are also widely used as packaging in other sectors (dental care, the food industry, cosmetics, industrial applications, etc.). Tubes made of plastic (cosmetics) and composite materials (dental care) account for a large share of the market in these sectors. The use of such tubes for pharmaceutical products is limited by the long shelf life required and by the comparatively low production/order volumes.
There are many standards relating to tubes as well, including the supply packaging and the final packaging. Here, too, it is advisable to study the current standards issued by the German Institute for Standardisation (DIN) because these standards are also accepted in many other (European) countries.
Glass and plastic bottles and accessories for liquid products
Liquid pharmaceutical products such as syrups, drops and emulsions for oral or external use are filled into containers made of glass or various plastic materials.
The glass bottles and bottle mouths and the metal or plastic closures are all standardised (see e.g. DIN Taschenbuch 231).
Various droppers, pipettes, spray attachments and metering systems are available, depending on the particular product, or a product-specific application system may be developed.
The interaction between the glass/plastic mouth of the bottle and the sealing element on the closure is particularly important. Ideally, the closure construction should seal at various points on the mouth and thus prevent product from leaking out during storage and use.
To ensure the leak tightness of this type of packaging it is absolutely essential to know the optimum limits of the screw-on torque and the resultant values for the screw-off torque after storage (vertical, horizontal and upside down).
As this type of packaging is often used for medicinal products for children, a tested child-resistant closure is also necessary.
Secondary packaging materials
Task and functions
Secondary packaging refers to all the constituents of a package that do not come into direct contact with the product. Essentially this means labels, patient information leaflets (package inserts) and folding cartons.
Their main purpose is to protect the primary packaging, identify the medicinal product and ensure the cost-effective production of a pharmaceutical package and its effective handling along the distribution chain to the final consumer.
Labelling is controlled by the regulatory authorities and in most cases constitutes an integral part of the approval documents.
Primary packaging such as plastic containers and glass bottles, which are either unprinted or difficult to print, are provided with labels or adhesive labels in order to ensure their clear identification.
One advantage of this system is that the primary packaging can be manufactured, tested and released in large batches. Partial quantities can then be processed as required, e.g. for different packaging orders for different countries. This approach requires clear specification and allocation of primary packaging materials and labels/adhesive labels.
To this end the labels or adhesive labels are clearly identified by means of a code (a bar code and/or a space-saving 2D matrix code), which must be checked and documented during the packaging process. In many cases serial numbers are printed on every adhesive label on the carrier strip in order to enable back-calculation of label consumption.
As packaging machine speeds increase, adhesive labels are increasingly displacing labels to which glue is applied in the packaging machine.
Ideally, labels or adhesive labels should be attached firmly to the primary packaging so that subsequent removal of the labels is not possible without destroying it. For this purpose the adhesive must of course be suited to the substrate.
For small objects (such as ampoules, syringes, vials, …) a low-stiffness label material should be chosen, and the labels or adhesive labels should also be designed in such a way as to reduce their resilience.
Adhesive labels, in particular, are used for special applications, e.g. as closure labels or as price or prescription labels (e.g. „Bollini“ system in Italy).
Patient information leaflets/package inserts
The patient information leaflet is an important element of a pre-packaged medicinal product. It provides the user of the medicinal product with the information required to use the product safely.
Over recent decades, the content of the patient information leaflets has grown dramatically. In addition, the registration authorities have compiled design and font guidelines, which are intended to improve readability for the patient. In countries with several different languages, the standard printing formats limits of the machines used for printing patient instructions have already been reached. Furthermore, the patient information leaflets must be folded until they are small enough to fit in the folding carton, and it must be possible to process them together with packaged product at high speed. It is increasingly the case that this can only be achieved using pre-folded instructions or instructions that have been folded to their final size. So-called inserts/outserts or adhesive-bound booklets are increasingly replacing the commonly used patient information leaflets supplied in packaged medicinal products. As a result, the folding process is shifting to the manufacturer of the patient information leaflet.
The patient information leaflets are printed with a unique barcode to prevent mix-ups, and visual marks are applied to the cut edge of unfolded sheets. In the case of package inserts that are folded at the final stage of production, 2D matrix codes are already used for verification purposes. A barcode printed over the final fold replaces the visual mark referred to above.
The use of 2D matrix codes to replace the barcodes formerly used is also an alternative worth considering for other types of packaging, because it does away with the complex management of code numbers.
The patient information leaflets are usually printed on thin paper with a basis weight of 50 g/m2. Suitable thin printing paper with a basis weight of 40 g/m2 is already available for both pre-folded package inserts and folded package inserts. It should be noted that the basis weight is merely a commercial parameter. When choosing a suitable paper for this specialist application, properties such as thickness, opacity, luminescence, stiffness, porosity, roughness and tear strength must be known and contractually agreed.
To ensure trouble-free handling of the patient information leaflets, the cutting and folding dimensions must be kept within narrow tolerances, and the humidity in the storage areas and the packaging plant must be monitored.
In almost all cases medicinal products are supplied to the end-user (a doctor or patient) in a folding carton. This encloses and protects the primary packaged medicinal product, patient information leaflet and any accessory components until the product is used.
The printing is used to clearly identify the medicinal product (product name, generic name of active ingredient, dosage), provide information on how to use the product and show the batch number and the expiry date in printed or embossed form. In addition, the folding carton has a barcode and/or a 2D matrix code which facilitates billing and ensures authenticity and the traceability, as well as other mostly country- or product-specific information.
In the case of folding cartons, the large number of printing requirements, especially when it comes to packaging for countries with three languages, and the subsequent increase in the size of the package inserts, results in larger folding cartons.
Folding cartons are usually offset-printed as sheets with up to 6 individual colours or four standard colours (cyan, magenta, yellow, black) plus a protective lacquer. In certain cases rolls of cardboard are flexo-printed.
In the next stage of production, the printed sheets are cut out on a flat-bed die-cutter and scored to create crease lines along which the carton is folded. The paperboard sheets are also embossed at this stage to produce the Braille characters. The scrap generated at this stage of folding carton production can be removed automatically.
In the final step, the flat, die-cut cardboard blanks are folded along the creases and glued together using dispersion adhesive to form a folding carton. After passing through a press, the boxes are accurately counted, placed in a transport pack and labelled. It is important not to subject folding cartons to excessive pressure in the transport pack, because that could lead to erection problems after storage.
In the pharmaceutical industry, GC2 (coated virgin fibre-based paperboard) or GD1 (coated paperboard with recycled fibre) are the standard paperboards used for folding cartons. Again, the specified weight of the paperboard in g/m2 is only a commercial parameter. A more accurate indication of the board quality is given by its bending stiffness in the machine/cross direction and its maximum thickness. Consistent quality can be ensured by selecting a particular type of board produced by one or more comparable paperboard manufacturers. It is also important to make sure that the surface of the board is suitable for different printing processes (ink jet, laser, etc.). In some cases the requirements of the printing methods are mutually exclusive!
As far as the standardisation of folding carton construction was concerned, a satisfactory solution already existed. DIN Standard 55429 Part 1 contained specifications for the construction, dimensions (A x B x H), limit deviations and testing of folding cartons. Customised designs could be specified on the basis of this standard. Unfortunately it was replaced in 2003 by a standard (DIN EN 14054) that was less suitable for folding cartons intended for medicinal products. The only solution now is to incorporate the content of DIN 55429 Part 1 into individual company specifications. It also makes sense to use the CAD data compiled by the folding carton manufacturer on the basis of these specifications as a template for typesetting.
Tight tolerances for die-cutting and creasing, as well as the monitoring of atmospheric humidity in the store room and on the packaging machine are also crucial for trouble-free processing of folding cartons. Common mistakes include subjecting the folding cartons to excessive pressure after gluing, and overloading the delivery package. This can damage the folding cartons so badly that they can no longer be erected on the packaging machine.
Corrugated board boxes
Boxes made of corrugated board are used for the outer packaging of individual or bundled sales packs. Designing the boxes to accommodate specific quantities of sales packs often results in a relatively large number of differently sized boxes, all of which have to be managed logistically. Consideration should therefore be given to standardising the boxes to conform with pallet sizes (which are generally 1200 x 800 mm or 1200 x 1000 mm) and with the height of shelf stacking and transportation vehicles, so as to ensure optimum loading of the boxes. Packaging by hand offers greater scope than end-of-line packaging by machine. But because the packaging of pharmaceutical products is not generally approached or optimized from the transport and storage standpoint, it is not easy to arrive at an ideal solution.
It is advisable to specify the lowest tolerance possible for interior dimensions (interior L x B x H) and, depending on the chosen material, to allow greater tolerances for the exterior dimensions (exterior L x B x H).
It has proved advantageous for light, mostly non-supporting content to specify a maximum pressure resistance together with a maximum compression distance as material requirement for the completed corrugated cardboard folding boxes. When specifying these values, the loads encountered during transport and storage (combined with a safety factor) should be taken as a basis.
Nowadays automatic machinery is also used when packaging pharmaceuticals. The machines open, load and close the corrugated board folding boxes, which must remain undamaged during delivery and storage. Special die-cut designs and the positioning of the glue flap on the outside help to ensure trouble-free operation. As with all packaging materials made of paper and paperboard, it is essential that an optimum level of relative humidity be maintained both during storage and in the packaging plant.
Labelling requirements depend on the provisions of the regulatory authorities in the countries being supplied. Within the EU, new medicinal products can be submitted for central authorisation by the EMA (European Medicines Agency). The EMA recommends marketing approval for all countries of the EU on the same day in accordance with a standardised procedure laid down by the European Commission.
The EMA comprises 31 states (including non-EU-member states), in which 24 languages are spoken. The EMA works with defined templates for each language, lays down precise rules for the positioning of the texts and prescribes minimum type sizes.
So-called mock-ups (PDF versions of the printed packaging materials) in English and multiple language versions (mostly trilingual for Belgium) and specimens (original packaging materials – neither glued nor folded) of all package sizes are submitted to the EMA. The standardised approach allows a combination of countries/languages in one pack.
Individual national laws have been harmonised within the EU in respect of labelling requirements and adapted to the EMA requirements.
Standardisation of packaging materials
Significant savings in both the production and processing of packaging materials can be achieved if common standards are used.
The material, dimensions, design and presentation/colours can all be standardised.
In the case of glass bottles, aluminium tubes and their closures, a material and design standard has been created that is used by many customers. All other types of packaging, particularly blister packs, are generally made to an individual company and/or site standard, and huge potential savings are wasted as a result.
Many efforts have been made to improve this situation. In this connection, the work of the FFPI (Research Association for Folding Cartons for the Pharmaceuticals Industry) should be mentioned in particular. Their PAS 1009 (Publicly Available Specification – published by Beuth) is a proposal that is worth consideration.
Protection against counterfeit medicinal products
All packaging materials can play an important role in protecting against counterfeit medicines. Since in some cases the authenticity of the products (tablets, liquids, ointments…) cannot be determined without very extensive tests, the packaging material has to take over this function.
A distinction has to be made here between overt and covert counterfeit protection features. The extent to which these features are known is also important. Ideally, patients should be able to recognize an original pack as such.
Integrated counterfeit protection is achieved through the consistent design of all packaging materials, awareness of the characteristic features of packaging material production, one’s own packaging process and the technology employed. Since retention samples of every packaged batch must be stored, it makes sense to keep at least one retention sample for the purpose of checking for counterfeits and to use this when necessary. A trained specialist will be able to distinguish a counterfeit from an original very quickly.
As far as unskilled persons are concerned, it would be feasible, where permitted, to take technologies used in the high-security sector (banknote production, ID and document security) and adapt them to the production of packaging materials for medicinal products. Although these technologies make counterfeiting more difficult, it should be borne in mind that they can only be truly effective as part of a comprehensive counterfeit protection concept.
Both the selection of technologies and their implementation require special expertise and must be treated confidentially.
The next few years will show to what extent the introduction of serialisation and monitoring of pharmaceuticals packaging in some countries will alter the requirements for counterfeit protection.
Specifications for packaging materials
A correctly formulated packaging material specification provides a comprehensive description of the packaging material and serves as a guideline for the respective packaging materials supplier. In addition, it forms the basis for quality testing by the packaging material suppliers and for incoming control at the medicinal product manufacturer.
Particular significance attaches to the correct allocation of all packaging material specifications and printed information (batch number, expiry date, price) in the form of a bill of packaging materials for the packaging plant.
It is obviously necessary to entrust highly qualified people with the coordination and compilation of these specifications and documents. In the case of packaging material ranges comprising 1,000 and more individual components, an IT-supported approach is needed.
Because important packaging material requirements depend on the packaging process and the machines used, the persons responsible for the packaging material specifications are normally located in or around production. The packaging material guidelines and packaging instructions required for packaging must be authorised and available in written form because they are also needed for the release by the person in charge of QC. These instructions are mainly technical instructions and must also include the printing instructions for the respective packaging materials. This is normally a PDF file created using DTP software. The specifications of the packaging materials manufacturer and logistic/purchasing are also required for an adequate packaging materials specification.
Depending on the medicinal product range for packaging, a change frequence of three to four changes per year must be expected, especially in the case of printed packaging materials such as instruction for use and folding cartons. The creation of packaging material specifications requires a clear and robust process, which can also handle an extremely short-term scope of change without problems.
The contents of the specification for primary packaging materials are generally already specified in the documentation of the pharmaceutical technology department and as a result, in the registration documentation of the medicinal product. Important aspects for the selection of primary packaging material are described in chapter primary packaging material. The number of products to be packaged, i.e. the content of the package, depends on the length of time the medicinal product is normally taken.
A suitable packaging machine is then selected on the basis of these specifications. The standards (e.g. the dimensions of the packaging) of this machine are also required for the packaging material specification.
In very many cases the packaging and/or packaging material manufacturer’s data sheets (e.g. paper and paperboard specifications, glue types in the case of adhesive labels) can also be made available. They contain key parameters for the packaging process, which can be carried over. data sheets can also be cross-referenced if they are clearly identified, i.e. using the publishing date.
There are also industrial standards in many areas (DIN, EN and ISO) that can be used as an excellent basis for packaging material specifications.
Country-specific standards (fond size, amount of text, use of colours, etc.) now have a considerable influence on the dimensions and design of printed packaging material (blister packs, labels, package inserts and folding cartons). In some cases different packaging techniques have to be used (e.g. an unfolded package insert becomes a multiple-fold insert or outsert). This again affects the choice of packaging technology.
Additional requirements from the area of logistics (such as delivery times) and purchasing (conditions) are generally included in the packaging material specifications.
In order to ensure the uniqueness of a package, multi-digit packaging numbers are assigned, which should be altered with every modification. To prevent any mix-ups between similar types of packaging, visual markers and bar codes or 2D matrix codes are used and monitored by the packaging material manufacturer and during the packaging process.
Some of the characteristics of packaging materials that must be defined in the specification are shown in Fig. 4. The checkpoints are usually monitored and verified during testing of the packaging material by the manufacturer. Particular checkpoints can also be monitored if required during acceptance testing by the manufacturer of the pharmaceutical product.
Fig. 4: Packaging material groups and typical tests (according to Harl)
The most important packaging material requirement of a medicinal product is the protection of the product to ensure that the specification-compliant original quality can be maintained throughout the lifespan of the product. Another important aspect is clear labelling in the interests of patient safety. There are also requirements with regard to user-friendliness and medicinal product safety, such as child-resistance and tamper-evident closure.
The most important primary packaging materials, their properties and areas of applications are described in the document. When selecting the primary packaging materials, it is important to take possible interactions with the medicinal product into account. Data from the early stages of development of the medicinal product is usually available for this purpose.
Secondary packaging materials are used to protect the primary packaging and identify the medicinal product. The labelling content is regulated by the regulatory authorities and is largely part of the approval documents.
The wide range of packaging types, materials and dimensions necessitates a high degree of technical processing. The definition and use of uniform standards would lead to a major reduction in costs.
On the other hand, the protection against medicinal product counterfeiting requires individual and, at times, costly measures to guarantee the authenticity of the medicinal product and make it recognisable to the consumer.
A packaging material specification provides a complete description of the packaging material and serves as a guideline for the supplier of the packaging material. It also forms the basis for quality testing carried out by the packaging material supplier and for acceptance testing by the manufacturer of the medicinal product.
Testing to ensure that the quality of the primary packaging materials complies with the specification is a major challenge for the medicinal product manufacturer because of the range of special methods used, and is therefore normally carried out by the packaging materials manufacturer. This requires qualification of the supplier and a contractual agreement. The medicinal products manufacturer then only needs to carry out reduced testings as part of the incoming goods inspection.
Handling packaging materials is a high-risk business because of the danger of mix-ups. These risks can be reduced by adhering to strict standardised procedures in storage, labelling and transport, and by employing qualified staff.