Materials and Adjuvants for Pharmaceutical Equipment Construction – An Overview

Excerpt from the GMP Compliance Adviser, Chapter 4.B.1

7 min. reading time | by Ruven Brandes
Published in LOGFILE 22/2024

When establishing the basic design of equipment, containers, components and machines for pharmaceutical use, a wide variety of materials is required. These are typically subdivided into materials of construction and adjuvants or production aids.

What significance do materials have in a GMP environment?

The selection of materials of construction is of great importance in the hygienic design of plants and equipment. Materials of construction not only affect the manufacturing process, but also the cleanability to a considerable degree.

The following points are decisive for the selection and usage of the materials of construction:

• resilience (strength, wear, corrosion),
• ease of processing (ability to machine, form, join, weld),
• cost.

With regards to hygienic design, as part of the Machine Guideline the following additional requirements also apply:

• The installations should comply with the relevant guidelines in all important aspects.
• The materials used should be physiologically harmless.
• There must be no migration of prohibited material components into the products to be produced.
• It must be possible to finish surfaces with the required quality without defects.
• The surface quality should not deteriorate over the life of the materials.
• The equipment should be easy to clean.
• The materials must withstand chemical and thermal stresses by exposure to low and high temperatures during production.

Which materials of construction are available?

A fundamental requirement of the production equipment used is that they do not adversely affect the quality of the product. Experience from recent years has shown that a specific requirement profile should be established for each individual application. This has resulted in various specifications for equipment manufacturing, installation and testing. For this reason, the majority of production equipment is made of high-grade alloyed steels.

In addition to stainless steel, plastics also play an important role as a material of construction. For plastics, it is of great importance to define precisely the application and to test the suitability carefully, as required. Plastics are frequently augmented with additives or fillers to yield specific properties. By adding plasticizers, for example, the interactions of the macromolecules are reduced, making the material softer and more flexible. Plastics are characterized by two different types of elasticity:

• At low temperatures they are energy-elastic, i.e. they are deformable and not brittle.
• At high temperatures they become viscoelastic – the material is deformable and retains its new form once cooled.

What should be considered for the use of stainless steel?

When processing or storing stainless steel, it is essential to enforce an absolute carbon–stainless-segregation of the materials. In addition to the requirements on the material’s strength and ductility its weldability is an essential requirement for the construction of plants and equipment. This is mainly influenced by the carbon content (C). By using optimized melting and resistance type welding methods, most stainless steels can be welded easily when using appropriate welding additives and inert-gas shielding of the welding zone.

What should be considered for the use of plastics?

When using plastics the following properties should be considered:

• Plastics exhibit creeping behavior under stress over time at temperatures above 130°C.
• Plasticizers contained in plastics can be extracted by cleaning and disinfecting agents.
• Many lipophilic compounds in the surface of plastics can migrate into the product and subsequently into other products.
• Colorants and flavors can persistently migrate into the surfaces of plastics and thereby impact the quality of subsequent products. In these cases the use of product-dedicated sets of the affected parts should be considered.

When choosing plastics, a number of legal requirements must be taken into account in addition to the properties relevant to their suitability.

Which adjuvants are available?

Within this chapter two significant groups of adjuvants, i.e. secondary materials are covered: lubricants and sealing materials.

For applications in the pharmaceutical industry only registered and certified lubricants are to be used so that the quality and safety of the drug are not impacted. The risk of potential contact with undesirable substances is an important concern of GMP regulations. On tablet presses, blister machines, capsule fillers, autoclaves, separators or centrifuges contact between the lubricants and the pharmaceutical product cannot be ruled out. Therefore, risk assessments must reflect all processes in production, including the lubricants used. For this reason, a special class of lubricants has been developed – so-called H1 lubricants. The producers of these lubricants and their production sites must be certified for H1 lubricant production by the NSF (National Sanitation Foundation) and according to the international norm ISO 21469.

Furthermore, the process technologies used in the pharmaceutical industry place extreme demands on media and temperature resistance of materials. This is the critical aspect for the selection of sealing systems. The complex nature of the holistic assessment of sealing systems is made more complex by the specific requirements for the hygienic design of seals.

What defines a GMP compliant lubricant?

The registration of lubricants and their components is primarily performed via the FDA and the NSF. Both of these institutions have published a white list which lists the certified lubricants. These lubricants are expressly certified for use on production machinery and are therefore unobjectionable for use.

Lubricants are categorized into three groups according to the NSF. These three group titles are used for labelling lubricants.

H1 lubricants may be used throughout the food industry where product contact may be technically unavoidable.

H2 lubricants may be used throughout the food industry where product contact can be ruled out.

H3 lubricants consist of water-soluble oils, which are used as corrosion proofing agents or for cleaning transport trolleys, hooks, etc. and are categorized as chemically acceptable.

What should be considered for the use of seals?

For the use of seals or gaskets the following aspects should be considered:

• temperature
• pressure
• material
• shear forces
• conditions during application
• documentation
• allowed fabrication tolerances
• seals/gaskets should be individually packed
• supplier selection criteria – which supplier can offer a performance test protocol?

In practice this means that the seals and gaskets have to be designed very specifically for the pharmaceutical industry. Functional tests for the specific application are mandatory prerequisites.

Do you have any questions or suggestions? Please contact us at: redaktion@gmp-verlag.de