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The special characteristics of mechanical, electrical and pneumatic elements are summarised in this chapter. A number of important components are listed that are important for machines and facilities in terms of Good Manufacturing Practice, and must therefore be specified and subsequently tested during qualification.
1 Construction and installation materials
Construction and installation materials, particularly those that come into contact with products, must be selected to ensure that no undesirable interaction with the product occurs during operation or cleaning. To achieve this, relevant criteria such as operation and cleaning temperatures and pressures must be defined. Product properties, such as chemical composition, decomposition products and abrasiveness, also influence the selection of materials and must therefore be described at the outset.
- If, for example, halogenides are likely to be produced during the manufacturing process, a higher-grade of steel (V4A) must be used instead of the usual V2A steel as there is a danger of corrosion.
- Granulates may undergo discolouration when coming into contact with aluminium, so contact between products and aluminium surfaces should therefore be avoided in solids operations.
Standard construction materials that come into contact with products are:
- V2A and V4A stainless steels according to DIN or AISI (US standard). The alloys selected depend on the chemical composition of the products being processed and the necessary surface qualities. The roughness of the surface must also be specified as well as the processing method (cold rolled, ground, electro-polished, etc.). For critical components, it is recommended that material certificates be requested from the steel manufacturer (e.g. 31B certificates).
- Plastics are mainly used as sealing materials. These must be suitable for use with foodstuffs and medicinal products and the FDA (21CFR177.2600) in particular has approved a range of plastics for this. Typical examples are polytetrafluoroethylene (Teflon), polypropylene, polyethylene and silicone.
- Glass is used to manufacture reaction vessels and pipes, or to provide visual contact with the product.
In addition to product contact surfaces cladding, covers and support braces must be specified in such a way that they do not have a negative effect on product quality: either during operation or cleaning. This also applies to screws and other fastening elements.
Filters are also important components of a facility. Filters have diverse applications and also have a huge impact on quality. The specification and qualification of filters should therefore at least include the following:
- Technical data: Separation efficiency, mesh/pore size, operating temperatures, pressures, etc.
- Filter materials must be asbestos-free - particularly if the filter cake or substrate is subsequently used in the manufacturing process.
- To avoid confusion, it is expedient also to record the precise type designation in the qualification documents.
2 GMP-compliant design characteristics
GMP-compliant design characteristics must be specified. In so doing, it must be considered that in practice detailed design requests are often not available for standard machines and are often only available for special machines in return for a (considerable) additional charge. Though many well known manufacturers have taken the most important GMP requirements on board in their designs, it is still recommended that all critical areas are precisely defined, discussed and checked. Several basic features of GMP-compliant facilities are:
- Simple, fast removal of components and facility parts during operation, maintenance and repairs - whenever possible without a tool - including good accessibility to all components.
- No particle, oil or grit-emitting (rotating) parts should be above the areas in which open products are located. Machine designs are now readily available where the drives, motors and other drive parts are positioned under or outside the production area. Where this is not possible, these machine components must be hermetically encapsulated or sealed.
- Use of maintenance-free or low-maintenance components. In sterile zones, components requiring maintenance should be installed outside the clean rooms.
- Cross-contamination and mix-ups must be avoided. Slits, holes, corners, cavities and dead spaces in which products may gather and then subsequently be released into the production process are not permitted. This particularly applies for screw holes, shaft or pipe bushings, covers made of folded sheets and screwed cladding. Whenever possible sheets should be (full-penetration) welded, not screwed or riveted.
- It must be possible to completely empty all fixed (CIP/WIP) components and they must be self-drying. (see chapter 1 CIP (Cleaning in Place))
- Main rings for purified water must be laid in such a manner that they can be completely emptied at the lowest point they must be CIP/SIP compatible or scrapable.
- Use of lubricants that are compatible with foodstuffs according to FDA/USDA-H1, e.g. white, silicone or ester oils.
- All wear and spare parts must be clearly identified in the technical documentation, e.g. using a numbering system. This avoids confusion when replacing components.
3 Electrical and pneumatic components
The following criteria in relation to electrical and pneumatic components should particularly be observed as part of Good Manufacturing Practice:
- Clear, easy-to-follow structure in the design.
- Modular concepts minimise the effort involved in order to qualify subsequent extensions.
- Use of a few different standard components rather than a variety of special subassemblies
- Systematic, clear use of conductor colouring
- Clear labelling of all (!) electrical components incl. cable
- The ventilation of electrical components (control cabinet, motors) in the vicinity of the product must be avoided. In environments where large quantities of dust are produced (as in the manufacturing of solid dosage forms) or in sterile zones, separation of the supply and exhaust air is advisable.
- Pneumatic components that discharge compressed air must not be installed close to an open product.
- The environmental conditions (temperature and moisture) must be defined for electrical and pneumatic components incl. proof of functionality.
- Design of appropriate electrical components to make them resistant to splashes or waves of water (IP 54/IP 64, electrical components according to DIN 40 050).
During qualification the following must be checked:
- Installation qualification: completeness of documentation; terminal strips; input/output lists; lists of components; calibration documentation (see chapter 2 Installation qualification)
- Operational qualification: safety devices, locks (see chapter 3 Operational qualification)
To maintain a clear overview, components for facilities are specified individually. In so doing, the special features of the product must be covered in addition to the machine functions. The components to be qualified must have been defined in order for them to be taken into account in the facility specification. When designing the mechanical components of the facility, attention must be paid to materials that come into contact with the product, facility of cleaning, labelling, and ease of qualification.