Material compatibility between plastics and pharmaceutical products
It is much more difficult to define material compatibility for plastics than it is for stainless steel.
The basic GMP requirement is that the material of the equipment or installation must not adversely affect the quality of the pharmaceutical product. A food contact certificate is often used as proof, i.e. it certifies that the material is non-toxic when consumed in small quantities.
The following certificates serve this purpose:
- US Federal Standard CFR 21.177
- The Federal Institute for Risk Assessment’s positive list ‘Recommendations on Materials for Food Contact’: Recommendations on Materials for Food Contact. Plastics Recommendations; Health Safety Food, Commodities and Feedstuffs Code (LFGB)
- EC 1935/2004 (Materials and articles intended to come into contact with food)
- EC 2023/2006 (Good manufacturing practices for materials and articles intended to come into contact with food).
However, it may also be useful to provide specifications to meet other requirements:
- 3A Sanitary Standard
- EHEDG (European Hygienic Engineering & Design Group)
- DIN 26055 – hose assemblies for use in the pharmaceutical and biotechnology industries
- ISO 3601-3 Shape and surface deviations of O-rings (for pharmaceuticals, observe ‘Grade characteristic S’)
US Pharmacopoeia and Biotechnology
The US Pharmacopoeia also makes statements regarding the pharmaceutical suitability of plastics and divides them into six classes of biocompatibility. USP Class VI represents the most stringent class and is equivalent to a pharmaceutical approval for polymeric materials. For a material to receive a Class VI classification, specific tests must be carried out in external testing laboratories. For this purpose, animal testing will be conducted to determine acute toxicity (irritation upon ingestion or inhalation), intradermal reactivity (tissue test) or an implantation test
In biotechnology production, it may also be useful to specify ‘ADI-free’. This means that no animal-derived ingredients (ADI) are used in the construction of the equipment or the facility. Such materials are also free from BSE (Bovine Spongiform Encephalopathy) and TSE (Transmissible Spongiform Encephalopathy).
It is the pharmaceutical manufacturer’s responsibility to ensure that the plastic used does not react chemically or interact with the pharmaceutical product.
In biotechnology, leaching from plastic materials is critical, so it is essential to identify the substances that may migrate from the plastic into the pharmaceutical product. For this purpose, worst-case studies are carried out in which, using model solutions, tests are conducted to determine which substances can be extracted from the plastic (determination of extractables).
Leachability studies use the actual pharmaceutical product to determine which substances leach under real-world conditions. The results of the studies must be evaluated from a toxicological perspective, taking into account the process, the product, the application, etc. It is the pharmaceutical laboratory itself that must determine whether leachability/extractability studies are required, based on a risk assessment.
GMP requires that the verification of construction materials be carried out during qualification, to ensure that the facility or equipment has been constructed using the materials required by the pharmaceutical laboratory, and that it has no adverse effect on the product.
Material certificates provided by equipment manufacturers
As not all pharmaceutical laboratories have the necessary facilities for testing or identifying materials, the material certificates provided by equipment manufacturers are very important:
- As a general rule, EN 10204 Type 3.1 inspection certificates are required for stainless steel components. This certificate can only be issued by the product manufacturer and certifies that the manufactured product technically complies with the order; as proof of this, the results of the tests requested by the customer are provided. The type of test and how it is to be carried out must be defined in advance in the order. The person signing the report is independent of the manufacturer’s production department; this is usually staff from the quality control laboratory. It involves a significant cost, as an individual test is carried out on the product to be supplied, and must be requested from the technical department prior to placing the order. This ensures that the certificate can be traced back to each component.
- In the case of plastic components, EN 10204 Type 2.1 certificates are generally accepted. In this case, the system manufacturer itself confirms compliance with the requirements. However, this does not provide 100% certainty. The 2.1 certificate does not allow for any traceability of the item in question; it is a declaration of conformity regarding what the customer purchases and what is delivered to them.
