As pharmaceutical products are manufactured, packaged and stored, they come into direct contact with packaging systems and their plastic materials. Such contact can result in interactions between the pharmaceutical product and its packaging, which must not only protect the medicine but also be compatible with the pharmaceutical products and do not compromise its stability, efficacy or safety.
The use of well-characterized plastic materials and appropriate analyses help to determine possible interactions with a pharmacological product. In this regard, the United States Pharmacopeia (USP) develops and reviews public standards that contribute to promoting the global quality of medicines.
Currently, in the case of plastic materials, the tests can follow chapter <661> ‘Plastic packaging systems and their materials of construction’ or <661.1> ‘Plastics materials of construction’ / <661.2> ‘Plastic packaging systems for pharmaceutical use’. Chapters USP <661.1> and USP <661.2> will become official on 1 May 2020. Until then, plastic materials can be analysed according to chapter <661> if someone chooses not to adopt chapters <661.1> and <661.2>. However, if early adoption of <661.1> and <661.2> is chosen, it will not be necessary to comply with chapter <661>. In this sense, plastic materials are considered characterized and suitable for use if they meet the requirements of chapter <661.1> and if the packaging meets the requirements of chapter <661.2>. Packaging and components that meet the requirements of chapter <661.2> do not need to meet chapter <661.1>.
From that date, chapter <661>, in its current form, will change completely. It has been proposed that it remains and, although there are no defined test procedures, that this chapter redirects to other chapters such as USP <1663> (determination of extractables) or USP <1664> (determination of leachables), in addition to the analysis of starting materials <661.1> and packaging <661.2>.
With the new chapters coming into force on May 2020, chapter <661> is divided into two chapters: chapter <661.1> and chapter <661.2>. Chapter <661.1> describes more specific tests, based on the formulation of plastic materials, which use chromatographic techniques (GC, HPLC or TLC) for the analysis of additives, stabilisers, residual solvents, etc., and is more detailed than chapter <661>. In this case, there will also be differences between the type of material, in the same way as in chapter <661>, depending on whether it is polypropylene, polyethylene, polyolefins, polyethylene terephthalate (PET and PET-G) or PVC. Chapter <661.2> adds a specific requirement for chemical risk assessment, which is based on the analysis of extractables and leachates, described in chapters <1663> and <1664> respectively, which is also not present in chapter <661>.
Chapters <1663> ‘Assessment of extractables associated with pharmaceutical/delivery systems’ and <1664> ‘Assessment of drug product leachates associated with pharmaceutical packaging/delivery systems’, discussed above, are based on tests to determine extractables and leachates from pharmaceutical packaging, respectively. All substances that can be extracted from the plastic material under laboratory conditions by applying specific solvents, temperatures and contact times are considered extractable. Therefore, these conditions may cause higher values to be obtained than under normal conditions of storage and use.
Moreover, the study of leachates provides information on substances that can leach from the material under normal conditions of storage and use, using the drug as an extracting agent.
Once these substances are known, which may be, for example, additives in polymeric components, contaminants in these additives, low-molecular weight oligomers, inks, label adhesives, contaminants or chemical substances on machine surfaces (antistatic, anti-slip agents, release agents, etc.) or even volatile in the packaging board or from the wooden pallet used for storage, a toxicological study of these substances must be carried out.
There is no doubt that chapters <661.1> and <661.2> provide more extensive information than that obtained from the analysis carried out according to chapter <661>, which will allow an adequate evaluation for the correct selection of materials and, ultimately, an assessment of the chemical risk of pharmaceutical packaging.