Standards must be adhered to when manufacturing pharmaceutical packaging to ensure hygiene and sterilisabality. Actega details the numerous packaging errors that could occur and how using the correct pharmaceutical closures will safeguard from them.
Pharmaceutical packaging, and primary packaging in particular, which is in direct contact with the dosage form or could potentially come into contact with it, is often much more than mere repositories. It can have an influence on the quality, effectiveness and safety as well as applicability of pharmaceuticals which cannot be underestimated. Typical examples include prefilled syringes or injection bottles (vials) with sealing plugs used as both repositories and for applying medication.
A multitude of packaging errors – representing 35 percent of mandatory annual reports to the AMK – have led to a very comprehensive catalogue of requirements which need to be examined and complied with prior to approval. Packaging errors can include breakage, turbidity and particle formation in injection solutions, or possible interactions between primary packaging and the dosage form.
Apart from the protection function aimed at preventing loss, degradation due to oxidation or influence of light and microbial contamination, the safety of the respective pharmaceutical must also be guaranteed. This means that the packaging materials used must not emit any substances of toxicological relevance into the formulation. Other standards must also be adhered to. These include ISO 22000 and FSSC 22000 (certification for food safety), BRCGS (global standard for food safety) and international featured standards (a range of food, product and service standards). The European Pharmacopoeia or the United States Pharmacopoeia (USP) demand that proof is required for each new or modified packaging product suitable for designated use of the respective pharmaceutical. A variety of material characteristics require testing, e.g. physical and mechanical properties, processability, resistance to chemicals, cleanliness, hygiene or sterilisability.
Individual primary packaging – including the pharmaceutical plugs and seals for injection bottles (vials) – requires additional certificates, such as those specified by USP 381 / EP 3.2.9 (Elastomeric closures for injections – Chemicals and penetration test). Primarily, this includes both the certificate of bio-compatibility and physical-chemical tests and functional tests.
Under maximum demands on hygiene and cleanliness, PROVAMED TPE have been compounded and the requisite tests conducted.
Evidence of bio-compatibility, i.e. proof that the materials or substances in direct contact with living tissue do not exert any negative influence on the metabolism thereof, had been provided in vitro. Maximum demands on low-migration, compatibility on contact with the body, and FDA conformity could be met.
In physical-chemical tests, various solutions were applied and their properties or modifications examined, whereby neither cloudy or change colour nor heavy metals, volatile sulfides or ammonium could be detected, or organic and inorganic contamination.
Then function tests were carried out to examine penetrability, fragmentation and self-sealing. Evidence has been provided of the fact that even after multiple piercing of the TPE material, no residue adheres to the needle or can be found in the test solution. This ensures that effective action can be taken to counter the risks of particle contamination. The sealant function prevents leakage of any components of the medication or vaccination and protects against permeation of microorganisms. It was possible to reduce gas and water vapour permeation to a minimum.
Self-sealing properties can only be confirmed if the sample in question is pierced at least ten times without revealing any leaks. The self-sealing features for safe resealing have also proved their worth, thereby extending the shelf life of the respective pharmaceutical as well as minimising the risk of contamination and therefore improving patient safety. With a force of less than 5 N (force for piercing the septum), the penetrability test represented an outstanding result. This means it can be ensured that puncturing is easily possible for both personnel and automatic equipment.
After all, a particular degree of purity can also be certified as there is no interaction with sensitive pharmaceuticals or active ingredients as neither sulfur nor zinc or other cross-linkers are used which would be required in the case of vulcanised rubber, for example.
Another requirement on the material for pharmaceutical closures is the sterilisability. PROVAMED TPE 6145 TL, 6245 NC and 6345 NC were subjected to conventional sterilisation methods – superheated steam, ethylene oxide, and Gamma radiation. Tests indicate no significant changes in their properties. The products are suitable for all sterilisation methods.
The TPE offered by Actega DS are also free of PVC, phthalates and latex. This is just one more reason why TPE are regarded as very suitable materials for manufacturing primary packaging. But also as a safe alternative to PVC, for example, as PVC can trigger interactions when it comes into direct contact with certain pharmaceuticals. PVC-incompatible substances are already known, e.g. Taxol, nitroglycerin, diazepam or even insulin. For one thing, plasticizers can leach out of the material. For another, certain pharmaceutical substances settle on the PVC surface which can lead to an undesirable loss of active agents. In such cases, suitable alternatives are required, e.g. TPE materials.
Find Actega DS at the METPACK in Essen, 5-9 May 2020, Hall 3, Stand 3C55.