The syringes are advertised as “ISO compliant” on the website of the manufacturer. This is suspiciously vague and does not necessarily mean that the product complies with all requirements of all relevant ISO standards. (Also note that, concerning compliance and quality, the website mentions that the manufacturing facility is “ISO certified”, which is not permissible. However, the manufacturer actually has been certified to comply with ISO 9001:2008 and ISO 13485:2003 – that’s more like it.)
Ideally, such prefilled syringes are made in accordance with the applicable standards of the ISO 11040 Prefilled syringes series and other documents that are referenced in these standards (e.g. ISO 7886-1:1993 Sterile hypodermic syringes for single use – Part 1: Syringes for manual use).
However, the normative minimum requirements for materials are very general and not very restrictive. For example for the material of the barrel according to ISO 11040-6:2012 Prefilled syringes – Part 6: Plastic barrels for injectables:
For the manufacturing of the barrels, suitable polymers shall be selected and used, based upon the intended application and processing techniques, which include, for example, the method of sterilization or the method of decontamination. The material shall exhibit the appropriate performance properties, e.g. oxygen and water permeability.
or the material of the plunger stopper according to ISO 11040-5:2012 Prefilled syringes –
Part 5: Plunger stoppers for injectables:
The elastomeric material used shall meet the requirements specified in Clause 7.
Plunger stoppers shall be made from the elastomeric formulation originally tested and approved by the end user. The manufacturer of the plunger stopper shall ensure the conformance of each delivery with the type sample and compliance with previously agreed functional and compendial requirements.
The elastomeric material shall withstand two sterilization cycles when autoclaving in saturated steam at (121 ± 2) °C for 30 min without impairment of its function under conditions of normal use. If other sterilization methods are used, e.g. irradiation, the suitability of the material shall be evaluated.
The mentioned Clause 7 includes minimum requirements on hardness
The hardness agreed between the manufacturer and the user shall not differ from the nominal value by more than ±5 Shore A when tested in accordance with ISO 7619‑1 on a special test specimen. Alternatively, the hardness can be tested on the plunger stoppers in accordance with ISO 48. If tested according to ISO 48, the microhardness shall not differ by more than ±5 IRHD from the type sample.
resistance to ageing
The maximum time between the date of manufacture of the plunger stoppers and their pharmaceutical use should be agreed upon between the manufacturer and the user.
The plunger stoppers shall maintain their performance characteristics throughout the entire shelf-life of the medicinal product, which is tested as part of the stability test by the user.
chemical requirements
The aqueous extractables of the plunger stopper material shall not exceed the limits specified for elastomeric parts defined in ISO 8871‑1.
and biological requirements
The requirements in ISO 8871‑4 shall apply.
In addition to the normative minimum requirements, ISO 11040-6:2012 also includes informative guidance on materials:
Materials used in the construction of syringe barrels for use in pre-filled syringes should be suitable for the process to be used, the sterilization method to be applied and for the specific requirements as primary packaging for injectable drug products. Materials used in the construction of pre-filled syringes should not cause the syringes to be detrimentally affected, physically or chemically, by the normal use of injectable preparations and should be safe for the intended use.
Certain grades of polypropylene (homo-polymer and/or co-polymer polypropylene), cyclo-olefin copolymer and cyclo-olefin polymer have been used for the barrels of pre-filled syringes in applications with a variety of injectable products (drugs and biologics).
The organization responsible for the marketing approval of the injectable drug product is required to demonstrate the appropriateness and compatibility of the selected material and the suitability of the prefillable syringe as a container closure system. This includes, among others, the verification of drug/container interactions (leachable, extractable and sorption assessments) in reference to regulatory guidance (e.g. FDA and EMA), pharmacopoeias and other guidelines (e.g. ICH).
To develop the necessary data as outlined above, a collaborative approach is recommended between the pharmaceutical company that holds the marketing authorization of the injectable product and the supplier of the packaging system, with reference to ISO 15378.
Furthermore, ISO 11040-6:2012 includes a list of polymer materials codification:
- Cyclo-olefin copolymer (COC)
- Cyclo-olefin polymer (COP)
- Polypropylene (PP)
- Other polymer (OTH)
Remarkably, the manufacturer mentions the materials glass, COP, and COC (without further context) for prefilled syringes on another page, whereas the package insert mentions “The luer lock syringes are made using polypropylene.”
For reliable information, you should directly inquire from the manufacturer of the prefilled syringes. Apparently, this company does not make the empty syringes but only fills syringes that are obtained from another supplier.
