The collaboration between Brevetti Angela and burster Italia in the pharmaceutical field deals with the validation tests of pre-filled syringes, according to ISO 7886-1. The result is a machine dedicated to the implementation of tests
by Ing. Luca Benedetti e Ing. Federico Acquati
A case study in the pharmaceutical industry, where pre-filled syringes need to comply with standard validation tests. The collaboration between Brevetti Angela and burster Italia leads to a successful achievement of the goals set, thanks to the shared know-how and a fruitful cooperation. Brevetti Angela is among the worldwide leaders in the manufacturing of innovative machines for the pharmaceutical industry, developed on the Blow Fill Seal technology. These machines, renowned as Syfpac®, are able to produce vials or bottles in one complete process that starts from the raw plastic granule and ends in a sterile and ready to use plastic container. The most advanced application of the BFS technology to the world of pre-filled containers lately resulted in the creation of the new Secureject® machine for the production of pre-filled syringes. Such a development generated the need to objectively determine the compliance of these syringes to ISO 7886-1 standard. As there is presently no product in the market for this kind of testing, Brevetti Angela has designed a machine dedicated to the implementation of several standard tests: the Securespect system. Among the tests required on the pre-filled syringes, a sealing test is performed by applying the axial and orthogonal forces under overpressure and in vacuum conditions. In addition, a further examination to measure the torque resistance has been introduced, to determine how the syringes are actually easy to open and their “ready to use” status (such test is not included in the standard ones). For each type of test the following aspects must be specifically considered: average and peak force during piston sliding; any leakage of the stopper or luer, which would compromise the integrity and the sterility of the product; any possible detachment of the stopper from the plunger, that would make the syringe unusable; the effort needed to release the syringe from the protective cover and make it ready to use.
Four work stations to perform the main tests
The added value of pre-filled syringes in the medical field is not only the rapid and convenient injection of the drug into the patient, but also the statistical reduction of the risk of contamination because of the presence of the drug inside the sealed syringe, which does not require any interaction with external devices. Generally, a syringe should be opened quickly and effectively, and should not have suffered any damage during storage or use of the product. The opening of the seal must be easy to perform manually and on the spot by medical staff, and it must be smooth and simple. These features make the product easy-to-use and give the perception of an overall reliable and quality product. These product specifications, which are also well synthesized in ISO 7886-1, merge with the goals pursued by Brevetti Angela. For this project, Eng. Thus the collaboration between Brevetti Angela and burster Italia started. The challenge is to build a dedicated machine that allows the final user to be completely autonomous in verifying and validating the finished product, by integrating in the machine in a modular way the measurement chain and thus the validation system according to ISO 7886-1.
A norm that regulates the field of disposable plastic syringes
ISO 7886-1 is a norm that regulates the field of disposable plastic syringes. The first part is dedicated to the definition of the specific components of the syringe itself; secondly, a table defines the nominal capacity (in ml) with its tolerances. Let us skip the section that classifies the size of the syringe including graduated scales, lubrication, labelling and packaging, and focus directly on the tests indicated in the norm concerning physical and not just visual evidence. Annex B  describes the procedures to test syringes for leaks during aspiration, and the separation of the piston from the plunger. This procedure consists in generating vacuum through a pump within the syringe and maintaining the vacuum for a set amount of time, to examine if there is any leakage of liquid or if the piston has somehow detached itself from the plunger.
Annex D  describes the tests where the filled syringe is exposed to a lateral force and to an axial compression force, in order to check any leakage. After holding this configuration for a certain amount of time, the syringe is visually examined to check for leaks. Annex G  describes the test to evaluate the force required to slide the plunger on the barrel. The procedure is applied to a syringe which is filled with a fluid and connected to a water container through a tube: during the sliding of the plunger it is possible to notice at first the value of the peak force, and secondly the average force recorded throughout the full extent. In order to comply with the norm, the reference limit values indicated in the table present in the same Annex must be respected.
The project development
Good practice and internal know-how lead Brevetti Angela to equip the machine not only with a solid structure, but also with sensors, electrical components, load cells and high-end torsiometers. A dedicated PLC software allows to automatically manage all the steps of the test through an HMI touch screen panel, monitored by a SCADA system that provides a user-friendly interface. The end user can easily manage the test results, which are provided in electronic format and can therefore be stored or printed at will. The goal of Securespect is to ensure that the operator shall only place the syringe inside the machine, and eventually read the results at the end of the test. Obviously, handling from one station to the next one should be done by the operator itself after the syringe has completed the single test. The care of materials and ergonomics was highly considered when building the machine. Securespect is equipped with a solid but light base that is suitable for its use within a laboratory. The test stations are geared with load cells, potentiometers and torque meters, which are in direct communication with the Digiforce® controller. The SCADA system allows the user to download and manage data as they are directly supplied by such controller. The PLC handles all the movement-related parts that allow the user to automatically perform the tests. The size of syringes to be tested determines the flexibility of the machine, which is able to operate on every sizes of syringes listed in the regulation. With a simple initial setting, the user can choose the kind of syringe to be tested, and the Securespect will accordingly undergo an automatic set-up to accommodate the size of the selected syringe.
The tests with different samples can be processed simultaneously, therefore the speed of station change and set up is actually the only limit.
A prototype of Securespect was presented to the PDA in Vienna in 2015 as a highly innovative product, even though that first prototype only allowed to perform one type of test besides the twist test for the detachment of the covers. Despite this initial limitation, Securespect was immediately greeted as an innovative product and has raised the expected interest in the pharmaceutical industry. Securespect machine is of course tightly bound to Brevetti Angela’s Securespect® machine, as it is able to process the syringes that are produced directly from Securespect®. The serial production of pre-filled syringes is thus proficiently paired with the confirmed compliance of the final product with the standard validation tests.