Medtech Manufacturing: Elastomer Gaskets For Injection And Infusion Systems

By Markus Rößler and Jörg Prescher, Raumedic

In medical engineering and in the pharmaceutical industry, elastomer gaskets are often used for injection and infusion systems in order to guarantee the integrity of the medication in the primary packaging. This article examines how different materials and production processes are leveraged to meet product- and customer-specific gasket needs.

The Three Material Groups

Elastomer gaskets can be divided into three categories: pharmaceutical rubber (the most widespread), silicone, and TPE (thermoplastic elastomer). With regard to the extensive and complex requirement profiles of elastomer gaskets for injection and infusion systems, all three gasket groups have strengths and weaknesses. Here are some of the commonly recurring aspects of the customer-specific and product-specific requirement profiles.

Extractables And Leachables

The extractables profile is an essential issue, since the gasket comes in direct contact with the medication. The profile provides a quantitative and qualitative disclosure of all substances that may potentially migrate from the gasket material when used under "strict" conditions (i.e., an extraction medium that is more soluble than the formulation of the medication to be used, combined with an increased temperature, is applied to the unit to determine the profile).

Within the various extraction methods and extraction media, silicone formulations exhibit the best results, compared to pharmaceutical rubber and TPE formulations. Small amounts of non-critical substances tend to migrate, regardless of formulation. Among the various silicone formulations, there is a gradient from the potentially harmless platinum-cured material mixtures to the peroxide-cured material mixtures. This is due to the cross-linking reaction that occurs in a controlled manner when the platinum catalyst is added.

In contrast, a higher proportion of volatile components are released by the peroxide cross-linking reaction, which occurs in a less controlled manner. The generally good results of silicone, compared to pharmaceutical rubber and TPE, are attributable on one hand to the relatively low number of components in the formulation — most of which can also be classified as non-critical — and on the other hand to the manufacturing process, which ideally occurs under clean room conditions.

Also, contrary to pharmaceutical rubber produced from natural rubber, silicone contamination of the medication will not trigger latex allergy symptoms in a patient. After all, approximately two percent of the overall population — and approximately 10 to 17 percent of people who have frequent contact with latex — are affected by a latex allergy.

The leachables study is performed after the extractables study. It examines the substances released in the extractables study that are classified as critical, analysing their potential interaction with the final medication. A pharmacist generally performs and analyses the leachables study independently. Based on the generally good results of silicone in the extractables study, there is a high probability of good results in the leachables study, as well.

Sterilization

Since the elastomer gasket of an injection and infusion system comes in direct contact with medication, the unfilled, pre-assembled system is sterilised. This sterilisation is mostly performed with gamma radiation, since sterilisation with a gas (ethylene oxide) is limited by the enclosed chamber system. Superheated steam sterilisation also is often unsuitable because, at a constant temperature of 121°C, many of the thermoplastic raw materials used in injection and infusion systems tend to shrink, deform, or even suffer thermal degradation with a resulting loss of mechanical properties.

Silicone is generally compatible with all three of the sterilisation processes mentioned. Irradiation with gamma rays does not exhibit negative effects on silicone, nor do long-term thermal stresses in the range of 120°C.

Microbiological Purity

Despite subsequent sterilisation, it is also important for the elastomer gasket and the entire system to be produced under microbiologically "clean" conditions, according to GMP (Good Manufacturing Practice) guidelines. The associated test is called the "bioburden test.”

Bioburden tests determine the population of viable microorganisms on a product and/or in its packaging, as well as whether subsequent sterilisation is necessary. To keep the number of microorganisms as small as possible, the production of the individual components, the intermediate transport and storage of injection and infusion systems, and their final assembly ideally occur under clean room conditions, as per ISO 14644.

The Various Production Processes

Significant differences in cleanliness can be seen in production of the elastomer gasket.  Pharmaceutical rubber is either obtained from natural rubber or, in many cases, produced from synthetic rubber and provided with fillers, plasticisers, and various chemicals (e.g., propellants, antioxidants, and processing additives) to adjust its properties. The production process occurs entirely outside the clean room, starting with the harvesting, preparation, and processing of rubber into semi-finished products. Next, the semi-finished rubber undergoes the shaping process by means of pressing or injection moulding, and subsequent stamping and tempering.

In particular, the stamping of plungers from the injection-moulded, semi-finished mat carries a risk of particle abrasion. The necessary clean room quality is only obtained during the subsequent washing process. By contrast, the silicone injection-moulding process and the thermoplastic injection-moulding process occur under clean room conditions, from the process of shaping the gasket element through its follow-up process steps. This significantly reduces the risk of contaminating the elastomer gaskets. In addition, these processes require neither subsequent stamping nor subsequent washing of the parts.

Breakaway And Sliding Friction Forces

Beyond biochemical and technical manufacturing issues, forces also play a significant role in injection systems. The first is the breakaway force of the gasket on the syringe plunger within the syringe body: A high breakaway force may make precise and fine dosing during injection difficult for doctors. Second, it is to the doctors' advantage when the sliding friction of the injection plunger against the siliconized syringe body remains constant throughout the injection, and does not exhibit a stick-slip effect.  Again, silicone plungers test superior to plungers made of pharmaceutical rubber or TPE.

Sealing

The real challenge in sealing an injection system is guaranteeing seal tightness throughout the entire production life cycle, and under extremely varied environmental conditions. This process begins with sterilisation of the unfilled injection system and continues through the filling of medication into the injection system. After packaging, seal integrity must hold through transportation and the system’s entire storage period, until its final use by doctors.

However, seal tightness is a property that must be tested according to the requirements of the particular application, under the given environmental conditions. "Absolute seal tightness" is practically unobtainable. Therefore seal-tightness is often given in terms of specified leakage rates. For example, "watertight" is defined as having a leakage rate of 10^-2 mbar/s, and "bacteria-proof" is defined as 10^-4 mbar/s. However, in addition to the basic gasket material, its hardness, the particular compression set, the environmental temperature, the ambient media, and the design all play a decisive role.

Conclusion

In summary, there is no generally applicable formula for manufacturing elastomer gaskets in injection and infusion systems. In each case, the sealing system has to be developed, qualified, and validated in a product-specific and customer-specific manner, since the requirements are diverse and complex. 

About The Authors

Markus Rößler is product manager in the Business Team, Marketing and Sales, within the strategic Molding / Pharma Solution business unit of RAUMEDIC AG. In this role, he oversees RAUMEDIC’s products, such as Silicone Injection Molded parts that are used in medical, as well as pharmaceutical production.

Jörg Prescher is head of Raumedic's Technical Center of Excellence, Silicone Moulding.