In medical engineering and in the pharmaceutical industry, elastomer gaskets are often used in injection and infusion systems in order to fulfil the primary requirement of ensuring the integrity of the medication in the primary packaging. This white paper submitted by Raumedic (Helmbrechts, Germany), a supplier of extrusion, injection molding and assembly services to healthcare OEMs, discusses the material sourcing and manufacturing issues that must be considered in these critical applications.
In terms of materials, elastomer gaskets can be divided into three categories: Pharmaceutical rubber, which is the most commonly used material; silicone; and thermoplastic elastomers (TPEs). Given the extensive and complex requirement profile of elastomer gaskets used in injection and infusion systems, all three groups have their strengths and weaknesses.
The extractables profile represents an essential issue, since the gasket comes in direct contact with medication. The profile provides a quantitative and qualitative disclosure of all substances that may potentially migrate from the gasket material under strict conditions: for example, the extraction medium may be more soluble than the final formulation of the medication and it may be exposed to elevated temperatures.
In the various extraction methods and extraction media, silicone formulations exhibit better results than pharmaceutical rubber and TPEs. Small amounts of non-critical substances tend to migrate. Among silicone formulations, there is a gradation from potentially harmless platinum-cured to peroxide-cured material mixtures. This is caused by the cross-linking reaction that occurs in a controlled manner when the platinum catalyst is added. 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 in comparison to pharmaceutical rubber and TPE can be attributed to the relatively low number of components in the formulation, most of which can be classified as non-critical, and the manufacturing process, which ideally occurs under cleanroom conditions.
Unlike natural rubber–based pharmaceutical rubber, silicone will not trigger latex allergy symptoms in the patient should contamination occur. Approximately 2% of the population and 10% to 17% of people who have frequent contact with latex are affected by a latex allergy.
The leachables study is performed after the extractables study. It covers the substances released in the extractables study that are classified as critical; an analysis of their potential interaction with the final medication typically is performed by the pharmacist. Because it achieves good results in the extractables study, silicone also is expected to do well in the leachables study.
Since the elastomer gasket of an injection and infusion system comes in direct contact with medication, the unfilled, pre-assembled system is sterilized. Gamma radiation is the most common method, since sterilisation with a gas, such as ethylene oxide, requires an enclosed chamber system. Superheated steam sterilisation is generally unsuitable, because thermoplastics tend to shrink, deform or even suffer thermal degradation with a resulting loss of mechanical properties when exposed to a constant temperature of 121°C. Silicone is generally compatible with all three sterilisation processes.
It is also important for the elastomer gasket and the entire system to be produced under microbiologically clean conditions in accordance with good manufacturing practice guidelines. The associated test is the so-called bioburden test. Bioburden means the determination of the population of viable microorganisms on a product and packaging. The purpose of this test is to find out how many viable microorganisms are found on the product after production and to determine whether subsequent sterilisation is necessary. To keep the number of microorganisms as small as possible, production of the individual components, the intermediate transport and storage of the injection and infusion systems and their final assembly ideally occur under controlled cleanroom conditions, as per ISO 14644.
Minimizing contamination during production
Depending on the material and production process, the cleanliness of elastomer gaskets can vary significantly. Pharmaceutical rubber is obtained from natural rubber or, in many cases, is formulated from synthetic rubber with fillers, plasticisers and various chemicals. The production process occurs entirely outside the cleanroom, starting with the harvesting of rubber to the molding, stamping and tempering processes. In particular, the stamping of the plungers from the injection molded, semi-finished mat entails a risk of particle abrasion. The necessary cleanroom quality is only obtained during the washing process.
By contrast, silicone and thermoplastics are injection molded under cleanroom conditions, starting from the shaping of the gasket element. This significantly reduces the risk of contamination. In addition, these processes do not require subsequent stamping or washing of the parts, as long as the process is performed in a cleanroom.
Mechanical 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 dosing during injection difficult for doctors. Also, doctors prefer that the sliding friction of the injection plunger against the siliconized syringe body remain constant and not show a stick-slip effect. Again, silicone plungers achieve the best test results in direct comparison to plungers made of pharmaceutical rubber or TPE.
Ensuring a tight seal
The real challenge in sealing an injection system is ensuring seal tightness throughout the entire production life cycle under extremely varied environmental conditions. This begins with sterilisation of the unfilled injection system to the transportation and storage of the filled system until its final use in surgical rooms and clinics.
Seal tightness is a property that must be tested according to the requirements of a particular application under given environmental conditions. "Absolute seal tightness" is practically unobtainable. Therefore, seal tightness is often given in terms of specified leakage rates. For instance, watertight is defined as having a leakage rate of 10-2 mbar/s, and bacteria-proof is defined as 10-4 mbar/s.
In addition to the basic gasket material, hardness, the compression set, environmental temperature, ambient media and design all play a decisive role.
There is no standardized formula for designing and manufacturing elastomer gaskets for use 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. Raumedic supports its customers from the initial idea through product and process development to industrial implementation.
This article is authored by Markus Rössler, Product Manager Silicone Molding, Business Unit Molding, Pharma Solutions, and Jörg Prescher, Head of Technical Center of Excellence, Silicone Moulding, at Raumedic.