Drug Discovery, Development & Delivery Pre-fillable Syringes for the Biotechnological Requirements of the Present and Future

Pre-fillable syringes are both pharmaceutical primary packaging and drug delivery devices. End users, drug administration agencies and the pharmaceutical industry are imposing increasingly stringent quality requirements on pre-fillable syringes in both these functions. Optimised production and inspection processes ensure that the syringes can meet these requirements. Although siliconisation is crucial as lubricant to the proper function of the plunger in the syringe body, it has to be reduced to the minimum in syringes used for innovative biotech drugs. A longterm study investigated the factors that affect break loose and gliding forces in syringes during the injection process. The findings make a valuable contribution to establishing certainty that syringes in auto-injectors, which are often stored for lengthy periods of time, will still reliably administer the required dosage. 1. Pre-fillable Syringes Pre-fillable syringes are still one of the strongest growth segments in the global primary packaging materials market. In 2015, approximately 3 billion prefillable syringes were sold worldwide. Pre-fillable syringes must fulfill the most varied requirements, both as the lowest interaction primary packaging material possible, and on the other hand as a secure delivery system ("drug delivery device"). Special requirements for purity are presented by innovative medications originating from biotechnological research. The classical application areas for medications in pre-fillable syringes (heparin as a thrombosis prophylaxis and vaccines) have today been supplemented by many additional illnesses that can be treated with the help of pre-filled syringes. Ophthalmological applications, the treatment of arthritis, growth hormones, various forms of cancer or applications for neurological conditions – every therapy requires adjustments and further developments that initially seem minor, but have very different syringe designs as a consequence when considered in detail (Fig. 1). Pre-filled Syringe as Primary Packaging Material The number of biotechnologically manufactured medications is increasing constantly. Many of these are filled and stored in syringes for the benefit of the user (pre-filled syringes). However, under certain circumstances proteins can react to components of the syringe that are not part of a classic vial. In addition to the packaging material glass (pharmaceutical glass, type I glass in accordance with Ph. Eur.), syringes contain the following "components": silicone oil as a lubricant for the plunger stopper, traces of tungsten from the production process of the glass syringes, stainless steel of the cannulas, as well as the glue used to fix the cannulas. As with the vial, these new sources for leachables and extractables (L&E) are supplemented by the elastomerbased sealing components. In the case of the syringe, one differentiates between halobutyl-based rubber types for plunger stoppers and synthetic isopreneor blends for sealing caps (tip caps and, in the case of needle syringes, so-called needle shields, Fig. 2). Other components such as the plunger rod and, e.g., the backstop, are not primary packaging materials, as they have no contact with the product’s primary packaging. The pre-filled syringe primarily protects the medication against oxidation and microbial contamination1. It should interact with the solution or contaminate this with L&E and particles to the least extent possible. This is especially important for the primary packaging of protein-based medications and for ophthalmological applications. In the context of stability studies, pharmaceutical companies are obliged to examine the possible interactions between packaging materials and medication. The drug stability must thereby be ensured until the expiration of the drug shelf-life. Actual Syringe Function End users such as doctors, nursing staff and increasingly patients themselves ("home use") expect and wish that injections can be administered as seldom as possible, meaning at long intervals, as simply as possible and with a minimum of pain. The syringe thus needs to be adapted not only to the medication, but also to the users. This means that prefillable syringes are increasingly being integrated into auto-injectors for use at home. Failure-free function, even with highly viscous solutions or low dosages, must thus also be ensured. Protection from needle stick injuries is another aspect that is increasing in importance. In the USA, "needle safety systems" have already been federally regulated to manufacturers since 1999 in the form of the "Needle Stick Safety and Prevention Act". Needle injuries ultimately represent a potential source of infections with life-threatening diseases like hepatitis or HIV for nursing staff. Auto-injectors also offer these properties, but are not normally used in hospitals or by specialist personnel. Most needle safety systems work by a spring-driven mechanism that shields the needle after the injection has been carried out. Packaging material development departments thus face a variety of challenges in coordinating automatic injectors, needle protection, syringe and medication with one another. In the biotech sector, the 1 ml long needle syringe is the most frequently used format for subcutaneous injections. The current trend toward larger dosage volumes also brings with it an increasing demand for 2.25 ml needle syringes. In ophthalmology, primarily Luer lock types are used, as special cannulas are needed. More Safety with Backstops In addition to the needle, the finger Figure 1