The advantages for drug developers using prefilled syringes are numerous; improved patient compliance and better cost efficiency, as well as mitigating the risks of drug wastage and product contamination. However, this rapidly expanding area is not without its hurdles.
Prefilled syringes act as the primary container for drug products. Therefore, they are required to provide seal integrity, compatibility and drug stability through the shelf life of the drug product.
There are some challenges associated with the current staked needle glass syringe system: the potential organic and inorganic chemicals in the syringe components have a tendency to leach into the drug solutions. Surface silicone oil has caused protein drug aggregation. Residual tungsten from the staked needle insertion process can cause protein degradation. Glass breakage problems have been the reason for several glass prefilled syringe products recalls.
The major drivers for prefilled syringes are due to the ongoing boom in biotechnology. In this market segment, highly individual products of high quality and value are produced in small batches. The traditional mass production, high speed operation of producing container closure method has been challenged. In order to meet the high quality requirement, multi-facet approaches have been taken.
The improvement in various aspects of prefilled syringe supply chain have been demonstrated, it is necessary to have the integrated approach in order to achieve the goal.
Material Construction
Quality standards for glass syringes have been raised, the dimension tolerance is tightened, the crack and cosmetic defects have been reduced or eliminated, the tungsten level has been minimized, and an upper limit of 5000 ppb is under discussion. A minimal level and evenly distributed silicone coating on the inside of the glass barrel is expected and the work is in progress.
Plastic syringes made of COC, COP and novel cyclic olefin polymer (custom formulated COP resin) systems have been developed. These cyclic olefin copolymers and polymers have excellent transparency, good moisture barrier properties, and are chemically clean with very low extractables. They are break resistant, have low protein surface adsorption, are compatible with wide pH range solutions, have good dimensional tolerance and high flexibility in design and no tungsten or adhesive is involved in fixing a staked needle to plastic syringes [1].
Fluorocarbon coatings on rubber plunger surfaces provide surface lubricity and chemical barrier. There are two companies that have commercially available fluorocarbon coatings on rubber plungers. One distributes a PVTF coating that provides some lubricity and barrier properties. The other produces an ETFE film that can eliminate silicone oil on the plunger and minimize extractables and leachables.
In order to meet the high quality requirements of glass syringes, the manufacturing process must be modified, such as in process control with vision systems and packaging inside of clean rooms. Automated visual inspection to check for dimensional, cosmetic defects and particles are becoming a common practice for both glass syringe and rubber components suppliers.
Pre-sterilized syringes are gaining popularity, the supplier will perform the washing, siliconization and sterilization processes; the nested syringes are packaged in plastic tubs ready for filling. An electron beam sterilization tunnel for the surface decontamination of tubs is becoming a common practice. Some film coated plungers often require the vacuum placement method; this method requires more time and decreases the syringe –filler line speed [2].
Manufacturing Equipment
In order to meet the process change for the purpose of quality or efficiency improvements, new equipment has been implemented, such as the automated vision system, barrier isolator, electron beam sterilization tunnel, automated bag and tub opening system, different closure methods such as the vacuum placement equipment etc. Automation in production will help leverage product quality, minimize manual interventions – the main cause for particles and sterility problems.
Syringe Design
Prefilled syringes are being driven by the need for convenience, efficiency and safety in delivery of injectable drugs. There are many needle safety devices that have been developed, most of them are passive needle guards with a plastic shield outside of the glass syringe to cover the needle after the injection; one specific developer of drug delivery systems has a different design with a retractable needle system, after the injection, the needle moves into the syringe barrel, it takes less space and generates less waste. Customized designs of the needle guard can be used as a product differentiation tool [3].
A new staked needle prefillable glass syringe has been developed by a leading glass manufacturer and developer. The geometry of the glass barrel does not require any tungsten during the glass forming process, the drug is not in contact with the needle during storage, the staked needle does not stick into a needle shield; therefore, it is tungsten free and has low extractables [4].
Summary
For needle phobic patients, the prefilled syringes can be put into an auto-injector to hide the needle. The auto-injector has been noticed to be very popular for patients to self- administer their injections. However, the prefilled syringe is still the most economical, efficient, and simple device to use for the vast majority of the population.
Much progress has been made in Prefilled Syringes; it takes an integrated effort in every step of the supply chain to cooperate and contribute in order to achieve the goal.
References
1. Kiang P. Future Materials for Prefilled Syringe components, American Pharmaceutical Review, July/August 2011: 54-58
2. Ullherr K. Processing Prefilled Syringes in the future how will manufacturers and suppliers approach PFS? Contract Pharma, September 2012: 90-94
3. Dubin C. Special feature handheld injection devices: Safer, simpler, and more customized, Drug Development & Delivery, September 2012: 49-58
4. Prefillable Glass syringe website
Author Biography
Patty H. Kiang, Ph.D., is a Pharmaceutical Consultant on Pharmaceutical Packaging and Delivery Devices for Liquid and Lyophilized Products, Prefilled Syringe System, Injection Devices and CMC Filing for Combination Products. Prior to the consultant position, she held delivery device roles at Catalent Pharma Solutions, Genentech, Inc., Schering Plough, and West Pharmaceutical Services. She is a member of the faculty of the PDA’s Training and Research Institute, where she teaches courses on Parenteral Packaging, Prefilled Syringe and Injection Devices, and served as a member of USP’s Expert Committee on Drug Packaging, Storage and Distribution. She was the chairperson for the PDA Gamma Radiation Sterilization of Polymeric Materials Committee. Patty is an expert in the area of drug and container/closure interactions and compatibility issues.