This article is part of a special feature on injectables that was published in the February issue of PTE Digital, available at http://www.pharmtech.com/ptedigital0211.

Raul Soikes

The pharma industry is constantly seeking drug delivery technologies that can increase compliance, improve the quality of delivered care, reduce medication errors and reduce the possibility of admixture-related contamination. Prefilled syringes, along with premixed infusion bags, are singledose, readytouse delivery systems that have the potential to positively impact patient care. From a pharma company's point of view, prefilled syringes can also contribute to a product's overall success.

Advantages of prefilled syringes include:

• Ease of use. Prefilled syringes meet the demands of physicians and patients for effective and easytouse administration methods.
• Reducing medication errors. A medication in a readytouse format, in conjunction with other related initiatives, can help reduce medication errors.
• Lifecycle management. Moving a product from a vial to a syringe may provide differentiation from competitive agents in the same therapeutic category.
• Pricing. Economic advantages may also be possible for pharma manufactures. Prefilled syringes meet the stated demand for increased safety and convenience, and may present the opportunities for premium pricing compared with vials.

Prefilled syringes also offer savings from a capital investment perspective. Vial washing, depyrogenation and vial component preparation equipment are not required because the syringes come presterilised and ready for use. Also, increased efficiency can be achieved by leveraging modern automated filling technology with barrier isolation systems, which can offer fill–finish lines with smaller footprints, higher throughputs and longer validation windows.

Manufacturing challenges

Biotech products, in particular, provide a number of unique manufacturing challenges compared with big therapeutic classes, such as anticoagulants and vaccines. The trend towards readytouse delivery systems combined with the decreasing manufacturing volume associated with biotech products and more targeted therapies poses an efficiency challenge. Batch sizes are typically smaller, requiring potential innovation and manufacturing optimisation to provide sustainable value.

For contract manufacturers, there are also complexities related to global regulatory compliance because there are marked differences in the expectations and best practices of key regulatory agencies. For example, specific structural changes needed for one client to ensure regulatory compliance may impact others using the same manufacturing line. Finding appropriate solutions to accommodate the broad spectrum of client and regulatory requirements is an intricate responsibility of utmost importance.

As with other sterile filling, such as vials, another challenge that can arise is the need to calibrate automated inspection equipment to meet the standards of multiple regional regulatory agencies, as well as client expectations. There is also often a lack of validated data to adequately handle product physicochemical limitations, such as air and/or light sensitivity, time out from refrigeration, shearing concerns and others.

Innovation

There have been a number of recent innovations in prefilled syringes:

• Restricted access barrier systems have had one of the biggest impacts on the sterility assurance of prefilled syringes.
• Electron beam sterilisation tunnels for the aseptic transfer of prefilled syringe tubs provide benefits by delivering high throughput and high levels of sterility assurance.
• Non-destructive control and inspection advances, coupled with improved cold chain management, are of great advantage to minimise the waste of highcost biologic APIs.
• Enhanced readability of fluid levels and accuracy of fluid draw helps ensure appropriate dosing.

Despite the advances made so far, there is still room for further improvement. There has been an increase in the requirements for documented processing and control of the glass syringe throughout manufacture including: tube processing, forming machines (including closedloop controls), ammonium sulphate treatment, coating and annealing controls, leachable and extractable analysis, dimensional and cosmetic inspection, needle assembly control, WFI washing, siliconisation, shield assembly and nesting. The systems that support the timely availability of this data will need to evolve and improve to support the requirements of pharma and biotech companies.

As drugs evolve to more targeted applications, manufacturing flexibility will be crucial. From a CMO's perspective, innovative equipment that supports this flexibility and optimisation (e.g., equipment that can handle multiple safety shield vendors with minimal change parts) will be very important. Another improvement that would be welcomed is easy interchangeability in fill and inspection equipment for glass and plastic syringes, which would increase efficiency and provide more flexibility.

Specifically for biologics, a siliconisation process or suitable substitute is needed that has zero to minimal impact on the biological material. New tools for funnel forming combined with lower forming temperatures currently provide the lowest Tungsten content, but alternates are needed, as this would improve stability by eliminating the potentially detrimental Tungsten–protein interaction. Further understanding of product/container interactions is also required to ensure hydrolytic resistance of the syringe to prevent delamination, an issue in recent product recalls seen in the market.