Following the more frequent request for ready for filling containers, ISO TC76 published in 2015 the standards for sterilized sub-assembled ready-to-fill glass syringes ISO 11040-4 and ISO 11040-7, including the corresponding packaging system. These two standards define the production of the glass syringes and the related test methods, as well as the “ready for filling” packaging.

In November 2016, ISO TC76 published ISO 11040-8 Requirements and test methods for finished prefilled syringes. Due to the increasing market presence of syringes “ready for filling” and the associated advantages of this product for the pharmaceutical industry, the suppliers of packaging materials started to develop systems of this type for vials.

ISO TC76 is developing two International Standards to specify the characteristics of sterile and ready for filling empty glass cartridges and vials, including the minimum requirements of materials, the packaging systems and analytical test methods (ISO DIS 21881 and ISO DIS 21882).

Many key healthcare stakeholders around the world (i.e. governments, IGOs and NGOs) are increasingly advocating the benefits of the localised production of medicines.  Many governments in particular are driving much of this localisation by offering incentives such as tender exclusivity, price preferences, tax relief and other non-financial benefits for those making all or a portion of a product locally. Sterile pharmaceuticals, vaccines and biologics have long been seen by many Western companies as too complex or costly to produce in all but a handful of global markets.  However, broader acceptance and use of technologies such as modular production facilities, single-use and ready to use materials are lowering some of the historic barriers to being able to product these products in some places.  

This session will introduce some of the ways these technologies are beginning to change the way some of these previously unattractive opportunities are viewed.

Through this presentation, we will review the recent project undertaken by Alexion to introduce a state of the art aseptic filling line. The presentation will cover aspects of the project such as: Conceptual design through to PPQ manufacture using the ASTM validation approach. With pre-sterilised nested vials as a primary requirement for Alexion, we will also discuss some of the handling technology required to load, fill and de-nest the vials. The presentation will also detail some lessons learnt along with FDA/HPRA feedback.

The FDA Draft Guidance “Container/Closure Systems for Packaging Human Drugs and Biologics” was issued in 1999.  But in the past decades, there has been a change in the scrutiny of the way FDA reviewers looked at E&L data.   They have gradually increased the requirements, not backed up with any official document (Guidance, guideline…) which left the Pharmaceutical Industry in the dark, second guessing of what the current position and requirements were of the FDA to support a submission.

In this presentation, the key factors of success of any given E&L project will be highlighted.  Crucial is to understand what regulators really want and aligning the design space of an E&L study to their expectations.

Facing the reality of the ever-evolving regulatory landscape, analytical testing labs need to be on the forefront with expertise in the field of extractables and leachables testing and state-of –the art technology.  Meeting the development needs and requirements, of the pharmaceutical and biopharmaceutical industries, also raises the bar for material suppliers.

Only through successful partnering between drug product vendors, material suppliers and the CRO performing the test, a true mitigation of the risk related to packing can be established. 

Glass containers for pharmaceutical use are glass articles intended to come into direct contact with pharmaceutical preparations. To guarantee drug quality, safety and efficacy, the glass material shall not release substances in quantities sufficient to affect the stability of the preparation or to present a risk of toxicity and particles release. In general, when a glass is faced with a solution, two mechanisms are involved: de-alkalization (commonly referred to as leaching) and network dissolution. The prevalence of one of these mechanisms is also a function of the glass chemical composition and enviromental conditions (e.g. temperature and humidity). The chemical resistance and weathering behavior of allegedly inert pharmaceutical glasses (Type I, II and III) is largely studied nowadays but an ad hoc study on the entire pharmaceutical packaging system to predict the stability in packaged product should be always recommended.

Case studies will highlight the elemental leachability and the chemical durability of pharmaceutical glass containers and they will give a general overview on the analytical investigation of the mechanisms of degradation in heterogeneous systems.

As for most other industries time to market in combination with flexibility and light financial assets are today key challenges in the pharma industry. The compliance requirements is also a factor that needs to be considered. This puts higher requirements on the flexibility aspect for new facility design and project execution. Utilizing pre-sterilized vials/syringes make the facility even more flexible, the absence of container washing and sterilization tunnel create an easily moveable “plug & play” solution for rapid deployment world-wide.
Can modularization and off-site construction be the most flexible solution for the next generation facilities?

Content:
• Platforms for new facility design
• Flexibility
• Off-site construction
• Flexibility of filling in pre-sterilized containers
• Case-Study ”Modular Aseptic Solution CMO Perspective”

Traditional “off-the-shelf” primary packaging solutions for parenteral use may not always meet all the different aspects associated to modern, evolved biotech and specialty applications, therefore the definition of correct design inputs is paramount in the development of a syringe intended for the delivery of biotech drugs. Covering aspects like “intended use”, chemical and biochemical compatibility, performance characterization, design for manufacturability, are the cornerstone of any development path required for combination products, securing a robust regulatory compliance.

Only the companies that can offer an holistic view and a combined set of capabilities, from project management to manufacturing assets through device integration, can help to mitigate the risk associated to the development challenges. This paper will explain how SG covered these challenges in recent developments for injectables.

Injectable drug manufacturers are challenged to minimize risk, accelerate product development, ensure patient safety and improve ease of administration. At the same time, companies must differentiate their new products within therapeutic categories that are very competitive. Prefillable syringes and cartridges offer many benefits when compared to vial formats, including precise dose accuracy, less drug overfills for lower unit cost, and drug product differentiation. Proper selection of primary elastomer components, used to package and deliver drugs in syringe or cartridge formats, is critical for patient safety and must be considered during development. The discussion will address the availability of different packaging options for Ready-to-Sterilize and Ready-to-Use components well adapted to the customer needs and provide insight on different sterilization methods, including steam and gamma, applied to plungers and stoppers, and the impact such methods might have regarding extractable profiles or functionality.

This workshop presentation is designed to educate participants, provide case study examples and includes content for:
• Market trends driven by regulatory expectations
• Matching component designs to meet user requirements
• Component material selection and criteria
• Considerations for functionality and container closure integrity
• Ready-to-sterilize and ready-to-use components to meet fill-finish technology

Innovative approach to handle nested syringes, vials and pre-capped cartridges.

Through this paper we will explore the value of the use of advanced robotic driven manipulations versus conventional handling systems, focusing on how the application of new technologies actually improves product quality and manufacturing efficiency. We will therefore get through the major benefits of advanced process flexibility and adaptability (easy size changeover operations of nested components, pre-oriented vials in trays or sterilized vials from depyrogenating tunnel), more gentle and fully automated material handling (reduction of human interventions and cross-contamination risks) and all-in-one integrated fill-finish solution (in-line lyo loading/unloading processes and integrated capping station).

The implementation of single-use technologies in the final filling process is steadily increasing. Single-use technologies can effectively meet the stringent requirements for this final process step with proper assembly design and integration. However there are also risks associated with their use that can include product loss and questions around sterility assurance and product safety. Best design considerations and practical applications for these assemblies in the final filling process will be discussed. Particular attention will be given to the risk mitigation during final fill assembly design, manufacturing, and use.

As a leading developer and manufacturer of self-injection systems, Ypsomed Delivery Systems is focussed on the market for subcutaneous injectors based on pens, autoinjectors and wearable patch-injectors. The presentation will focus on the current market and trends in self-injection, and in particular on the recent success of customisable YpsoMate and UnoPen platform products. In addition, the presentation will focus on the new therapies and market dynamics that are increasing the need for larger volume injection devices including patch-injectors, and driving the demand for smart injection devices that operate within connected healthcare ecosystems.