FAQ

    What is “Ready to Use” or “Ready to Fill” and what container options are available ready-to-use?

    The term “ready to use” or “ready to fill” describes containers that have undergone washing, depyrogenation, packaging and a final sterilization process using gamma irradiation, EtO or autoclave sterilization.  The packaging typically consists of a plastic nest that holds each individual and is located within a plastic tub.  A loose sheet of Tyvek, referred to as a “liner”, is placed over the tops of the containers within the nest and the tub is sealed with another Tyvek sheet, often times called a “lid”, to seal the sterile containers until it is removed prior to aseptic filling.

    The advantages of getting containers in this pre-sterilized state include eliminating expensive equipment that has to be purchased with the filling machine to wash and depyrogenate the containers before filling.  One must also consider the facilities, utilities and personnel activities that are required to support the process of preparing containers to receive the sterile drug product.  The Water for Injection (WFI) system, cleanroom space, maintenance and validation for these systems all go away.  This enables a simple and more nimble manufacturing environment with less infrastructure and support requirements.

    There are many commercially available Ready to use options available for syringes vials and cartridges from several reputable suppliers including; Ompi, Schott, Becton-Dickenson, and West to name a few.

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    What are the best options for dosing drug product into the final product container?

    Many different factors need to be considered when selecting the optimal dispensing system.  Both the ASEPTiCell and GENiSYS systems can be integrated with several different dispensing systems such as peristaltic and rotary piston pumps.  Below are a couple of key considerations;

    Product viscosity can greatly influence dispense accuracy and limit dispense options. Generally viscous products are best suited for rotary piston pumps.  However, products with a viscosity similar to water experience product “slippage” and leak between the piston and cylinder.  The slippage can reduce dose accuracy.

    Many of the biologic products such as mono-clonal antibodies (MABs), proteins and other biologic proteins can be shear sensitive.  Therefore choosing a dispensing technology that induces the least amount of shear is preferred.  Peristaltic pumps and time-pressure dispense are the best options, however peristaltic has the advantage of providing a completely disposable option that is pre-sterilized and doesn’t have to be cleaned post filling.

    Product potency can be challenging because of the cleaning and product carry-over risk from one batch to another.  Also keeping protection of personnel is essential to minimize product exposure to potent material.  Single-use disposable fluid pathways are generally the best means of isolating and disposing of potent materials while minimizing cleaning and exposure risks.  Given this, peristaltic pumps would be the recommended option.

    Peristaltic and rotary piston pumps provide repeatable and accurate dosing typically within 1%-2% of the desired dispense volume.  Peristaltic pumps are extremely versatile with accuracy being highly dependent upon the diameter of the fluid path tubing and filling needle.  Rotary piston pumps are equally accurate but require specific cylinder and piston combinations to dispense the correct volume.

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    When processing syringes which process is better for placing the piston into the syringe; vacuum or mechanical vent-tube?

    Product, container – piston combination, and whether the syringe or cartridge will be used with a medical device like an injection pen, are the most common factors to consider when deciding which method is best for placing the piston within a syringe.

    Vacuum piston insertion has the advantage of eliminating the air bubble that is common to the mechanical vent-tube method.  The elimination of the air bubble within the syringe eliminates potential oxidation problems with the product and can increase product shelf life.  Vacuum can be provided with a mechanical assist, uses a pin to accurately position the piston after vacuum has been pulled.  This is commonly done for syringes that will be used with medical devices so that they can dispense accurately.  Finally, certain silicon free syringes like West Pharmaceuticals CZ syringe require vacuum to be used because of the material mechanical properties of the piston exterior coating.

    Syringe piston insertion using a mechanical vent-tube approach is good for application using a glass syringe with a bromobutyl stopper, for products with low vacuum pressure and where product oxidation is not a risk.

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    How do you determine the amount of viable and non-viable monitoring locations within an aseptic filling system?

    Non-viable and viable monitoring is required to provide qualitative (viable active and passive air sampling) and quantitative (non-viable particle sample) data to confirm that the environment the drug product was filled within met the regulatory requirement for an aseptic process.  Therefore, it is important that each application determine the risk areas of the aseptic process and place monitoring instrumentation in these locations such that ample supportive data can be provided to assure the quality of the aseptic environment and process.  AST works with each one of our customer’s to properly assess the risk of the particular line design to determine the amounts of station required for the given application.

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    Are robots compatible with aseptic environments?

    Robots are uniquely suited for aseptic applications and environments.  Aseptic processed require absolute repeatability and exactness, and to do so without compromising the aseptic environment.  Robots are able to provide extremely repeatable, are factory certified to be ISO Class 100 or better, and can be bio-decontaminated either manually or automatically. 

    Not all robots designs are well suited for aseptic applications because of the design, particle generation, compatibility with typical industry disinfectants, and materials of construction.  AST is an Elite Partner Integrator for Staübli Robotics and integrates the Staübli TX series Stericlean robots within the ASEPTiCell and GENiSYS aseptic filling systems.  The Staübli Stericlean robot is the most widely used robotic system for aseptic applications worldwide.  Their industry leading reliability, aseptic design and compatibility with bio-decontamination is second to none for critical aseptic applications.

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    Can robots be bio-decontaminated using vapor phase hydrogen peroxide inside of an isolator?

    There are various robotic systems available that are compatible with isolator integration and bio-decontamination using hydrogen peroxide.  AST’s ASEPTiCell and GENiSYS i20 aseptic filling systems integrates Staubli’s TX series Stericlean robot for isolator applications that require in-situ bio-decontamination using hydrogen peroxide.  The Stericlean was the very first robot designed specifically isolator environments and is the most widely used robot in the pharmaceutical industry in critical aseptic applications.

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    What does the FDA think about robots used within aseptic applications?

    The FDA has openly endorsed robotic technologies as an acceptable solution to reduce risk to an aseptic process.  In the FDA cGMP Guidance it states that “automation of other process steps, including the use of technologies such as robotics, can further reduce risk to the product” (Guidance for Industry: Sterile Drug Products Produced by Aseptic Processing – Current Good Manufacturing Practice, Pg. 10).  

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