How To Get Your Product Into a Prefillable Syringe

Design improvements have made prefillable syringes appropriate for a wider range of injectable products than ever before. This piece discusses these improvements and their impact on the suitability of your product's placement in a prefilled syringe.

Q. How do I know if my product belongs in a prefillable syringe?

A. The first and most important question you must ask yourself is: "Does providing additional convenience and safety to the users (hospitals, nurses, and-in the case of self-administered drugs-patients) add value to my product?"

Q. How does a prefillable syringe add value?

A. It adds value when the end user can perceive additional benefits from your choice of package. Hospitals, for example, perceive additional value from increased safety, and reduced potential for mix-ups, because the product can be clearly identified by labeling or printing on its barrel.

In general, prefillable syringes simply make injections easier to perform.

Q. Are these the only advantages of a prefillable syringe?

A. No. Prefillable syringes also reduce the risk of cross-contamination because they are single-use devices. Additionally, Schott Parenta syringes which are filled by Ben Venue have a unique locking plunger rod which prevents the syringe from re-use.

The potential for contamination is reduced because prefillable syringes, in many cases, reduce the number of drug transfers to zero.

Their ready-to-use feature is an obvious advantage for emergency drugs. Also, their format makes them naturally tamper-evident, which explains why many narcotics are currently packaged in prefilled syringes.

Finally, any product that is administered by the patient can be seen as more valuable if available in a convenient, ready-to-inject package. Particular value is perceived by home care patients that have physical impairments which make typical syringe preparation and administration difficult.

Q. What other considerations are there?

A. As a practical matter, prefillable syringes are only appropriate when a dosage is to be uniform across the entire patient base. All prefillable syringes are unit dose devices, i.e. the entire contents are used at one time. So, each patient must have the same volume of solution administered. This feature can be seen as an advantage by hospitals (or drug manufacturers) that want to insure a very accurate volume of product enters the patient, reducing the potential for dosage adjustments by doctor or nurse. This consideration is why oncology drugs are usually not recommended for prefillable formats, because patient-specific dosages are required.

Q. What about biotech products? Are prefillable syringes appropriate for large proteins?

A. Some prefillable syringe designs are not as appropriate for proteins as others. The Schott Parenta Prefillable Syringe has a unique "closed system" design, which means only glass and rubber touch the drug. (Just like a vial.) Other designs expose the drug to steel and resins, which can compromise stability. If your product can be packaged in a vial, it can be successfully packaged in the Schott Parenta syringe.

Q. Are there other concerns for biotech products?

A. Yes. Proteins react with free silicone, which is present on the inside surface of prefillable syringes. Schott significantly reduces the presence of free silicone on the syringe because it polymerizes the silicone on its glass barrels at high temperatures. This baking process is impossible with designs which require an epoxy adhesive to affix the needle.

Q. Are prefillable syringes just for liquid products? What about lyophilized drugs?

A. Products which require diluents can also benefit from prefillable syringes. If a product's diluent is packaged in the syringe, it eliminates a major step in the reconstitution process. With a traditionally packaged lyophilized product, a syringe is used to remove diluent from its vial or ampoule and inject it into the drug's vial for reconstitution. After reconstitution, a syringe is used to withdraw the drug. The needle is changed before administration to the patient. Using a prefilled syringe for the diluent eliminates the first step.

Q. How do I determine the size and configuration of a syringe for my product?

A. Start with dosage volume. Schott currently offers seven sizes of prefillable syringes: 1, 1.5, 2.0, 2.5, 3, 5, and 10 mL. Next, decide whether an assembled needle or Luer Lock is required. If your drug is a liquid, you can use either an assembled needle or the Luer Lock. If a diluent is going into the syringe, you must use a Luer Lock to allow the needle to be changed. The Luer Lock permits the doctor or nurse to choose an appropriate size needle or to link the syringe to an I.V. line or any other device which accepts a Luer Lock.

Q. What is the best time in a product's life to put it into a prefillable syringe?

A. Phase II or early Phase III, so that additional development costs will not be incurred. If you select a prefillable syringe, your Phase III clinicals should be manufactured entirely in the prefillable syringe.

Q. What additional compatibility studies must be done?

A. None, if you are in Phase II. Development of a prefillable syringe is essentially the same as if a traditional vial were being used. Compatible rubber formulations must be selected and stabilities run. A large variety of compounds are available. If a prefillable syringe is to be added after your NDA or PLA has been filed, you will have to file a separate packaging supplement.

If your product is already on the market, or you are considering a generic version of a product on the market, new stability studies with the prefillable syringe will be required.

Q. Who usually does preliminary stability studies?

A. Many companies do preliminary in-house stability studies with two or three rubber formulations. Some firms elect to have a contract development facility such as Ben Venue do the preliminary work.

Q. What are the pluses and minuses of doing stabilities in-house versus outside?

A. Preliminary stability studies can be done in-house or at a contract manufacturer. However, your stabilities to prepare your filing must be conducted using the machinery and facility you intend to use for commercial production. If you plan on doing your production work in-house, you will have to invest in specialized automated-filling equipment now. Likewise, if you have an outside lab do your preliminary stabilities they should also have the ability to do your full-scale production work. Otherwise, you will be required to add a site transfer amendment to your filing.

Q. Which contract facilities can do both our stabilities and our full scale production work?

A. In the U.S., Ben Venue Laboratories in Bedford, Ohio has the equipment to handle all aspects of development and production for the Schott Parenta Prefillable System. Other contract firms can do preliminary stabilities; Ben Venue can do automated contract filling from the early stages on.

Q. At what point does it make sense to produce a product in-house versus with a contractor?

A. A rough cut-off for many firms to justify in-house production is around 3 million units per year. If your anticipated volume is less, the capital investment for your own equipment usually does not make sense. Obviously, if your volume projections are uncertain, contract filling is the prudent way to get started.

Q. Are there any negative aspects of prefillable syringes?

A. Prefillable syringes require more shelf space to store, a consideration if refrigeration is required. (Freezing of prefillable syringes is not recommended.)