With biologics accounting for a greater percentage of the drugs on the market today, manufacturers, healthcare professionals and home-care patients are looking for safer, easier, and more cost-efficient means of delivering these therapies as well as vaccines.
Leaders in the prefilled syringe market shared their thoughts with the Pharmaceutical Sciences, Manufacturing & Marketplace Report about prefilled syringes (PFSs), including specific drivers for growth, their advantages, current issues, and recent technology advances. Participants in the roundtable discussion included: Brian Lynch, program lead for health science and technology, immunization, and Justin Wright, director of pharmaceutical development, both with BD (Becton, Dickinson and Company); Jo Anne Jacobs, manager, technical sciences and services of drug products with Cook Pharmica; William J. Lambert, PhD., fellow, drug-delivery and device development at MedImmune; Peter Soelkner, managing director with Vetter Pharma International; and Graham Reynolds, vice-president of marketing and innovation for West Pharmaceutical Services.
Drivers in demand
Pharmaceutical Sciences, Manufacturing & Marketplace Report: What are the drivers for the growth in the use of prefilled syringes?
Jacobs (Cook Pharmica): One of the primary drivers is the growth in biotechnology-derived therapeutic agents, particularly those that are organ or tumor-specific. These drugs are generally lower dose, but are rarely oral dosage forms.
Lambert (MedImmune): Another primary driver for the growth in the use of PFSs is the need for convenient self-administration of protein and peptide drugs by patients, and, of course, the number of these drugs has been increasing dramatically over the past two decades.
Reynolds (West): We are seeing a significant trend in the use of injection devices to deliver drug products effectively in the home environment, especially where there may be repeated treatments necessary for chronic conditions.
Lynch (BD): Because they require minimal overfill (enough to manage the dead space of the needle and hub), PFSs offer an opportunity to extend supply in both the biologics segment for chronic care and the vaccines segment. Supply extension can be important for public health in times of shortages. A vial, on the other hand, must have sufficient excess to allow a dose to be drawn out —20% overfill or more is typical.
Pharmaceutical Sciences, Manufacturing & Marketplace Report: What advantages do prefilled syringes provide?
Soelkner (Vetter): PFSs offer advantages to both pharma/biotech companies and healthcare professionals and patients. For manufacturers, prefilled syringes are a safer form of packaging that offer a means for higher quality manufacturing. In addition, it is possible to achieve real cost savings because of the increased efficiency of the delivery system. Furthermore, PFSs are often seen as an added value and can help differentiate products from others on the market. For healthcare professionals, there is reduced risk of needle sticks, and, in general, the risk of contamination of the drug is lower when using prefilled syringes.
Reynolds (West): As patients take an even greater role in decisions regarding their treatment, prefillable syringe systems offer a convenient solution that can be used in the home environment by a patient or caregiver. PFSs also can be combined with auto-injectors and other safety systems to create an integrated drug-delivery system that may help manufacturers offer patients a variety of choices for delivery from one standard container system.
Lynch (BD): PFSs offer a unit-dose, ready-to-administer format that simplifies the preparation and administration of injectables by a patient or caregiver (versus, for example, a vial, which requires many more steps and ultimately the transfer of the injectable from the vial to a syringe). The time savings can mean more time on higher value activities involving patient care or shorter patient wait times. A recent study by the Johns Hopkins Bloomberg School of Public Health found that the time savings in preparing a vaccine for injection using a PFS vs. a vial was 37 seconds, which translates to over 15 minutes for every 25 doses given. This time can be significant in a busy pediatric office or during the flu immunization season.
Greater safety is another important advantage. There is a heightened focus in the United States (FDA Safe Use Initiative, for example) for greater safety in injectable medications due to a number of preparation mistakes that have led to problems ranging from the wrong drug being administered to re-use of syringes that can lead to infection transmission. Because they are filled, labeled, and packaged by the pharmaceutical company, and because they are unit doses and ready-to-administer, there are fewer steps involved in the preparation and fewer opportunities for human error.
Jacobs (Cook Pharmica): There are cost advantages for the manufacturer, the practitioner, and the patient. There is also a gain in patient compliance. A regimen involving a premeasured dose that can be delivered at home is much more likely to be followed than if the patient has to go somewhere to be dosed. For medical practitioners, prefilled syringes offer ease of administration, require less storage space, and can decrease the overall inventory space required. Also, dosing precision is increased with the single-dose syringe versus having to draw up the dose from a vial.
Pharmaceutical Sciences, Manufacturing & Marketplace Report: What major hurdles do prefilled syringes still face?
Lambert (MedImmune): The viscosity of concentrated antibody formulations is probably one of the most significant challenges we face today for PFSs. Formulators attempt to balance the desire to minimize the subcutaneous injection volume while avoiding the dramatic increase in viscosity that is seen as concentration increases. Injection time in a PFS is primarily dictated by the flow rate through the needle, and the flow rate is inversely related to the viscosity. Furthermore, patients prefer narrow gauge needles. A flow rate, however, is related to the needle’s inside diameter to the fourth power. Thus, using a slighter smaller needle can lead to a large decrease in flow rate (and long injection times).
Reynolds (West): Many biologic products exhibit increased sensitivity to materials found in traditional glass-syringe systems, such as silicone oil, tungsten and adhesives, and may also need to be delivered in higher dose volumes due to increased concentration or molecular weight. Tighter requirements/standards for visible and subvisible particles, cosmetic defects, interaction with devices, and concerns about glass breakage are leading companies to consider very carefully the selection of an appropriate container for their newer molecules.
Soelkner (Vetter): Prefilled syringes are more sophisticated and thus require more sophisticated manufacturing processes, particularly given the increased number of transfers that take place. On the patient side, the needs of different homecare patients who are self-injecting must be considered. Many patients that are using PFSs have arthritis and problems with their joints, and need delivery systems with broader finger flanges for self-administration. Manufacturers must have knowledge about both production issues and patient needs, which requires extensive experience in biologics manufacturing and packaging.
Pharmaceutical Sciences, Manufacturing & Marketplace Report: What advances in technology and other approaches are being developed to address these issues?
Wright (BD): Methodologies now exist to evaluate the sensitivity of a molecule/formulation to discrete surfaces and materials in the syringe. These shorter and less expensive tests help minimize time risk by demonstrating any potential interactions in advance of longer and much more expensive stability studies.
In addition, continuous improvement programs have reduced the occurrence of residual tungsten species to near undetectable levels, and advances have led to significantly better control of silicone deposition amounts and uniformity. Innovations in glass handling and processing have also yielded glass PFSs with significantly enhanced strength and durability profiles and reduced defects.
Lambert (MedImmune): The introduction of “thin wall” needles and formulation-based approaches to minimize viscosity has led to some improvement, but viscosity is still a significant problem. Dozens of companies are currently working on novel designs for subcutaneous large volume injectors (LVIs). These devices typically are attached to the skin with an adhesive, hide the needle from view, and are able to deliver larger volumes of the formulation (up to 10 mL or so) over a longer period of time than is practical for a PFS. LVIs should significantly increase the number of drugs that can be self-administered by the patient.
Reynolds (West): When developing sophisticated devices, plastic PFSs may offer advantages such as consistent functionality, increased dimensional precision, break resistance, and reduced extractables and leachables, particularly when combined with fluoropolymer-coated plungers. Plastic systems offer the ability to contain larger volumes more effectively, and can be customized to offer the ability to develop novel, patient-focused delivery systems that are optimized for size and functionality.
Soelkner (Vetter): Automation in the clean rooms at Vetter is helping to minimize risk and human error, and the use of robots is becoming more commonplace as the benefits become apparent. Separately, with increasing numbers of smaller volume, niche drugs being developed, the ability to allow for dedicated production of specific products while still maintaining efficient and flexible manufacturing facilities has been necessary. Adoption of quality by design and process analytical technology for the manufacture of PDSs is also becoming more formalized and having a positive impact on quality.