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There is growing interest in the development of liquid formulations in prefilled syringes and autoinjectors, which offer convenience and ease of administration in a home setting.
The personalized medicines era is shifting the focus of pharmaceutical development and manufacturing activities from small molecules to biologic drug products. The formulation of these complex macromolecules, however, is not as straightforward as their small-molecule counterparts. The high patient doses required for biologic therapeutics, for example, present significant drug-delivery challenges, according to Johann Stasny, director, Global Sales Development, Bioavailability Enhancement & Custom API, Merck Millipore KGaA, Darmstadt, Germany. “On average, a dose of 0.1 mg to 3 mg per kg of patient body weight is required,” Stasny notes. Because of their nature, biopharmaceuticals are not easy to deliver via the oral route, explains Kate Hudson-Farmer, market insight strategist, Drug Delivery, Cambridge Consultants. A large proportion of these drugs are currently injected using intravenous infusion in the hospital, or increasingly in the home, she says.
Most biologic products for parenteral administration are freeze-dried in vials to help maintain drug stability and increase shelf life. But interest is growing in the development of liquid formulations in prefilled syringes and autoinjectors, which offer convenience and ease of administration in a home setting. Stasny observes a shift for certain biologics-especially those indicated for chronic conditions such as inflammatory diseases-toward prefilled syringes for subcutaneous administration. “This delivery method has better patient compliance and efficiency in cases where a high concentration of the drug is required due to the low dosage volume that can be administered,” he says.
“The trend in self-administration continues to grow,” Hudson-Farmer notes. Claus Feussner, PhD, senior vice-president, Development Service, Vetter, attributes it to the expanding home healthcare market, which he says is a direct reflection of a constantly aging population, particularly in the more established countries. And as a means to control costs and avoid expensive therapies in either a hospital or a doctor’s office, healthcare authorities are putting pressure on the industry to develop medicines that patients can self-administer in a private setting, according to Feussner.
Hudson-Farmer, nonetheless, points out that self-administration has its challenges. Patients require training and education to ensure that these drug-delivery systems are used correctly. “But this is not the only problem,” she asserts, “because self-injection, whichever way you look at it, is not a pleasant thing to have to do, and adherence and compliance to such drugs is often a problem.”
In addition, drug companies are faced with the challenge of having to deliver larger volumes of biologic formulations, often beyond the capacity allowed by a syringe or an autoinjector. “This is in part due to the trend towards less frequent injection and in part, to drug formulation issues,” says Hudson-Farmer. Patch pumps or on-body injectors that can deliver the drugs in a subcutaneous manner are being developed, she adds. “There have been some interesting advances in this area including the pre-timed, worn-on-body injector that Amgen launched for its Neulasta drug using Omnipod’s on-body injector,” Hudson-Farmer highlights.
Andy Fry, founder of Team Consulting, notes that wearable devices, which provide an alternative to prefilled syringes and autoinjectors, are attracting a great deal of interest. “A wearable device allows drug delivery over a significantly longer period than the typical 10- to 20-second window associated with an autoinjector. Because of this feature, a wearable device can enable large-volume doses, or high-viscosity formulations, or even larger-volume payloads at high viscosity, to be delivered at acceptable levels of patient discomfort,” he explains. “There has also been renewed interest in all-in-one dual-chamber devices, which aim to take the fiddle and complication out of reconstitution of lyophilized products for self-injection while avoiding the necessity of cold-chain transportation and storage.”
Graham Reynolds, vice-president of marketing and communications, Delivery Systems, West Pharmaceutical Services, sees an increased need for innovative and effective drug packaging and delivery of biopharmaceuticals. “Additionally, as biologics begin to come off patent, demand for delivery systems that can safely contain and deliver biosimilars should continue to rise, especially as easy-to-use delivery systems can help differentiate drug products,” he says.
The industry also continues to seek alternatives to glass, such as polymer-based systems, for drug packaging and delivery systems, according to Reynolds. “This is particularly true for biologics, which can be sensitive to their containers,” he observes. “Glass-related risks, such as delamination, breakage, and chemical incompatibility with the drug product do not exist with the newer polymer offerings. These platforms offer a range of options for dose volume and injection time and are designed to help improve patient compliance and outcomes, while meeting the challenges of injectable drug products.”
Biologics are sensitive drug products, and therefore, require ultra-clean packaging components to ensure low risk of contamination or particulate-which is why manufacturers are, in turn, demanding that drug containment and delivery systems from suppliers offer the highest levels of quality possible to maintain the purity of their biopharmaceuticals.