To simplify drug delivery for patients and practitioners, drug-delivery devices are becoming more complex. Many of today’s devices include special features designed to ease self-dosing and encourage patient adherence with novel regimens. Wearable devices are further easing use by promoting active lifestyles. And some devices are offering connectivity to support digital health monitoring.
With so many possibilities, where do device developers and pharmaceutical companies begin? MD+DI asked Eric Resnick, vice president and chief technology officer, innovation and technology, West Pharmaceutical Services Inc., a few questions on market trends, regulations, container options, and delivery system designs, and more.
MD+DI: What are some current market needs for drug-delivery devices, and what is driving those needs?
Resnick: Current market trends include increased regulatory demands regarding combination products, digitalization, and new biologic drug innovation.
On the regulatory front, regulators are looking for data specific to the drug/device combination product performance and not just the device performance. This means they are taking a more holistic view of the combination product than did the previous standard 510(k) review. In other words, how does the device perform with the specific drug in question?
West is also seeing a trend toward digital aspects that have been added to devices and combination products to reinforce user experience and desirability. The digital experience is spreading into the drug-delivery device space in the form of apps for wellness, education, and adherence, helping to ensure that patients receive the proper therapeutic regimen for their particular condition. This is all tied to improving patient adherence as payers put pressure on pharma to demonstrate results from these especially costly drugs.
While pens and autoinjectors still dominate small molecule and mature biologic delivery, the next-generation drugs are pushing device developers to seek out and create new delivery methods. In addition, some biologics are requiring less dosing frequency. For example, AbbVie’s Skyrizi biologic, for the treatment of plaque psoriasis, will require two injections, back-to-back, but only four times per year. Compare this to AbbVie’s highly successful Humira treatment, which requires bi-weekly dosing.
Finally, new biologic treatments are requiring greater dose volumes, which in turn pushes devices to be able to deliver larger and larger volumes. This is driving the need for alternative delivery solutions such as wearable injectors including West’s SmartDose drug-delivery device. These wearable injectors eliminate the need for multiple injections via pre-filled syringes or autoinjectors.
MD+DI: Are there any trends moving toward or away from any of these approaches:
- Drug supplied in an auto injector
Resnick: While prefilled syringe systems (PFS) remain dominant, the success of drug products like Lilly’s Trulicity treatment, which uses an autoinjector, are driving the increased use of autoinjectors. Syringes of up to 2.25 mL and cartridge-based systems are leading to newer autoinjector designs that are capable of delivering volumes beyond the traditional 1 mL. Whether patients desire a single 2.25-mL injection or double 1-mL injections remains a critical question.
- Drug supplied in a prefilled syringe
Resnick: As noted previously, PFS systems remain the primary packaging option for drug containment, but we are seeing more cartridge-based systems that go into a device like a pen or auto injector. As dose volume needs increase, we’ll see larger syringes and greater use of cartridge-based systems.
- Drug supplied in an IV bag
Resnick: While the use of IV bags for drug delivery is still quite common, there are clear trends happening now moving from IV treatment in a clinical setting to self-administration options through the use of a wearable device like West’s SmartDose drug-delivery platform, which offers options for subcutaneous delivery of up to 10-mL doses via a prefilled cartridge system. Once again, this is about enhancing the patient experience while removing costs from the healthcare system. Patients see benefits in that they no longer need to go to the clinic or healthcare provider for IV infusion. Instead, they can self-administer in the comfort of home with a possible 15-minute dose versus an hour or more spent in the clinic. Alexion recently disclosed that they are planning on offering both IV and subcutaneous versions of their new Ultomiris drug, which will be offered in the SmartDose injector.
MD+DI: How are projects for drug-delivery devices typically begun? What roles can medical device manufacturers play in developing drug-delivery solutions?
Resnick: Historically, pharmaceutical manufacturers have been focused—and rightly so—on the drug product itself, and they often waited until the last minute before they determined how to deliver the drug to patients. Today, drug developers are starting the delivery considerations much earlier. Even though final dosing and formulation may not be finalized, starting the device development process earlier, as well as providing clinical and human factors studies, can provide a better start for clearing regulatory hurdles when it comes to combination products. For injectables, the first hurdle is compatibility and stability of the drug product in the primary containment system. If the device requires a novel design for the primary package, or new materials, these risks need to be addressed immediately or the manufacturer may risk delays further down the line. Early conversations also enhance the ability to develop a platform of delivery options that can address patient-centric options, like multiple dosing and alternate dose volumes/therapeutic regimens.
MD+DI: What differences should medical device manufacturers be aware of when working with FDA’s CDER or CBER as opposed to CDRH?
Resnick: FDA’s Office of Combination Products (OCP) will decide whether the product is a drug or a device, at which point CDER covers drug and CDRH reviews device. The issue is that depending on the route of review, a combination product may be reviewed by a regulator who is more familiar with the drug product than the device, so pharmaceutical manufacturers will need to be prepared, particularly since combination product guidance is constantly evolving.
In the case of drug-delivery systems, the OCP will manage filings and, according to the FDA Web site:
- Serve as a focal point for combination product issues for FDA staff and industry.
- Develop guidance, regulations, and standard operating procedures to clarify the regulation of combination products.
- Classify products as drugs, devices, biological products, or combination products and assign an FDA center to have primary jurisdiction for premarket review and postmarket regulation where the jurisdiction is unclear or in dispute.
- Ensure timely and effective premarket review of combination products by overseeing the timeliness of and coordinating reviews involving more than one agency center.
- Ensure consistency and appropriateness of postmarket regulation of combination products.
- Facilitate resolution of disputes regarding the timeliness of premarket review of combination products.
- Update agreements, guidance documents, or practices specific to the assignment of combination products.
- Develop annual reports to Congress on the Office’s activities and impact.
- Provide training to FDA staff and regulated industry on combination product regulation.
MD+DI: How much custom work is needed for developing drug-delivery devices?
Resnick: Everyone wants a platform device since it offers the ability to address multiple drugs, treatments, and patient populations with a single device. However, that’s easier said than done owing to the need for different volumes and dosing frequencies and delivery options as therapeutic classes and indications may differ. A good platform for a cancer treatment may be completely unsuitable for an autoimmune drug owing to drug product characteristics, patient needs, treatment regimen, and many other factors. Customization is really required for the drug and the disease.
Manufacturers should start by determining what makes the platform. Is it:
- Delivered dose volume?
- Therapeutic classes?
- Route of Administration?
- Primary container system?
Unless you are developing a drug-delivery device for a specific therapy, like an insulin pump, the odds are your device will be treated as a combination product. That means it will require specific data to demonstrate how the device, container, and drug combination perform to meet the desired outcomes.
Above: West's SmartDose drug-delivery devices
MD+DI: What benefits are there to selecting off-the-shelf designs? How could these be tailored for specific drugs and brands?
Resnick: While many manufacturers believe an off-the-shelf (OTS) design is the way to go, depending on the device, OTS can vary from simple to complex. A design that may work for a patient with psoriasis may not work for an oncology application. Design validation will be required for each drug, so while the physical design may be the same, the intended use, patient population and other factors will change.
MD+DI: What should medical device companies know about pharmaceutical container closure regulations and standards when developing a drug-delivery device? Are there any regulatory changes on the horizon?
Resnick: Regulation and guidance changes are occurring all the time. The new regulation in Europe, Medical Device Regulations (2017/745), stipulates that marketing authorization applications for medicines with an integral medical device must include the results of the device’s assessment of conformity by a notified body. Approximately one in four centrally authorized medicines includes a medical device component, and the majority of these involve an integral device. This includes for example, prefilled syringes and pens, patches for transdermal drug delivery, and prefilled inhalers.
MD+DI: How would the need for sterile drug delivery and/or terminal sterilization impact the choice of a drug-delivery device?
Resnick: Method of sterilization, drug substance, and device design are all interrelated. For instance, a traditional autoinjector usually includes two mechanical sub-assemblies and the prefilled primary drug container. The primary drug container is sterilized usually via steam or irradiation and introduced into a sterile field for filling. The drug is aseptically filled and after stoppering can be removed from the sterile space. The mechanical subassemblies do not have to be sterilized if the drug remains in the primary packaging.
Devices with patient needles or a drug path require sterilization, and the method will be dependent on materials of construction and packaging. The key point here is that how you sterilize affects both the drug and the device. The system must be developed and put together in order to ensure that manufacturers are using the best method(s) for both the drug and the delivery device and most importantly provide safe product to patients.
MD+DI: Are there any other challenges in developing a drug-delivery device?
Resnick: When developing a drug delivery device, we look at three things:
- Desirability. Will patients or caregivers want to use it? Is it easy to use? Most drugs are offered in multiple presentations, and patients will have options.
- Feasibility. What is the device expected to do functionally, and is it possible from an engineering standpoint? Is the platform realistic?
- Viability. Does the business case make sense? You may have a device people love, but the market won’t pay for it. Does it make economic sense to payors?
If an option passes all three tests, then we work with partners to ensure that they have the right device for the drug product that can clear regulatory hurdles and help to promote patient loyalty and adherence.
For more details, be sure to attend the panel discussion at MD&M East, “Drugs and Device: A Match Made in Healthcare Heaven,” held Thursday, June 13, 12:00 PM - 12:45 PM, at the Medtech Hub, Booth #1669. Chris Evans, vice president, global Innovation at West Pharmaceutical Services, will be among the panelists, who also include Michael Noderer, associate principal scientist, device development & packaging, product development at AstraZeneca, who was involved with the development of the MDEA finalist Bydureon autoinjector; Mathias Romacker, senior director, device strategy at Pfizer; and Craig Scherer, co-founder and senior partner at Insight PD.
Visit West at MD&M East Booth #1538.