Advice to drug companies: Don’t do devices if you don’t have to. It adds complexity and compliance risk to the drug manufacturing process. It requires a whole new way of thinking—device is by design rather than the exploratory nature of drug discovery that you’re used to. It requires significant customer support, complete with training programs and handling of complaints. It adds complexity to the number of supply chain and distribution systems. And it reduces margins because of the increased cost of goods sold (COGS).
This advice comes from Robin Hwang, a consultant specializing in injectable combination products (ICPs), the rapid growth of which is driving the device market, he says. Hwang has been in industry for more than 30 years, approaching it from a Ph.D. in polymers and six years with GE Plastics before moving on to medical devices, where the drug-device interface became a big focus of his work.
Now for the caveat: That advice goes out the window when competition enters the picture. With increased competition, drugmakers must ease preparation and dosing, enable self-injection, and improve patient compliance (drugs don’t work in patients that don’t use them). Biologics are growing exponentially, and self-injection is the driver, Hwang said. With insulin and human growth hormone leading the way in self-injection, there are more and more injection devices found in mature and competitive markets these days, including fertility therapy, rheumatoid arthritis, migraine drugs and more.
在大多数情况下，必须将药物从小瓶中绘制成塑料注射器的患者的日子结束。“如果你是唯一的救命药物，你可以基本上用铲子推进它。塑料注射器效果很好，“王说。“曾经有竞争，你必须更多地考虑交付。”
Over the past 10-15 years, he noted, self-injection and the patient/user experience have been moving into the center of chronic disease management. Drug delivery has moved over time from the vial/syringe option to pre-filled syringes and cartridges to pen injectors and auto-injectors. By way of example, Hwang pointed to Enbrel, a drug that treats autoimmune diseases. Released in 1998 as a 25 mg vial, it moved on to a 50 mg pre-filled syringe (PFS) in 2004, then 50 mg auto-injector in 2006. Since 2017, it’s been offered with AutoTouch, a reusable auto-injector that uses a pre-filled cartridge.
PFS-based auto-injectors are dominant at this point, but on-body injectors (OBIs) are gaining ground for large dose delivery.
In some cases, drug delivery is even moving into the realm of an injector with connectivity—one example beingBiocorp’s Smart Cap Easylog, which was cleared earlier this year in Europe, Hwang noted.
与设备，设备制造商合作
Hwang was speaking at a recent seminar organized byStevanato Group- 基于意大利的主要玻璃包装，工程系统，特种塑料和送货设备提供者 - 以及合作伙伴，以展示如何缓解药物输送制造过程。
随着市场预付款的越来越多的药物送货设备，毒品公司需要以某种方式地滚动。大型制药公司可能能够处理开发设备的高成本内部 - 几个辉瑞员工参加了Stevanato研讨会，例如，R＆D程序专门针对设备开发。但较小的公司可以提供必要的投资吗？
Roche, for example, spent up to $200 million to develop biobetters through a more convenient intravenous subcutaneous dosage format and device. The MyDose device was commercialized in 2013 but has yet to be launched today, Hwang noted. “So that’s a $200 million fiasco for the company,” he said. “As a small company, can you afford it?”
A new device program—including device and clinical development, subassembly and final assembly, and testing—could take five years to develop and more than $50 million, Hwang said. And that’s not something many companies can afford. Leveraging existing injector platforms to speed up clinical and commercial supplies, he has helped clients get where they needs to be for less than $3 million in just a couple years.
Partnering with a system provider could also reduce the timeline and lower the cost for the pharmaceutical company. “Drug companies are defending market share with device capabilities,” Hwang said. “Although there are challenges, successful partnerships between drug and device companies are out there.”
Nasal drug delivery
Aptar Pharma., one of the partners presenting at Stevanato’s seminar, showed what it could do to help drug companies repurpose drug formulations for nasal delivery. Nasal drug delivery, like injections, have been on an evolution as well—first explored in the 1970s for local treatment to a number of nasal devices for a range of systemic uses today, noted Valerie Otte, regional market development manager for Aptar Pharma.
为制药公司反对是有道理的sider reformulating their drugs for nasal delivery, Otte said, for economic, physiological and regulatory reasons. But there are challenges as well: Drugmakers will still have to undergo phase 2 and 3 clinical trials, nasal drug delivery can be particularly challenging, and technical and regulatory expectations for nasal and sublingual sprays have evolved over the past few years.
“重要的是,它能够在一起工作tween the drug and device for other regulations. You need an experienced partner to help mitigate the risk,” Otte said. “At Aptar, we have proven technology ready to use and available now.”
评论一些挑战和发展形式ulations, Otte noted challenges with viscosity and how it can affect the nasal spray. It’s important to address these challenges early in the drug development process. “Often times, the device is looked at in a later stage. But more and more, we try to work with customers earlier on,” she said. “If it’s a later stage, it can lead to delays.”
Collaboration examples
整个机器制造商和服务提供商的例子都有例子，以及彼此共同努力以及制药商，帮助减少推广和生产药物输送装置的市场，成本和复杂性。从合同制造组织（CMO）的角度来看，文艺复兴的药物谈到它如何与药品公司和设备公司一起与Aptar一起开发，以与填充系统一起开发设备。CMO又配备了像Optima（也参与Stevanato研讨会）的设备制造商，以确保一切都被正确填补。“一切都至关重要，”文艺复兴的战略倡议主任鲍勃伍德说。
Optima showed how its flexible turnkey systems could process ready-to-use devices. “The market trend is going from mass production to smaller batch sizes and more customized solutions,” noted Mevluet Yilmaz, director of sales forOptima pharma北美。但随着机器制造商的灵活灌装系统和全面的科学工艺工程（CSPE），Pharma公司可以将时间提高到市场并降低风险。
Yilmaz also showed how Optima is using 3D virtual reality (VR) as part of the machine design process to reduce risks, time and costs. “There’s a great advantage to explore the equipment prior to even the build phase,” he said.
市场上有几种趋势和挑战，包括更多个性化的诊断和药物，从医院到家庭，生物学和大分子的增长，增加监管质量和合规性期望，以及新兴市场的增长，并注意到Riccardo Prete，产品史凡纳集团初级包装与工程设备经理。这些趋势对机器供应商提出了更多要求，斯科特史密斯（Scott Smith）北美为Stevanato销售经理增加，因为市场上有许多设备，所有这些都需要更快的验证和增加的灵活性和可扩展性。
Stevanato’s BasiQX XTV platform provides the scalability and flexibility needed for the pharmaceutical industry by enabling customers to start with one module and scale up to an entire full-bore machine, Smith said. Helping with this isBeckhoff的XTS线性传输系统，这使机器能够基于时间，自然，在组中独立地或同步地调整移动器。根据需要，它也很容易添加或删除移动器。“你可以从几个搬家者开始。然后如果你想更快地去，你只需添加更多的搬运工，“史密斯说。“这是非常有效，非常可扩展，非常灵活。”
There are several ways for Stevanato to partner with pharma companies, said Olivier Baudin, head of sales for North America for Stevanato. They can provide integration with primary packaging, partner on a contract manufacturing site, or support the drug company with its own proprietary device solution. He highlighted several examples, including its work with Israel-based Sorrel Medical’s wearable drug delivery device platform, and for another customer the integration of a container closure system (CCS) that avoids aseptic device assembly.
