Pharma Tech Readies Line for New Nasal Delivery Device

Custom filling, line automation, and humidity control are developed as OptiNose prepares for an NDA filing.
As an outsourcing partner with pharmaceutical companies, Pharm Tech Industries (PTI; www.pharma-tech.com) often develops complete solutions for customers in providing turnkey contract manufacturing and packaging services.
The Royston, GA–based CMO and packager draws on a staff of in-house engineers to accomplish a technology transfer and to meet custom requirements with first-of-kind solutions.
For the OptiNose Delivery System, PTI is developing a complex filling and packaging line and providing development services to support the device’s NDA application.
“OptiNose was looking at a larger CMO that does more ethical products than we do, but this company didn’t have our expertise in powders. We are the largest CMO for pharmaceutical powdered products in the world. They were impressed by our interest and some of the innovation we conveyed in our initial discussions. Then they did their homework and found we have a very good track record in execution and reliability,” says Tee Noland, PTI’s chairman.
“In conveying our interest in the project, we described our ‘total system’ capabilities, which can even include making injection-molded components. Our ability to vertically integrate the various processes in the supply chain and manufacturing for the product appealed to them,” Noland says.
One selling point was that PTI had manufacturing and packaging suites capable of maintaining the stringent environmental conditions required for the product’s production, says Peter Miller, CEO, OptiNose US Inc. (Yardley, PA; www.optinose.com).
“PTI had demonstrated the ability to integrate diverse and complex technologies for several customers into their facility. They possessed the generic packaging technology required for our product but also, and this is significant, demonstrated innovative modifications to that base equipment, making it uniquely applicable to a customer’s product,” says Miller.
“The company leadership and key technical team welcomed the unique challenges our product created for them. It was also apparent they had a culture of partnership with their customers versus a more traditional transactional relationship,” he adds.
NOVEL DELIVERY
OptiNose is a nasal delivery system that uses the patient’s breath to propel medication into the nasal cavity. The patient fixes a disposable nose piece containing the encapsulated powdered drug to the OptiNose device. The patient pushes a button to pierce the capsules with steel piercing pins that autoretract with the button’s release. The nose piece is then slid into a nostril, and the patient takes a deep breath and blows into a mouth piece, propelling the powder into the nasal cavity.
The device is more comfortable to use than a nasal spray and delivers drugs more consistently and reliably to all regions of the nasal cavity, OptiNose says.
OptiNose completed a Phase III trial in November with 16-mg OptiNose sumatriptan succinate, a migraine drug that successfully met its primary end point. The target for OptiNose regulatory submission is the end of this year, with an approval date target the third or fourth quarter 2014, Noland says.
Development services—leading to support for commercialization— include running batches and conducting lab testing.
“In development trials, we will be defining and optimizing environmental variables such as humidity, and doing studies on the holding time of material. We are transferring methods to do a lot of the test procedures and validation on custom equipment in-house in our labs, with test methods designed specifically for an inhaled product,” Noland says.
The product has to be manufactured with tight humidity control to avoid product degradation, says Rich Loughlin, PTI’s VP strategic sales.
“The lower you keep the humidity, the more challenging it is to manufacture—the engineering requirements, and the energy costs, will be higher. The client doesn’t know what the minimum and maximum humidity thresholds will be so they are asking us to do an optimization study on the environmental conditions. There is the possibility of simplifying the manufacturing process and extending shelf-life,” Loughlin says.
Miller notes that much of the development work at this point is completed. “We will be running trials to assess the impact of typical events that can occur during commercial operation, such as bulk hold studies, and [looking at] future efficiency improvements, [such as] run speed and maximum batch size. We consider it contingency planning that we address as time and resources permit,” Miller says.
CUSTOM FILLING
The line uses a Planeta Capsule Filler from MG America, a subsidiary of MG2, that is configured for the OptiNose application and filling the system’s capsules. The state-of-the-art filler weighs the cap and the filled cap for powder-weight verification.
“Working with MG America was another example of excellent collaboration and innovation on the part of our supplier. Not only was the machine dosing unit modified to meet the tight weight tolerances for our product, but the MG team had to further modify the filling bed and how that is manipulated during operation to enable the machine to fill low doses of pure API. When the standard modifications couldn’t maintain the tight tolerances, they were able to quickly assess the cause and implement the modifications without extending the scheduled delivery date,” Miller says
After OptiNose worked with MG America on the filler’s design, the equipment was transferred to PTI for the qualification and validation work, Noland adds.
Post-capsule filling, capsules have to be inserted into the disposable nose pieces, with one cap per nose piece cartridge. PSI has been handling that in manual mode.
“We are in the process of working with OptiNose on the design and selection of a vendor for automating the [capsule insertion],” says Loughlin.
WEIGHING ALTERNATIVES
“We will be developing this as one continuous line. We fill the caps, and they are placed in the nose pieces and then indexed to our Bartelt pouching machine,” he says.
At the Bartelt unit, each filled nose piece is packaged in a foil sachet. PSI designed and had made custom robotic arms for handling the odd-shaped nose pieces. Arms hold the pouch open, and pick-and-place one nose piece into one pouch. Pouches are heat-sealed closed and fall to a counting conveyor.
PSI is presently packaging 16 nose pieces along with one device in a carton—the shelf cartons patients will receive.
“The limiting factor on speed is the Bartelt machine. We can design and build the nose piece assembly [capsule into nose piece] to any speed we’d like. With the client, we are considering replacing the Bartelt with a second generation machine [for increasing pouch machine output],” Rich says.
In accommodating tandem sachets, two sachets side-by-side attached with perf, the new model would also support a commercial purpose besides speeding output. A two-pack configuration is more convenient for patients that will use two of the nose pieces each time they deliver the product, one for each nostril.
For its solution with OptiNose, PTI has worked in close collaboration with the client to design and develop the process and equipment.
“Historically, these are the types of projects PTI specializes in, where there is no ‘out-of-box’ solution on the market. At the end of the day, we will have a one-of-a-kind and robust manufacturing process. Additionally, we are building in flexibility so we can capitalize on the investment, potentially with other powdered products used with delivery devices,” Loughlin says.
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