Albany Molecular Research Inc. (AMRI; www.amriglobal.com
) is manufacturing sterile prefilled syringes at its Burlington, Massachusetts, site in support of the U.S. introduction of Cardium Therapeutic’s Excellagen topical gel.
Excellagen is a new, highly refined fibrillar collagen-based gel for treating diabetic foot ulcers, pressure ulcers, and other dermal wounds. It is topically applied through prefilled single-use syringes.
The aseptic fill-finish line for Excellagen at Burlington uses an Inova filling machine with product-dedicated stainless-steel rotary piston pumps. “The line has a maximum filling rate of 4000 syringes per hour,” says Chris Phillips, director, operations, AMRI Burlington.
The line supports efficient, contamination-free filling of pre-sterilized nested syringes, in a RABS (restricted access barrier system) ISO-5 environment. All manipulations within the fill machine enclosure are automated and facilitated via servo motors, Phillips says.
Syringe tubs are fed manually into the enclosure onto an automated syringe tub conveyance system. “The tubs are then transported to the first station where the syringe nest is removed from the syringe tub via a vacuum frame. The syringe nest is placed into an XY Table that is machined to articulate directly with the syringe nest array. The XY Table then indexes to the filling and stoppering station where filling needles, supported by rotary piston pumps, deliver the required dose to the syringe barrels, Phillips says.
“After the syringes are filled with the required amount of Excellagen, the syringes are vacuum stoppered. Once all syringes in the nest are filled and stoppered, the XY table indexes to the exit pick up station where a second vacuum frame picks up the syringe nest from the XY Table and places it back into the syringe tub. The tub is then conveyed out of the filling machine enclosure,” Phillips says.
Excellagen is a unique high molecular weight bovine Type 1 collagen formulation. “Filling challenges associated with Excellagen are due to its physiochemical properties as a viscous biopolymer emulsion,” Phillips says.
“The fluid dynamics of the product presented challenges with respect to maintenance of sterility and homogeneity as well as accuracy of fill volume. Solutions were engineered through adjustments in upstream processing as well as optimization of filling parameters and equipment configuration,” he adds.
After filling, the Excellagen syringes are bulk packaged in the syringe tubs and plastic seals are placed on to the tubs. The tubs are then bulk labeled and shipped to a commercial packaging company.
Excellagen lots are 100% visually inspected by operators trained and qualified to inspect final product for all attributes including cosmetic defects and foreign particulate, Phillips says.
“Once the 100% visual inspection is complete, an AQL inspection is performed on a statistically significant number of the accepted units by Quality Assurance. Once the AQL inspection is performed and deemed acceptable, the lot is transferred to shipping for final packaging and shipment from AMRI Burlington,” he says.
AMRI provides integrated drug discovery, development, and manufacturing services as a global contract research and manufacturing organization. AMRI has launched SmartSourcing to provide customers with strategic sourcing options.
“Projects are complex in nature and inherently prone to unforeseen logistical and technical challenges. A real strength of SmartSourcing is the ability to tap into a wealth of collective experience and knowledge that identifies and manages risk in a way that continuously imparts preventive measures to avoid problems from manifesting in the first place,” Phillips says.
“When the project scope is initially defined, the expectation for project deliverables/timelines and risk is discussed and fully agreed with the customer. SmartSourcing takes advantage of integrated service offerings across the entire life cycle of drug discovery, drug development, and drug substance/product cGMP manufacture. These services and business sectors all operate as one company, under one global quality system and one global procurement and project management team.
“While AMRI Burlington has its own capabilities, if we encounter an issue with procurement of packaging materials or are looking for better solutions than we have come up with, we can tap into the many other procurement channels existing across the AMRI global operations,” he says.
“Finally, SmartSourcing includes working under one quality system that does not change at each juncture of the project that might otherwise involve a third party under a separate quality system. This allows for continuity and cost control to keep projects moving forward as expected.”—David Vaczek