The shift from blockbuster drugs to more targeted biologics has left contract manufacturers struggling to adapt. The smaller batch sizes for biologics, gene therapies, and personalized medicines require a different strategy if manufacturers are going to maintain their efficiency and keep costs under control. One option they’re exploring is ready-to-use (RTU) packaging.
But, while RTU can enable more flexible filling, that alone will only add so much flexibility. In a world with more than 200 biologics on the market, and thousands more in various stages of the development pipeline, manufacturers looking to implement RTU will have to take it a step further. RTU needs more automation, standardization, and pre-validation.
Pharmaceutical filling lines at many companies were built with blockbuster drugs in mind, suited to drug runs in the millions rather than the tens of thousands. By enhancing RTU with these three key initiatives, contract manufacturers can reduce downtime, keep costs under control, and allow for more flexibility and faster changeovers on large lines.
A Model for Pharma?
The semiconductor industry has reaped the benefits of harmonized packaging for years with the Front Opening Unified Pod (FOUP), which has become the primary vehicle for processing chips in semiconductor workcells. The FOUP supports the transfer of silicon wafers between the steps of semiconductor manufacturing, and between systems from many suppliers.
Semiconductor workcells rely on robots and machine vision to cleanly and efficiently handle manufacturing with limited intervention. It’s a system that ensures safe handling of sensitive parts and reduces the likelihood of human contact or particle contamination.
Pharma, however, is only recently coming around to the benefits of FOUPs and workcells.
RTU containers, arranged in a nest and packaged in a tub with a protective cover, fit pharma’s version of the FOUP. It allows robots to fill and close containers without human intervention.
Vanrx Pharmasystems, for example, has created an automated, aseptic filling workcell with no glove ports. There are no conveyors, belts, sortation devices, or mouse holes either. The only reason for human intervention in the past was the process flaws that can be eliminated through automation.
This gives contract manufacturers a process that’s not only safer, but repeatable. Simple robotic movements allow for more uptime and reliability. The environment has semiconductor-grade particle control, and the filling stations meet the exacting standards for working with sensitive biotech products.
Standardization Is Crucial
For automation to change the way filling lines operate, the nests and tubs will have to be standardized across syringes, vials, and cartridges.
While RTU packaging is nothing new, drug containers usually come in tubs of different sizes, so that when it comes time to change delivery formats, manufacturers must either re-tool, or use an entirely different machine.
Imagine if shipping containers were all different sizes. Freight companies would need different boats, different cranes, different trucks and rail cars to carry containers of various sizes and shapes. Instead, there’s a standardized container size that allows a company to ship any freight using the same equipment. Pharmaceutical manufacturing should be no different.
By standardizing the nests that hold vials, cartridges, and syringes—making a true FOUP for pharma—manufacturers can fill various drug and container configurations on the same line.
For example, SCHOTT’s new iQ platform makes use of standardized tub formats. It allows pharma manufacturers to reduce changeover times to as little as 10 to 20 minutes and easily switch from one container to another, one dosage to another, and one drug to another.
Such a system adds a significant level of flexibility for contract manufacturers looking to maximize uptime and efficiency, without the expense of adding new filling lines.
With modular fill & finish lines, contract manufacturers now can offer production runs with as little as two weeks of lead time, compared to the six months that has been the norm. The machines can run batches of less than 10,000 units, which are suited for rare disease treatments. They can more easily run medicines for clinical trials and personalized medicines.
Pre-Validation Adds Efficiency, Removes Risk
The harmonization of packaging goes beyond the containers. The next logical step in pharmaceutical filling systems is the stopper. Vendors across the globe are looking to standardize the cap on cartridges and vials, and replace aluminum crimp caps, which produce metal particles that can potentially enter the vial.
New systems use plastic press-fit caps that stopper and seal containers in one step, as a single unit, eliminating particle risk and increasing efficiency.
At the same time, a common packaging standard can reduce complexity of pharmaceutical filling lines because RTU containers are available in pre-validated bundles. Vanrx, for example, initiated the Matrix Alliance, which features primary packaging leaders cooperating on nested container and closure compatibility.
Member companies include SCHOTT, Daikyo Seiko, and ARaymondlife, among others. The resulting “product sets” feature proven compatibility and machinability within Vanrx aseptic filling workcells, helping pharma companies move drug products to market with greater speed and confidence.
With less of a need for large manufacturing lines, pharmaceutical companies are looking to shrink their footprints. Using a standardized nest-and-tub system reduces the number of machines that manufacturers need, cutting investment costs by up to 40 percent, operating costs by up to 40 percent, and the amount of clean room space by 60 percent. Modular clean room capacity gives them the flexibility to build up capacity incrementally as well.
The growth of biologics has significant ramifications for the utilization of pharmaceutical filling lines, and vice versa. Because biologics are highly specialized drugs with smaller target populations and production runs, they require more changeovers, and thus more downtime. Traditional manufacturing limitations are prolonging the time it takes to get these products to market, putting pharmaceutical companies at the mercy of rapidly changing market dynamics.
For contract manufacturers in particular, the flexibility of automated, standardized, pre-validated RTU can reduce the risk of overproduction or underproduction, allowing them to respond quickly to market conditions or adopt lean manufacturing approaches.
The future of pharmaceutical packaging is fast and flexible, brought about by changes in the scale of cures. With fewer mass-market drugs on the horizon, pharmaceutical companies will continue to focus on highly targeted markets.
With more automation, standardization, and pre-validation around RTU, contract manufacturers and drug companies can vastly reduce the complexity of pharmaceutical filling operations and focus on their core competencies.
About the Author
Gregor Deutschle is Head of Business Development, Sterile Solutions, at SCHOTT Pharmaceutical Systems