Flexibility is the clincher for contract fillers, all the more so if they have to package biopharmaceutical medicines. The new vial line for a contract filler in the United States combines insulator technology with freeze-drying. The line will be on view at Achema.
Contract packers in the pharmaceuticals sector are responsible for ensuring an uncompromisingly safe and sterile filling and packing process. This benefits patients but is in their own interests as well. After all, it’s what their business is all about. At the same time the packing process must also meet economic criteria and generate profits, but again without compromising safety. The medicine itself does not generate any profit margin.
The vial line from Optima Group Pharma has a particularly extensive insulator-protected area, further improving safety—particularly that of the machine operators. At the same time attention was also given to flexibility. For example, both liquid and freeze-drying medicines can be processed on the line. The fully integrated freeze-drying process can be started up “at the push of a button” without any further conversion work. The T-shaped layout of the line saves space too, thereby reducing the workforce required to maintain and operate the overall system.
Coping with complexity
The line as a whole consists of the following components: unwrapping machine, washing machine, sterilizing tunnel, filling and capping machine, loading and unloading system for the freeze-dryer, insulator, sealing machine and a coding machine.
The processing of the vials starts with them being fed into the washing machine manually using an unpacking tool. After the washing process, the vials proceed to the sterilizing tunnel, which removes pyrogens using hot air and then cools the vials down to room temperature again. The filling and capping machine immediately downstream receives the vials from the tunnel en masse and separates them on a rotary table. The vials are continuously taken from here and transferred to the rake transport system of the filling machine in synchronized groups of four by means of a segment wheel. All vials are weighed at tare weight and filled using a time-pressure dosing system from Inova. The gross weight is weighed at a second weighing machine, enabling the net weight to be calculated from these values. If vials are outside of defined tolerance limits, these will not be capped but will be consigned to scrap.
A pick-and-place module fits the correctly filled vials with a rubber stopper as a seal. The stopper is pushed in fully for liquid products but only part of the way for freeze-drying products: a sensor system checks that a stopper is present and that it is inserted to the correct depth. Incorrectly sealed vials will be rejected.
A second segment wheel at the end of the filling and capping process takes the vials from the synchronized rake transport back into the continuous movement of the downstream transport and distribution system. Depending on the format chosen, the vials are either fed into the loading and unloading unit of the freeze-dryer or—in the case of products that are sold in liquid form—transported directly to the capping machine.
If freeze-drying products are processed, the filled vials are arranged into rows in the loading and unloading unit and these rows are pushed into the freeze-dryer in a hexagonal formation so that the freeze-dryer can be loaded with maximum possible use of the cooling surfaces.
After the freeze-drying process the vials are again removed in rows and fed into the capping unit on the line. In the capping machine the presence of a stopper on the vial is checked before an aluminum roll-on cap is crimp-fitted in a continuously running rotor that takes ten vials at a time. Seals checked by the sensor system that do not meet the requirements are consigned to scrap.
To ensure maximum product protection, the entire line from the exit of the sterilizing tunnel to the end of the capping machine is fitted with an M&P insulator. On leaving the insulator, a 2D data matrix code is printed onto the containers by a coding machine in order to identify the product clearly. The vials are carefully counted out and packed on trays in the double-magazine system. These trays are then removed manually from the line. For maximum hygiene, the whole line in the area protected with insulators has been made from stainless steel 316L. All surfaces in this area are polished. The entire insulator-protected area is sanitized with hydrogen peroxide vapor.
The time-pressure dosing system used here meets the requirements of a contract packer who also has to fill and pack active biopharmaceutical ingredients. Its high filling accuracy of srel <0.5% offsets the cost of the active ingredients, which are usually extremely expensive even in small quantities. In addition, the sensitive product is handled with care so that the effectiveness of the medicine is not impaired. The dosing system is also equipped with a full in-process check—a self-optimizing system that on the one hand contributes to and is responsible for high filling accuracy, and on the other hand ensures extensive use of the available product quantity: overfilling during the start-up phase due to temperature conditions is avoided; manual, relatively inaccurate random samples that inevitably result in product loss can be dispensed with; and finally, maximum use is also made of the quantity of product available when the line is emptied, without running the risk of underfilling.
A filling range of 0.05–20 ml filled into vials with a volume of 2–20 ml stands for an extremely flexible system. Stoppers and roll-on caps can be processed in nominal sizes of 13 mm and 20 mm. The yield of the four-point filling system is 150 vials/min; the finishing line is configured for an output of 400/min in order to unload the freeze-dryer quickly.
Format changes are carried out almost entirely by means of the operating system. A CIP/SIP system is used to clean the dosing system for product changes. A format change takes 30 to 60 minutes, depending on the processing sequence.
Optima Group Pharma has equipped the customer’s entire plant with a range of solutions for the contract processing of parenteral pharmaceuticals. The vial line described here is one of these solutions.
ACHEMA Hall 3.0, Stand B2-C11
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