Greatest demands on hygiene properties - East European drugs for the world market
inova: With safety into the blood / the importance of pharmaceutical safety
Schwäbisch Hall. Liquid drugs that are filled in compliance with the strictest safety and hygiene regulations, cleanroom class 100 according to US Federal Standard 209 B, are processed on an extensive inova filling line. The injection and infusion bottles made of glass contain sterile watery or oily solutions of different viscosities. The customer is the global acting Slovenian company KRKA.
Drugs that enter the human bloodstream must meet the highest requirements regarding hygiene and quality. This is a matter of course which is legally protected by regulations and standards, primarily by the American health authority FDA, but which is always a technological challenge. Quality and hygiene do not only depend on the ingredients, the pharmaceutical production and packaging process is just as important. Pharmacists must be sure that they can rely unconditionally on the competence of their suppliers. Since many years inova specializes in filling and packaging of drugs that are mostly administered intravenously. New pharmaceutical forms are also inova’s domain.
Inova conceived an extensive filling and closing line for the Slovenian company KRKA Sterile Solutions. Today KRKA is a global player on the pharmaceutical market. KRKA products are sold in more than 70 countries. The glass bottles that are filled on KRKA’s inova line have volumes of 50 to 250 ml, both for injection and infusion bottles. In addition to the filling of the liquids, the operations of the inova line comprise the washing and sterilizing of the bottles, the insertion of plugs, the closing and 100% in-process inspection.
Safe sterilizing of the glass bottles on a small footprint was one of the customer’s specific requirements. Starting with the station for turning of the bottles up-side-down, an inova washing machine follows with extended infeed zone and combined ultrasonic bath for pre-washing and subsequent drying, followed by an inova SHT sterilizing tunnel. The sterilizing tunnel combines laminar flow and infrared hot-air radiation tunnel in a state-of-the-art patented way: In order to shorten the hot-air zone the bottles are additionally heated from below by means of infrared heating elements.
The bottle gapping unit inova BFB is followed by the modularly designed filling and closing machine VFVM 4833 with a rake conveyor system shifting the bottles in pairs. At the filling station the filling is done by means of servo-controlled traveling needle motion and peristaltic pumps. In order to ensure continuous sterility the filling and also the following plug insertion are done under laminar flow within a Restricted Access Barrier System (RABS). The product is likewise supplied under laminar flow. For the inspection of the filling results a tare weighing of the bottles is carried out before the filling.
The gross weight that is subsequently acquired is then transferred to the dosing system as information so that it can be continuously optimized. At the following closing machine with double-head plug insertion station, plug sorter and supply bunker the position of the plugs is checked prior to insertion. The following crimping is also done under cleanroom conditions. Furthermore the line is equipped with a positively monitored reject track.
One of the advantages of transport rake systems is the low depth of the machines, which makes them perfect for the RABS concept. The optimized accessibility and process monitoring are further advantages, just like the quick format changeover with the transport rake. Especially during format changeover the superordinate control system (SCADA) comes into operation, transferring all relevant data. The line can handle formats of 2 to 250 ml; however, currently only fill volumes of 50 ml and more are processed. The maximum output of the line is approx. 6,000 units/h with 50 ml formats. The dosing accuracy is +/- 0.5 %.
Compactly built, rapidly filled
From the very beginning inova was involved in the planning. Since the bottles were standard bottles according to ISO 8362 and DIN 58363, it was not possible to change the shapes or the material used. The inova engineers then implemented some custom-tailored solutions that optimally meet the customer’s requirements. These included the adaptation of the design of machine parts to the high surface requirements; moreover the layout of the machine was redesigned in order to further optimize the laminar flow zone. The plug infeed system has been optimized so that it would fit into the RABS. Last but not least, even a mock-up model was built for the optimization of the machine operation.
The total timeframe for the planning and implementation is twelve months. Before the end of the year maximum three KRKA staff members will operate the inova line in Ljubljana, Slovenia. As customary with pharmaceutical products, the line is located in three different rooms that are linked by airlocks. The line is not yet in production, but a similar inova machine is already in operation at KRKA. One thing is for sure: With this project inova gained the full confidence of the Slovenian company.