Process and device for the sterilisation of filling plants.

The present invention concerns a process and a device for washing and sterilising plants for filling vials and similar containers, and more in particular plants for filling pharmaceutical vials.

Said plants essentially comprise, besides a (trailer-mounted or fixed) container for the liquid to be metered, a pumping system consisting of one or more syringes, one or more corresponding filling nozzles to fill the vials, and one or more nozzles to inject nitrogen into each vial before its filling with the product in order to avoid a product oxidation.

Chiefly in the case of plants treating medicinal products, it is necessary to perform washing and sterilisation of the plant before each operating cycle, namely when the type of product treated is changed, or for example at the beginning of the day, when the filling plant, off since the previous evening, is started again.

In any case, sterilisation must be performed immediately before the plant use, because, if time passes between sterilisation and use, the plant can be contaminated again. Furthermore it is current practice to perform a washing operation at the end of the operating cycle in order to avoid that the products remaining in the plant crystallize or harden so clogging it in some points; the operations of cleaning-sterilisation are thus doubled.

It is obvious that this represents a considerable disadvantage in that the number of working hours of the plant during the day is reduced by the time necessary for its sterilisation.

There is therefore the need to perform sterilisation of the plant out of the time periods in which it is used for filling vials, though maintaining the plant sterile until its subsequent use.

An object of the present invention is to solve the aforementioned problems providing a method and a device for sterilising said filling plant at the end of its operating cycle and keeping it sterile until its subsequent use.

More in particular, the invention relates to a process for the sterilisation of a plant for filling vials and similar containers, of the type comprising one or more washing steps and one or more steps of steam sterilisation, characterized by the step of injecting sterile gas into the plant at the end of said sterilisation stage and maintaining said plant in overpressure by means of said inert gas until its subsequent use.

Furthermore the invention relates to a device for the sterilisation of a plant for vials and similar containers, the plant being of the type comprising means to alternatively feed water or steam to said plant, characterized in that it comprises means to feed a sterile gas to said plant after its sterilisation and to put and maintain said plant in overpressure by means of said gas until its subsequent use.

The invention will be now further described with reference to the accompanying drawings, wherein: <ul id="ul0001" list-style="dash"><li>figure 1 is a scheme of a device according to the present invention; and</li><li>figures 2 and 3 are partial cross-sectional views of the syringes of the plant in two different positions during their sterilisation.</li></ul>

According to the principle of the invention, the plant is submitted to the normal steps of washing and sterilisation (and possibly to various washings and sterilisations) in a known way. At the end of the sterilisation step, before steam pressure inside the plant falls down to a value equal to the atmospheric one, the plant is fed with sterile gas and then put under light overpressure by means of said gas and maintained in overpressure until its subsequent use.

This allows to perform the plant sterilisation at the end of its operative cycle, for instance at the end of a working day, when the plant has been stopped, in a way to have it ready for use the day after. Moreover, the time saving thus obtained can be advantageously maximised by performing the different steps in an automatic way.

Figure 1 shows a scheme of a preferential embodiment of a device to perform the steps of washing/sterilisation and inertisation according to the aforedescribed process.

The device according to the invention comprises, besides the usual lines 6 and 7 for water and steam feeding to the plant, also means for feeding nitrogen or other sterile gas, such as for instance sterile air, along a line 5.

The device of figure 1 comprises a filling plant 1 consisting of a syringe 2 and a filling nozzle 3 connected thereto, and of a nozzle 4 for the injection of nitrogen (or similar substantially inert gas such as air) connected to said nitrogen feeding line 5. For greater simplicity, only one syringe with relevant filling and injection nozzles is illustrated, despite such plants usually foresee more than one; furthermore all those parts of the filling plant which need no sterilisation are not illustrated.

It is here pointed out that the word filling nozzle as used herein means the nozzle which serves to fill the vial with the product, while the term injection nozzle means the nozzle which serves to blow in nitrogen into the vial before its filling in order to avoid the product oxidation.

The lines 5, 6 and 7 are each provided with valve means, 10, 8 and 9 respectively, to regulate the flow of the relevant fluids therein during the different steps of the process. Downstream of said valves, the lines 5, 6 and 7 are connected to each other by a common duct 11 from which comes out a line 11a for feeding the syringe 2 and the nozzle 3 connected thereto. The syringe 2 is connected in a reversible way to the line 11a by means of a junction 31.

The duct 11 presents, along its portion between the lines 5 and 7, a valve 12 to regulate the passage of the fluids to and from the line 5. On the line 5, downstream of the junction with the common duct 11 there is provided a second valve 13 controlling the passage of the fluids to the nozzle 4. Still on the line 5, upstream of said junction, there is provided a sterile filter 14 of the "PALL" type, to filter nitrogen coming along the line 5 and guarantee its sterility.

As it can be noticed from the scheme of figure 1, the filter 14 can therefore receive steam too, or water, from the duct 11, whether the valve 12 is switched off or on. The process according to the invention only foresees steam injection to sterilise the filter together with the plant 1 and the remaining circuit of the device. The filter 14 is provided with outlets equipped with a manual discharge valves 15, and with a valve 16 for releasing condensate from the filter, said valves being connected to each other by a duct 18.

There is also provided a line for steam outlet from the filter 14, which is equipped with a manual valve 17 and is connected with the line 5 in a position between the filter and the valve 10, and with the duct 18 downstream of the manual valve or throttler 16. Downstream of this latter, along the line 18 there is a valve 19 to control the passage of fluids (steam and condensate) towards the drain discharge BA.

As mentioned above, valves 15, 16 and 17 are a kind of throttlers to be manually adjusted in an appropriate position at the moment of the plant installation and to be left in such a position during the different stages of the process.

Figure 1 shows the nozzles 3 and 4 already housed inside their relevant sheaths of the manifold 20, which is also directly connected to the syringe 2 by means of a flexible duct, as well as with a drain line 21, which is provided with means to throttle or stop the flow along the same.

Although these means might be constituted by whatever type of throttling, they preferably comprise a condenser 22 mounted with a valve 23, downstream of same, on an offtake 21a of the drain line 21. Said offtake connects itself again with the drain line 21 in a point from which a recovery line for condensates 24 comes out.

In order to control the passage of fluids along the lines 21, 21a and 24 there are provided, besides the already mentioned valve 23 and condenser 22, a first valve 25 mounted on the line 21 between two junctions with the offtake 21a, a second valve 26 also mounted on the line 21 and placed downstream of the offtake for the recovery of condensates, and a third valve 27 to regulate the passage of condensate to the line 24. Preferably, on the line 24 there is a further valve 28 to control the condensate flow back.

In correspondence with the housings of nozzles 3 and 4 in a manifold 20 there are provided means 29 to detect the temperature at the nozzles during the sterilisation step. Similar means 30 are provided on the offtake 21a to control, as a function of temperature and by way of valves 23 and 25, the passage from the direct drain line 21 to the condenser 22.

The detectors 29, 30 are connected to a temperature recorder of known type (for example a recorder of CHESSEL type) which is on turn connected to a control console, of known type as well, such as for instance the one called SIMATIC 55 of Siemens, and inserted in the general control board of the machine. Recorder and console are shown in fig. 1.

Detectors 29 are preferably set at 121 degrees C and the sensor 30 at 40 degrees C.

For better operating safety, mainly in case of automatic operation, a plurality of sensors are also envisaged to control the correct execution of each stage, and more in particular sensors for the nozzles positioning, namely sensors for checking the actual connection of the plant circuit to the lines for water, steam and inert gas feeding, sensors checking the actual insertion of the nozzles into their relevant housings of the manifold 20; sensors of correct positioning of the syringe plunger in the washing/sterilisation position, and sensors for checking the condensate level in said condenser 22, to detect presence of excessive condensate due for example to the partial relaxation of a flexible tube and the subsequent formation of much more condensate than it normally occurs.

There are also pressure switches, one for each feeding line 5, 6,7, to check the actual feeding of water, steam and nitrogen along said lines.

Said pressure switches, too, are connected to said console to generate an alarm signal in case feeding stops.

All these are sensors of known type and commercially available and are connected in a known way to the control console to generate an alarm signal and stop the machine cycle in case preset operating conditions are not met.

As already previously mentioned, the aforedescribed device allows to carry-out the process according to the invention in an automatic way, by control from said console which controls a panel of solenoids controlling in turn a circuit for operating the valves which are preferably pneumatic valves.

To carry-out said process, at the end of the operations of the vials filling, first of all the nozzles 3 and 4 are positioned into their relevant housings of manifold 20 and the junction 31 is displaced from the trailer-mounted container of the product connecting it to the line 11a. Then the syringes are brought in washing/sterilisation position (as shown in fig 2 and as known in the technique) to be emptied from the remaining product.

At this point all valves are closed except the throttlers 15, 16 and 17 which, as already said, are adjusted at the moment of the plant installation and are no more modified. Then a first "dynamic" washing of the syringe and the nozzle 3 is performed by opening only the valves for water feeding, 8, and direct drainage, 25 and 21. In this type of washing, the syringe operates by sucking water and conveying it to the nozzle 3.

At the end of this washing, whose duration is set on the control board in a known way, the water flow is stopped by closing the valve 8 and the syringe is brought to the position of washing/sterilisation shown in fig. 2.

Afterwards a second washing of the "static" type is carried out with the valves under similar conditions as for the preceding dynamic washing, for a further period of time which, too, can be set in a known way (e.g. by means of a keyboard unit OP 393 by Siemens) on said control board.

At the end of this washing, according to a preferred embodiment of the invention, the valve 8 is closed and the valves 12 and 10 are opened to inject nitrogen into the lines and discharge water from them and from the nozzle 3. The predetermined and set time for this operation is generally very restricted, of the order of approximately 1 minute, at the end of which the valve 10 is closed again while valves 12, 25 and 26 remain open.

In the subsequent step of sterilisation, the valves of condensate flow back 28, of steam feeding 8, of steam exhaust from the sterile filter 19 and the valve 13 allowing passage to the nozzle 4 are opened.

Steam thus begins to circulate along all the lines and the filter 14, until it escapes from the exhaust line 21 and the valve 19.

Once the previously set temperature is reached (generally 40 degrees C) and detected by the detecting means 30 placed on the line 21, the drainage valves 25 and 26 are automatically closed and simultaneously the valve 23 for the condenser 22 operation and the condensate recovery valve 27 are opened, thus connecting the line 21 to the condensate recovery line 24 through the condenser 22. As previously mentioned, the function of the condenser 22 is mainly that of throttling the line 21a, limiting the steam flow therethrough and so keeping the lines of the device and the plant under pressure.

In this way it is possible to bring said lines at the preferred sterilisation temperature, which is generally at least 121 degrees C. More in particular, when this temperature is detected by sensors 29, the temperature recorder actuates through the console the start up of the period of sterilisation at 121 degrees, which period generally lasts approximately 0.5 hours.

Sensors 29 also check that during said period no significant falls in temperature at the nozzles 3 and 4 take place. In this way sterility of the plant and of the device lines is ensured.

Furthermore, in this step, the filter 14 as well is sterilised.

Once the preset period of time is over, the valve 8 of steam inlet is closed.

The last step of inertisation and maintenance of the sterile conditions of the circuit begins when the pressure of steam remaining in the device lines has decreased to sufficiently low values to allow to inject nitrogen at slight overpressure, in any case at a pressure higher than the atmospheric one to avoid that the circuit may be contaminated again by the external environment.

At this point, all the valves are closed except the valve 12 and the valve 10 of nitrogen inlet.

The duration of this stage depends on the time that intervenes between sterilisation and the subsequent use of the filling plant, and it is manually terminated at the moment of plant re-use.

According to a different embodiment of the process, the sterilisation step is subdivided into two parts, lasting approximately 0.5 hours each. In the first part, sterilisation is carried out as previously described. In the second part the valve 34 of the syringe is moved upwards to the position shown in fig. 3: in this position the valve cuts off the steam flow towards the side outlet 32 and the relevant filling nozzle, conveying all steam towards to the other outlet 33 and thus improving the sterilisation of the lower section of the syringe.

As previously mentioned, the correct execution of the different stages of the process is controlled by different types of sensors which, in case of failure or troubles, generate a signal activating an alarm and simultaneously stopping the device operation. This is particularly useful in case of automatic operation controlled by said console included in the machine control board. In case of troubles and alarm the operator will manually restore the plant operation after having eliminated the causes of the trouble.

Moreover, it is here pointed out that, despite the invention has been described with particular reference to a filling plant of the type using a trailer-mounted product container, a similar device and similar procedure can be used in case of a fixed container. In this case the product tank will be equipped with exhaust means for the condensate similar to those described with reference to the sterile filter 14, and the line 11a will be connected to said tank.

Similarly the device and the process according to the invention can be applied to a plant not provided with nozzles for nitrogen injection during vials filling. In this case the only difference consists in the absence of the nozzle 4 and of that section of line 5 which leads from the common duct 11 to said nozzle 4. Also the valve 13 and the temperature sensor 29 related to the nozzle for nitrogen injection will obviously be absent.