Română
It happened in 2005, when we were faced with a challenge, namely that of rebuilding the production unit in the section of injectable parenteral solutions in small volumes from Sicomed SA, currently Zentiva SA.
Basically, we were asked through the Specifications (URS) to redo the entire production process, with automation panel to monitor the entire technological process, from the phase of introduction and dosing of raw materials, to the phase of CIP / SIP and total drying e equipment at the end of each batch.
Of the entire existing equipment chain, only the original cooking vessels remain. The rest has been cut and replaced with new elements.
We worked with specific pipes and fittings for the pharmaceutical industry, respectively with AISI316L stainless steel, Ra 0.5 µm, the couplings being made by orbital welding and TC connections.
The most spectacular phase of the entire process of rebuilding the production section and the one that took us the longest to find the optimal solutions that correspond to customer requirements, were those related to the implementation of the CIP / SIP system and total drying with nitrogen. hot.
The technological process of washing, sterilization and drying “in place” designed by us was based on a sequential process, as simple and precise as it is easy to monitor and operate by the microprocessor included in the installation, but also by the operators. The operational sequences are followed in their development by the automatic program inscribed in the microprocessor, so that the advancement of the respective technological process and the transition to the next sequence can take place only under the conditions of successful completion of all previous, mandatory steps written in the microprocessor memory.
The aim of the project was to prepare the injection molding plant for a new batch.
This process has three stages:
Washing with purified water
Pure steam sterilization
Hot nitrogen drying
Three situations are possible:
- use of the installation without storage vessel 1;
- use of the installation without storage vessel 2;
- use of the entire installation.
The process takes place in the following order of sequences:
1. Washing
Washing has three phases, as follows:
a) Coarse washing 1.
It is done from one end of the installation to the other in two phases. First wash the preparation vessel using the sprayball and the vessel shaker with the amount of water required by the operator. The water from the preparation vessel is transmitted via the pump to the storage vessels. From the storage vessels, the water is transmitted further from the installation to the channel, with the help of nitrogen pressure.
b) Coarse washing 2.
It is made for each vessel using either water from the supply network or water from the beneficiary’s mobile CIP.
c) Washing with distilled water.
It is done from one end of the installation to the other, as in coarse washing 1.
This washing can be repeated as many times as necessary.
The sequence is considered to be successfully completed when the conductivity parameter reaches a value, set by the program, which must not differ from the conductivity of the inlet water before the process. The location of the conductivity sensor is located at the farthest point of the system, ie the drain pipe to the sewer.
2. Vacuum.
It will start only after the validation of the previous sequence by the microprocessor accepting the value of the programmed conductivity displayed on the display and printed on the paper strip of the printer corresponds to the value initially set (value of the conductivity of distilled water).
In order to start the sterilization phase, the part of the installation to be sterilized will be connected to a vacuum pump. The vacuum pump as well as the separation valve will close when the pressure reaches -0.5 bar.
3. Sterilization “in place”.
Pure steam enters the system automatically after the steam supply system has been automatically purged beforehand. The access of the steam in the installation is conditioned by reaching the temperature of minimum 1210C, in order to avoid the impregnation of the fine filter with condensation from the steam network. The same system is provided for the second fine filter.
The recording of the sterilization process will have the starting point after reaching the temperature parameter (programmed value min. 1210C) in the farthest point of the system, respectively the drain pipe to the sewer. After reaching the starting point and maintaining it throughout the sterilization sequence, set to 30 minutes, without deviating from the minimum condition, the automatic shut-off of the pure steam in the installation takes place automatically. The two parameters, minimum temperature measured at the farthest point in the system and time are interdependent.
In order to ensure the complete drainage of the condensate of the installation and the filters, it is necessary to introduce hot nitrogen, practically the initiation of the drying phase, immediately after the sterilization phase is finished. Thus, by introducing hot nitrogen at a pressure higher than that of sterilization by at least 0.5 bar (to ensure the flow of nitrogen in the desired direction) will achieve almost complete elimination of condensation from the plant. Drying will be much easier and nitrogen consumption will be reduced.
4. Drying “in place”.
The final sequence, ie drying “in place” will begin only after validation of the sterilization sequence. Drying will be done with nitrogen under pressure at a temperature of 1100C for a period delimited by reaching the absolute humidity parameter. This parameter will be established experimentally in the SAT tests taking into account the fact that an extremely sensitive absolute humidity sensor will be used, but also taking into account the avoidance of excessive nitrogen consumption. The absolute humidity sensor will be placed at the farthest point of the system, ie the nitrogen discharge pipe into the atmosphere.
The drying process is structured in two phases due to the division of the installation into two modules: sterile and non-sterile.
Once the technological tests were completed, we went, together with the beneficiary’s specialists, to test the equipment. For this, the option of using a culture medium was chosen – the environment most favorable to the microbiological load of the final product.
Thus, after the installation was ready for production, going through the mandatory phases of washing, sterilization and total drying described above, the product obtained from the sample preparation of the culture medium, was sent to the vial firing equipment.
The maximum number of ampoules admitted as unsuitable (from which a possible microbiological and endotoxin load could be detected by laboratory tests) was 5 pieces per batch of 5,000 ampoules of samples.
On this occasion, two rows of tests were carried out, with two different work teams,
The result of both tests was ZERO CONTAMINATED, INCORRESIBLE VIALS!