Vial washing is one of the processes that is performed before the filling process in a Parenteral pharmaceutical product production line. Today, the production line for such products is a Compact Line.
This system includes a washing machine, a thermal tunnel and a filling machine. Vial washing machines or vial washing machines are designed and used in different ways, which are explained below, but in these machines, filtered compressed air (pharmaceutical) Purified Water and W.F.I are used to wash the vials.
To confirm the efficiency of the vial washing machine, decontamination of the vials should be carried out with relevant tests on the various sizes of vials used. Since the internal surfaces of the vial are in direct contact with the injection powder and any foreign particles, microorganisms, dust, chemical contaminants and also residual endotoxin in the vial can be transferred directly to the powder, therefore, validation of the vial washing process is of particular importance.
Although after washing the vials, sterilization and pyrogenation are performed with dry heat, if the washing process cannot eliminate chemical contaminants or remove non-living particles and particles, it can lead to diseases or problems in humans or animals that use the drug. Therefore, particles and chemical contaminants must be removed in the vial washing process so that they do not pose a risk to the quality of the product.
As indicated in the FDA Guide, 21CFR: The containers of sterile drug product contents (vials) and their caps must be sterilized and pyrogenated completely before use for medicinal purposes, to ensure that they are suitable for the intended use. The FDA Guide for factories producing sterile drug powders states: After determining the type and dimensions of the vials and storing them in appropriate conditions, the washing process will be validated by washing, sterilization and dehydrogenation.
Types of Vial Washing Machines:
In general, there are three different types of vial washing systems, which are:
In-Line Washing Machines
In these systems, the vial washing machine washes the vials in linear rows and the washing sequence is performed row by row.
Rotary Washing Machines
In this system, the vial washing machine is rotary and the vials are divided into small groups (for example, 8) around an axis to which the nozzles are also connected, and the vials are placed upside down, and the nozzle moves into the vial and injects water and air into the vials in a washing sequence and moves around a circular axis.
Exterior Vial Washers
This system is a separate device that the containers must be transferred into for washing. These devices are used for small numbers of containers.
Characteristics of water used in vial washing:
The water used in the vial washing system is . W.F.I. A complete vial washing cycle includes several stages of washing the internal and external surfaces of the vial. The external surfaces of the vial and the internal surfaces of the vial are washed in several stages with . P.W respectively, but in the last stage, the washing of the internal surfaces of the vial must be done with . W.F.I.
Parameters to be considered in the bottle washing system:
The parameters that should be considered in the evaluation of the bottle washing system are as follows:
– Return water pressure and spray pressure uniformity
– Fresh water pressure and spray pressure uniformity
– Compressed air pressure and spray pressure uniformity
– Distance between the water nozzle and the air nozzle to the bottom of the bottle (centering of the nozzles)
– Water spraying duration
– Volume of water and air used per spray
– Compressed air spraying duration
– Water temperature used for washing (if the system has the ability to adjust the temperature).
When validating the bottle washing performance, these parameters should be designed in such a way that the worst case washing condition is considered.
Conditions corresponding to the worst and most inappropriate case
All conditions applied in validating the bottle washing device are based on the worst case conditions. To select the Worst Case, the spraying time (fresh water, return water and air) is the criterion, which depends on the following factors:
– The size of the container (vial) (in terms of height and volume of the vials) The larger the size of the vial, the longer the spraying time. (The weight of the vial and its material)
– The speed of the vial washing machine based on the production of clean vials. The higher the production speed, the longer the vial stays inside the vial washer and, as a result, the shorter the spray time of the nozzles.
Contaminants:
Because the inside surface of the vial is in direct contact with the drug product, contamination, if present, will enter the product. Any foreign particles or dust or chemical and microbial contaminants, as well as any residual endotoxin in the vial, will be transferred directly to the powder, so it is important to ensure that the vials are washed to ensure the quality of the drug.
Validation Process:
In some pharmaceutical industries, the detection of traces of dye residues used in washing is used to visually check the correct and complete functioning of the device. However, this method is a qualitative method and cannot measure the amount of particle residues, dust, endotoxin, and other chemical contaminants. Therefore, the Spike method is used to measure the level of contamination of vials in validation. Three studies are conducted to check the contamination for each type of vial. In each study, the efficiency of the system is evaluated three times for repeatability.
Tests used to check the efficiency of the vial washing device:
Particle Test:
This test is performed to study the level of particle contamination of vials, which after washing should reduce the particle level to a standard level.
Chemical Contamination Test:
The chemical contamination test is performed to study the level of chemical contamination of vials with a specific concentration.
Endotoxin Test:
This method is used to determine the effectiveness of the vial washing process, based on the reduction of endotoxin in the vial. Given that WFI is used in the last stage of each vial washing process, the reduction of endotoxin in the vial should be within the endotoxin range of WFI water.
Microbial Load Test:
Determining the microbial load of vials after washing and comparing it with the microbial load before the washing process is also one of the parameters for determining the efficiency of the vial washing machine. In this test, the internal surfaces of the vials are washed using Peptone Water and the microbial count of the above liquid indicates the microbial load of the internal surfaces of the vial.
How to take samples from contaminated vials:
The washed vials should be carefully removed with gloves and forceps in sterile, particle-free packaging in the same form as they are removed from the machine and prepared for analysis of contaminants (chemicals, endotoxins and particles). For this purpose, the required number of washed and sterilized rubber caps should be prepared to close the vials to be tested. Since external contaminants affect the level of contamination of the vial, special care should be taken in collecting the vials when they leave the machine.
Vial Washer Validation Documentation:
In addition to recording all test procedures, test results, and system changes, the following must be included in the validation documentation:
Record the number of samples and vial sizes, and how labeled vials are collected or arranged in the vial washer.
Record the scope of all processes and equipment parameters such as (air and water nozzle settings, speed, sequence, time sequence, etc.).
The pressure and quality of compressed air and water WFI and PW and its electrical conductivity, as well as the water temperature, must be recorded.
The machine speed (Vials/Min) and the time of air and water spraying must be recorded in the documentation.
Filter specifications and their calibration documents and other items such as pressure gauges and all items that require calibration must be available.
Alarms:
After the device has been calibrated and installed based on the DQ and manufacturer’s recommendations as well as GMP principles. General alarms and controls should be checked at the OQ stage.
Revalidation:
Of course, any change in the valid conditions of any of the above processes can create the possibility of contamination in the product. Therefore, when changes are made to the vial washing machine such as fresh and inlet water pressure or compressed air pressure, nozzle distance to the bottom of the vial, pressure changes during washing time, and similar items that affect the quality of washing, revalidation must be performed.
