DIFFERENT TYPES OF CLEANING METHODS USED IN PHARMA
CLEAN-IN-PLACE: – Cleaning applications can be classified into two groups based on the extent of disassembly-CIP (clean-in-place) and COP (clean-out-of-place). Technically, CIP applies to all situations in which disassembly is not performed and can apply to situations in which process equipment is merely flooded with cleaning solution. As a practical matter, CIP has usually come to mean an automated cleaning system involving spray devices to distribute the cleaning solution to all process vessel surfaces.
CIP systems are usually designed for cleaning with aqueous cleaning solutions. The key parts of the CIP system are the
- Spray device(s),
- The CIP unit, and
- The associated piping to carry the solution to and from the equipment to be cleaned.
The CIP unit consists of one or more CIP tanks, a recirculation pump, and a process control unit. The concentrated cleaning agent storage tank is usually a plastic tank or carboy, although a drum of the cleaning agent may serve as the vessel for the concentrated cleaning agent. A separate CIP wash tank (also called the recirculation tank) is used for cleaning agent dilution and serves as the reservoir of diluted cleaning agent for recirculation throughout the CIP system.
The recirculation pump is usually a centrifugal pump that pumps the cleaning solution from the wash tank to the spray devices. Usually the spray device (a device not unlike a shower head, albeit one that typically sprays up rather than down) sprays the cleaning solution around the dome of a process vessel so that the cleaning solution is adequately distributed within the process vessel.
Spray devices are usually of either fixed (sometimes called stationary) or rotating (sometimes called dynamic) types. Fixed spray devices (usually spray balls) are mounted in one orientation, and the direction of spray does not change during the cleaning process. Fixed spray devices are simple in design, have no moving parts, are free draining, and are therefore ideal for “sanitary” applications.
Fixed spray devices are generally used at lower pressures of about 15-40 psi. Fixed spray devices may be permanently installed in a tank, or they may be installed in place immediately before CIP cleaning is performed.
Rotating spray devices are also mounted in one orientation; however, the head will rotate through a pattern providing direct impingement over a larger area. Rotating spray devices are generally operated at higher pressures, up to 100 psi or greater. The higher pressure allows more mechanical energy to be inputted into the system, therefore making the cleaning process more efficient in some cases. Because of the rotation and the complexity, these spray devices are usually not free draining and are not sanitary (although there are some designs described as sanitary). Therefore, they are used in systems in which the spray head is removed from the system after cleaning. They must be reinstalled for the next cleaning procedure. Depending on the number and location of “inserts” within a process vessel, one or more spray devices may be needed. The location and spray orientation of spray devices may be near the dome. Fixed spray devices will spray up onto the dome (to get good overall coverage) but may also have to be strategically placed to assure adequate cleaning and rinsing. After the cleaning solution is distributed within the vessel, the cleaning solution cascades down the sides of the process vessel, across the vessel bottom, and down the discharge pipe. For once-through CIP systems, the cleaning solution is not reused; the discharge pipe leads to either a holding tank (for chemical neutralization) or directly to a waste treatment facility.
To prevent redeposition of residues in the CIP cleaning solution tanks, it may be necessary to include a spray device in the CIP tank. This spray device would effectively clean and rinse all surfaces of the storage tank.
AGITATED IMMERSION: – Agitated immersion involves filing a process vessel (and associated piping) with a cleaning solution and then agitating the solution with a mechanical agitator already in place in the process vessel. The cleaning solution can be either an organic solvent or an aqueous cleaning agent. In such a system, after the cleaning step, the vessel is drained and then filled multiple times with rinse water (or other rinsing solvent) to remove soil residues and the cleaning solution. During the rinsing steps, the rinse solutions are agitated just as in the cleaning step. It should be noted that pumping a cleaning solution, for example, from the discharge pipe of a vessel, through a recirculation pump, and back to the top of the vessel, generally will not be very effective in achieving agitation. In such a system, it is difficult to achieve adequate flow within the larger vessel. There are likely to be significant areas with low flow rates.
In agitated immersion cleaning, the major cleaning effect is due to the chemical action of the cleaning agent. The effect of the agitation is to bring fresh cleaning solution in contact with the residue on the surface. This maximizes the cleaning effect. The second purpose of the agitation is to remove solubilized/ emulsified/suspended soils from the equipment surfaces and carry them to the bulk cleaning solution. This prevents soil concentration gradients from forming near the equipment surfaces; such gradients can slow down the cleaning process.
Agitated immersion can be performed under a variety of process conditions, including various times, temperatures, cleaning agents, and flow conditions. The emphasis is contact of the agitated cleaning solution with all surfaces.
STATIC IMMERSION: – Static immersion is agitated immersion without the agitation. In static immersion, a process vessel is merely flooded with the cleaning solution (either aqueous or organic solvent). The sole cleaning effect is due to the chemical action of the cleaning solution. Even this chemical cleaning action is minimized because concentrations gradients of residues solubilized, emulsified, or suspended near the equipment surfaces tend to retard the cleaning process. Depending on the nature of the residue and the cleaning agent, times for the cleaning step can take from 50 percent longer to as much as 500 percent longer than with agitated immersion. Static immersion is generally a cleaning method of last resort.
AUTOMATED PARTS WASHING: – Automated parts washing is in the domain of true COP applications. Parts that are disassembled from process equipment or other small parts such as scoops that are used in the manufacturing process can be cleaned in this manner. The parts are placed in a mechanical washer and processed through cleaning, rinsing, and drying cycles. The cleaning solution and the rinse water are applied to all surfaces of the objects to be cleaned by spray jets and nozzles. Automated washers are of two types: –
In cabinet washers the parts are placed on racks inside the washing cabinet, and all cycles occur with the racks in a fixed position (similar to a home dishwasher).
In tunnel washers the parts are placed on racks that travel through the tunnel washer. Cleaning, rinsing, and drying occur at different locations within the tunnel washer (similar to some commercial car wash facilities). The degree of controls on a washer can vary considerably. With some washers, there are minimal controls and recording of data. With so-called “GMP” (Good Manufacturing Practice) washers, there is considerably more documentation to enable the washer to be more easily validated. The performance of the automated washer is due to both the mechanical impingement of the spray systems and to the chemical action of the cleaner used.
With the systems discussed previously (CIP, agitated immersion, and static immersion), the chemical cleaning agent has been significantly more important than any mechanical effects. In automated parts washers, the mechanical cleaning effects are at least as important as the cleaning agents used. In parts washers, spray pressures may be only in the 5-20 psi range. The spray is designed so that all of the parts (but not necessarily all surfaces of a given part) obtain adequate spray impingement. For this reason, issues like clogged spray nozzles can significantly affect cleaning performance. Because of the spray pressure, the issue of detergent foaming is significant. Foam is very difficult to rinse from cleaned parts, thereby increasing the possibility of leaving detergent. Careful selection of the cleaning agent is required for automated parts washers.
ULTRASONIC WASHERS: – Ultrasonic washers are essentially open or covered tanks with a cleaning solution in the tank. Tanks may be covered to prevent evaporation or aerosolization of the cleaning solution. The tank is equipped with ultrasonic transducers, which pass high frequency sound waves through the cleaning solution. At the surfaces of objects placed in the ultrasonic cleaning solutions, the sound waves cause tiny bubbles to form. As these bubbles grow, they eventually collapse upon themselves. The mechanical energy of the collapse helps dislodge any residues or particulates on the surface. This process is called cavitation. The cleaning agent solution helps to wet the residue and then keep it suspended or emulsified. As a general rule, ultrasonic are run at temperatures below about 55°C. Ultrasonic baths come in different sizes, from 1 L up to 20 L or more. The ultrasonic process is most appropriate for cleaning delicate parts that might be damaged by other cleaning processes or for parts with small orifices or other openings. For example, filling needles might best be cleaned by an ultrasonic process. Following the exposure in the ultrasonic bath, the part is manually removed and rinsed by any suitable method, such as with flowing water. For small orifices, rinse water may have to be pumped or aspirated through the orifice.
HIGH-PRESSURE SPRAYING: – A high-pressure spray application involves using a high-pressure, continuous, directed water or detergent solution to clean parts or to clean the inside of process equipment. Water pressures may be on the order of hundreds of psi. This usually involves the use of a spray “wand” of some type. In its simplest version, the spray wand is manually controlled to clean small parts. In a more sophisticated version, an automated spray wand is inserted inside process vessels, where the spray direction and orientation are robotically controlled to clean and rinse all surfaces. High-pressure spray applications involve a more significant contribution from mechanical energy inputted from impingement of the cleaning solution on the surface. This serves to dislodge any residues on the surface. While water alone would be effective in dislodging residues, a detergent solution is usually needed to wet the residue and to assist in suspending and/or emulsifying it so it is not redeposited in other parts of the system. The selection of detergent will depend on the residues being cleaned. The time of cleaning is determined by the operator or by the pre -programmed system for automated systems. The temperature of the water is usually hot (> 50°C). The same high-pressure system, with water alone, is used to rinse the parts or the vessel interior. Because of the possibility of “splash back from the high-pressure detergent solution, extra care should be used in considering the safety of the operator, particularly eye safety.
MANUAL CLEANING: – Manual cleaning covers a variety of cleaning types. The types of manual cleaning covered are wiping, sink brushing, and equipment brushing. They all have the inherent advantage of low capital costs and the inherent disadvantage of higher variability. When done right, they can be very effective. Manual methods of cleaning also allow operators some degree of immediate feedback on their cleaning performance.
- Wiping: – The simplest manual cleaning is wiping with a lint free cloth of some kind and using a cleaning solution, for example, the manual wipe-down of a tableting Wiping depends to a large extent on the mechanical energy input by the person doing the wiping. The effect of the cleaning agent is mainly to wet soils and to keep them from redepositing on the surface. Since most of the cleaning is coming from mechanical energy, and because of the safety concerns of using highly aggressive cleaning agents in a manual operation, the cleaning agents used are generally neutral, mildly alkaline, or mildly acidic. Depending on the application, an alcohol solution in water may be used. The cloth used is a knit or nonwoven, low linting fabric. A key issue in manual wiping processes is to insure 100 percent coverage of the surface to be cleaned. For this reason, wiping should be done with overlapping strokes. If the surface is visibly soiled, then the operators can easily see where they have wiped. A second issue in wiping is the need for rinsing. Certainly, all product contact surfaces cleaned with detergent solutions should be rinsed. Rinsing may not be needed if cleaning is done with an alcohol/water solution alone (in that case, the alcohol/water wipe may be repeated to assure the removal of residues).
- Sink Brushing: – This is closest to manually washing dishes at home. Parts are taken to a sink, placed in a detergent solution, manually scrubbed using a brush or abrasive pad, and then rinsed under flowing water. This method has the advantage of allowing for an extended soaking time (to wet and loosen the soil) in the warm (< 50°C) detergent solution prior to manually brushing it from the surface of the part. The detergent solution is typically a neutral or mildly alkaline detergent, selected because of the greater potential of skin or eye contact in this type of manual cleaning. Cleaning performance depends to a large extent on the consistency (time and pressure) of the brushing The keys for validation of this process are control of temperature, consistency in brushing, and control of any presoaking time. A carefully written cleaning SOP, along with adequate training and retraining, are required.
- Equipment Brushing: – Equipment brushing is similar to sink brushing in that a detergent solution is introduced into the interior of a process vessel. The detergent solution is manually applied to all surfaces with a brush (usually on a long handle). In some cases, the brushing is performed through a man way at the top of the equipment. In other cases, operators may enter the vessel (under appropriate lockout procedures) and clean the equipment from the inside. This latter approach is generally avoided from a safety perspective. Equipment brushing differs from sink brushing in that only enough detergent solution is introduced into the vessel to provide enough solution to cover all surfaces by brushing (that is, the vessel is not flooded with the cleaning solution). Following brushing of all surfaces, the detergent solution is drained, and the vessel is rinsed with water using a hose. Equipment brushing is used when most other alternatives are not feasible or practical.
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