The clean-in-place is a unique system, which allows pharma process equipment cleaning without taking it into cleaning or washing area. It consists of different accessories designed to clean equipment without disassembly from its installed area.

All the necessary components, such as cleaning agents, nozzle, piping, and tank are incorporated into the CIP system.

During the cleaning stages, the CIP automatically completes the process in pre-defined steps. Process equipment’s critical components, such as tanks, piping, and nozzles, are flushed through the cleaning agents.

Clean in Place system does not come with a standard machine. Instead, it is separately purchased from the machine manufacturer. 

CIP system comes in two configurations. First, it is attached to the machine as a dedicated part and cannot be used with other machines. Its control is integrated with the machine's control system.

In the second configuration, CIP is a separate system in the form of a skid. In this configuration, the skid is not a dedicated part of the process equipment and is attached when required. It is individually controlled without a machine's control system. 

Components of Clean In Place Systems?

Some standard components of CIP systems include the following.

Vessels

Vessels are used to prepare and store cleaning chemicals used during the cleaning process, and pumps take their supply from these vessels. The vessel is connected to the nozzle through appropriate piping to spray the cleaning agent in the equipment ( to be cleaned).

The capacity of the vessel depends on the CIP system specifications. 

The vessel design characteristics are the same as that of pharmaceutical products, i.e., material that offers resistance to corrosion, no dead points, and surface finish requirements. 

Pumps

Pumps transfer cleaning agents and other fluid types from vessels and other CIP components. A centrifugal pump is commonly used due to its ability to pump large volumes of liquid.

Two pumps are used in the CIP system: supply and return pumps. The supply pump is used to supply the cleaning agent and water to the nozzles, while the return pump is used to pump the used cleaning agent or water to the waste or recovery unit.

Piping and valves

Piping is used to interconnect different components, such as vessels with nozzles. The piping for CIP must follow specifications related to the pharma industry, such as Stainless Steel and surface finish.

Valves control the fluid flow between different components of the CIP system. If the CIP system is automatic, valves are controlled through the main controller, such as the Programmable Logic controller. Otherwise, valves are manually controlled to perform the function. 

Heat Exchangers

The primary function of heat exchangers in CIP systems ( as in other applications) is to heat water and other cleaning agents when required.  

Heat exchanges increase temperature by using steam through thermally conducting plates or tubes. Steam does not mix with the cleaning agents but through indirect heat transmission. 

Clean in Place Cycle

In a typical CIP system, cleaning is performed through the following steps.

Pre - Rinse

The first phase of the CIP cycle is pre-rinse, where the equipment is flushed to prepare for the CIP process. It includes removing solid particles, such as sugar or fats. 

In this phase, nonchemical fluid is used, i.e., purified or deionized water. Recovery water from the last rinse phase can also be used.

Caustic Wash Cycle

The equipment is washed with caustic after pre-rinsing it with nonchemical fluids. 

Its purpose is to remove stuck and adhering debris in the form of fat and other residuals.  It can be re-used by returning it to its storage tank.

Intermediate Wash Cycle

The intermediate wash cycle removes residual caustic trances in the caustic wash cycle. In this stage, fresh water is used to neutralize the caustic effects.

Final Wash

After intermediate washing, the CIP applies the final wash to the equipment. It removes any residual cleaning agents and chemicals to prepare equipment for production. 

In many cases, the residual water from this stage is recovered and used in the first stage.

Drying

Drying is the process of removing residual water from the cleaned equipment. Compressed air blows the equipment or surface and forces the moisture out of the equipment. 

Considerations for Clean-In-Place Systems

A clean-in-place system is an effective way of ensuring cleaning while also reducing the time spent in cleaning. However, this system also requires specialized requirements and features, without which the CIP system will become ineffective. 

Let's discuss some important considerations for implementing CIP in a pharma facility.

Washing Strategies

When implementing CIP for your facility, it is necessary to determine whether it can be implemented. Purchasing a CIP system and connecting with any equipment won't work. A thorough study and feasibility work are required to select equipment for the CIP system.

Some common equipment for which CIP is used include,

• Tanks

• Tablet coating machine

• High Shear Mixer Granulator, Intermediate Bulk Container

• Piping systems 

• Filters

Besides the above, it is better to consult the CIP manufacturer to determine if your target machine suits the CIP system.

Are you able to provide water requirements?

Like other cleaning systems, the most critical aspect of CIP systems is a continuous supply of cleaning agents or water that must be provided at the point of the CIP system through an appropriate piping network. Constant supply ensures quality cleaning.

There are different types of fluids used in cleaning, such as 

• Purified water for the initial and final rinse. Other forms of water, such as deionized and RO water, can also be used depending on the equipment application and type. Water can be directly supplied to the water plant through dedicated piping or stored locally in the vessels of the CIP system.

• Different chemicals, such as acids, remove hard and struck materials. These are stored in dedicated vessels attached to the CIP skid.

• Compressed air blows particles before applying the CIP system or after the cleaning. Compressed air must be supplied with the required air pressure to achieve its purpose entirely. It can be fulfilled through appropriate piping design, valves and regulators. 

Cycle Time

Cycle time is the period during which the cleaning stage is executed. Before using the CIP system, it is necessary to determine the cycle time for each stage because different chemicals and substances require different cycle times to eliminate their traces.

Following the CIP manufacturer's recommendation, an adequate cycle time can be determined. The quality department can also be consulted to determine an effective cycle.

Spray Nozzles

Spray nozzles are small mechanical devices to apply the CIP fluid to the equipment. These devices affect the pattern of sprayed fluid, which, in turn, defines the CIP’s effectiveness. 

There are two types of spray nozzles for the CIP systems - Static and Dynamic. Each spray nozzle type must be selected according to the manufacturer's recommendation or application requirement.

Static Spray Nozzles

Static spray nozzles have a holes in it and a fixed spray pattern. They are motionless, and their installation location is carefully selected to get spray fluid in all directions and the location of the equipment.

Static spray nozzles are low-pressure and high-volume, where sprayed fluid provides much of the force for spray.

Dynamic Spray Nozzles

Dynamic spray nozzle heads are driven by the force of spraying fluid by continuously spinning around its axis and spraying it in multiple directions.  They are high-pressure, low-volume, and have high mechanical energy applications due to the spinning effects. 

Material requirements of piping, valve, and components used

Since the CIP system remove contaminants, it itself must be protected from contamination. There are many ways to implement, and one of the methods is selecting the appropriate construction material.

Stainless Steel

The standard material of construction for pharma equipment is stainless steel, with two common variants.  - SS304 and SS3016L 

SS316L is mainly used in the equipment that comes in direct contact with the pharma product, and SS304 is used when the part does not come in direct contact with the pharma product.  The main benefit of using stainless steel is its excellent resistance to corrosion and material degradation to the moisture and other chemicals.

Seals and gaskets

Like other mechanical equipment, seals and gaskets seal the equipment. When selecting them, their material must not react with the cleaning agent, water, and residual product. Otherwise, seals and gaskets will degrade, resulting in leakage or leaching.

Surface Finish

Surface finish measures surface roughness and indicates the degree of surface finish. The benefit of a finished surface is that it can be easily cleaned, and no residues will be left over. Similarly, rough surfaces will be difficult to clean and require more resources and time. 

For pharma applications, the surface roughness must be greater than 0.8, indicated by the unit Ra, which is average surface roughness. 

Welding

Welding is an integral part of metal fabrication; the industry can barely avoids it. For the pharma industry, welding must meet specific design characteristics to nullify the effects of traditional welding techniques.

Like other pharma process applications, welding must be of the orbital type. It welds the joint form both inside and outside, and prevents any dead points during welding, which is a significant source of bacteria and microorganism growth

About the Author:

Muhammad Asim Niazi

Muhammad Asim Niazi has a vast experience of about 11 years in a Pharmaceutical company. During his tenure he worked in their different departments and had been part of many initiatives within the company. He now uses his experience and skill to write interested content for audiences at PharmaSources.com.