Cleaning-In-Place (CIP)

CIP is the process of cleaning equipment, tanks and production lines without dismantling them, by pumping detergents and water while they are in place, to save time and ensure the stability of cleanliness.

Basic steps of CIP

1. Pre-Rinse:
   The first step is to pass plain or purified water into pipes or tanks to remove large residues from the product. This rinse should be sufficient to ensure that as much material residue as possible is removed before we begin the actual cleaning process.
2. Detergent Wash:
   Here we use the appropriate detergents according to the type of product manufactured. For example, if the product contains fatty substances or proteins, we use alkaline detergents because they help break down fats.
   All of this must be done under specific temperatures and concentrations documented according to validation in order to ensure that all product residues are removed.
3. Intermediate Rinse:
   After cleaning with detergent, we use water to rinse off any detergent residue to ensure that these substances do not react with the LG product.
4. Final Rinse:
   The final rinse is done using purified water or WFI (Water for Injection), depending on the type of product. The goal here is to ensure that there is no detergent residue or material accumulated in the equipment.
5. Sanitization:
   In some cases, sterilization after rinsing is required, especially in sterile productions. Here it is possible to use steam or chemically sterilized materials.

Common challenges in CIP

1. Residue Build-up :
   Some substances, such as creams or gelatin, can leave sticky residues on surfaces, requiring stronger detergents or increasing temperature and concentration. Here you may need to do a revalidation if you notice that the remains are not completely removed.
2. Incomplete Cleaning:
   If there are areas that are not well cleaned, it may be due to the design of the pipes or the timing of the cleaning. The solution is to review these variables and modify the system if needed.
3. Cross-Contamination:
   The most important challenge facing factories that produce more than one product is cross-contamination between products. The solution here is to document each cleaning step well, and make sure that the system is able to remove all the remnants of the previous product.

Monitor performance and ensure efficiency

1. Conductivity Monitoring:
   It measures the conductivity of water to ensure that all detergent residue is removed.
2. TOC Testing:
   Measure any organic residue after cleaning, to ensure that there are no residues of the product or detergent.
3. Corrosion Monitoring:
   Some detergents and high temperatures can cause corrosion in equipment. Periodic inspection of metallurgical equipment is very important, preferably 316L stainless steel for corrosion resistance.

Periodic maintenance and best practices

1. Routine Maintenance:
   Regular maintenance of filters, pumps and valves is required. Timely change of filters helps prevent any blockages and disruptions of the process.
2. Verification and Validation:
   You must check the efficiency of the system periodically and document each stage to ensure good performance.
3. Customize Your CIP:
   Each product needs a different type of cleaning. You should choose detergents, their concentration, and temperatures based on the nature of the product.

Guidelines

In order to properly apply CIP and comply with standards, you must review the rules set by regulators:

• FDA CFR 21 Part 211.67 – regulates the cleaning and maintenance of equipment.
• EU GMP Annex 15 – talks about cleaning verification and validation.

Read also:

• Bowie-Dick Test in Sterilization
• Why is a 0.22-micron Filter Considered a Sterile Filter?
• Media Fill in Pharmaceutical Industry
• Difference Between CIP and SIP