Cleaning In Place (CIP) Vs Cleaning Out of Place (COP)

  • 0


The basic regulatory requirement is to provide pharmaceutical products of highest quality to the patients. A cleaning problem can have various consequences to health, economics, environment and regulatory approvals. Absence of good cleaning, leads to contaminated drugs, which pose risks for patients as well as manufacturing personnel.

Regulatory risk includes possible removal of authorization. Economical risk involves production delays and stock shortages or losses but also manifest as public relations problems for a company.

There are four main cleaning processes used in regulated environments.  These include:

  • Cleaning-in Place (CIP)
  • Cleaning-out-of-place (COP)
  • Manual Cleaning
  • Immersion Cleaning

So whats the difference between all of these cleaning techniques?

Cleaning In Place (CIP)

Cleaning in place can be described as the cleaning of equipment and vessels at the same place without movement of them to a different place. The cleaning agents can be transferred to the vessel or equipment types either thorough fixed piping or flexible hoses.

The CIP process can consist of the following elements:

  • Supply pump
  • Return pump
  • Heat exchanger with Black/Plant steam supply
  • Chemical tanks i.e Acid, Alkali tanks
  • Supply Pressure gauge or transmitter
  • Supply temperature sensors
  • Conductivity meter with sensor

Cleaning Out of Place (COP)

Cleaning Out of Place is defined as a method of cleaning equipment items by removing them from their operational area and taking them to a designated cleaning station for cleaning. It requires dismantling an apparatus, washing it in a central washing area using an automated system, and checking it at reassembly.

Manual Cleaning

Manual cleaning is the universal practise among the pharma and biopharma industries. The design, configuration and construction of equipment or the whole equipment which necessities the manual cleaning for the piece of equipment. The efficiency of the manual cleaning accomplished by training the cleaning operators, ensuring exact method of cleaning in the manual cleaning SOP, validating the method from different operators and verifying the procedure with interval of time.

The manual cleaning is dependent on,

  • Concentration of detergent used
  • Temperature of washing liquid

Immersion Cleaning

This is the type of cleaning in which the parts to be cleaned are placed in the cleaning solutions to come in contact with the entire surface of the parts.

Immersion cleaning is preferred for parts that must be placed in baskets and for processes requiring a long soaking time because of the type of contamination to be removed or the shape of the parts to be cleaned.
It is the most effective method, even if not the fastest one, and can be used with any type of cleaner for any process, heated or at room temperature. Immersion washers can be portable or stationary; single or multi-compartment; and are available with a variety of options, controls and valve configurations including CIP capability.

The important aspects during design of immersion washer should be

  • To minimize cycle time
  • Lower chemical usage
  • Reduce water and utility costs

Performance for immersion cleaning can be improved by moving the parts within the liquid or with agitation of the liquid, mechanically or with the addition of ultrasonic energy.

Cleaning Validation Forum

If you would like to learn more about CIP or COP please read the following threads:

Cleaning Validation Help

If you would like help with a cleaning validation project please contact Premier Validation.



    it was fine ,i would like to know more abourt validated chemicals using for cleaninga and their hazourd.


    it was fine ,i would like to know more abourt validated chemicals using for cleaninga and their hazourd.

  • govind

    what are the guidelines required for API manufacturing facility except ICH, GMP, Schedule M

  • govind

    what are the guidelines required for API manufacturing facility except ICH, GMP, Schedule M

  • arashzmani

    Your Comment

  • arashzmani

    Your Comment

  • G Sudhakara Reddy

    Dear Sir,
    PLease give me a clarity on the Cleaning validation topic.

    In cleaning validation for each equipment cleaning result (Rinse/Swab) will receive upon cleaning sample analysis, for suppose the train of equipments are 10 and the Total cleaning sample result of all 10 equipments are 80 ppm (The sum of all equipment cleaning result). Is it meeting the APIC guideline requirement? Please brief me.
    Thanks in advance…….

  • j.w.

    does a clean hold time need to be defined for COP items in vaccine mfg?

Similar articles:

7 Top Tips for Validating Computer Systems in a Regulated Environment [Video]

The validation of any computer system in a regulated environment is always a tricky task with so many areas to cover. Not only do you have to ensure that the application adheres to 21 CFR Part 11 but it must also be validated to ensure that data integrity is not compromised throughout it’s life cycle.

To help you successfully validate a computer system remember the following:

1. Development Methodology

Select a development methodology that best suits the nature of the system – the risk analysis you do will help decide what level of validation is required.

For example, if you purchase the system from a third party vendor you may be able to leverage some of the testing they have already performed to streamline the effort.

2. Hardware

Select hardware based on capacity and functionality – vendors and IT personnel will guide this part of the process.

3. Opertional Limits

Identify operational limits to establish production procedures

4. Opertional Functions

Identify operational functions associated with the

  1. Users
  2. Processes
  3. Regulations
  4. Company standards
  5. safety requirements

5. Worst Case Scenrios

Identify and test worst-case production scenarios

6. Master Validation Plan

Clearly document the validation process and start by creating a master validation plan to define the effort involved

7. Written Procedures

Ensure the availability of written procedures to maintain the validated state of the computer system.

21 CFR Part 11 - Electronic Records

This video is taken from our online course on 21 CFR Part 11 – Electronic records. Click here to find out more about this course.


Similar articles:

The 9 Golden Rules – Ensuring Laboratory Data Integrity [Video]

The enduring assets of a laboratory’s work are the records that document those activities. When laboratory records are used to support a regulatory function, they are considered to be legal documents.

For records to be considered reliable and trustworthy they must comply with the following criteria:

1. Legible and Understandable

They must be able to be read and understood for the lifetime of the record, without having to refer to the originator for clarification. The information may be needed in five, ten or twenty years’ time, perhaps after the originator is no longer available.

2. Attributable

Who made the record or created the data and when?

3. Contemporaneous

The record must be made at the time the activity was performed

4. Original

The information must not be written on a post-it, piece of scrap paper, sleeve of a lab coat etc. and then transcribed.

5. Accurate

No errors or editing without documented amendments.

6. Complete

All the information and data associated with the analysis is included.

7. Consistent

All elements in the sequence of analysis must be date & time stamped and must be in the expected order.

8. Indelible

Records are made on to controlled documents, such as laboratory notebooks or controlled worksheets, or saved to electronic media.

9. Available

Over the entire lifetime of the record for review, audit and inspection.



Similar articles: