Cleaning Validation Mechanism’s – The Top Four!

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Cleaning can be defined as the removal of residues from previous batch, other residues, and traces of cleaning agents. There are several mechanisms associated with cleaning of equipment.

The mechanisms involved can be mechanical action, chemical action between the residues and the cleaning agent. The selection of cleaning agent and mechanism involved in cleaning is largely dependant on the process residue to be cleaned.

Cleaning Mechanisms

The cleaning mechanism totally depends on the selection of cleaning agent and type of residue to be cleaned. The four main types of cleaning mechanisms are:

  • Dissolution
  • Saponification
  • Wetting
  • Emulsifying

Many cleaning compound agents perform several functions at once. Butyl, for instance, can serve as a wetting or surface tension reducing agent as well as a solubilizing agent. It also can contribute to emulsifying capabilities when combined with anionic surfactants or soaps (alkali-metal salts of carboxylic acids).

Many cleaning compound agents perform several functions at once. Butyl, for instance, can serve as a wetting or surface tension reducing agent as well as a solubilizing agent. It also can contribute to emulsifying capabilities when combined with anionic surfactants or soaps (alkali-metal salts of carboxylic acids).


Dissolution is the process by which a solid or liquid forms a homogeneous mixture with a solvent or solution. This can be explained as a breakdown of the crystals into individual ions, atoms or molecules and their transport into the solvent.

The mechanism involved in this type of cleaning is solubility of the residue in the cleaning agent or solvent. The monobasic buffers i.e. sodium chloride are soluble in cool and hot WFI. Ethylene glycol butyl ether is soluble in water as well as oil is also used in solubilizing agent. Chelating agents and builders are added to the formula to keep water hardness from interfering with the cleaning process.

Rate of dissolution is depend on:

  • Nature of solvent or residue to be dissolved
  • Temperature of solvent
  • Presence of mixing
  • Area of contact
  • Presence of inhibitors


Saponification can be defined as “hydration reaction where free hydroxide breaks the ester bonds between the fatty acids and glycerol of a tri-glyceride, resulting in free fatty acids and glycerol”, which are each soluble in aqueous solutions. This process specifically involves the chemical degradation of lipids, which are not freely soluble in aqueous solutions. Heat treated lipid residues are difficult to remove than non-heat residues due to polymerization.

Saphonification plays a critical role in cleaning lipids which are present in the areas of process involving cell growth and cell processing i.e. Bacterial fermentation, Cell disruption process


Wetting can be defined as a process “involves the lowering of the surface tension of the cleaning solution, thus allowing it to better penetrate residues that are adhered to equipment and piping surfaces”. Wetting agents, or surfactants, are often used in relatively small amounts and they can substantially reduce the quantities of cleaning agent (in this case, alkali) required for residue removal.

Advantages of Wetting include:

  • Lowers the surface tension of the cleaning solution
  • Allow better penetrate residues which are adhered to equipment
  • Used in small amount
  • Sticky residues which are hydrophobic in nature get easily removed

Water acts as a solvent that breaks up soil particles after the surfactants reduce the surface tension and allow the water to penetrate soil (water is commonly referred to as “the universal solvent”).


Emulsifying and suspending agents are often used to keep residues from precipitating by providing “hydrophobic groups” onto which hydrophobic areas of residues can associate, thus preventing them from associating with other residues and forming larger particles which are likely to leave solution. These agents also typically have “hydrophilic groups” which keep them very soluble in aqueous solutions of moderate to high ionic concentrations.

Emulsifiers increase the capacity of a cleaner to emulsify non-soluble compounds in the cleaner. i.e. anionic soap surfactants, cationic surfactants, neutral surfactants

Advantages of Emulsifying agents include:

  • Prevent association of residues
  • Allow the residue to precipitate and not allow thdse residue to redeposit on surface


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Part 11 compliant systems must be designed so that unauthorized attempts to use e-signatures are detected and reported to security management.

Access must be limited to authorized individuals.

The FDA recommends the following.

1. Individual Account

Each user of the system has an individual account.

2. Data Entry Session

Users should log into their accounts at the beginning of a data entry session, input information (including changes) on the electronic record, and log out at the completion of the data entry session.

3. Limit Number of Logins

The system be designed to limit the number of log-in attempts and to record unauthorized access log-in attempts.

4. Unique User ID

Users should work only under their own user profiles encompassing unique user IDs and individual passwords or other access keys and not share these with others.

5. Admin Functionality

The system will not allow an individual to log into the system to provide another person access to the system.

6. Admin Functionality

Passwords or other access keys can be changed at established intervals commensurate with a documented risk assessment.

7. Log Off System

When leaving a workstation, users should log off the system. Alternatively, an automatic log off may be appropriate for long idle periods.

8. Automatic Screen Saver

For short periods of inactivity, an automatic protection (for example, an automatic screen saver) be installed against unauthorized data entry.

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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

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  3. Regulations
  4. Company standards
  5. safety requirements

5. Worst Case Scenrios

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6. Master Validation Plan

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7. Written Procedures

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

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