Detergents Used for Cleaning of Pharmaceutical Equipments and Utensils

Cleaning pharmaceutical processing equipment is challenging. Cleaning methods, soils present, type of manufacturing equipment, surfaces cleaned, choice of cleaning detergent and temperature should all be considered when setting up a cleaning procedure. Cleaning validation methods are required. The entire cleaning process must be standardized and documented according to the FDA’s cGMP regulations.

Cleaning detergents and chemicals for the pharmaceutical industry are far different from household cleansers. Specific powders and liquids are created for precise sanitization that include biotechnology and laboratory settings. Each detergent will contain a specific formula to meet the needs of the unique cleaning requirement, which can vary from a hard surface, to manufacturing equipment, to laboratory glassware. Types of detergents include anionic detergents, cationic detergents, amphoteric detergents, alkaline detergents, and more.

Why Clean Pharmaceutical Processing Equipment?
  • Maintain product quality.
  • Remove all trace ingredients to prevent the transfer of ingredients from one product to the next. This is especially important when multiple products are produced on the same equipment.
  • Prevent equipment malfunctions that may lead to product contamination.
  • Provide a clean surface for disinfection. Surfaces cannot be properly sanitized or disinfected if they are not thoroughly cleaned first.
  • Comply with local and international standards and regulations to ensure consumer safety and avoid legal issues.
  • Increase plant performance and productivity by diminishing waste, maintaining equipment and preserving product quality.

  • There are different types of detergents such as anionic detergents, cationic detergents, amphoteric detergents, alkaline detergent etc. This nature of the detergent depends upon the nature of the surfactant found in the detergent. These all have their specific use due to their cleaning properties.
  • All of the above detergents have free ions and these are left after cleaning the cleaned surface. A mixture of nonionic and anionic detergent is found to be an anionic detergent. These free ions can have a harmful effect on the pharmaceutical products and affect their stability.
  • Therefore, nonionic detergents are used for cleaning of equipment in pharmaceutical manufacturing. Nonionic detergents are also required to clean the glassware used in the pharmaceutical analysis because these free ions can alter the results of the analysis.
  • These are prepared by the reaction of molecules containing hydroxyl groups like alkylphenol and ethylene oxide. This reaction is an exothermic reaction which generates heat. Ethylene oxide is very toxic and explosive in nature. Therefore, these are synthesized carefully in special equipment.
  • Nonionic detergents do not ionize when these are dissolved in water. These are manufactured using the same quantity of acids and bases of the same strength and don’t have the acidic or basic nature.
  • Therefore pH value remains neutral. These detergents make less foam than cationic or anionic detergents when used with water. Due to this property, these can be cleaned easily from the equipment surface. These are very much effective against the oily material. Generally, these pharmaceutical detergents are found in liquid form.
  • Enhance worker safety by providing a clean working environment and smoothly functioning equipment.

Every pharmaceutical cleaning procedure is unique and should be created based on the unique residues created and cleaning capabilities. Without consideration of these variables:
  1. Incorrect cleaning procedures can cause manufacturing challenges - such as unnecessary use of excess resources.
  2. Optimal Cleaning is not taken into consideration during product development.
  3. Understanding capabilities of your equipment is the most important thing before cleaning.
  4. Different types of equipment pose unique challenges - you can't always expect one thing to work for everything.

Establishing A Cleaning Procedure
Pharmaceutical manufacturers are required to set up a fully documented written cleaning procedure for each piece of processing equipment. Documentation should include:
  1. Responsibility for equipment cleaning and maintenance
  2. Cleaning and sanitization schedules
  3. A detailed description of the cleaning procedure
  4. Removal of previous batch identification
  5. Protection of clean equipment
  6. Inspection of equipment prior to use

How to Clean
Several factors must be taken into consideration to set up an effective cleaning process and remain in compliance with federal regulations.

1.   Soils
  • Soils found on pharmaceutical processing equipment may be traces of the various ingredients used in production or soils from the actual manufacturing process such as oil, grease, dust or minerals. Understanding the soils that are present will guide your choice of cleaning detergent.
  • Gels, polyethylene glycol, oils, titanium dioxide, dyes, silicons, flavorings, petrolatum, paraffin, proteins, steroids, sugars, alcohol, stearates, and cornstarch are some of the typical foulants that are often found on pharmaceutical processing equipment.
  • Each type of soil is unique and requires the proper detergent to thoroughly clean the surface. Choose a cleaner that will best attack the soils you are trying to remove. Alkaline cleaners are the best choice for cleaning soils such as gels, dyes and petrolatum, while citric acid based cleaners are better suited for removing titanium dioxide. Protein or starch-based soils may require the use of an enzyme cleaner. 
  • Use the table below to help match the most effective type of cleaner to each kind of soil.

2.   Type of Equipment
  • Mixing tanks, tablet presses, capsule fillers, centrifuges, granulators, filling lines, mixers, conveyors, filters, fluid lines, batch process tanks, tubes and flasks all need to be thoroughly cleaned. The design of the equipment must be taken into consideration. By nature of its construction, some types of equipment will be more difficult to clean than others. Hidden parts and blind holes present unique challenges.
  • Another important factor to consider is the how the equipment is used. Are you cleaning a dedicated production system or equipment that is used to produce a range of products? Processing equipment used to produce multiple products has a greater chance of cross contamination of ingredients.
  • It’s also important to select a cleaner that is compatible with the surface of the equipment you are cleaning. The cleaner manufacturer should be able to guide you and provide compatibility studies for their products.

3.   Cleaning Method and Location
Clean-in-place (CIP) or Clean-out-of-place (COP)?
  • CIP is generally used for large systems and components that cannot easily be taken apart. CIP often results in less downtime since it eliminates the need to take apart or move the equipment. Automated systems, spray systems and immersion are all examples of CIP operations.
  • COP is most often used for smaller pieces of equipment or smaller parts of larger equipment that can be removed and re-assembled after cleaning. COP can involve either manual washing or use of machine washers. Specific instructions for disassembling and re-assembling equipment must be followed.

What cleaning method will you use?
  • Manual, ultrasonic, spray, machine and automated systems are all used for cleaning pharmaceutical equipment. The type of cleaning method used will impact your choice of detergent. Automatic parts cleaners and high-pressure washers require low foaming detergents.

4.   Temperature
  • In most cases, increasing the temperature is one of the best ways to speed up or improve the cleaning action. The temperature parameters that should be used for any individual cleaning application will depend upon the equipment and the soils that are present, as well as your choice of detergent and wash method. Check with the manufacturer for the maximum suggested operating temperature for your detergent.

5.   Dwell Time
  • The length of the cleaning cycle contributes to the effectiveness of your cleaning application. In most cases, a longer dwell time will improve the results. However, all factors – soils, temperature, substrate, detergent and cleaning method must be taken into consideration.

6.   Rinse Step
  • Rinsing removes any excess detergent left on the item. For critical cleaning applications, it is best to use deionized or distilled water, as rinsing with ordinary water may introduce new contaminants.

7.   Cleaning Validation
  • Cleaning validation is a part of the regulatory compliance process for cleaning pharmaceutical processing equipment. Validation ensures that all equipment is washed according to previously determined standards and that all traces of soil and detergent are removed. Validation methods are unique to each detergent and should be available from most cleaner manufacturers.

Post a Comment