Pharmaceutical cleaning is not only the best practice to keep your manufacturing operation clean. It is also a critical regulatory and quality requirement. All equipment and tools that are used during pharmaceutical product processing must be cleaned to prevent any cross contamination between products, maintain the integrity of the product during manufacturing and be in compliance with Good Manufacturing Practices (GMP).
Ultrasonic cleaning has become one of the most effective and efficiently validated methods of cleaning today. Ultrasonic cleaning uses high-frequency sound waves to dislodge and thereby remove residues, particles and all contaminants from the surfaces of equipment. These are difficult to clean manually because of complex geometries of equipment, hard-to-reach areas and tight spaces.
In this article we will discuss what ultrasonic cleaning is, how it works and why ultrasonic cleaning is useful to the pharmaceutical manufacturing process.
Ultrasonic cleaning uses a method referred to as cavitation. Cavitation occurs when tiny bubbles form and collapse quickly within the cleaning solution causing shockwaves and microjets to clean debris, oils and deposits from the surfaces of the items being cleaned, even in areas that are difficult to reach such as minute pockets and hidden holes.
Ultrasonic cleaning is a safe and nondestructive cleaning method. It is frequently employed to clean a wide variety of items in the pharmaceutical industry, including tools, filters, filling nozzles, dies or molds and glassware. It is also useful for cleaning of many other components made of stainless steel that need to be extremely clean before use.
- Lower frequencies (20 KHz to 25 KHz) create large cavitation bubbles during cleaning that can be used to clean heavily contaminated items.
- Higher frequencies (35 KHz to 40 KHz) create a softer cleaning action during cleaning and are used to clean delicate items.
The energy created by the collapse of the bubbles results in extremely high local pressures (approximately 10,000 psi) and temperatures (approximately 5,000°C at a micro level) which aid in the removal of contaminants from surfaces.
They clean those areas of product surfaces where the cleaning method did not reach as well as provide the benefit of getting into the smallest areas like filling needles, dies, punches, filters and surgical instruments.
1. Stainless Steel (316L) Tank: It is used to contain equipment and tools to clean and can tolerate chemical exposure while remaining compliant with GMP regulations.
2. Ultrasonic transducer: A transducer transfers ultrasonic sound waves from generator to tank.
3. Generator: It converts electricity into high-frequency ultrasonic waves, those are main cause of cleaning.
4. Cleaning Solution: The cleaning solution contains purified water and detergent or solvent.
5. Heater: Heater is an optional device that can maintain the temperature of the cleaning solution (usually 40 to 60 degrees celsius).
6. Rinsing and drying compartments: Traditionally associated with a rinsing and drying area after cleaning has been completed.
1. Mild alkaline detergents and enzymatic solutions are effective in removing oily residue from surfaces.
2. Weak acidic solutions such as citric acid can be used to clean surfaces of inorganic residue build-up.
3. It is recommended that a neutral detergent having surfactants should be used for general cleaning.
It is important to validate the cleaning solution for its compatibility with the material to be clean and equipment should rinse thoroughly after cleaning to avoid residue transfer to other materials.
1. Production: Ultrasonic cleaning is used to clean dies, punches, compression tooling, filling needles and nozzles.
2. Quality Control Laboratories: Ultrasonic cleaning is used to clean analytical instruments, glassware, vials, syringes and sampling devices.
3. Maintenance: Ultrasonic cleaning is used to clean filters, seals and small machinery parts.
4. Sterilization: Ultrasonic cleaning is used to prepare sterile manufacturing machine parts for sterilization by removing particles from their surfaces.
Ultrasonic cleaning has become useful in the various processes involved in pharmaceutical manufacturing due to its capability of removing many types of residues from the equipment surfaces.
1. Acceptance Criteria: Identification of cleanliness standards for all aspects of the product (visual, chemical, and microbiological).
2. Protocols: Development of cleaning procedures which specify the cleaning cycles, frequency of use, concentration of cleaning solutions and temperature during cleaning.
3. Test Runs: Performance of cleaning tests on tools that are commonly utilized in the manufacturing process using representative contaminants.
4. Sampling and Analysis: Performance of rinse sampling, swab analysis and Total Organic Carbon (TOC) analysis.
5. Results Documentation: Compilation of all test results and documentation demonstrating that results are reproducible.
Regular monitoring, revalidation, and preventive maintenance on the ultrasonic cleaning equipment must occur to maintain the validated status of the ultrasonic system.
- Confirmed (via validation) to eliminate cross-contamination.
- Able to produce repeatable results that satisfy defined limits.
- Supported by the results signifying successful cleaning (source of verification) & calibration records.
Ultrasonic-based cleaning equipment must be qualified according to the protocols of the user and the manufacturer in conjunction with the cleaning validation master plan.
- Replace ultrasonic cleaning solutions regularly to avoid accumulation of contaminants.
- Take periodic measurements of temperature, frequency and power level.
- Do not overfill the but ensure that all of your components are immersed in cleaning solution.
- All components must be properly rinsed with purified water to remove detergent before drying.
- Use filtered air or drying ovens to dry.
- Document each cleaning cycle to maintain traceability.
- It is not suitable for large machines or parts that cannot be submerged into the cleaning solution.
- Cavitation power is weakened when using viscous liquids.
- Ultrasonic transducers must be maintained periodically to work consistently.
These limitations when using ultrasonic cleaning are outweighed by the advantages of its usage in most applications for pharmaceuticals.
In the pharmaceutical industry, the standard for precision cleaning is ultrasonic cleaning, allowing for maximum efficiency, consistency and compliance to ensure that all pharmaceutical equipment and tooling conform to the highest standards of cleanliness.
When pharmaceutical facilities implement ultrasonic cleaning as part of their routine maintenance and validation programs, they will experience longer-term cleaner surfaces, reduced turnaround times and enhanced confidence regarding their product quality and safety as it relates to patients.
Cleanliness goes beyond regulatory requirements and it represents a basis of trust with pharmaceutical companies. Ultrasonic cleaning helps maintain pharmaceutical trust therefore companies must consider ultrasonic cleaning where it may be applicable.
Ultrasonic cleaning has become one of the most effective and efficiently validated methods of cleaning today. Ultrasonic cleaning uses high-frequency sound waves to dislodge and thereby remove residues, particles and all contaminants from the surfaces of equipment. These are difficult to clean manually because of complex geometries of equipment, hard-to-reach areas and tight spaces.
What is Ultrasonic Cleaning?
Ultrasonic cleaning is an important precision cleaning method that employs ultrasonic frequencies (usually 20-40kHz) applied to a cleaning liquid medium, which may contain a cleaner solution, to free contamination on the surfaces of items being cleaned.Ultrasonic cleaning uses a method referred to as cavitation. Cavitation occurs when tiny bubbles form and collapse quickly within the cleaning solution causing shockwaves and microjets to clean debris, oils and deposits from the surfaces of the items being cleaned, even in areas that are difficult to reach such as minute pockets and hidden holes.
Ultrasonic cleaning is a safe and nondestructive cleaning method. It is frequently employed to clean a wide variety of items in the pharmaceutical industry, including tools, filters, filling nozzles, dies or molds and glassware. It is also useful for cleaning of many other components made of stainless steel that need to be extremely clean before use.
How Ultrasonic Cleaning Works
Ultrasonic cleaning process has three key steps:1. Ultrasonic Wave Generation
Ultrasonic transducers are fixed to the tank that changes electrical energy to high-frequency sound waves. The frequency of ultrasonic waves used in ultrasonic cleaning ranges from 20 KHz to 40KHz and determines how intense the cleaning action.- Lower frequencies (20 KHz to 25 KHz) create large cavitation bubbles during cleaning that can be used to clean heavily contaminated items.
- Higher frequencies (35 KHz to 40 KHz) create a softer cleaning action during cleaning and are used to clean delicate items.
2. Cavitation and Collapse of Bubbles
As the ultrasonic waves pass through the cleaning solution, alternation in pressure occurs within the cleaning solution creating zones of compression and rarefaction. As a result, tiny bubbles are created, then subsequently implode violently as the sound wave passes through them.The energy created by the collapse of the bubbles results in extremely high local pressures (approximately 10,000 psi) and temperatures (approximately 5,000°C at a micro level) which aid in the removal of contaminants from surfaces.
3. Removal of Contaminants
The imploding bubbles generate jets of water travelling at a high rate of speed which scrub the surfaces and remove any loose debris that may have accumulated on them.They clean those areas of product surfaces where the cleaning method did not reach as well as provide the benefit of getting into the smallest areas like filling needles, dies, punches, filters and surgical instruments.
Components of an Ultrasonic Cleaning System
Ultrasonic cleaning systems usually include various components.1. Stainless Steel (316L) Tank: It is used to contain equipment and tools to clean and can tolerate chemical exposure while remaining compliant with GMP regulations.
2. Ultrasonic transducer: A transducer transfers ultrasonic sound waves from generator to tank.
3. Generator: It converts electricity into high-frequency ultrasonic waves, those are main cause of cleaning.
4. Cleaning Solution: The cleaning solution contains purified water and detergent or solvent.
5. Heater: Heater is an optional device that can maintain the temperature of the cleaning solution (usually 40 to 60 degrees celsius).
6. Rinsing and drying compartments: Traditionally associated with a rinsing and drying area after cleaning has been completed.
Cleaning Solutions Used in Ultrasonic Cleaning
The cleaning solution selection for cleaning depends on the type of material being cleaned and composition of the residue.1. Mild alkaline detergents and enzymatic solutions are effective in removing oily residue from surfaces.
2. Weak acidic solutions such as citric acid can be used to clean surfaces of inorganic residue build-up.
3. It is recommended that a neutral detergent having surfactants should be used for general cleaning.
It is important to validate the cleaning solution for its compatibility with the material to be clean and equipment should rinse thoroughly after cleaning to avoid residue transfer to other materials.
Benefits of Ultrasonic Cleaning in the Pharmaceutical Industry
There are numerous advantages of ultrasonic cleaning over manual or mechanical cleaning. Some important points of those are listed below.1. Superior Cleaning Efficiency
The efficiency of ultrasonic cleaning is great as it eliminates microscopic residues from complex geometries of equipment including threads and holes where manual cleaning is not possible.2. Time-Saving
The amount of time required for ultrasonic cleaning is far less than the time needed to manually clean. The items that may take several hours in manual cleaning can be successfully cleaned in 10- 20 minutes using ultrasonic cleaning method.3. Gentle yet Effective
Ultrasonic cleaners are gentle yet effectively clean the equipment. Ultrasonic cleaners are designed to ensure that precision tooling and polished stainless steel do not suffer any damage by rough cleaning.4. Consistency and Validation
The simplicity and repeatability of the ultrasonic cleaning process require validation to prove its consistency in cleaning. So that it can meet the requirements of GMP standards.5. Reduced Human Error
The automated ultrasonic cleaning helps to eliminate or reduce the impact of human error during cleaning. The potential for variability between operators can be minimized through the use of an automated ultrasonic cleaning process.6. Compatibility
Many types of materials are used for pharmaceutical tooling and those all can be cleaned with ultrasonic cleaning technology.7. Eco-Friendly
Ultrasonic cleaning method is environmentally friendly and requires very little cleaning solution and water compared to traditional cleaning methods. It significantly reduces the overall environmental footprint associated with cleaning processes.Applications in Pharmaceutical Manufacturing
Ultrasonic cleaning is widely used throughout the industry in the following areas:1. Production: Ultrasonic cleaning is used to clean dies, punches, compression tooling, filling needles and nozzles.
2. Quality Control Laboratories: Ultrasonic cleaning is used to clean analytical instruments, glassware, vials, syringes and sampling devices.
3. Maintenance: Ultrasonic cleaning is used to clean filters, seals and small machinery parts.
4. Sterilization: Ultrasonic cleaning is used to prepare sterile manufacturing machine parts for sterilization by removing particles from their surfaces.
Ultrasonic cleaning has become useful in the various processes involved in pharmaceutical manufacturing due to its capability of removing many types of residues from the equipment surfaces.
Ultrasonic Cleaning Validation
Ultrasonic cleaning as a GMP controlled procedure requires validation to ensure reproducibility. To validate ultrasonic cleaning, it is necessary to define acceptance criteria, develop protocols, perform test runs, collect samples, analyze samples and document results.1. Acceptance Criteria: Identification of cleanliness standards for all aspects of the product (visual, chemical, and microbiological).
2. Protocols: Development of cleaning procedures which specify the cleaning cycles, frequency of use, concentration of cleaning solutions and temperature during cleaning.
3. Test Runs: Performance of cleaning tests on tools that are commonly utilized in the manufacturing process using representative contaminants.
4. Sampling and Analysis: Performance of rinse sampling, swab analysis and Total Organic Carbon (TOC) analysis.
5. Results Documentation: Compilation of all test results and documentation demonstrating that results are reproducible.
Regular monitoring, revalidation, and preventive maintenance on the ultrasonic cleaning equipment must occur to maintain the validated status of the ultrasonic system.
GMP and Regulatory Compliance
Regulators such as the FDA, EMA & WHO anticipate that cleaning methods employed by pharmaceutical manufacturers are:- Confirmed (via validation) to eliminate cross-contamination.
- Able to produce repeatable results that satisfy defined limits.
- Supported by the results signifying successful cleaning (source of verification) & calibration records.
Ultrasonic-based cleaning equipment must be qualified according to the protocols of the user and the manufacturer in conjunction with the cleaning validation master plan.
Best Practice Guidelines for Ultrasonic Cleaning
- Use filtered and purified or deionized water to produce the cleaning solutions and rinse water.- Replace ultrasonic cleaning solutions regularly to avoid accumulation of contaminants.
- Take periodic measurements of temperature, frequency and power level.
- Do not overfill the but ensure that all of your components are immersed in cleaning solution.
- All components must be properly rinsed with purified water to remove detergent before drying.
- Use filtered air or drying ovens to dry.
- Document each cleaning cycle to maintain traceability.
Limits of Ultrasonic Cleaning
The ultrasonic cleaning procedure is effective but has some limitations:- It is not suitable for large machines or parts that cannot be submerged into the cleaning solution.
- Cavitation power is weakened when using viscous liquids.
- Ultrasonic transducers must be maintained periodically to work consistently.
These limitations when using ultrasonic cleaning are outweighed by the advantages of its usage in most applications for pharmaceuticals.
In the pharmaceutical industry, the standard for precision cleaning is ultrasonic cleaning, allowing for maximum efficiency, consistency and compliance to ensure that all pharmaceutical equipment and tooling conform to the highest standards of cleanliness.
When pharmaceutical facilities implement ultrasonic cleaning as part of their routine maintenance and validation programs, they will experience longer-term cleaner surfaces, reduced turnaround times and enhanced confidence regarding their product quality and safety as it relates to patients.
Cleanliness goes beyond regulatory requirements and it represents a basis of trust with pharmaceutical companies. Ultrasonic cleaning helps maintain pharmaceutical trust therefore companies must consider ultrasonic cleaning where it may be applicable.
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