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ORG

Advance Glassware Cleaning Validation

Chaudhari Rutuja Ravindra ,Dr.Amol U.Gayke
JESs SND college of pharmacy,Yeola

Abstract
Cleaning Validation is the methodology used to assure that a cleaning process removes residues of the active
pharmaceutical ingredients of the product manufactured in a piece of equipment, the cleaning aids utilized in the
cleaning process and the microbial attributes. All residues are removed to predetermined levels to ensure the quality of
the next product manufactured is not compromised by waste from the previous product.
Cleaning validation in pharmaceutical companies is a critical process aimed at ensuring that pharmaceutical manufacturing
equipment, facilities, and processes are effectively cleaned and free from contamination, residues, or impurities. This is a
vital part of pharmaceutical manufacturing, as it directly impacts product quality, patient safety, and regulatory compliance.
This practice is essential for maintaining data integrity, ensuring the accuracy of experimental results, and adhering to strict
regulatory standards.

Introduction
Pharmaceutical products can be contaminated by a variety of substances such as contaminants associated with
microbes, active pharmaceutical ingredients (API) and excipient residues of previous products, residues of cleaning
agents, airborne materials such as dust and particulate matter, lubricants and ancillary material, such as disinfectants,
and decomposition residues from:

• Product residue breakdown occasioned by. e.g. the use of strong acids and alkalis during the cleaning process
and

• Breakdown products of the detergents, acids and alkalis that may be used as part of the cleaning process.

The objective of cleaning validation is to prove that the equipment is properly cleaned of products, detergents and microbial
residues to an acceptable level to prevent contamination and cross contamination.

REGULATORY REQUIREMENTS FOR CLEANING VALIDATION :

Regulatory requirements for cleaning validation vary by industry and location, but they are essential to ensure product
quality, safety, and compliance with established standards. Here are some key aspects of regulatory requirements for
cleaning validation:

1. FDA (U.S. Food and Drug Administration):

The FDA provides specific guidance on cleaning validation for pharmaceutical, biopharmaceutical, and medical device
industries. It emphasizes the need for a documented and validated cleaning process. FDA's "Guidance for Industry:
Validation of Cleaning Processes" outlines the expectations and recommendations for cleaning validation in the
pharmaceutical and biopharmaceutical sectors. The FDA also requires manufacturers to establish scientifically sound
acceptance criteria for residues or contaminants on equipment and in manufacturing areas. Cross-contamination

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prevention is a primary focus of FDA regulations. Firms must demonstrate that there is no risk of cross-contamination during
manufacturing processes.

2. EMA (European Medicines Agency):

The EMA has its own set of guidelines for cleaning validation in Europe. These guidelines are similar to FDA requirements
and are applicable to pharmaceutical companies operating in the European Union. EMA expects manufacturers to follow a
risk-based approach when setting acceptance criteria, taking into account the potential impact on product quality and
patient safety.

3. cGMP (Current Good Manufacturing Practices):

cGMP regulations are essential in many industries, including pharmaceuticals, food, and medical devices. They provide a
framework for ensuring that products are consistently produced and controlled according to quality standards. Cleaning
validation is a fundamental part of cGMP requirements, focusing on maintaining a clean and contamination-free
manufacturing environment.

4. ICH (International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use):

ICH provides guidelines that harmonize regulatory requirements across different regions, making it easier for
pharmaceutical companies to conduct global business. ICH Q7, a guideline on Good Manufacturing Practice for Active
Pharmaceutical Ingredients, includes information on cleaning validation, emphasizing that the process should be consistent
with cGMP principles.

5. ISO (International Organization for Standardization):

ISO standards play a significant role in setting international benchmarks for various industries. ISO 17664, "Processing of
Health Care Products — Information to Be Provided by the Medical Device Manufacturer for the Processing of Medical
Devices," includes requirements related to the cleaning of medical devices.

6. Industry-Specific Standards:

Different industries have their own unique standards for cleaning validation. For instance, the food industry may follow
standards like HACCP (Hazard Analysis and Critical Control Points) to ensure food safety.

7. Risk-Based Approaches:

In many regulatory requirements, there is an increasing emphasis on a risk-based approach to cleaning validation. This
involves evaluating the potential risks of contamination and setting acceptance criteria and cleaning protocols accordingly.

8. Documentation and Record-Keeping:

Most regulatory bodies require thorough documentation of cleaning validation activities. This includes records of cleaning
procedures, sampling methods, test results, and any corrective actions taken.

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9. Inspections and Audits:

Regulatory agencies conduct inspections and audits to ensure compliance with cleaning validation requirements. Non-
compliance can lead to regulatory actions, including product recalls or legal consequences. It's important for companies to
stay up-to-date with the specific regulatory requirements in their industry and location and to maintain a proactive and
comprehensive approach to cleaning validation to meet those requirements. Failure to comply with these regulations can
have serious consequences, including the suspension of manufacturing operations or the recall of products from the
market.

CLEANING VALIDATION PROGRAM :

A cleaning validation program is a structured and systematic approach implemented by companies to ensure that
equipment, facilities, and processes are effectively cleaned and free from contamination or residues. This program is
particularly important in industries such as pharmaceuticals, biotechnology, food production, and healthcare where product
quality, patient safety, and regulatory compliance are paramount. Here's an overview of how to establish a cleaning
validation program:

1. Define the Scope:

Begin by identifying the equipment, facilities, and processes that require cleaning validation within your organization.
Consider the specific requirements of your industry.

2. Regulatory Compliance:

Familiarize yourself with the regulatory requirements and guidelines relevant to your industry. This includes understanding
the expectations of regulatory bodies like the FDA, EMA, and local regulatory agencies.

3. Establish Acceptance Criteria:

Define clear acceptance criteria for residues or contaminants on cleaned surfaces. These criteria are based on the type of
equipment, materials processed, and regulatory requirements.

4. Develop Cleaning Procedures:

Create standardized cleaning procedures for different equipment and processes. These procedures should specify the
cleaning agents, methods, equipment, and cleaning cycles required.

5. Risk Assessment:

Perform a risk assessment to identify potential sources of contamination and prioritize the validation efforts accordingly.

6. Sampling and Testing:

Determine the appropriate sampling methods for collecting residues, such as swab sampling, rinse sampling, and visual
inspection. Select testing methods that are sensitive and specific to the substances being tested.

7. Validation Protocols:

Develop comprehensive validation protocols before initiating the cleaning validation process. These protocols should
outline the entire validation approach, including acceptance criteria, sampling procedures, testing methods, and a timeline
for validation activities.

8. Execute Cleaning Validation:

Implement the cleaning validation process according to the established protocols. Ensure that the cleaning process adheres
to the procedures, and samples are collected systematically.

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9. Documentation:

Maintain thorough documentation of the cleaning validation process, including records of cleaning procedures, sampling
methods, test results, and any corrective actions taken. Documentation is essential for regulatory compliance and audits.

10. Data Analysis and Interpretation:

Analize the data collected during cleaning validation to ensure that the results meet the predefined acceptance criteria.
Interpret the data to confirm that cleaning procedures are effective.

11. Continuous Monitoring and Revalidation:

Regularly monitor and revalidate the cleaning process to ensure that it remains effective over time. Any changes to
equipment or processes may require revalidation.

12. Corrective and Preventive Actions (CAPA):

If validation results are not in compliance with acceptance criteria or if issues are identified during the cleaning process,
take appropriate corrective and preventive actions to address these issues and prevent their recurrence.

13. Training and Competency:

Ensure that personnel involved in the cleaning validation program are adequately trained and competent in the relevant
procedures and regulations.

14. Quality Assurance and Auditing:

Implement a robust quality assurance system to oversee the cleaning validation program. Conduct regular internal and
external audits to verify compliance with regulatory requirements.

15. Reporting:

Prepare comprehensive reports summarizing the results of cleaning validation activities, including the effectiveness of the
cleaning procedures and adherence to regulatory standards.

A well-designed cleaning validation program helps organizations meet regulatory requirements, maintain product quality
and safety, and ensure the integrity of experimental data. It is a critical component of quality control and assurance in
industries where cleanliness and contamination control are of utmost importance.

SAMPLING PROCEDURE:
There are two methods of sampling.

1. Direct surface sampling(swab method).

2. Rinse samples (Indirect method).

ADVANCED CLEANING METHODS

1.Safety and residue considerations
Safety data sheets (SDS) must be available, studied, and carefully followed, with all appropriate personal protective
equipment (PPE), before using any of the following cleaning methods. Chromic acid solutions are not recommended for
routine use because it is a hazardous waste and hazardous to health! Suitable education or training in the handling of
chemicals is highly recommended.

Care should be exercised when using most cleaning solutions because they can cause skin irritations or severe burns on
contact. Dilute solutions become concentrated as the water evaporates; therefore, always flush the exposed area
immediately with large quantities of water.
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Suitable chemical-specific-resistant goggles or a face mask should be worn to protect the eyes from splashes and rubber
gloves should be worn to protect the hands. It is advisable to wear an acid resistant laboratory coat or a rubber apron to
protect clothing when using strong acids for cleaning. The glassware should be handled gently to avoid breakage and to
prevent spilling acids and other cleaning fluids. All cleaning should be done in a laboratory sink or on an acid proof laboratory
bench, preferably within a fume hood, to the extent possible.

Some of the cleaning materials mentioned leave minute traces or residues unless the rinsing process is carried out
thoroughly. While such traces may not be harmful if the purpose of cleaning is to prepare the glassware for calibration, they
can give trouble when the glassware is used in certain laboratory operations. For example, manganese and chromium
compounds, even in extreme dilution, may retard or inhibit growth of micro-organisms, and traces of phosphorus may
interfere with delicate tests for this element. When glassware is to be calibrated, final rinsing must be with pure distilled or
deionized water.

2.Solvents
Frequently it is desirable to give glassware a preliminary rinse or soak with an organic solvent such as xylene or acetone to
remove grease, followed by a water rinse. The rinsing with water must be done thoroughly if acid will be used later to clean
the glassware.

Unless autoclaving is necessary, glassware should be cleaned as soon as possible after use to avoid setting and caking of
residues. Pipets, for example, may be placed in a jar containing a weak antiseptic solution immediately after use. Autoclaving
is necessary to disinfect glassware that may have been used to contain potentially dangerous biological fluids.

3.Chemical cleaning optional methods

When a piece of glassware is badly contaminated with stopcock grease (except silicone grease), it may be necessary to rinse
with acetone once or twice before using one of the methods below. For silicone grease, the acetone can be omitted, and
the piece soaked for 30 min in fuming sulfuric acid. Warm decahydronaphthalene (decalin) also has been suggested as a
solvent for silicone grease. In this case, let the piece soak for 2 h, drain, and rinse once or twice with acetone, followed by
a water rinse.

 Fill with sulfuric acid dichromate mixture and let stand. After removal of the mixture, rinse with
distilled water at least six times. To make the cleaning mixture, dissolve 60 g to 65 g of sodium- or
potassium-dichromate by heating in 30 mL to 35 mL of water, cool and slowly add concentrated sulfuric
acid to make one liter of solution. This solution is available from laboratory supply companies. Note:
Extreme care should be exercised in handling acidic solutions.
 Scrub with a 1 % to 2 % hot solution of a detergent. Rinse well after brushing. Several suitable,
commercial washing compounds are available.
 Fuming sulfuric acid (very hazardous material) is an excellent cleaning agent. Usually, cleaning can
be accomplished by use of a comparatively small amount of acid, manipulating the vessel so that the acid
contacts the entire surface, and immediately emptying and rinsing.

4.Drying and protection

See GLP 13, Good Laboratory Practice for Drying Containers for appropriate drying techniques. It is not necessary to dry any
container marked “to deliver.” If an article is to be dried after cleaning, as is necessary for all vessels marked "To Contain",
acetone, followed by ethyl alcohol may be used. American Chemical Society, ACS, grading specification for reagents may be
selected based on glassware use. Where ACS, reagent, or USP grades are selected the quality is suitable for use with food
or medical processes and will meet or exceed other application requirements. Drying may be hastened by blowing clean,
dry air into the vessel (or drawing the air through the vessel). Be sure not to mix acetone with alcohol.

Efficient air filters must be provided to remove any particles of oil or dirt from compressed air used for drying purposes.

CLEANING LABORATORY GLASSWARE

Wash labware as quickly as possible after use. If labware is not cleaned immediately, it may become impossible to remove
any residue.
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If a thorough cleaning is not possible immediately, soak glassware in water.

Most new glassware items are slightly alkaline in reaction. For precision chemical testing, new glassware should be soaked
for several hours in acid water (a 1% solution of hydrochloric or nitric acid) before proceeding with a regular washing
procedure.

Brushes with wooden or plastic handles are recommended as they will not scratch or otherwise abrade the glassware's
surface.

GLASSWARE CLEANERS

When washing, soap, detergent, or cleaning powder (with or without an abrasive) may be used. Cleaners for glassware
include Alconox ®, Dural®, M&H®, Lux®, Tide®, and Fab®. The water should be hot. For glassware that is exceptionally dirty,
a cleaning powder with a mild abrasive action will give more satisfactory results. The abrasive should not scratch the glass.
During the washing, all parts of the glassware should be thoroughly scrubbed with a brush. This means that a full set of
brushes must be at hand, including brushes to fit large and small test tubes, burettes, funnels, graduates, and various sizes
of flasks and bottles. Motor driven revolving brushes are valuable when a large number of tubes or bottles are processed.
Do not use cleaning brushes that are so worn that the spine hits the glass. Serious scratches may result. Scratched glass is
more prone to break during experiments. Any mark in the uniform surface of glassware is a potential breaking point,
especially when the piece is heated. Do not allow acid to come into contact with a piece of glassware before the detergent
(or soap) is thoroughly removed. If this happens, a film of grease may be formed.

SAFE USE OF CHROMIC ACID

If glassware becomes unduly clouded or dirty or contains coagulated organic matter, it must be cleansed with chromic acid
cleaning solution. The dichromate should be handled with extreme care because it is a powerful corrosive and carcinogen.

When chromic acid solution is used the item may be rinsed with the cleaning solution or it may be filled and allowed to
stand. The length of time it is allowed to stand depends on the amount of contamination on the glassware. Relatively clean
glassware may require only a few minutes of exposure; if debris is present, such as blood clots, it may be necessary to let
the glassware stand all night. Due to the intense corrosive action of the chromic acid solution, it is good practice to place
the stock bottle, as well as the glassware being treated, in flat glass pans, pans made from lead or coated with lead, or
plastic polymer pans determined to be compatible with the concentration of chromic acid you are using. Extra care must
be taken to be sure chromic acid solution is disposed of properly.

Special types of precipitates may require removal with nitric acid, aqua regia, or fuming sulfuric acid. These are very
corrosive substances and should be used only when required.

REMOVING GREASE

Grease is best removed by boiling in a weak solution of sodium carbonate. Acetone or any other fat solvent may be used.
Strong alkalis should not be used. Silicone grease is most easily removed by soaking the stopcock plug or barrel for 2 hours
in warm decahydronaphthalene.

Drain and rinse with acetone or use fuming sulfuric acid for 30 minutes. Be sure to rinse off all of the cleaning agents.

RINSING

It is imperative that all soap, detergents, and other cleaning fluids be removed from glassware before use. This is especially
important with the detergents, slight traces of which will interfere with serologic and cultural reactions.

After cleaning, rinse the glassware with running tap water. When test tubes, graduates, flasks, and similar containers are
rinsed with tap water, allow the water to run into and over them for a short time, then partly fill each piece with water,
thoroughly shake and empty at least six times. Pipets and burettes are best rinsed by attaching a piece of rubber tubing to
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the faucet and then attaching the delivery end of the pipets or burettes to a hose, allowing the water to run through them.
If the tap water is very hard, it is best to run it through a deionizer before using.

Rinse the glassware in a large bath of distilled water. Rinse with distilled water. To conserve distilled water, use a five gallon
bottle as a reservoir. Store it on a shelf near your clean-up area. Attach a siphon to it and use it for replenishing the reservoir
with used distilled water. For sensitive microbiologic assays, meticulous cleaning must be followed by rinsing 12 times in
distilled water.

STERILIZING CONTAMINATED GLASSWARE

Glassware which is contaminated with blood clots, such as serology tubes, culture media, petri dishes, etc., must be
sterilized before cleaning. It can best be processed in the laboratory by placing it in a large bucket or boiler filled with water,
to which 1-2% soft soap or detergent has been added, and boiling for 30 minutes. The glassware can then be rinsed in tap
water, scrubbed with detergent, and rinsed again.

You may autoclave glassware or sterilize it in large steam ovens or similar apparatus. If viruses or spore-bearing bacteria are
present, autoclaving is absolutely necessary.

HANDLING AND STORING

To prevent breakage when rinsing or washing pipets, cylinders, or burettes, be careful not to let tips hit the sink or the water
tap.

Dry test tubes, culture tubes, flasks, and other labware by hanging them on wooden pegs, placing them in baskets with
their mouths downward and allowing them to dry in the air, or placing them in baskets to dry in an oven. Drying
temperatures should not exceed 140 °C. Line the drying basket with a clean cloth to keep the vessel mouths clean.

Dry burettes, pipets, and cylinders by standing them on a folded towel. Protect clean glassware from dust. This is done best
by plugging with cotton, corking, taping a heavy piece of paper over the mouth, or placing the glassware in a dust-free
cabinet.

Store glassware in specially designed racks. Avoid breakage by keeping pieces separated.

Do not store alkaline liquids in volumetric flasks or burettes. Stoppers or stopcocks may stick.

Proper care and handling of Pyrex® and Pyrex Plus® labware will greatly increase its life and increase the safety of your work
place.

AUTOCLAVING-CLOUDINESS

Should the coating appear clouded due to dissolved moisture, simply let dry overnight at room temperature or briefly heat
to 110 °C (230 °F).

CLEANING

As is common practice, clean all glassware before use. Any non-abrasive glassware detergent may be used for hand or
automatic dishwasher cleaning. If using a dishwasher or glassware dryer, care should be taken to be sure the drying
temperature does not exceed 110 °C (230 °F). Exposure to dry heat should be minimized .Avoid brushes and cleaning pads
which could abrade the glass or damage the coating. If using a chromic acid cleaning solution minimize contact of the
solution with the coating.

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LABELING AND MARKING

Use water-based markers for temporary marking or labelling of the Pyrex Plus® labware coating. Solvent-based markers,
dyes, and stains cannot be removed from the coating.

NOTE: A slight "plastic" odour may be detected when handling Pyrex Plus® labware. This is due to additives in the plastic
coating which are responsible for its superior performance. The odour is normal and will not affect the inertness of the
inside borosilicate glass surface.

The Use and Care of Pyrex Plus® Laboratory Glassware for additional information.

BURETTES

Remove the stopcock or rubber tip and wash the burette with detergent and water. Rinse with tap water until all the dirt is
removed. Then rinse with distilled water and dry. Wash the stopcock or rubber tip separately. Before a glass stopcock is
placed in the burette, lubricate the joint with stopcock lubricant. Use only a small amount of lubricant. Burettes should
always be covered when not in use.

CULTURE TUBES

Culture tubes which have been used previously must be sterilized before cleaning. The best method for sterilizing culture
tubes is by autoclaving for 30 minutes at 121 °C (15 psi pressure). Media which solidifies on cooling should be poured out
while the tubes are hot. After the tubes are emptied, brush with detergent and water, rinse thoroughly with tap water, rinse
with distilled water, place in a basket, and dry.

If tubes are to be filled with a media which is sterilized by autoclaving, do not plug until the media is added. Both media
and tubes are thus sterilized with one autoclaving.

If the tubes are to be filled with sterile media, plug and sterilize the tubes in the autoclave or dry air sterilizer before adding
the media.

DISHES AND CULTURE BOTTLES

Sterilize and clean as detailed under Culture Tubes. Wrap in heavy paper or place in a petri dish can. Sterilize in the autoclave
or dry air sterilizer.

PIPETS

Place pipets, tips down, in a cylinder or tall jar of water immediately after use. Do not drop them into the jar. This may break
or chip the tips and render the pipets useless for accurate measurements. A pad of cotton or glass wool at the bottom of
the jar will help to prevent breaking of the tips. Be certain that the water level is high enough to immerse the greater portion
or all of each pipet. The pipets may then be drained and placed in a cylinder or jar of dissolved detergent or, if exceptionally
dirty, in a jar of chromic acid cleaning solution. After soaking for several hours, or overnight, drain the pipets and run tap
water over and through them until all traces of dirt are removed. Soak the pipets in distilled water for at least one hour.
Remove from the distilled water, rinse, dry the outside with a cloth, shake the water out, and dry.

BLOOD CELL COUNT DILUTING PIPETS

After use, rinse thoroughly with cool tap water, distilled water, alcohol, or acetone, and then ether. Dry by suction. Do not
blow into the pipets as this will cause moisture to condense on the inside of the pipet.

To remove particles of coagulated blood or dirt, a cleaning solution should be used. One type of solution will suffice in one
case, whereas a stronger solution may be required in another. It is best to fill the pipet with the cleaning solution and allow
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to stand overnight. Sodium hypochlorite (laundry bleach) or a detergent may be used. Hydrogen peroxide is also useful. In
difficult cases, use concentrated nitric acid. Some particles may require loosening with a horse hair or piece of fine wire.
Take care not to scratch the inside of the pipet.

AUTOMATIC PIPET WASHERS

Where a large number of pipets are used daily, it is convenient to use an automatic pipet washer. Some of these, made of
metal, can be connected directly by permanent fixtures to the hot and cold water supplies. Others, such as those made
with polyethylene, can be attached to the water supplies by rubber hose. Polyethylene baskets and jars may be used for
soaking and rinsing pipets in chromic acid cleaning solution. Electrically heated metallic pipet dryers are also available.

After drying, place pipets in a dust-free drawer. Wrap serologic and bacteriologic pipets in paper or place in pipet cans and
sterilize in the dry air sterilizer. Pipets used for transferring infectious material should have a cotton plug placed in the top
end of the pipet before sterilizing. The plug will prevent the material being measured from being drawn accidentally into
the pipetting device.

SEROLOGICAL TUBES

Serological tubes should be chemically clean, but need not be sterile. However, specimens of blood which are to be kept
for some time at room temperature should be collected in a sterile container. It may be expedient to sterilize all tubes.

To clean and sterilize tubes containing blood, discard the clots in a waste container and place the tubes in a large basket.
Put the basket, with others, in a large bucket or boiler. Cover with water, add a fair quantity of soft soap or detergent, and
boil for 30 minutes. Rinse the tubes, clean with a brush, rinse and dry with the usual precautions.

It is imperative when washing serological glassware that all acids, alkali, and detergents be completely removed. Acids,
alkalis and detergents in small amounts interfere with serologic reactions. Serologic tubes and glassware should be kept
separate from all other glassware and used only for serologic procedures.

SLIDES AND COVER GLASS

It is especially important that microscope slides and cover glass used for the preparation of blood films or bacteriologic
smears be perfectly clean and free from scratches. Slides should be washed, placed in glacial acetic acid for 10 minutes,
rinsed with distilled water, and wiped dry with clean paper towels or cloth. Once the slides have been washed, place them
in a wide jar of alcohol. As needed, remove from the jar and wipe dry. If the slides are dry stored, wash them with alcohol
before use.

Chromic acid cleaning solution - Use powdered commercial or technical grade sodium dichromate or potassium
dichromate. If the compound is in the form of crystals, grind to a fine powder in a mortar. To 20 grams of the powder in a
litter beaker, add a little water, sufficient to make a thin paste. Slowly add approximately 300 mL of commercial concentrated
sulfuric acid, stirring well. Transfer to a glass-stoppered bottle.

Larger amounts can be made in the same proportions. Use the clear supernatant solution. Chromic acid solution can be
used repeatedly until it begins to turn a greenish colour. Dispose of in accordance with appropriate regulations. Dilute with
large volumes of water before discarding, or carefully neutralize the diluted solution with sodium hydroxide.

Importance of Cleaning Validation:

Effective cleaning validation is crucial for several key reasons:

 Product Quality Assurance: In industries like pharmaceuticals, medical devices, and food production, any residual
contamination can jeopardize product quality and patient safety. Proper cleaning validation helps maintain the integrity of
products.
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 Patient and Consumer Safety: In healthcare and food industries, ensuring that equipment and surfaces are free from
harmful contaminants is essential for safeguarding patients and consumers from potential harm.

 Regulatory Compliance: Regulatory bodies like the FDA, EMA, and others mandate cleaning validation to meet stringent
standards. Compliance with these regulations is not only a legal requirement but also vital for gaining and maintaining
market access.

 Cross-Contamination Prevention: Preventing the unintended transfer of residues from one product or process to another
is a central aspect of cleaning validation. Cross-contamination can lead to serious health hazards and regulatory violations.

 Data Integrity: In research and development, maintaining data integrity is paramount. Clean, uncontaminated equipment
and glassware are essential to produce reliable results.

The Cleaning Validation Process:

The cleaning validation process typically involves a series of well-defined steps:

 Setting Acceptance Criteria: The first step is to define the acceptable level of cleanliness or the maximum allowable
residue limits. These criteria are determined based on factors like product type, risk assessment, and regulatory guidelines.

 Cleaning Procedures and Methods: Developing standardized cleaning procedures and methods is essential. This includes
selecting appropriate cleaning agents, techniques, equipment, and cleaning cycles.

 Sampling and Testing: Various techniques are used to collect samples from cleaned equipment or surfaces. These
samples are then analyzed to ensure that they meet the established acceptance criteria. Common methods include swab
testing, rinse sampling, visual inspection, and more advanced analytical techniques like HPLC and TOC.

 Documentation and Record Keeping: Comprehensive documentation of the cleaning process, sampling methods, results,
and any corrective actions taken is critical. Thorough records are vital for regulatory compliance.

 Validation Protocols and Reports: Validation protocols are established before the cleaning process begins, outlining the
entire validation approach. After successful cleaning validation, reports are generated to demonstrate compliance and the
effectiveness of the cleaning process.

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Challenges and Evolving Practices:

Cleaning validation faces evolving challenges, including adapting to new technologies, addressing environmental concerns,
and the need for automation to improve efficiency and reliability. As industries progress, cleaning validation practices are
also evolving to meet changing demands.

In conclusion, cleaning validation is an essential practice in industries where product quality, patient safety, and regulatory
compliance are paramount. It ensures that equipment and facilities are consistently cleaned to prevent contamination and
maintain the highest standards. By implementing robust cleaning validation processes, industries can guarantee that their
products and processes consistently meet quality and safety standards.

Glassware cleaning validation in pharmaceutical companies is a specialized and critical process designed to ensure that
laboratory glassware and equipment used in pharmaceutical research, development, and quality control are thoroughly
cleaned and free from any residues or contaminants. This practice is essential for maintaining data integrity, ensuring the
accuracy of experimental results, and adhering to strict regulatory standards. Here's an overview of glassware cleaning
validation in pharmaceutical companies:

Importance of Glassware Cleaning Validation:

 Data Accuracy: In pharmaceutical research and quality control, the accuracy and reliability of experimental results are
paramount. Contaminated glassware can introduce variables that affect the outcomes of experiments and analyses.

 Patient Safety: In the pharmaceutical industry, ensuring the safety and efficacy of drug products is a top priority.
Contaminated glassware could lead to the introduction of impurities or contaminants into pharmaceutical formulations,
potentially harming patients.

 Regulatory Compliance: Regulatory bodies like the FDA (U.S. Food and Drug Administration) and the EMA (European
Medicines Agency) require pharmaceutical companies to validate their cleaning processes to ensure product quality and
safety. Non-compliance can result in serious regulatory repercussions.

 Cross-Contamination Prevention: Glassware cleaning validation is essential to prevent cross-contamination between

different samples or compounds, which can compromise the quality of research and product formulations.

Key Aspects of Glassware Cleaning Validation:

 Acceptance Criteria: Establishing clear acceptance criteria is a fundamental step. These criteria specify the maximum
allowable residue limits (e.g., in micrograms) for each substance or compound on glassware surfaces.

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 Cleaning Procedures: Pharmaceutical companies must develop standardized and validated cleaning procedures. These
procedures define the appropriate cleaning agents, methods, equipment, and cycles needed to effectively clean the
glassware.

 Sampling and Testing: Sampling methods such as swab sampling, rinse sampling, and visual inspection are employed to
collect samples from glassware surfaces. These samples are then subjected to rigorous testing to ensure that they meet the
predefined acceptance criteria.

 Advanced Analytical Techniques: Glassware cleaning validation often employs advanced analytical techniques like High-
Performance Liquid Chromatography (HPLC), Gas Chromatography (GC), Total Organic Carbon (TOC) analysis, and Atomic
Absorption Spectroscopy (AAS) for testing residues and contaminants.

 Documentation: Comprehensive documentation is essential to demonstrate compliance and the effectiveness of the
cleaning process. This includes records of cleaning procedures, sampling methods, test results, and any corrective actions
taken.

 Validation Protocols: Pharmaceutical companies establish validation protocols before initiating the cleaning validation
process. These protocols outline the entire validation approach, specifying the acceptance criteria, sampling procedures,
testing methods, and validation timelines.

Challenges and Continuous Improvement:

Pharmaceutical companies continually face challenges in glassware cleaning validation, including difficult-to-clean
glassware surfaces and the need for rapid and efficient cleaning processes. To meet these challenges, companies often
invest in new technologies and automation to improve cleaning processes and ensure data integrity.

In conclusion, glassware cleaning validation is a crucial practice in pharmaceutical companies to ensure the integrity of
research and product quality. By implementing robust glassware cleaning validation procedures, pharmaceutical companies
can maintain data accuracy, protect patient safety, and comply with stringent regulatory requirements. This, in turn,
contributes to the overall success and reputation of the pharmaceutical industry.

Advanced glassware cleaning validation is a critical process in various industries, including pharmaceuticals, healthcare,
food and beverage, and research laboratories. This process ensures that glassware used for experiments, production, or
analysis is free from contaminants and residues, which could compromise the integrity of results or the safety of consumers.
Here is a review of advanced glassware cleaning validation:

Importance of Validation:
Advanced glassware cleaning validation is crucial for maintaining the quality and reliability of results in industries that rely
on glassware for research or production. It helps prevent cross-contamination, ensures the safety of consumers, and
complies with regulatory requirements. Failure to validate cleaning processes can lead to costly errors and potential health
risks.

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Regulatory Compliance:
Industries like pharmaceuticals and healthcare are subject to strict regulatory requirements. Glassware cleaning validation
is essential to demonstrate compliance with these standards, such as the FDA's Current Good Manufacturing Practices
(cGMP) or the USP <1058> Analytical Instrument Qualification guidelines.

Method Development:
Developing a robust and effective cleaning validation method is a critical step. It involves determining the appropriate
analytical techniques and acceptance criteria for residues and contaminants, as well as establishing worst-case scenarios to
test the cleaning process thoroughly.

Risk Assessment:
A key component of advanced glassware cleaning validation is conducting a risk assessment. This identifies potential sources
of contamination, which can vary based on the specific application, and prioritizes high-risk areas or processes for validation.

Analytical Techniques:
Advanced glassware cleaning validation typically involves the use of analytical techniques such as high-performance liquid
chromatography (HPLC), gas chromatography (GC), mass spectrometry (MS), and spectroscopy to detect and quantify
residues. These techniques help ensure that the glassware is free from even trace amounts of contaminants.

Documentation:
Rigorous documentation is essential in advanced glassware cleaning validation. Detailed records of validation procedures,
results, and any corrective actions taken must be maintained for regulatory purposes. This ensures transparency and
traceability of the cleaning process.

Validation Protocols:
The development and execution of cleaning validation protocols are essential to ensuring consistency and repeatability.
These protocols should outline the entire validation process, from sample collection and analysis to acceptance criteria and
reporting.

Validation Frequency:
Glassware cleaning validation should not be a one-time event. It needs to be a recurring process to account for changes in
equipment, procedures, or contamination risks. Regular revalidation ensures that glassware remains clean and free from
contaminants over time.

Training and Education:

Proper training and education of personnel involved in the cleaning and validation process are critical. Employees need to
understand the importance of their roles in maintaining the cleanliness and integrity of glassware.

In conclusion, advanced glassware cleaning validation is an essential aspect of quality control in industries that rely on
glassware. It ensures the integrity of research, production, and safety standards while complying with regulatory
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requirements. Developing effective validation methods, risk assessments, and utilizing appropriate analytical techniques
are all critical components of this process. Furthermore, maintaining thorough documentation and conducting regular
revalidation helps to guarantee the ongoing cleanliness of glassware.

References:
1.Journal of Atoms and Molecules (An International online journal) review article by Abhishek Raj.

2.Cleaning Validation in Continuous Manufacturing by Elizabeth Rivera.

3. The validation of cleaning processes, Pharmaceutical Technology – S.W. Harder

4. Cleaning Validation: An overall perspective – Jenkins M, Vanderweilen AJ

5. ICH: Good Manufacturing Practice guideline for Active Pharmaceutical Ingredients.

6. Pharmaceutical Quality Assurance: Cleaning Validation – Manohar A. Potdar

7. Determining cleaning validation limits for pharmaceutical manufacturing operations, Pharmaceutical Technology – Fourman,
G.L. and Mullen, M.V.

8. Points to consider in the validation of equipment cleaning procedures, Journal of Parenteral science and Technology - James
Agalloco.

9. Process Analytical Technology and Cleaning – Verghese, G. and Lopolito, P.

10. Cleaning Technology for Pharmaceutical Manufacturing – LeBlanc, Destin A.

11.Pharmaceutical quality assurance by M.A.Potdar (page no. 8.28 8.31)

12.Drug regulatory affairs by V.Kishore (page no. 213).

13.METHOD DEVOLPMENT AND VALIDATION OF CLEANING PROCEDURE FOR FENBENDAZOLE RESIDUAL DETERMINATION by sunil
kumar yelamanchi.

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