This document discusses current Good Manufacturing Practices requirements for cleaning validation according to the FDA. It provides an overview of microbial monitoring methods and their advantages and disadvantages. The document also provides examples of how to determine appropriate acceptance criteria for cleaning validation based on the equipment dimensions and volume of product being processed, to ensure the microbial limits for non-sterile and sterile products are met.
This presentation is basic knowledge about the aseptic processing and media fill validation in pharmaceutical industry and media fill procedure. How to validate aseptic process in the powder drug products , data guidance and record for media fill validation.
It is process of “Establishing documentary evidence that provide a high degree of assurance that a specific process will consistently produce a product meeting its predetermined specifications and quality attributes”.
In the pharmaceutical industry, it is very important that in addition to final testing and compliance of products, it is also assured that the process will consistently produce the expected results.
Validation is action of proving in accordance with the principles of good manufacturing practices, that any procedure, process, equipment, material, activity or system actually leads to expected results.
Cleaning validation is documented evidence with a high degree assurance that one can consistently clean a system or a piece of equipment to predetermined and acceptable limits.
The primary regulatory concern driving the need for cleaning validation is cross contamination of the desired drug substance either by other API from previous batch runs or by residues from the cleaning agents used.
The prime purpose of validating a cleaning process is to ensure compliance with federal and other standard regulations
1. Cross contamination with active ingredients
Contamination of one batch of product with significant levels of residual active ingredients from previous batch cannot be tolerated.
In addition to the obvious problems posed by subjecting consumers or patients to unintended contaminants, potential clinically significant synergistic interactions between pharmacologically active chemicals are a real concern.
2. Contamination with unintended materials or compounds
While inert ingredients used in drug products are generally recognized as safe for human consumption, the routine use, maintenance and cleaning of equipment's provide the potential contamination with such items as equipment parts, lubricants and chemical cleaning agents3. Microbiological contamination
Maintenance , cleaning and storage conditions may provide adventitious microorganisms with the opportunity to proliferate within the processing equipment.
Aseptic / sterile- “ A state of control attained by using an aseptic work area and performing activities in a manner that precludes microbiological contamination of the exposed sterile product”
This presentation is basic knowledge about the aseptic processing and media fill validation in pharmaceutical industry and media fill procedure. How to validate aseptic process in the powder drug products , data guidance and record for media fill validation.
It is process of “Establishing documentary evidence that provide a high degree of assurance that a specific process will consistently produce a product meeting its predetermined specifications and quality attributes”.
In the pharmaceutical industry, it is very important that in addition to final testing and compliance of products, it is also assured that the process will consistently produce the expected results.
Validation is action of proving in accordance with the principles of good manufacturing practices, that any procedure, process, equipment, material, activity or system actually leads to expected results.
Cleaning validation is documented evidence with a high degree assurance that one can consistently clean a system or a piece of equipment to predetermined and acceptable limits.
The primary regulatory concern driving the need for cleaning validation is cross contamination of the desired drug substance either by other API from previous batch runs or by residues from the cleaning agents used.
The prime purpose of validating a cleaning process is to ensure compliance with federal and other standard regulations
1. Cross contamination with active ingredients
Contamination of one batch of product with significant levels of residual active ingredients from previous batch cannot be tolerated.
In addition to the obvious problems posed by subjecting consumers or patients to unintended contaminants, potential clinically significant synergistic interactions between pharmacologically active chemicals are a real concern.
2. Contamination with unintended materials or compounds
While inert ingredients used in drug products are generally recognized as safe for human consumption, the routine use, maintenance and cleaning of equipment's provide the potential contamination with such items as equipment parts, lubricants and chemical cleaning agents3. Microbiological contamination
Maintenance , cleaning and storage conditions may provide adventitious microorganisms with the opportunity to proliferate within the processing equipment.
Aseptic / sterile- “ A state of control attained by using an aseptic work area and performing activities in a manner that precludes microbiological contamination of the exposed sterile product”
Manufacturing Control Systems. J R Controls provides control systems for the manufacturing industry. A typical control system will monitor the progress of parts through the manufacturing and finishing process.
The presentation was an overview of the GMP regulations specific to cleaning validation for medicine manufacturers. New guidelines for Health Based Exposure Limits were discussed along with common GMP deficiencies observed during TGA inspections.
Validation: Validation is a documented program that provides high degree of assurance that a specific process, method or system consistently produces a result meeting pre-determined acceptance criteria.
This presentation gives an overview of : Validation of microbiological methods , Considering some of the limitations and
Key criteria that may be applicable for assessment.
Effective process validation contributes significantly to assuring drug quality. The basic
principle of quality assurance is that a drug should be produced that is fit for its intended use.
This principle incorporates the understanding that the following conditions exist:
• Quality, safety, and efficacy are designed or built into the product.
• Quality cannot be adequately assured merely by in-process and finished-product
inspection or testing
Good Manufacturing PracticeFor LVP,SVP, ophthalmic veterinary medicine, bulk chemicals & invitro diagnostic
For Good business Practice
A control process gives reproducibility & product consistency with in known limits
Provides license to do business.
ICH Q7A means the good manufacturing practice guidance for active pharmaceutical ingredients developed under the auspices of the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use.
Auditing of Granulation Operation in Dry Production AreaPritam Kolge
Auditing of Granulation Operation in Dry Production Area.....
This topic comes under Audits and Regulatory Compliance....
This is useful for M.Pharm (Pharaceutical Quality Assurance) Students who studying in First year sem II....
This Presentation Contain following...
#Objectives
#Fundamentals of Granulation
#Reasons for Granulation
#Methods of Granulation
#Agglomeration
#Fundamentals and Audit of Dry Granulation
#Steps in Dry Granulation
#Fundamentals and Audit of Fluid Bed Granulation
#Scale-Up of Fluid bed Granulation
#High share granulation-Fundamentals, Audit and Scale-Up
#Overview and Comparison of Different Granulating Techniques
#Audit of Mixing and Blending, Wet granulation, Wet milling, Drying, Milling
#Conclusion
#References
Thanks For Help and Guidance of Mr. D.P.Mali Sir
Manufacturing Control Systems. J R Controls provides control systems for the manufacturing industry. A typical control system will monitor the progress of parts through the manufacturing and finishing process.
The presentation was an overview of the GMP regulations specific to cleaning validation for medicine manufacturers. New guidelines for Health Based Exposure Limits were discussed along with common GMP deficiencies observed during TGA inspections.
Validation: Validation is a documented program that provides high degree of assurance that a specific process, method or system consistently produces a result meeting pre-determined acceptance criteria.
This presentation gives an overview of : Validation of microbiological methods , Considering some of the limitations and
Key criteria that may be applicable for assessment.
Effective process validation contributes significantly to assuring drug quality. The basic
principle of quality assurance is that a drug should be produced that is fit for its intended use.
This principle incorporates the understanding that the following conditions exist:
• Quality, safety, and efficacy are designed or built into the product.
• Quality cannot be adequately assured merely by in-process and finished-product
inspection or testing
Good Manufacturing PracticeFor LVP,SVP, ophthalmic veterinary medicine, bulk chemicals & invitro diagnostic
For Good business Practice
A control process gives reproducibility & product consistency with in known limits
Provides license to do business.
ICH Q7A means the good manufacturing practice guidance for active pharmaceutical ingredients developed under the auspices of the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use.
Auditing of Granulation Operation in Dry Production AreaPritam Kolge
Auditing of Granulation Operation in Dry Production Area.....
This topic comes under Audits and Regulatory Compliance....
This is useful for M.Pharm (Pharaceutical Quality Assurance) Students who studying in First year sem II....
This Presentation Contain following...
#Objectives
#Fundamentals of Granulation
#Reasons for Granulation
#Methods of Granulation
#Agglomeration
#Fundamentals and Audit of Dry Granulation
#Steps in Dry Granulation
#Fundamentals and Audit of Fluid Bed Granulation
#Scale-Up of Fluid bed Granulation
#High share granulation-Fundamentals, Audit and Scale-Up
#Overview and Comparison of Different Granulating Techniques
#Audit of Mixing and Blending, Wet granulation, Wet milling, Drying, Milling
#Conclusion
#References
Thanks For Help and Guidance of Mr. D.P.Mali Sir
Upstream Viral Safety – Protect your bioreactor with Virus FiltrationMilliporeSigma
This poster summarizes the performance of a filter specifically developed for virus removal from chemically defined cell culture media. The filter removes high levels of virus, mycoplasma and bacteria without impacting cell growth, antibody titer, or protein quality. The filter has robust performance over a broad range of conditions offering an effective, easy to implement solution for media treatment.
A scientific presentation that describes the steps to perform antimicrobial sensitivity assay for water insoluble compounds and the type of data that can be obtained.
5.1.3. Efficacy of antimicrobial preservation (EP 5.0)Guide_Consulting
Salah Satu Referensi Yang Digunakan Dalam One Day Seminar "Preservative Effectiveness Validation" 04 Desember 2014.
Detail : info@traininglaboratorium.com
Cell Culture Media Filtration – Filter Selection and SizingMilliporeSigma
The purpose of this application note is to provide estimated filtration areas for different sterilizing-grade filters with a panel of media used for Chinese Hamster Ovary (CHO) cell culture processes.
Anti-Adhesion and Anti-Biofilm Effectiveness of Disinfectants Used In Hemodia...IJERA Editor
Biofilms are communities of microorganisms attached to a surface and included in an extracellular matrix making it resistant to exogenous deleterious agents. The aim of this study is to evaluate the anti-adhesive and anti-biofilm effect of five commercials disinfectants having different active principles (hydrogen peroxide, sodium hypochlorite, isopropyl alcohol and ethanol) on four Staphylococcus strains isolated from hemodialysis unit surfaces. The disinfectants anti-adhesive effect was estimated to an exceeding rate 70% for the various studied dilutions and 90% towards the pure products. Whereas the anti-biofilm effect showed an elimination rate varying between 10 % and 95 % according to the following parameters: active principle, time of contact, concentration and bacterial strain. Our study demonstrated that all tested products have an interesting anti-adhesive effect and that the peroxide of hydrogen is endowed with important anti-biofilm efficiency, followed by the alcoholic products and the sodium hypochlorite.
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
- ARTIFICIAL INTELLIGENCE AND ETHICS
- GENE THERAPY
- BEYOND BORDERS: GLOBAL INITIATIVES FOR DEMOCRATIZING LIFE SCIENCE TECHNOLOGIES AND PROMOTING ACCESS TO HEALTHCARE
- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
Factory Supply Best Quality Pmk Oil CAS 28578–16–7 PMK Powder in Stockrebeccabio
Factory Supply Best Quality Pmk Oil CAS 28578–16–7 PMK Powder in Stock
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Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
3. Wyeth-Ayerst Pharmaceuticals
CLEANING VALIDATION
21 CFR 211.67 Equipment cleaning
and maintenance
a) Equipment and utensils shall be
cleaned, maintained and sanitized
at appropriate intervals to prevent
contamination that would alter the
safety, identity, strength, quality
or purity of the drug product.
4. Wyeth-Ayerst Pharmaceuticals
CLEANING VALIDATION
21 CFR 211.113 Control of
microbiological contamination
(a) Appropriate written procedures,
designed to prevent objectionable
microorganisms in drug products
not required to be sterile, shall be
established and followed.
5. Wyeth-Ayerst Pharmaceuticals
CLEANING VALIDATION
21 CFR 211.113
Control of microbiological
contamination
(b) Appropriate written procedures,
designed to prevent objectionable
microorganisms in drug products
required to be sterile, shall be
established and followed. Such
procedures shall include
validation of any sterilization
process.
8. Wyeth-Ayerst Pharmaceuticals
CLEANING VALIDATION
FDA Guide to Inspection of
validation of Cleaning processes
(July, 1993) states that
microbiological aspects of
equipment cleaning should be
considered. There should be some
evidence that routine cleaning and
storage does not allow microbial
proliferation.
9. Wyeth-Ayerst Pharmaceuticals
CLEANING VALIDATION
PhRMA report on microbiological
monitoring in nonsterile
pharmaceutical manufacturing
areas (March, 1997)
recommended that depending on
the product, e.g. inhalation
products,oral aqueous liquids,
vaginal creams, etc, cleaning
validation should include
microbial sampling to ensure
microbiological quality.
10. Wyeth-Ayerst Pharmaceuticals 1
CLEANING VALIDATION
PhRMA Guidelines for the Validation
of Cleaning Procedures for Bulk
Pharmaceutical Chemicals
published in September, 1997
declared that microbial issues was
not within the scope of the report.
11. Wyeth-Ayerst Pharmaceuticals 1
CLEANING VALIDATION
Microbial contamination can be
prevented by:
Selection of suitable equipment
Sound cleaning programs
Cleaning equipment directly after
use
Dry storage of equipment
14. Wyeth-Ayerst Pharmaceuticals 1
CLEANING VALIDATION
Swab Method
Advantages: Most common
method used with selective media
to isolate directly different
microbial populations.
Disadvantages: Recovery may not
be reproducible & quantitative.
15. Wyeth-Ayerst Pharmaceuticals 1
CLEANING VALIDATION
Surface Rinse Method
Advantages: Higher counts
obtained than swab method &
better overall assessment
possible.
Disadvantages: Entire surface
evaluated, microbial population
must be detached & membrane
filtration necessary to obtain
countable numbers.
16. Wyeth-Ayerst Pharmaceuticals 1
CLEANING VALIDATION
RODAC Plate Method
Advantages: Direct growth on
media in contact plate is
convenient, neutralizers may be
included in media & different
media may be used.
Disadvantages: Only applicable to
surfaces that are smooth & have
low counts.
17. Wyeth-Ayerst Pharmaceuticals 1
CLEANING VALIDATION
Limulus Amoebocyte Lysate Method
Advantages: Rapid, sensitive,
quantitative measure of bacterial
endotoxin levels.
Disadvantages: Indirect
measurement of high numbers of
gram-negative bacteria only.
18. Wyeth-Ayerst Pharmaceuticals 1
CLEANING VALIDATION
Bioluminescence Method
Advantages: Rapid, highly
accurate & reliable method.
Disadvantages: Suitable for
microbial counts in the range of
104
to 108
organisms as
insufficiently sensitive for low
microbial counts.
19. Wyeth-Ayerst Pharmaceuticals 1
CLEANING VALIDATION
Microbial requirements for non-
sterile pharmaceutical drug
products: Control of the total
bioburden, elimination of USP
indicator and objectionable
microorganisms.
20. Wyeth-Ayerst Pharmaceuticals 2
CLEANING VALIDATION
Microbial Limit for a oral solid dosage form,
i.e., Tablet or capsule.
Total Aerobic Microbial Count NMT 1000
cfu/g
Total Combined Yeast & Mold Count
NMT100 cfu/g
Absence of USP Indicator organisms, i.e., E.
coli, S. aureus and Salmonella spp.
21. Wyeth-Ayerst Pharmaceuticals 2
CLEANING VALIDATION
Case history: What should be the
acceptance criteria for a blender
used to process a wet granulation
tablet?
22. Wyeth-Ayerst Pharmaceuticals 2
CLEANING VALIDATION
Approach: The microbial limit in
terms of cfu per 25 cm2
can be
determined from a knowledge of
the internal surface area of the
blender, the quantity of
granulation processed and the
Microbial Limit for the product
(oral solid dosage form)
23. Wyeth-Ayerst Pharmaceuticals 2
CLEANING VALIDATION
Example: A Gemco 20 blender has
an internal surface area of 46,128
cm2
& a capacity of 220 kg of
granulation.
With a surface bioburden of 100 cfu/
25cm2
there is potential to transfer
<1 cfu/g to the granulation. cf.
Microbial Limit for an oral solid
dosage form NMT 1000 cfu/g.
24. Wyeth-Ayerst Pharmaceuticals 2
CLEANING VALIDATION
Example: A Gemco 75 blender has
an internal surface area of 100,944
cm. sq. & a capacity of 500 kg of
granulation.
With a surface bioburden of 100
cfu/25cm2
there is potential to
transfer <1 cfu/g to the
granulation. c.f. Microbial Limit for
an oral solid dosage form NMT
1000 cfu/g.
25. Wyeth-Ayerst Pharmaceuticals 2
CLEANING VALIDATION
Example: A Littleford blender has an
internal surface area of 22,718 cm.
sq. & a capacity of 100 kg of
granulation.
With a surface bioburden of 100
cfu/25 cm2
there is potential to
transfer <1 cfu/g to the
granulation. c.f. Microbial Limit for
an oral solid dosage form NMT
1000 cfu/g.
26. Wyeth-Ayerst Pharmaceuticals 2
CLEANING VALIDATION
Recommended Acceptance Criteria
for Blenders:
NMT 100 cfu per 25 cm2
&
Absence of USP Indicator
Organisms.
Recommended Monitoring Method:
Swab Method
27. Wyeth-Ayerst Pharmaceuticals 2
CLEANING VALIDATION
Microbial requirements for sterile
pharmaceutical drug products:
Control of total bioburden to
maintain the Sterility Assurance
Level & elimination of endotoxin
to prevent pyrogenic reactions.
28. Wyeth-Ayerst Pharmaceuticals 2
CLEANING VALIDATION
Case history: What should be the
acceptance criteria for a pre-
sterile bulk solution tank used to
aseptically fill a parenteral
product?
29. Wyeth-Ayerst Pharmaceuticals 2
CLEANING VALIDATION
Approach: The microbial limit in
terms of cfu per 25 cm2
can be
determined from a knowledge of
the internal surface area of the
bulk tank, the volume of the bulk
solution processed and the
square footage of the cartridge
filter used to sterile filter the
product.
30. Wyeth-Ayerst Pharmaceuticals 3
CLEANING VALIDATION
Calculations:
Challenge cfu per sq. cm of Filter =
Fill Volume(Liters) X Bioburden
(cfu/l)/Surface Area of the Filter
(sq.cm)
Conversion factor: 10 sq. ft. = 9290
sq. cm
31. Wyeth-Ayerst Pharmaceuticals 3
CLEANING VALIDATION
Example:
A 1000 Liter bulk tank with a
bioburden of 10 cfu per 100 mL
will represent a total bacterial
challenge of 105
to a 10 sq. ft.
cartridge filter, i.e., 10 cfu per cm2
of filter surface , which well below
the filter retention rating of 107
per
sq. cm.
32. Wyeth-Ayerst Pharmaceuticals 3
CLEANING VALIDATION
Acceptance criteria (Sterile
products): Based on pre-sterile
bulk solution bioburden limit, i.e.
NMT 10 cfu/100 mL (aseptically-
filled products), heat resistance of
bacterial spores (terminally-
sterilized products or equipment)
& endotoxin contribution.
33. Wyeth-Ayerst Pharmaceuticals 3
CLEANING VALIDATION
Example: 125 Liter pre-sterile
filtration bulk tanks (Precision
Stainless, Inc.) with a product
contact surface area of 2356 sq.
cm. With a surface bioburden of
33 cfu/25 cm2
there is potential to
transfer 4 X 103
organisms or 1
cfu/100 mL to the bulk solution.
34. Wyeth-Ayerst Pharmaceuticals 3
CLEANING VALIDATION
Endotoxin considerations:
Endotoxin limits for parenteral
products are set using the
maximum human dose for the
individual products.
Since a bacterial cell weights 10-13
grams, 105
cells in the bulk
solution represents 10-8
gram of
cellular material (10 ng).
35. Wyeth-Ayerst Pharmaceuticals 3
CLEANING VALIDATION
Endotoxin considerations:
If endotoxin represents 10% of
the cell weight then a bulk
solution of 125 Liters will
contain less 0.00001 ng/mL of
endotoxin.
36. Wyeth-Ayerst Pharmaceuticals 3
CLEANING VALIDATION
Example: 125 Liter pre-sterile
filtration bulk tanks (Precision
Stainless, Inc.) with a product
contact surface area of 2356 sq.
cm. With a surface endotoxin level
of 0.5 EU/25 cm2
there is potential
to transfer up to 20 EU or 0.002
EU/mL to the bulk solution.
37. Wyeth-Ayerst Pharmaceuticals 3
CLEANING VALIDATION
Recommended Acceptance Criteria
for pre-sterile filtration bulk tanks
NMT 33 cfu per 25 cm2
& NMT 0.2 EU
per sq. cm
Recommended Monitoring Method:
RODAC Plate Method &/or Rinse
sampling.
38. Wyeth-Ayerst Pharmaceuticals 3
CLEANING VALIDATION
Conclusions: Based on the desired
Microbial Limit for a non-sterile
product or a pre-sterile filtration
bulk solution, given a certain
equipment surface to material
quantity ratio, it is possible to set
appropriate surface bioburden
limits for cleaning validations.