This session from the Institute of Validation Technology's Contamination and Control Week discusses regulatory expectations and industry drivers for aseptic cleaning and environmental monitoring, regulatory expectations for cleanrooms, and current FDA and EU expectations during inspection of sterile and aseptic operations.
Control on Cleanroom Environmental Monitoring (Pharmaceutical)Srinath Sasidharan
A general consideration of Environmental Monitoring in Pharmaceutical manufacturing area. Cleanroom Monitoring Tools and Utilities: Author Sreenath Sasidharan (Geltec Healthcare FZE)
We specialise in Bioaerosols, Sick Building Syndrome, Fenceline Monitoring, Urban air quality, Industrial air quality, construction air quality, CEMS, CAMS and much more.
Control on Cleanroom Environmental Monitoring (Pharmaceutical)Srinath Sasidharan
A general consideration of Environmental Monitoring in Pharmaceutical manufacturing area. Cleanroom Monitoring Tools and Utilities: Author Sreenath Sasidharan (Geltec Healthcare FZE)
We specialise in Bioaerosols, Sick Building Syndrome, Fenceline Monitoring, Urban air quality, Industrial air quality, construction air quality, CEMS, CAMS and much more.
If you work in food growing, food processing, or food distribution, there are many concerns to consider about the presence of pathogens and contaminants in the same environment as your product. This presentation answers frequently asked questions about establishing a pathogen environmental monitoring program for your facility.
Aseptic Area and Microbial Control. - Pharmaceutical Microbiology (SYBpharm) ...Kiran Shinde
Prof.Mr.Kiran K. Shinde (M.Pharm), Assistant professor (VNIPRC)
Pharmaceutical microbiology (Second year b.pharm) (3rd semester)
Introduction to Aseptic area & room
Designing of Aseptic Room
Laminar Airflow Equipment
Sources of Contamination & Method of Prevention
Classification of Aseptic Area-Room
Testing of Clean Aseptic Room
An understanding on requirements to produce Hazardous Pharmaceutical Products. The concept of containment facility and practices are described in easy to understand fashion.
A Brief Overview on Active Air Sampling Procedure for Environment Monitoringijtsrd
In this paper, we are going to discuss the ‘Active Air Sampling procedure for EM'. EM stands for Environment Monitoring. Environment monitoring is performed in the pharmaceutical manufacturing plants to monitor the contamination of viable and non viable particle count. Viable particle count can be observed through the ‘Settle Plate method, Active Air Sampling, Surface Monitoring contact plate and swab test , and Personnel Monitoring method'. Non viable particles are dust particles and other non living particles. Active Air sampling is performed by microbiologist in the production and manufacturing area using the equipment known as ‘Air Sampler'. A media plate of SCDA Soybean Casein Digest Agar prepared under sterile condition by the microbiologist. The media plate is then allowed to adjust under the ‘Air Sampler hood' and then it is used for sampling purpose. Air sampler captures 1000L air as per validated time in a 1cubic meter of volume and therefore air sampling is thus performed in the middle of the surrounding area. The sampled plate is then incubated, and after then the required incubation is provided, and the plate is thus analyzed to determine whether our manufacturing area meets the level of expected counts or it crosses the required limit and, on this basis, the reporting is thus generated on regular basis. Juhi Rastogi | Faiz Hashmi ""A Brief Overview on Active Air Sampling Procedure for Environment Monitoring"" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-3 | Issue-3 , April 2019, URL: https://www.ijtsrd.com/papers/ijtsrd22987.pdf
Paper URL: https://www.ijtsrd.com/pharmacy/pharmacy-practice/22987/a-brief-overview-on-active-air-sampling-procedure-for-environment-monitoring/juhi-rastogi
In this presentation from the Institute of Validation Technology's Life Sciences Aseptic Processing, Kim Van Antwerpen discusses collecting environmental data, methods for trending, and interpreting and sharing environmental monitoring data.
If you work in food growing, food processing, or food distribution, there are many concerns to consider about the presence of pathogens and contaminants in the same environment as your product. This presentation answers frequently asked questions about establishing a pathogen environmental monitoring program for your facility.
Aseptic Area and Microbial Control. - Pharmaceutical Microbiology (SYBpharm) ...Kiran Shinde
Prof.Mr.Kiran K. Shinde (M.Pharm), Assistant professor (VNIPRC)
Pharmaceutical microbiology (Second year b.pharm) (3rd semester)
Introduction to Aseptic area & room
Designing of Aseptic Room
Laminar Airflow Equipment
Sources of Contamination & Method of Prevention
Classification of Aseptic Area-Room
Testing of Clean Aseptic Room
An understanding on requirements to produce Hazardous Pharmaceutical Products. The concept of containment facility and practices are described in easy to understand fashion.
A Brief Overview on Active Air Sampling Procedure for Environment Monitoringijtsrd
In this paper, we are going to discuss the ‘Active Air Sampling procedure for EM'. EM stands for Environment Monitoring. Environment monitoring is performed in the pharmaceutical manufacturing plants to monitor the contamination of viable and non viable particle count. Viable particle count can be observed through the ‘Settle Plate method, Active Air Sampling, Surface Monitoring contact plate and swab test , and Personnel Monitoring method'. Non viable particles are dust particles and other non living particles. Active Air sampling is performed by microbiologist in the production and manufacturing area using the equipment known as ‘Air Sampler'. A media plate of SCDA Soybean Casein Digest Agar prepared under sterile condition by the microbiologist. The media plate is then allowed to adjust under the ‘Air Sampler hood' and then it is used for sampling purpose. Air sampler captures 1000L air as per validated time in a 1cubic meter of volume and therefore air sampling is thus performed in the middle of the surrounding area. The sampled plate is then incubated, and after then the required incubation is provided, and the plate is thus analyzed to determine whether our manufacturing area meets the level of expected counts or it crosses the required limit and, on this basis, the reporting is thus generated on regular basis. Juhi Rastogi | Faiz Hashmi ""A Brief Overview on Active Air Sampling Procedure for Environment Monitoring"" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-3 | Issue-3 , April 2019, URL: https://www.ijtsrd.com/papers/ijtsrd22987.pdf
Paper URL: https://www.ijtsrd.com/pharmacy/pharmacy-practice/22987/a-brief-overview-on-active-air-sampling-procedure-for-environment-monitoring/juhi-rastogi
In this presentation from the Institute of Validation Technology's Life Sciences Aseptic Processing, Kim Van Antwerpen discusses collecting environmental data, methods for trending, and interpreting and sharing environmental monitoring data.
This presentation aims to give a quick guide on new technologies in environmental cleaning. The decision of choosing a specific type depends on each healthcare setting and its need.
MANUFACTURING OF PARENTRALS
1. Formulation and Raw Materials:
Concept: The process begins with the formulation of the parenteral drug, determining its composition and concentration.
Raw Materials: High-quality pharmaceutical-grade raw materials, including active pharmaceutical ingredients (APIs), excipients, and solvents, are selected based on their compatibility and purity.
2. Sterilization of Raw Materials:
Concept: Due to the sterile nature of parenteral products, all raw materials, including the API and excipients, must undergo rigorous sterilization.
Methods: Common sterilization methods include autoclaving, filtration, and aseptic processing to ensure aseptic conditions throughout the manufacturing process.
3. Manufacturing Process:
Preparation: The formulation is prepared, and various components are weighed and measured precisely.
Mixing: The ingredients are mixed under controlled conditions to achieve a homogeneous blend, ensuring uniform distribution of the API and other components.
Filtration: The solution is then filtered to remove any particulate matter and ensure clarity.
Filling: The sterile drug solution is filled into vials, ampoules, or other suitable containers in a controlled environment, maintaining sterility.
4. Sterilization of Final Product:
Terminal Sterilization: The final product, in its container, undergoes terminal sterilization methods like autoclaving or gamma irradiation to eliminate any microbial contamination that may have occurred during the manufacturing process.
University Institute of Pharmaceutical Sciences is a flag bearer of excellence in Pharmaceutical education and research in the country. Here is another initiative to make study material available to everyone worldwide. Based on the new PCI guidelines and syllabus here we have a presentation dealing with "Aseptic requirements for parenteral products".
Thank you for reading.
Hope it was of help to you.
UIPS,PU team
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”
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”
Validation of aseptic process should be designed to provide assurance through appropriate testing that all phases and activities of the process remain sterile and it is controlled within the predetermined parameters.
Drug product, container, and closure are subject to sterilization separately, and then brought together.
In this presentation from, Janeen Santorosa discusses the best practices for harmonization of GMP auditing, domestic and international regulations for supplier auditing, integration of risk-based practices, and supplier audit practice tools.
In this presentation from IVT's 4th Annual Validation Week EU, Paul Pluta, discussed the differences between the traditional approach to cleaning validation and the lifecycle approach, applicable regulatory guidance, current industry trends, the necessary phases of the lifecycle approach (design and definition, cycle development, validation, and implementation), how to continously monitor the process, change control, and common obstacles to compliance.
This session from the Institute of Validation Technology's 14th Annual CSV Conference looks at B. Braun’s journey in moving from an in-house validated training tracking system to learning management in the cloud.
In this session from the Institute of Validation Technology's Validation Week Europe, Kurtis Epp and John Kandl discuss how to implement QbD to all three stages of process validation.
This presentation from the Institute of Validation Technology's first annual Validation and cGMP Compliance Week Singapore discusses the obstacles to quality such, the key components to improve quality, and the tools for strategic teamwork.
Regulatory inspections have had a significant impact on the number of drug shortages and companies facing adverse regulatory actions.
Review of the inspection trends can be useful in assessing the regulatory status of your own company and help aid in the preparation for upcoming inspections. This session from IVT's Contamination and Control Week provides an in-depth, practical look at some of the recent Warning Letters and discusses current trends.
The Validation Master Plan is a a valuable opportunity to provide an overview of your company’s validation process, including organization structure, content, and planning.
Regulatory guidelines on stability testing are mainly designed to address studies that will be applied to support NDAs. However, in any pharmaceutical development program, a number of other stability studies are also required, for example, to help select appropriate formulations and to support regulatory applications for clinical programs. This session from the Institute of Validation Technology's Stability Programs Forum outlines a number of examples of early development stability studies.
This presentation from IVT's 4th Annual reviews what to do when you have an exception, critical vs. non-critical exceptions, and learning how to prevent exceptions.
This presentation from IVT's 4th Annual Validation Week Europe provided a thorough explanation of developing a gap analysis, areas in validation that are issues of concern, and FDA expectations of a manufacturer's gap analysis.
In this presentation from Validation Week Europe, Karen Ginsbury discusses the rigors, preparations, strategies, and the do's and the don't of the FDA Inspection process.
This workshop examines the approach to Continued Process Verification and demonstrating that your product and process are operating in a state of control and continue to do so over the life of the product. Without any prior coordination, the theme was elaborated by the afternoon speakers once the conference itself was underway. The concept of “step up step down” for adjusting the level of product scrutiny both for process parameters monitoring and for sampling and testing quality attributes was explored and developed.
In this presentation from IVT's GMP Week, Journal of Validation Technology Editor-in-Chief, Paul Pluta, Ph.D., asks "can compliance be improved by using quality by design [QbD] concepts?" Pluta discussed the QbD application, development of validation master plans, and the lifecycle approach to process validation. Furthermore, he discusses how to incorporate these essential parts of the validation process to implement effective, and efficient, compliance by design into the quality system.
This presentation from IVT's 2nd Annual Validation Week Canada covers the 2011 FDA Process validation and the subsequent statistical processes. Statistics in process validation is introduced as well as the integration with six sigma and solutions to common mistakes.
A comprehensive presentation on GMP systems and integration. This includes validations, vendor qualification, preventative maintenance, audits, CAPA, and utilization of system results.
This presentation from IVT Network's Method Validation Conference covers required and suggested regulations and guidances for biological process specifications. It also covers dosage form considerations and specifications for other components.
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
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
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!
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
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.
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
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
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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
Understand the Evolving Regulations for Aseptic Cleaning and Environmental Monitoring
1. Session 5 • Understand the Evolving
Regulations for Aseptic Cleaning and
Environmental Monitoring
IVT’s Contamination Control Week
June 25-27, 2012
Boston, Massachusetts
2. For more information on aseptic cleaning and environmental monitoring,
please visit www.ivtnetwork.com.
Use the promo code SLIDE1 for a 10% discount on a membership!
3. CONTACT INFORMATION
for Course Leader:
David Vincent, CEO
Validation Technologies, Inc.
San Diego, CA
Office: 800-930-9222
Fax: 858-638-5532
Email: davidv@validation.org
4. Topics Addressed
§ Regulatory requirements & expectations
§ Potential sources and types of microbial
contamination
§ Implementation of microbial control
measures
§ Disinfection/Sanitization
§ Environmental monitoring
6. CFR 21- 211.113 (a)
Control of Microbiological Contamination Microbial
“Appropriate written procedures, designed to
prevent objectionable organisms in drug products
not required to be sterile, shall be established.”
§ Control of bioburden
§ Absence of objectionable organisms
7. WHAT IS
CONTAMINATION?
§ There are two types of contamination.
Non-viable (Particulate)
– Air Filtration
– Materials shedding
Viable (Microbiological or Bioburden)
– Molds
– Bacteria
– Viruses
7
9. NONVIABLE
CONTAMINATION
§ This is any type of contamination that is not
viable. It is usually filterable. For example:
§ Dirt, sand, powders, etc.
§ Particulate
§ Debris
§ Molding flash
§ Chemical contamination such as crystals, etc.
§ Oils and Mold Release agents
§ Insect parts
§ Controlled room classifications are defined by
particulate contamination sizes and numbers.
9
10. What is Contamination
Control?
§ Contamination control is not simply a task or
function. It is a science and applied
technology that interacts continuously with all
products, processes, materials, equipment,
and personnel entering the manufacturing
areas.
11. Microbiological
Control
§ Identify possible sources of
contamination
§ Identify possible types of contamination
likely to occur
§ Implement and validate/qualify
preventative and control measures
13. Raw Materials/Excipients
§ Bioburden in raw materials and excipients
v natural vs synthetic products
v water activity level
§ Bioburden in water systems
v potable water, purified water, WFI
v biofilm
14. Equipment and Process
§ Process and Equipment § Carbon filters/DI
Design resins/membrane
§ Material/Surface filters
§ Unprotected storage tanks § Sampling/transfer
hoses
§ Back flow
§ Valves
§ Perforated heat exchangers
§ Dead legs
18. Facilities: Cleanroom
Classification
FS209 ISO 14644-1 Viable Ave Airflow
Cleanroom Cleanroom ≥0.5um Microbes Velocity Air
classification classification particles/m3 (cfu/m3) (fpm) changes/hr
100,000 8 3,520,000 100 5-10 5-48
10,000 7 352,000 10 10-15 60-90
1000 6 35,200 7 25-40 150-240
100 5 3,520 1 40-80 240-480
§ a- All classifications based on data measured in the vicinity of exposed materials/articles during periods of
activity.
§ b- ISO 14644-1 designations provide uniform particle concentration values for cleanrooms in multiple
industries. An ISO 5 particle concentration is equal to Class 100 and approximately equals EU Grade A.
§ c- Values represent recommended levels of environmental quality. You may find it appropriate to establish
alternate microbiological action levels due to the nature of the operation or method of analysis.
§ d- The additional use of settling plates is optional.
§ e- Samples from Class 100 (ISO 5) environments should normally yield no microbiological contaminants.
19. Equipment
and Process
§ CFR 211.63, “Equipment used in the manufacture,
processing, packing, or holding of a drug product shall
be of appropriate design, adequate size and suitably
located to facilitate operations for its intended use and
for its cleaning and maintenance.”
§ Q7A, 5.15, “Closed or contained equipment should be
used whenever appropriate. Where open equipment is
used, or equipment is opened, appropriate precautions
should be taken to minimize the risk of contamination.”
20. Equipment and Process
§ Equipment
v easily disassembled and cleaned
v use sanitary fittings and valves/avoid dead legs
v product contact surfaces resistant to corrosion
v store cleaned equipment in a sanitary condition
21. Equipment
and Process
§ Equipment flow and location
v no cross flow of clean and dirty and contaminated
equipment/materials
§ Process
v evaluate each step in a process for the potential of
microbial contamination
v use closed systems whenever possible
v open operations should be contained within HEPA
stations
22. Environment & Facility
§ Flooring and wall materials must be easily
cleaned
§ Surfaces must be resistant to chemicals,
abrasion, and flaking
§ Ensure concave coving at the junction of walls
and floors
§ Floors must be sloped toward the drain
§ Clean/sanitize floors daily
§ Cover floor drains when not in use
§ Avoid standing water
23. Environment & Facility
§ Evaluate traffic patterns and room capacity
§ Production and packaging areas need to be
under positive pressure
§ Establish and monitor operating parameters and
environmental controls
§ Use HEPA filtration systems
§ Clean up spills immediately
§ Cover air ducts, pipes, and light fixtures
§ Avoid build-up of dust and moisture
accumulation
26. Disinfection/Sanitization
Program
§ CFR211.56 (b)
“ There shall be written procedures assigning
responsibilities for sanitation and describing in
sufficient detail the cleaning schedules, methods,
equipment, and materials to be used in cleaning
the buildings and facilities; such written
procedures shall be followed.”
27. Preparation and Use of
Disinfectants
Preparation and Storage
• EC Guide, Annex 1,
“Disinfectants and detergents should be monitored for
microbial contamination: dilutions should be kept in
previously cleaned containers and should only be
stored for defined periods unless sterilised.
Disinfectants and detergents used in grade A and B
areas should be sterile prior to use.”
28. Current regulatory expectations
for use of disinfectants
Rotation
• EC Guide, Annex 1, 37
“Where disinfectants are used, more than one type
should be employed. Monitoring should be undertaken
regularly in order to detect the development of resistant
strains.”
• ISO Recommendation
• Industry Practice
29. Product Classification
§ Sanitizers
v proper use results in 99.9% (3 log) reduction of bacteria
v cannot handle soil; use on pre-cleaned surfaces
§ Disinfectants
v proper use results in 100% (> 4 log) reduction of bacteria and
yeast. Limited reduction for mold.
v most have surfactants/cleaning ability
§ Sterilants
v proper use results in 100% (> 6-7 log) reduction of all
microorganisms, including bacterial spores.
v require application on pre-cleaned surfaces
30. Disinfection efficacy
§ Suitability, efficacy & limitations of
disinfectant agents and procedures should
be assessed.
§ The disinfection program should include the
use of a sporicidal agent used according to a
written schedule and when environmental
data suggests presence of spore forming
agents (Baccilus spp.).
31. Disinfectant Efficiency
Most Resistant
Endospores
Mycobacteria
Fungal Spores
Small Non-enveloped viruses (polio, rotavirus, rabies)
Vegetative Fungal Cells
Enveloped Viruses (Herpes, Hepatitis B, Hepatitis C, HIV)
Vegetative Bacteria
Least Resistant
32. Equipment and bacteria
Even seemingly smooth
surfaces can harbor
bacteria !
Scanning electron micrograph of Listeria monocytogenes forming a biofilm
in soy on a stainless steel chip. Courtesy of Professor Amy Wong.
33. Cleaning/Sanitization
Program
An effective cleaning and sanitization
process is attained by:
§ Treatment with strong acids and bases
§ Use of high velocity hot water or steam
§ Use of detergents and/or sanitizers
§ Rinsing with high quality water (Purified or WFI)
§ Use of solvent rinses
§ Drying at elevated temperatures
34. Disinfectant Selection
§ Population and types of organisms
§ Spectrum of activity of disinfectant
§ EPA registrations
§ Method of application
§ Contact time
§ Nature and surface to be disinfected
§ Compatibility of surface with disinfectant
35. Disinfectant Selection
§ Corrosiveness of disinfectant
§ Organic compounds present on surface
§ Operator safety
§ Compatibility with cleaning agents
§ Planned rotation of disinfectants
§ Needed steps to avoid contamination of
pharmaceutical products by disinfectant
§ Need for residual bactericidal activity
36. Disinfectant Selection -
Other Factors to Consider
§ Quality, sterility, and stability of product
§ Ease of application
§ Cleaning ability
§ Supporting vendor documentation
§ Cost and availability
§ Factors that may affect performance (temp.,
organic matter, contact time, pH, etc…)
§ Regulatory expectations/regulations
37. Current regulatory expectations
for use of disinfectants
§ Disinfectants Qualification
v Studies to evaluate the effectiveness of the
disinfectants as they are used and prepared
v Studies to evaluate the storage conditions of
disinfectants for possible loss of efficacy
v Use of environmental isolates in the qualification
studies
v Neutralization studies
38. Disinfectant Qualification
- Studies
In-Situ
§ Use actually cleaning procedures
§ Monitoring pre and post cleaning at worst-case conditions/
document activities
§ Increased number of sample sites
§ Compare EM data before & after
In-Vitro
§ Surface Tests (use of coupons or pieces of equipment/
material)
§ Carrier Tests (AOAC method)
§ Use-Dilution Tests (modified AET )
40. Disinfectant Qualification
Surface Test
§ Preferred method by inspectors
§ No guidance document available
§ Must select types of surfaces (coupons)
§ Variable microbial challenge level
§ Quantitative method
§ Must select contact times (1-5-10 minutes)
§ Variable test conditions (wet vs dry)
§ Sampling/recovery technique (swab, rinse, contact
plate)
§ Need neutralization studies
41. Disinfectant Qualification -
User’s Approach/Decisions
§ Type of agent and materials/surfaces and sites
to be evaluated.
§ Testing protocol (In-vitro vs In-situ)
§ Types of challenge organisms
§ Contact times
§ Sampling methods (swab, rinse, or contact
plate)
44. Monitoring and
Trending
§ Establish an EM program
§ Employee training and monitoring
§ Enforce personal hygiene
§ Enforce cGMPs
§ Schedule regular PMs
§ Product bioburden testing/trending
§ Re-qualification vs on-going verification of
cleaning (bioburden and endotoxin)
§ Change control
45. EM Program
§ Regulatory requirement
§ Must be tailored to a facility
§ Must be manageable and efficient
§ Must be well documented
§ Must be defendable
§ Must not add possible sources of contamination
into the environment
§ Do not rely solely on EM data for assurance of
product quality
46. EM Program
EM is a tool to assist a company
manage the microbiological
control program
47. EM Program
Choice of Equipment
§ Active vs passive
§ Air and surface monitoring devices
§ Detection of potential problems must be
done in a timely manner
§ Sampling activities should not contribute to
contamination of the process
48. EM Program
Test Methods
§ EM procedures must be qualified
§ Use same methods used during qualification studies
§ Viable and non-viable monitoring
§ Use of specific media for fungi: is it really needed?
§ Monitoring for anaerobes: is it really needed?
§ Levels are established based on industry guidelines
and/or historical data
49. EM Program
Frequency and Sites
§ Depends on area being monitored
§ More intensive monitoring for “cleaner”
areas
§ Usually frequency is reduced once
qualification is complete
§ Trend towards continuous monitoring
§ Site selection: depends on room design,
activities, equipment and personnel flow
50. EM Program
Data Management
§ Results are retrospective
§ Useful information can be obtained by trending
data
§ Evaluate data based on Alert and Action Levels
§ Identify isolates
§ Frequent isolates should be maintained and used
in challenge studies
51. EM Program - Hot Topics
§ EM data linked to batch release
EC Annex 1, 5 “Where aseptic operations are
performed, monitoring should be frequent…
Results from monitoring should be considered
when reviewing batch documentation for finish
product release…”
§ EM requirements for non-sterile operations
§ Use of PAT and Rapid Methods
52. EM Program – Focus of
Regulatory Inspections
§ Create presentation describing program
v area classifications
v methods
v frequency
v rationale for choice of sites
v rationale for setting alert and action levels
v describe data management and trending
§ Create trend reports for each area
v tabular and graphical format
v trend by values and organisms
§ Create executive summary reports
v address deviations, adverse trends, CAPA