The document discusses analytical and sampling methods used for cleaning validation in the pharmaceutical industry. It describes specific and non-specific analytical methods, such as HPLC and TOC, and the validation criteria for such methods including specificity, range, accuracy, and precision. The document also outlines different sampling techniques used to collect residues from surfaces for analysis, including direct surface sampling, swab sampling, rinse sampling, and placebo sampling. It provides details on how to properly perform each sampling method and factors to consider.
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)
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)
Bioburden Validation Strategy for Cleaning Validationangelsalaman
This presentation is based on the article published by Pharmaceutical Technology (USA) entitled “BIOBURDEN METHOD SUITABILITY FOR CLEANING AND SANITATION MONITORING: HOW FAR WE HAVE TO GO?”, Aug 2010. by Angel L. Salaman-Byron
A short presentation on containments which is used for potent drug manufacturing facilities and labs also these are used in biotechnology industries.
Very useful for BSL facility and Oncology/Hormones/Esteroids manufacturing and research.
Bioburden Validation Strategy for Cleaning Validationangelsalaman
This presentation is based on the article published by Pharmaceutical Technology (USA) entitled “BIOBURDEN METHOD SUITABILITY FOR CLEANING AND SANITATION MONITORING: HOW FAR WE HAVE TO GO?”, Aug 2010. by Angel L. Salaman-Byron
A short presentation on containments which is used for potent drug manufacturing facilities and labs also these are used in biotechnology industries.
Very useful for BSL facility and Oncology/Hormones/Esteroids manufacturing and research.
Ipqc tests for sterile formulations are as follows :
Leakage Test
Clarity Test
pH
Particulate Matter Injection
SterilityTest
Pyrogen Test
Content Uniformity & Weight
Volume Filled
The tests For Sterile products are as per IP, BP & USP
Cleaning Validation Protocol for Cannabis Certificate Programs.docxNACPT Pharma College
The cannabis industry is rapidly growing in Canada, the world industry leader, and there is a lack of skilled workers in the cannabis space. According to the research performed by International Medical Cannabis Association in 2019, many growing cannabis Licensed Producers and related companies are struggling to find skilled workers in the space. Many individuals have a growing experience, but most do not have the appropriate education, credentials, and regulatory updates to be genuinely successful in the cannabis industry. Therefore, educational training is an essential and critical element in the cannabis space.
CLEANING VALIDATION for M.pharm and industry personabhishek pandey
YOU CAN EASY WAY TO UNDERSTAND A PROCESS AND ANLYTICAL METHOD OF CLEANING VALIDATION
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.[1] 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 and the quality of future products using the equipment, to prevent cross-contamination and as a GMP requirement.
The U.S. Food and Drug Administration (FDA) has strict regulation about the cleaning validation. For example, FDA requires firms to have written general procedures on how cleaning processes will be validated. Also, FDA expects the general validation procedures to address who is responsible for performing and approving the validation study, the acceptance criteria, and when revalidation will be required. FDA also require firms to conduct the validation studies in accordance with the protocols and to document the results of studies.The valuation of cleaning validation is also regulated strictly, which usually mainly covers the aspects of equipment design,cleaning process written, analytical methods and sampling. Each of these processes has their related strict rules and requirements. Regarding to the establishment of limits, FDA does not intend to set acceptance specifications or methods for determining whether a cleaning process is validated. But some limits that have been mentioned by industry include analytical detection levels such as 10 PPM, biological activity levels such as 1/1000 of the normal therapeutic dose and organoleptic levels.[2][3][4]
Cleaning Validation in the context of Active Pharmaceutical Ingredient manufacture may be defined as: "The process of providing documented evidence that the cleaning methods employed within a facility consistently controls potential carryover of product (including intermediates and impurities), cleaning agents and extraneous material into subsequent product to a level which is below predetermined levels".
Non-destructive testing or non-destructive testing (NDT) is a wide group of analysis techniques used in science and technology industry to evaluate the properties of a material, component or system without causing damage.
"This ppt also includes some notes in the slide so to see notes go to the view options and select notes page."
IPQC For Parenterals - By Kaleem PetkarKaleem Petkar
IN PROCESS QUALITY CONTROL (IPQC) means controlling the procedures involved in manufacturing of the dosage forms starting from raw materials purchase to dispatch of the quality product in ideal packaging
Thin layer chromatography technique - easier, cheaper.
Handling is easy. Used as an identification test also purity test. It comprises of stationary and mobile phase. There are various types of chromatography technique. TLC consists of three steps - spotting, development, and visualization. The Rf value is used to quantify the movement of the materials along the plate. Rf is equal to the
distance traveled by the substance divided by the distance traveled by the solvent. Its value is
always between zero and one. A TLC analysis might be summarized something like, "Using a silica
gel plate and ethyl acetate as the development solvent, unknown mixture X showed three spots
having Rf's of 0.12, 0.25, and 0.87". CThere are three components in TLC:
(1) the TLC plate (stationary phase), the development solvent (mobile phase), and the sample to be
analyzed (solute). In our experiment the TLC plate consists of a thin plastic sheet covered with a
thin layer of silica gel.
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- 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
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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
New Drug Discovery and Development .....NEHA GUPTA
The "New Drug Discovery and Development" process involves the identification, design, testing, and manufacturing of novel pharmaceutical compounds with the aim of introducing new and improved treatments for various medical conditions. This comprehensive endeavor encompasses various stages, including target identification, preclinical studies, clinical trials, regulatory approval, and post-market surveillance. It involves multidisciplinary collaboration among scientists, researchers, clinicians, regulatory experts, and pharmaceutical companies to bring innovative therapies to market and address unmet medical needs.
NVBDCP.pptx Nation vector borne disease control programSapna Thakur
NVBDCP was launched in 2003-2004 . Vector-Borne Disease: Disease that results from an infection transmitted to humans and other animals by blood-feeding arthropods, such as mosquitoes, ticks, and fleas. Examples of vector-borne diseases include Dengue fever, West Nile Virus, Lyme disease, and malaria.
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
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
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
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
Acute scrotum is a general term referring to an emergency condition affecting the contents or the wall of the scrotum.
There are a number of conditions that present acutely, predominantly with pain and/or swelling
A careful and detailed history and examination, and in some cases, investigations allow differentiation between these diagnoses. A prompt diagnosis is essential as the patient may require urgent surgical intervention
Testicular torsion refers to twisting of the spermatic cord, causing ischaemia of the testicle.
Testicular torsion results from inadequate fixation of the testis to the tunica vaginalis producing ischemia from reduced arterial inflow and venous outflow obstruction.
The prevalence of testicular torsion in adult patients hospitalized with acute scrotal pain is approximately 25 to 50 percent
Title: Sense of Smell
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 primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
Maxilla, Mandible & Hyoid Bone & Clinical Correlations by Dr. RIG.pptx
Cleaning validation
1. ANALYTICAL AND SAMPLING
METHODS FOR CLEANING
VALIDATION
(PQA-MQA-202T. Pharmaceutical Validation)
Presented by Guided by
T V Sarath Chandra Dr. Sudheer Moorkoth
170609008 Associate Professor
M Pharm I year (Sem II)
DEPARTMENT OF PHARMACEUTICAL QUALITY ASSURANCE
MANIPAL COLLEGE OF PHARMACEUTICAL SCIENCES
MAHE
1
2. Contents
Analytical Methods
Specific Methods
Non Specific Methods
Method Validation
Sampling Methods
Direct Surface Sampling
Swab Sampling
Rinse Sampling
Placebo Sampling
Recovery Studies
Summary
Reference
2
3. Analytical Methods
Specific Methods:
They are the methods that target a specific molecule or species and are designed so
that possible interferences are eliminated.
They are HPLC, Ion chromatography, Atomic Absorption and SDS PAGE etc.
The second way is to use a non specific method.
3
4. Non Specific Methods
They measure a gross property that results from contributors form a variety of
chemical species.
They are conductivity and total organic carbon (TOC).
This generally involves expressing property as if all the measured property is due to
target species.
If the amount calculated by this method is below acceptance criteria, then we can say
that residue is less than the acceptance criteria.
If the amount is above the acceptance criteria, then one should develop a specific
method or use a more robust cleaning procedure.
4
5. Method Validation
Analytical methods used for measuring residue in cleaning validation protocols should
be validated.
This includes evaluation of Specificity
Linearity
Range
Precision
Accuracy
LOD/LOQ
5
6. Specificity
Specificity is a measure of the validity of the result based on expected interferences.
Interferences may include changes in retention time, peak height, or peak shape (in
HPLC).
Methods such as TOC or an alkalinity titration are generally considered nonspecific
because, in most cases, there is more than one species that can contribute to the
measured property.
6
7. Range
Range is a series of values of the measured species or property over which the
analytical procedure was evaluated.
It is only necessary to assure that the procedure is valid over a range of expected
values.
LOD/LOQ
LOD is the assay value at which it is still possible to say that the material is present, but
it may be not possible to quantify with a specific value.
LOQ is the lowest assay value for which a reasonable confidence exists that the value is
precise.
7
8. Linearity
Linearity refers to the characteristic of the relationship of the measured property to
the level of analyte present.
Linearity is an indication that the measured signal is directly proportional to the
concentration of the analyte over the range.
Accuracy
Accuracy refers to the trueness of the measurements to known values.
This is determined by analysing known standards.
However, more accurate methods are preferred over less accurate methods.
8
9. Precision
Precision refers to the reproducibility of the method and is often measured by standard
deviation.
Simple precision is the reproducibility of the results in the same lab over a series of
replicate assays using the same operator, the same equipment, and usually on the same
day.
Intermediate precision is the reproducibility of results in the same lab using different
operators, different pieces of equipment, and generally done on different days.
Ruggedness is interlab reproducibility, involving reproducibility in different labs.
9
10. Sampling Methods
The sampling procedure refers to the selection of which surfaces are targeted for
collecting residues for measurements and to the method of collecting the residues
from the surface so that they can be measured
The sampling methods are
Direct surface sampling
Swab sampling
Rinse sampling
Placebo sampling
10
11. Direct Surface Sampling
Direct surface sampling involves an analytical instrument directly "applied to" the
cleaned surface.
The most common example of direct sampling is visual evaluation. In that case, the eye
is the means of both analysis and sampling.
The key items to consider:
Eyesight of the viewer: The viewer should have suitable vision, or such vision should
be correctable by glasses or contact lenses.
The available light for viewing: Particularly inside equipment, external lighting may
have to be introduced to adequately sample the surface.
It may also be helpful to use ultraviolet light (black lights) to assist in viewing
residues that may fluoresce under UV light.
11
12. The distance of the viewer from the surface: It is generally the case that the farther
away from the viewer, the less sensitive visual examination will be.
A surface 1 ft in front of you may appear dirty, while the same surface 12 ft away
may appear visually clean.
The angle of the Light and the viewer to the surface: These factors can also affect
whether a surface is rated clean or dirty.
The nature of the surface: This includes both the material of construction as well as
its surface texture, roughness and may be different for different residues.
12
13. The nature of the residue: One figure used in the literature for the dividing line
between visually clean and visually dirty is 4 µg/cm2.
Particulate residues, such as from powders, can produce visually dirty surfaces
levels considerably below 4 µg/cm2.
The availability of the surface: Surfaces that are readily visible can be easily
examined.
Other surfaces (such as the interior surfaces of ball valves) may require
disassembly of the equipment in order to examine them.
13
14. Swab Sampling
A swab is a fibrous material that is used to wipe a surface to remove residues from the
surface.
Typically, the swab is a textile fabric of some kind attached to a suitable handle.
The swab "head" (the fabric portion) is typically wetted with a solvent (water, an
organic solvent, or a mixture).
14
16. The nature of the swab: For microbiological swabbing, the swab head is generally
cotton fibres attached to a handle.
In some cases for microbiological sampling, the sampling head is made of
calcium alginate fibres.
Microbiological swabs should be sterilised prior to use.
The most common are made of a knitted polyester fabric head, which is then
attached to a plastic handle by a suitable welding process so that adhesives are
avoided.
16
17. Use of solvent for wetting and desorption of the swab: The solvent used should be
appropriate for assisting in the removal of the residue from the surface.
In addition, it should be compatible with any subsequent analytical procedure.
The number of swabs used: Generally, only one or two swabs are used per target
surface area.
The concept behind using more than one swab is to increase the recovery of the
target residue.
One swab cannot pick up all of the residues, but it will leave behind a finite
of solvent, which probably contains some of the target residue.
A second swab will pick up an additional amount of the target residue.
17
18. The surface area swabbed: The surface area typically swabbed per site varies from
about 25 sqcm to about 100 sqcm.
There is no number in terms of what is best. One is to use a template placed over
the surface to be sampled.
Swabbing location: The locations selected for swabbing are generally those locations
that are the most difficult to clean, representative of different material and
representative of different functional locations.
It is most important to identify those locations that are the most difficult to clean.
If these locations are swabbed, and if the residues in these locations are
then residues in other locations should also be acceptable.
18
19. The swabbing pattern: This includes the pattern the swab head makes as it goes
across the surface, whether the swabbed pattern is repeated at a 90" angle, as well
any "flipping" of the swab head.
Swab handling and transport: Proper handling will depend to a given extent on the
analytical procedure utilized.
If the analytical method is TOC, then extreme care needs to be used in
19
20. Rinse Sampling
Rinse sampling involves using a liquid to cover the surfaces to be sampled.
There are two cases of this: single point final rinse sampling and a sampling rinse
separate and distinct from the final rinse.
There are two objections for the FDA.
The water which is collected after the rinsing is containing the potent drug in
unacceptable levels, still it is meeting the USP specifications.
The rinse water is examined for the target residues, not the equipment.
20
21. Single point Final Rinse Sampling
In single point final rinse sampling, a sample is obtained at the end of the final rinsing
process.
If the rinsing medium is water, then it is a water sample; if a solvent is used for the
rinse, then it is a solvent sample. The volume of rinse sample taken will depend on
analysis done but it is commonly 500-1000ml.
This is the most common method of rinse sampling.
21
22. Separate Sampling Rinse
A separate and distinct rinse is performed with a fixed amount of sampling
after the process rinsing is completed.
The only function of the sampling rinse is to sample the equipment for analytical
purposes.
This rinse sampling procedure can either be done on a batch or continuous basis.
The sampling solution is different from the washing solution.
The solution used for the sampling purpose will have a fixed volume.
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23. PLACEBO SAMPLING
Placebo sampling involves manufacturing a placebo batch of the subsequently
manufactured product in the cleaned equipment.
Following manufacture of the placebo product, the placebo is analysed for the target
residue.
For example, the active in the drug product that was cleaned from the equipment. If it
is having X ppm of the target residue then it is assumed that there is contamination of
X ppm.
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24. Recovery Studies
In a recovery study, a fixed amount of the target residue is spiked onto a model
surface, the surface is sampled with the sampling procedure.
The amount of target residue is then expressed as a percentage of the amount spiked
to give the "percent recovery."
This percentage must then be used to adjust the analytical results obtained to
accurately reflect potential contamination.
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25. Summary25
The analytical methods include specific and non specific methods.
Specific methods give the results specifically without interferences. Non specific
methods give results which include all the results of targeted species.
The sampling methods include direct observation sampling which involves eye
observation.
Swab sampling includes the use of swab through which the sample is analysed.
Rinse sampling includes analysing the wash solution for contaminants.
Placebo sampling includes analysing the placebo which is without the drug for the
contaminants.
26. Reference
LeBlanc D. Validated cleaning technologies for pharmaceutical manufacturing. 2nd
ed. new york: crc; 2000. p.151-190.
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