A review on role of cleaning validation protocol in Pharmaceutical manufacturing unit
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大扫除时突出卫生委员的解决能力作文英文版As the designated health committee member in charge of the annual spring cleaning, I take pride in my problem-solving abilities. The task of cleaning and organizing the entire school may seem daunting to some, but I approach it with a positive attitude and a clear plan in mind.One of the biggest challenges I face during the spring cleaning is coordinating with my fellow committee members to ensure that each area of the school is thoroughly cleaned and maintained. I have learned that effective communication and delegation are key to a successful cleanup operation. By assigning specific tasks to each member and setting clear deadlines, we are able to work efficiently and make sure that no corner is left untouched.In addition to coordinating with my team, I also have to address any unexpected issues that may arise during the cleaning process. Whether it's a broken mop or a spill that needs immediate attention, I am always prepared to handle any situation that comes my way. My quick thinking and resourcefulness have helped me overcome numerous obstacles and ensure that the spring cleaning is completed on time.Overall, being the health committee member in charge of the annual spring cleaning has taught me valuable lessons in leadership, teamwork, and problem-solving. I am proud of the work that my team and I have accomplished, and I look forward to taking on new challenges in the future.大扫除时突出卫生委员的解决能力作为一名负责每年春季大扫除的卫生委员,我以自己的解决问题能力为荣。
an environmental activity 听后转述-回复[An Environmental Activity: Clean Up the Beach]Introduction:Beaches are often considered as picturesque landscapes with pristine blue waters and soft sandy shores. However, due to human activities and irresponsible behavior, many beaches around the world have become polluted and littered with garbage. To address this issue and raise awareness about the importance of protecting our beaches, an environmental activity was organized called "Clean Up the Beach." This article will describe the step-by-step process of the event, from planning to execution and its impact on the environment.1. Planning:The planning stage involved identifying the beach that needed cleaning, securing necessary permits from local authorities, and setting a date for the event. A team of environmental enthusiasts collaborated with local organizations, including environmental NGOs and tourism boards, to organize the activity successfully. A budget was created to cover the expenses of necessary equipment and materials required for the beach clean-up, such as gloves, trashbags, and transportation for volunteers.2. Promoting the Event:In order to maximize participation and impact, the event was widely promoted through various channels. Social media platforms, community noticeboards, and local newspapers were utilized to spread the message. Eye-catching posters highlighting the pollution problem were placed in strategic locations, encouraging individuals and groups to join hands and make a difference. The environmental activity gained significant attention and generated enthusiasm among the locals and tourists alike.3. Volunteer Recruitment:In the weeks leading up to the event, efforts were made to recruit volunteers. The organizers reached out to schools, universities, local clubs, and businesses to encourage their members to participate. Public presentations were conducted to educate the community about the detrimental effects of beach pollution and the importance of environmental conservation. The response was overwhelming, with individuals and groups expressing their eagerness to be a part of this significant environmental activity.4. Safety Precautions:Ensuring the safety of the volunteers was of utmost importance. Guidelines were developed, emphasizing the importance of wearing appropriate clothing, such as hats, sunscreen, and closed-toe shoes, to protect against potential hazards. First aid kits, as well as trained medical personnel, were present on-site in case of any injuries. Additionally, safety signage and instructions were prominently displayed to keep everyone informed about potential risks during the clean-up process.5. The Clean-Up Day:On the designated day, all the volunteers gathered at the specified beach. They were provided with gloves and trash bags to collect and categorize the litter, such as plastic bottles, food wrappers, and cigarette butts. Several teams were formed, each responsible for a designated area of the beach. The organizers ensured that there were designated areas for recyclable and non-recyclable waste, promoting sustainable waste management practices.6. Education and Awareness:Throughout the clean-up activity, experts and volunteers engaged in discussions about the harmful effects of pollution on marine life,the importance of recycling, and steps individuals can take in their daily lives to reduce waste. Education stations were set up to provide information about local marine ecosystems, the impact of pollution, and ways to support ongoing conservation efforts. The event aimed not just to clean the beach but also to instill a sense of responsibility and awareness among the participants.7. Waste Disposal and Follow-Up:Once the clean-up activity was completed, trucks were organized to transport the collected waste to appropriate disposal facilities. All recyclable materials were separated for recycling, whilenon-recyclable waste was disposed of in an environmentally responsible manner. A follow-up report was compiled, highlighting the amount and types of waste removed, the number of participants, and the overall impact of the activity. This report was shared with the community, local authorities, and environmental organizations to showcase the achievement and further advocate for the importance of responsible waste management.Conclusion:The "Clean Up the Beach" environmental activity brought together individuals, communities, and organizations to address the issue ofbeach pollution. Through careful planning, effective promotion, and active participation, the event successfully raised awareness about the impact of human activities on the environment. The collaborative effort of cleaning the beach and educating participants left a lasting impression on everyone involved, encouraging them to make sustainable choices in their daily lives and serve as environmental stewards. By empowering communities and promoting responsible environmental practices, such activities contribute to creating a cleaner and healthier planet for future generations.。
2021年职称英语阅读判断试题及答案:卫生类An Observation and ExplanationIt is worth looking at one or two aspects of the way a mother behaves towards her baby. The usual fondling, cuddling and cleaning requite little comment, but the position in which she holds the baby against her body when resting is rather revealing. Careful studies have shown the fact that 80 per cent of mothers hold their infants in their left arms, holding them against the left side of their bodies. If asked to explain the significance of this preference most people reply that it is obviously the result of the predominance of right-handedness in the population. By holding the babies in their left arms, the mothers keep their dominant arm free for manipulations. But a detailed analysis shows that this is not the case. True, there is a slight difference between right-handed and left-handed females; but not enough to provide an adequate explanation. It emerges that 83 per cent of right-handed mothers hold the baby on the left side, but so do 78 per cent of left-handed mothers. In other words, only 22 per cent of the left-handed mothers have their dominant hands free for actions. Clearly there must be some other, less obvious explanation.The only other clue comes from the fact that the heart is on the left side of the mother's body. Could it be that the sound of her heart-beat is the vital factor? And in what way? Thinking along these lines it was argued that perhaps during its existence inside the body of the mother the unborn baby gets used to the sound of the heart beat. If this is so, then the re-discovery of this familiar sound after birth mighthave a calming effect on the infant, especially as it hasjust been born into a strange and frighteningly new world. If this is so then the mother would, somehow, soon arrive at the discovery that her baby is more at peace if held on the left against her heart, than on the right.1. We can learn a lot by observing the position in whicha mother holds her baby against her bodyA. RightB. WrongC. Not mentioned2. Most left-handed women feel comfortable by holding their baby in their left arm and keep the right arm freeA. RightB. WrongC. Not mentioned3. The number of right-handed mothers who hold the baby on the left side exceeds that of left-handed ones by 22%A. RightB. WrongC. Not mentioned4. The fact that most left-handed mothers hold the baby on their left side renders the first explanation unsustainableA. RightB. WrongC. Not mentioned5. The fact that the heart is on the left side of the mother's body provides the most convincing explanation of allA. RightB. WrongC. Not mentioned6. A baby held in the right arm of its mother can be easily frightenedA. RightB. WrongC. Not mentioned7. The writer's explanation of the phenomenon is supported by the fact that babies tend to be more peaceful if held in their mothers' left arms than in the right armsA. RightB. WrongC. Not mentionedKEY: ACBABCA。
cleaning monitor作文Cleaning MonitorAs the cleaning monitor of our classroom, I take pride in ensuring a tidy and hygienic environment. Each day, I lead the team in sweeping the floors, dusting the desks, and wiping the blackboard clean. We also organize the books and papers to maintain an orderly workspace.Monitoring the cleanliness is not just about physical tidiness; it's about fostering a culture of responsibility and discipline. It teaches us to appreciate the value of hard work and the importance of maintaining a clean environment. Through this role, I have learned the significance of leading by example and encouraging others to pitch in.The experience has been rewarding. Seeing the classroom sparkle under our efforts, knowing that we have contributed to creating a better learning environment for everyone, brings a sense of fulfillment. I am grateful for this opportunity to serve as a cleaning monitor and hope to continue inspiring others to value cleanliness and responsibility.翻译:清洁监督员作为我们教室的清洁监督员,我自豪地确保了一个整洁且卫生的环境。
read the installation andoperating instructions before you use the dishwasher for the first time.Switch on the appliance the dishwasher starts...Switch off the appliance that’s it...Press the on/off switch, the cycle time for the programme selected appearsPress the on/off switch whenthe indicator shows 0 (programme end)Pour in the water/special saltPour in the rinsing agentPour in the cleaning agentSelect the programme S u m m a r y o f i n s t r u c t i o n s f o r d i s h w a s h e rRead off the setting ...Dissolves limescale (not required for set value 0!)Only before using the dishwasher for the first time pour approx. 1 l /1 1/4 pt water into the salt opening.Everything is sparkling clean ...Refill whenever level indicator is light!Press mark 1,Very dirty dishes, a lot of detergent ...If required, open the lid (press the Warning,Quick, economical or intensive ...Programme overviewThis overview lists the max. possible number of programmes. The programmes supplied with your appliance are indicated on the fascia.The programme data are values measured in the laboratory in compliance with Standard EN 50242.Deviations is practice are possible.1121,6021181401,0514–720,801512300,7010–95-1451,15-1,5011-19–45_70_55_ /6540_Auto Intesive Quick GentleAdditional programmes **Increased flexibility ...Time reduction/time saving ...shortens thecleaning time, reduces the drying.** on some modelsLower basket cleaning ...Only the crockery in the h.Time selection...switches on as soon as you press the time selection button:Alters the programme start in hourly stepsInsert lower arm ...Screw in upper arm Eliminating minor faults yourself ...... Self–help pays!Possible CauseDevice does not work/stops Supply fitting not openSupply hose kinked Open supply fitting.Lay supply hose without kinks.2. Clean filter in the water connection.3. Flow rate must be min. 9 l/min when If the flow rate is less, replace the RemedyToo little cleaning product Discoloration caused by food colourings (tomato sauce)Follow manufacturer’s specifications Discoloration is quite safe; fades afterResidual water in the device Waste-water pump blockedProgramme not yet ended Clean waste-water pump (see above).Switch on appliance and close orterminate programme (see Terminatingthe programme).Fault Possible CauseStains and streaksMilky residues on dishes(can be removed)Rinse aid dosage too high / too lowMilky film, glasses cloudy /dull (cannot be removed)Dishes not cleanSand or grainy residueson dishesUtensils are situated too close to eachother or on top of each otherToo little cleaning productUnsuitable programme selectedSpray nozzles blockedFilters dirty, not installed securely。
清理蓝藻的工人,作文英文回答:Cleaning up blue algae is a crucial task that requires dedicated workers to ensure the safety of water bodies. Blue algae, also known as cyanobacteria, can produce harmful toxins that pose a threat to the environment and public health. Therefore, the role of workers in cleaning up blue algae is of utmost importance.First and foremost, workers involved in cleaning up blue algae must be equipped with the necessary knowledge and training to identify and handle the algae safely. They should be aware of the potential health risks associated with exposure to blue algae and the proper safety protocols to follow while carrying out their tasks.Furthermore, the cleaning process often involves the use of specialized equipment and tools to remove the algae from the water. Workers may need to use nets, vacuums, orother mechanical devices to physically remove the algae from the affected area. In some cases, chemical treatments may also be necessary to eliminate the algae and prevent its regrowth.In addition to the physical cleaning of the water, workers may also be responsible for monitoring and testing the water quality to ensure that it is safe for human and animal consumption. This may involve collecting water samples and conducting various tests to assess the levels of toxins and other contaminants present in the water.Overall, the work of cleaning up blue algae is both challenging and essential. It requires a dedicated team of workers who are committed to preserving the health and integrity of our water systems.中文回答:清理蓝藻是一项至关重要的任务,需要专门的工人来确保水体的安全。
When it comes to grading papers, especially in a middle school setting, its essential to approach the task with a keen eye for detail and a fair, unbiased perspective. Here are some key points to consider when writing an essay on the topic of grading papers for seventh graders:1. Importance of Accuracy: Begin by emphasizing the importance of accuracy in grading. Every mark given can significantly impact a students confidence and understanding of their academic performance.2. Fairness: Discuss the concept of fairness in grading. Its crucial to ensure that each student is evaluated based on the same criteria to maintain an unbiased grading system.3. Time Management: Mention the time constraints that teachers often face when gradinga large number of papers. Effective time management is key to ensuring that each paper is given the attention it deserves.4. Use of Rubrics: Explain how using rubrics can help standardize the grading process. Rubrics provide clear guidelines for what is expected in an assignment, making it easier for both teachers and students.5. Feedback: Highlight the importance of providing constructive feedback. Students should not only know their grades but also understand how they can improve.6. Technology in Grading: Discuss how technology can assist in the grading process. Tools like online grading systems can make the process more efficient and organized.7. Student Involvement: Suggest that involving students in the grading process can be beneficial. Peer review, for example, can help students learn from each other and understand different perspectives.8. Continuous Learning: Conclude by stating that grading is not just about assigning a score its also about continuous learning for both the teacher and the student. Teachers can learn about their students strengths and weaknesses, while students can learn from their mistakes.Remember to structure your essay with a clear introduction, body paragraphs that elaborate on each point, and a conclusion that summarizes the main ideas. Use examples where appropriate to illustrate your points and make your essay more engaging.。
清洁英文作文技巧2022Writing an effective English essay on the topic of cleaning requires a blend of language skills, organization, and clarity. Here are some tips to help you craft a compelling essay:1. Understand Your Audience: Before you begin writing, consider who will be reading your essay. Are they familiar with the topic of cleaning, or will you need to provide some background information? Tailor your language and examples accordingly.2. Develop a Clear Thesis Statement: Your thesis statement should clearly state the main point or argument of your essay. In this case, it could be something like, "Effective cleaning techniques are essential for maintaining a healthy and organized environment."3. Organize Your Ideas: Divide your essay into clear sections, such as introduction, body paragraphs, andconclusion. Each paragraph should focus on a single main idea, with supporting evidence and examples.4. Use Descriptive Language: When describing different cleaning techniques or products, use descriptive language to paint a vivid picture for your readers. This will help them better understand your points and engage with your essay.5. Provide Evidence and Examples: Support your arguments with evidence and examples. This could include scientific studies on the effectiveness of certain cleaning methods, real-life anecdotes, or expert opinions.6. Address Counterarguments: Anticipate potential counterarguments to your thesis and address them in your essay. This demonstrates critical thinking and strengthens your overall argument.7. Edit and Proofread: Once you've written your essay, take the time to edit and proofread it carefully. Look for any grammatical errors, awkward phrasing, orinconsistencies in your argument.8. Conclusion: Summarize your main points and restate your thesis in the conclusion. Leave your readers with a final thought or call to action related to the importance of effective cleaning practices.By following these tips, you can write a compelling English essay on the topic of cleaning that effectively communicates your ideas to your audience.。
In2017,the English composition for the Henan province exam likely focused on topics that were relevant and engaging for high school students.Here are some possible themes and a sample outline for a composition that could have been part of the exam:Title:The Importance of Environmental ProtectionIntroduction:Briefly introduce the topic of environmental protection.State the importance of the issue in the context of global challenges.Body Paragraph1:The Current State of the EnvironmentDiscuss the various environmental issues such as pollution,deforestation,and climate change.Provide examples of how these issues are affecting different parts of the world.Body Paragraph2:The Impact on Human LifeExplain how environmental degradation affects human health,quality of life,and economic stability.Mention the consequences of inaction,such as increased health problems and natural disasters.Body Paragraph3:Individual and Collective ActionsSuggest ways in which individuals can contribute to environmental protection,such as reducing waste,conserving energy,and supporting sustainable practices.Discuss the role of governments and international organizations in creating policies and regulations to protect the environment.Body Paragraph4:The Role of TechnologyHighlight technological advancements that can help in environmental conservation,such as renewable energy sources and efficient waste management systems.Discuss the potential of technology to mitigate the effects of climate change and promote sustainable development.Conclusion:Summarize the main points discussed in the essay.Emphasize the urgency of taking action to protect the environment for the sake of future generations.End with a call to action,encouraging readers to contribute to environmental protection efforts.Sample Composition:The Importance of Environmental ProtectionIn recent years,the issue of environmental protection has become a global concern.The Earth is facing numerous challenges,from air and water pollution to the rapid depletion of natural resources.It is crucial that we address these issues to ensure a sustainable future for all.The current state of the environment is alarming.Deforestation,for instance,has led to a loss of biodiversity and contributes to climate change by reducing the planets ability to absorb carbon dioxide.Similarly,pollution from industrial activities and vehicles has led to a decline in air quality,affecting the health of millions of people worldwide.The impact of environmental degradation on human life is significant.Poor air quality can lead to respiratory diseases,while water pollution can result in waterborne illnesses. Moreover,the effects of climate change,such as rising sea levels and more frequent natural disasters,pose a threat to human settlements and food security.Individuals and collectives have a role to play in environmental protection.Simple actions such as recycling,conserving water,and using public transportation can make a ernments and international organizations must also step up by implementing policies that promote sustainable development and reduce environmental harm.Technology can be a powerful tool in our fight against environmental degradation. Renewable energy sources,such as solar and wind power,offer a cleaner alternative to fossil fuels.Innovations in waste management,such as recycling technologies and biodegradable materials,can help reduce the amount of waste that ends up in landfills.In conclusion,the importance of environmental protection cannot be overstated.It is a responsibility that falls on each of us,as well as our governments and global institutions. By taking action today,we can ensure a healthier and more sustainable world for future generations.Let us all contribute to this noble cause and make our planet a better place to live.。
Microline Surgical Case Study: Mercy Hospital CadillacSeptember 2009The Challenge:Mercy Hospital Cadillac in Cadillac, Michigan is a non-profit, acute care hospital providing health care to more than 80,000 residents across seven counties. In 2009, Thompson Reuters named the facility one of the nation's 100 Top Hospitals for its achievements in clinical outcomes, patient safety, patient satisfaction, financial performance and operational efficiency.The surgeons at Mercy Hospital Cadillac were using a broad range of instruments from various manufacturers to cut, grasp, dissect and seal tissue during laparoscopic procedures. Even within a single manufacturer’s line, surgeons were using different generations of the same product. This presented a number of administrative, clinical, financial and safety issues.“It was absolute chaos - a hodge podge of anything and everything,” said Rachel Chase, RN, operating room manager for Mercy Hospital Cadillac. “There wasn’t a standard set so it was very difficult to ensure that each physician got what he or she needed for a case.”With so many different instruments, the Central Supply team had to pull and wrap individual trays based on the preferences of each surgeon. In the OR, the staff had a difficult time identifying the correct instrument when a surgeon requested it. This increased time and labor, disrupted the flow of surgery and decreased staff and surgeon satisfaction.“Because there wasn’t a standard set, it was very difficult to service the physicians with what they really wanted and needed,” said Chase.Instrument maintenance was a challenge as well. The wide variety of instruments required different cleaning procedures so there was confusion among the staff on how to clean them. According to Chase, some earlier instruments did not feature a cleaning port so the staff never really knew whether or not they were cleaned properly.“We just didn’t have the knowledge or the employees to maintain and check the functionality of the equipment,” said Deb Lindsey, Central Supply Manager Mercy Hospital Cadillac.The electrocautery devices proved the most challenging to maintain, which presented a patient safety concern. The staff had a difficult time evaluating the instruments to ensure the insulation was intact. If the insulation was damaged, there was the potential for electrical energy to spread beyond the intended areawithin the patient’s body, causing inadvertent thermal damage to surrounding tissue.Compounding the issue, the components for the electrocautery devices were sent to a reprocessor for reinsulation. Because the reprocessor reinsulated components from many different hospitals, Mercy Hospital Cadillac never knew if they were receiving back their own components and how many times the components that they were receiving had been used and reinsulated.“Luckily we never had any patient injuries but the potential was always there,” said Chase.The other laparoscopic instruments were sent back to their respective manufacturers for repair. In some cases, the turnaround time was so long that the staff at Mercy Hospital Cadillac had to reschedule surgeries because they did not have the correct instruments in-house. In other cases, surgeons would have to use earlier generation instruments that did not completely meet their needs. All of these issues increased costs for the hospital - costs associated with having to purchase and repair the instruments, as well as the time and labor required to manage and maintain them.The SolutionIn 2002, Mercy Hospital Cadillac found a solution when they met with a representative for Microline. He proposed a single line of laparoscopic instrumentation and a tip replacement program that would address the hospital’s many challenges.The Microline reposable laparoscopic surgical system is comprised of the ReNew™ universal reusable hand piece and a wide variety of disposable tips for tissue cutting, grasping and dissecting. This reposable system offers the clinical and economic benefits of a fully reusable instrument combined with the quality and precision of a disposable instrument. The scissor tips and electrocautery probes are changed after every case, while the grasper and dissector tips can be used many times before they must be discarded, providing a significant cost savings over single-use devices.“We realized that having one handle that could be used with a wide variety of tips would provide a huge cost savings all around,” said Chase.“Another great benefit is that we can add and remove tips as the technology advances so that we’re always meeting the changing needs of our physicians,” said Lindsey.Under the tip replacement program, Microline Pentax replaces all of Mercy Hospital Cadillac’s reusable grasper and dissector tips with new tips on a monthly basis. A technician visits the facility each month to inspect the quality of the handles and tips, which includes a quality check of the electrocautery device insulation. In addition, Microline has trained Mercy Hospital Cadillac’s Central Supply team on how to inspect the condition of the instruments, enabling them to perform assessments between procedures.“We always know that the handles and tips are in good working order and we never need to worry about not having what we need for a case,” said Chase.According to Chase and Lindsey, they had no problem transitioning the surgeons to the Microline system.“Microline has such great products that the surgeons were happy to switch,” said Lindsey. “They’ve found the handles and the tips to be well constructed and dependable. Another plus is that the tips are interchangeable, so they can multitask with the same instrument.”The single system has greatly improved workflow for the Central Supply staff. Since surgeons now use a single product line versus products from a variety of manufacturers, the staff now counts, assembles and wraps standard instrument trays that can be used across multiple procedures and specialties. They take photos of the standard trays to ensure that they are assembled the same way every time, streamlining the process and ensuring the surgeons have exactly what they need for each case.“The continuity of having the same instruments for every one of the surgeons has been a blessing,” said Lindsey. “Our productivity has increased since we no longer have to pull everything separately. When a set is wrapped and complete it is ready to go.”This standardization benefits the staff in the OR as well.“There are no longer any arguments about who gets what set because it is all the same and it all works extremely well,” said Chase. “It is much more efficient to have a standard tray because you know exactly where things are when you’re reaching for them in the OR.”The Microline instruments and program has simplified Mercy Hospital Cadillac’s cleaning and maintenance regimen. Since the surgeons are using a single instrument line, the technicians follow the same process to clean all of the components. According to Lindsey, the resposable design is easier to dissemble and clean, saving time and facilitating proper hygiene. And because the instruments are durable, they require minimal repairs.According to Chase and Lindsey, there has been a patient safety benefit as well. Since the handles and tips are regularly inspected and replaced, surgeons are always using the highest quality instrumentation. And since the electrocautery tips are replaced after every use, there is less risk that the insulation will become compromised, minimizing the danger of inadvertent tissue damage.“Patient safety is one of the greatest benefits,” said Lindsey. “If an instrument does not pass the quality test, there is a one-day turnaround to replace it.” Another key benefit is Microline’s exceptional customer service.“From ordering all the way through to in-servicing the process is worry-free,” said Lindsey. “Our representative is awesome – he’s always there to make sure that we have what the surgeons want – the convenience is wonderful.”In closing, Chase states, “All of our struggles are gone. Microline has met all of our needs 10 fold – patient safety, surgeon satisfaction and staff/technician satisfaction. I just can’t say enough.”# # #。
2021年英语6月四级作文题目Title: 2021 June CET-4 Writing TopicIn the June 2021 CET-4 exam, one of the writing topics given to students was about the importance of environmental protection. Students were asked to discuss the reasons why it is important to protect the environment and the role that individuals can play in this effort. This topic is particularly relevant in today's world where environmental issues like pollution, climate change, and biodiversity loss are becoming increasingly prominent.There are several reasons why it is crucial to protect the environment. Firstly, a clean environment is essential for the health and well-being of all living beings. Pollution from various sources such as factories, vehicles, and agriculture can have harmful effects on human health, leading to respiratory problems, skin diseases, and even cancer. Protecting the environment also ensures the availability of clean air and water, which are vital for sustaining life on Earth.Secondly, environmental protection is necessary for preserving the natural resources that we rely on for our survival. Resources like water, land, and forests are finite, and theirdepletion can have serious consequences such as food and water shortages, loss of biodiversity, and natural disasters. By conserving these resources and using them sustainably, we can ensure their availability for future generations.Individuals can play a crucial role in environmental protection through their everyday actions. Simple habits like reducing, reusing, and recycling waste can help in conserving resources and reducing pollution. Using public transport, biking, or walking instead of driving can help in reducing carbon emissions and combating climate change. Supporting environmentally-friendly products and companies can also encourage sustainable practices in the marketplace.In conclusion, environmental protection is an issue of utmost importance in today's world, and individuals have a responsibility to do their part in preserving the environment for future generations. By raising awareness, adopting sustainable practices, and advocating for change, we can all contribute to creating a cleaner, healthier planet for ourselves and for future generations.。
【英语】高三英语阅读理解(科普环保)解题技巧讲解及练习题(含答案)及解析一、高中英语阅读理解科普环保类1.犇犇阅读短文,从每题所给的A、B、C和D四个选项中,选出最佳选项。
Robots are now being employed not just for dangerous tasks, such as discovering mines or rescuing people in disasters. They are also finding application as household helps and as nursing assistants. As increasing numbers of machines, equipped with the latest artificial intelligence, take on a growing variety of specialized and everyday tasks, the question of how people see them and behave towards them becomes ever more urgent.A team led by Sari Nijssen of Radboud University and Markus Paulus, Professor of Developmental Psychology at Ludwig-Maximilians-Universitaet (LMU), have carried out a study to determine the degree to which people show concern for robots and behave towards them based on moral principles.According to Sari Nijssen, the study set out to answer the following question:" Under what circumstances would adults be willing to sacrifice robots to save human lives?" The participants were faced with a hypothetical (假设的) moral dilemma: Would they be prepared to put a single person at risk in order to save a group of injured persons? In the situations presented the intended victim was either a human, a humanoid robot that had been humanized (人性化的) to various degrees or a robot that was clearly recognizable as a machine.The study suggested that the more the robot was humanized, the less likely participants were to sacrifice it. Situations that included vivid stories in which the robot was described as a merciful being or as a creature with its own understandings, experiences and thoughts, were more likely to stop the study participants from sacrificing it in the interests of anonymous (无名的) humans. "This result indicates that our study group attached a certain moral status to the robot," says Paulus. "One possible suggestion of this finding is that attempts to humanize robots should not go too far. Such efforts could come into conflict with their intended function—to be of help to us."(1)What has become a concern about robots?A. How to humanize them.B. How to treat them in life.C. How to use them effectively.D. How to find more applications.(2)In the study the participants probably have to decide ________.A. when to sacrifice a robotB. where to experience risksC. which robot to work withD. what robots should be like(3)What can be inferred from Paulus' words?A. Humanized robots offer less help to people.B. Humanizing robots too much may be improper.C. Certain moral status should be attached to robots.D. Conflicts often happen between humans and robots.(4)Which of the following would be the best title for the text?A. Robots, A Must for FutureB. Humanized Robots, A New TrendC. Robot Saved, People Take the HitD. Humanized Robots, Replace Human【答案】(1)B(2)A(3)B(4)C【解析】【分析】本文是一篇说明文,随着越来越多的机器人具有人性化,它们承担越来越多样化的专业和日常任务,人们如何看待他们,如何对待他们的问题变的迫在眉睫。
Annex 2 附录2Points to consider when including Health-Based Exposure Limits (HBELs) in cleaning validation 清洁验证中包括基于健康的暴露限(HBEL)时的考虑要点1. Introduction and background 介绍与背景The World Health Organization (WHO) has published the guideline entitled Good manufacturing practices for pharmaceutical products: main principles in the WHO Technical Report Series, No. 986, Annex 2, 2014 (1).WHO已在2014年WHO 第986号技术报告附录2发布了题为《药品GMP:主要原则》的指南.The WHO Supplementary guidelines on good manufacturing practice: validation were published in 2006 and were supported by seven appendices. The main text (2) and its appendixes (3, 4, 6, 7, 8, 9) were revised between 2006 and 2019. Appendix 3, relating to cleaning validation (5), was not updated at that time. Its revision, however, was discussed during an informal consultation held in Geneva, Switzerland, in July 2019. The outcome of the discussion was presented to the WHO Expert Committee on Specifications for Pharmaceutical Products (ECSPP) meeting in October 2019. The ECSPP acknowledged the importance of harmonization in regulatory expectations with regards to cleaning validation approaches. The Expert Committee recommended a “Points to consider” document be prepa red in order to describe the current approaches used in cleaning validation and highlighting the complexities involved in order to establish a common understanding.A revision of the relevant appendix would then be considered by the Expert Committee thereafter.WHO《GMP补充指南:验证》于2006年发布,有7个支持性附录。
高考英语阅读理解(科普环保)解题技巧讲解及练习题(含答案)一、高中英语阅读理解科普环保类1.犇犇阅读下列短文,从每题所给的A、B、C和D四个选项中,选出最佳选项。
After a morning hike in the Saneum HealingForest, 46-year-old firefighter Kang Byoung-wook has tea made from the bark of an elm tree, practices yoga (瑜伽), and makes a picture with dried flowers. He is one of 40 firefighters taking part in a three-day program, the aim of which is to offer "forest healing" (森林治愈); the firefighters all have posttraumatic stress disorder (创伤后应激障碍).Saneum is one of three official healing forests in South Korea. Soon there will be 34 more. South Koreans-many of whom suffer from work stress, digital addiction, and great academic pressure have accepted the medicalization of nature with great enthusiasm.There is increasing evidence that being outside in a pleasant natural environment is good for us. But how many of us get to enjoy nature regularly? Fewer and fewer, it seems. According to Lisa Nisbet, a psychology professor at Canada s Trent University, evidence for the benefits of nature is pouring in at a time when we are most disconnected from it."We don't think of being outdoors as a way to increase happiness," says Nisbet. "We think other things will, like shopping or TV." But South Korea is starting to challenge this opinion.So what are some of the benefits of nature that Nisbet refers to? Being surrounded by nature has one obvious effect: It calms us and reduces our stress levels. This has been shown to lower blood pressure and heart rates.Another experiment conducted by psychologist Stephen Kaplan found that people who took a 50-minute walk in a park had better attention and short-term memory than those who took a walk along a city street.Perhaps what's more surprising is that nature may also make us more creative. David Strayer, a psychologist at the University of Utah, showed as much with a group of participants, who performed 50 percent better on creative problem-solving tasks after three days of wilderness backpacking.In fact, we may never know exactly what nature does to the brain. Something mysterious will always remain, and maybe that's as it should be.(1)What is Kang Byoung-wook doing?A.Getting lost in nature.B.Building up his strength.C.Trying to control a forest fire.D.Helping firefighters under stress.(2)What does Lisa Nisbet think of being outdoors?A.It is overlooked by people.B.It has nothing to do with happiness.C.South Koreans show great interest in it.D.We need more evidence for its benefits.(3)What benefit of nature did Stephen Kaplan find?A.It affects people's feelings.B.It lowers the risks of diseases.C.It helps improve mental performance.D.It does more good than physical exercise.(4)What would be the best title for the text?A.Your life in forestsB.Your brain on natureC.The future of forest healingD.The benefits of a stress-free life【答案】(1)A(2)A(3)C(4)B【解析】【分析】本文是一篇说明文,由韩国患创伤后应激障碍的消防员接受森林治愈谈起,介绍了大自然对我们身心健康的益处。
Excessive nitrogen (N) concentrations, often in the form of nitrate, present a water-quality problem of growing concern. Nitrate concentrations in groundwa-ter and rivers in developed areas of the world have risen substantially as a result of the use of synthetic N fertilizers and cultivation of N-fixing crops (Turner and Rabalais 2003). Increasing N export from landscapes to coastal waters has been implicated in coastal eutrophi-cation and the development of hypoxic zones (eg in the Gulf of Mexico; Rabalais et al . 2001) and harmful algal blooms (Paerl et al . 2002). There is still some debate over whether N alone is the main driver of these problems (Dodds 2006), but there is no question that the increases in N loading represent a major per-turbation of streams, rivers, estuaries, and coastal marine waters.A lthough N loading to coastal zones has increased,regional watershed mass-balance studies (wherein all N inputs and outputs are accounted for) indicate that most of the anthropogenic N that enters watersheds is removed before reaching the oceans (Howarth et al . 1996;Alexander et al . 2000). A s nitrate-rich water flows through landscapes, it enters riparian wetlands and head-water streams, which can efficiently remove nitrogen (Peterson et al . 2001; Zedler 2003). Thus, key interfaces along landscape flow paths control nitrate export to downstream surface waters, such as large rivers and lakes,and ultimately to estuaries and marine ecosystems. Here,we discuss the many possible fates for this removed nitrate, which include some grossly underestimated and understudied microbial pathways, many of which have only recently received attention from the scientific com-munity. The importance and possible prevalence of these pathways have profound implications for the manage-ment of aquatic ecosystems to promote nitrate removal.Where does the nitrate go?Up to 75% of the N added to a landscape may be removed before reaching marine ecosystems (Howarth et al . 1996). The various transformations and eventual fate of this N as it is carried along hydrologic flow paths is a problem that has interested scientific and management communities alike. The current consensus is that the dis-Front Ecol Environ 2007; 5(2): 89–96appearance of N is due largely to biological transforma-tions, since increased N storage (eg in groundwater or bio-mass) cannot explain most of the “missing N” (Howarth et al. 1996). Biological removal of nitrate from water passing through or over sediments is often assumed to be due either to assimilation into algal or microbial biomass, pro-ducing organic N that may be remineralized later, or to respiratory denitrification by bacteria, producing gaseousN2as a byproduct of organic matter oxidation. (For anintroduction to microbial metabolism, please refer to Panel 1.)In respiratory denitrification, nitrate acts as the termi-nal electron acceptor for the oxidation of organic matter under anaerobic conditions; in aquatic sediments, most ofthe nitrate is usually converted to N2, with a variable butsmall fraction escaping as nitrous oxide (N2O; Figure 1).Because N2is unavailable for use by most organisms, res-piratory denitrification is considered a permanent removal of N from the ecosystem. Denitrification rates have been estimated in soils, wetlands, and surface waters, but estimates vary greatly within and among envi-ronments, as well as between different measurement techniques. Nevertheless, denitrification is thought to remove substantial fractions of the total nitrate loads to lakes, rivers, and coastal estuaries (Seitzinger 1988; Cornwell et al. 1999). However, while nitrate disappear-ance in soils and aquatic sediments is usually assumed to be largely due to denitrification, estimates of denitrifica-tion based on direct assays (eg acetylene block tech-detail as it is thoroughly examined elsewhere (eg Knowles 1982; Tiedje et al. 1982; Seitzinger 1988; Cornwell et al. 1999). This paper is not meant to lead the reader to the conclusion that these alternative pathways are generally more important than denitrification, but to show that there are several processes that could rival denitrification in importance, which have been much less studied until now. While there is some evidence for the importance of each of these pathways, much more research is needed, particularly in freshwater ecosystems, to ascertain their value relative to respiratory denitrification in whole-ecosystem nitrate removal.Dissimilatory nitrate reduction to ammonium (DNRA) The existence of dissimilatory nitrate reduction to ammo-nium (DNRA) has been widely recognized for at least the past 25 years, although its potential importance as a nitrate removal pathway on an ecosystem scale has gener-ated increased interest within the past decade. This microbially mediated pathway involves the dissimilatory transformation of nitrate to ammonium (NH4+), in con-trast to assimilatory processes that incorporate N into cel-lular constituents. Compared to nitrate, the resultant ammonium is a more biologically available and less mobile form of inorganic N (Figure 1). Little is known about the eventual fate of the nitrate that is converted to ammo-nium via DNRA pathways, but it is possible that, under appropriate conditions, the ammonium is converted backAerobic respiration Anaerobic respiration Organic C CO2Organic C CO2+ ENERGY+ ENERGYO2H2O e- acceptor(other than O2)ReducedproductElectron acceptors:O2> NO3> Fe3+> SO42–(Tiedje 1988; Megonigal et al . 2004).Many microbes perform fermentative DNRA , including species of Clostridia,Desulfovibrio, Vibrio,and Pseudomonas ;these organisms can also carry out fermen-tation without using nitrate (Tiedje 1988). Although the conditions promoting fermentative DNRA and respiratory denitrification are similar (ie anoxia, available nitrate, and organic substrates), fermentative DNRA is thought to be favored in nitrate-limited environments rich in labile car-bon (carbon forms that are more easily broken down),while respiratory denitrification would be favored under carbon-limited conditions (Kelso et al . 1997; Silver et al .2001). Tiedje (1988) argued that high labile carbon avail-ability would favor organisms that used electron acceptors most efficiently; DNRA transfers eight electrons per mole of nitrate reduced, whereas denitrification only transfers five. Some studies have supported Tiedje’s (1988) hypothe-sis that DNRA is more important in high-carbon, low-nitrate systems, including Bonin (1996) and Nijburg et al .(1997). The oxidation state of the sediments may also be important. For example, Matheson et al . (2002) hypothe-sized that microzones of oxygen leakage from roots of emer-gent plants in wetland sediments may favor the faculta-tively aerobic denitrifiers over the obligately anaerobic fermentative bacteria. Much more work is needed to understand where and when DNRA is prevalent in ecosys-tems before we can fully understand what factors govern its importance relative to other nitrate removal processes.A very different form of DNRA is chemolithoau-totrophic and couples the reduction of nitrate to the oxi-dation of reduced sulfur forms, including free sulfide (H 2S and S 2–) and elemental sulfur (S; Brunet and Garcia-Gil 1996; Otte et al . 1999). The nitrate may be reduced either to ammonium, as a form of DNRA, or to N 2, as a form of denitrification, although not all species can do both (Zopfi et al . 2001). In this pathway, the predominant fate of the reduced nitrate may be determined by the ambient concentration of free sulfide, which is known to inhibit the final two reduction steps in the denitrification sequence. Sulfide inhibition of these terminal steps may drive the reduction to ammonium rather than to N 2O and N 2. Brunet and Garcia-Gil (1996) studied the effects of various sulfur forms as potential electron donors, and found that only free sulfide yielded ammonium and N 2O,lending support to the idea that the enzymes that sustain respiratory denitrification may be inhibited by the pres-ence of sulfide. On the other hand, metal-bound sulfides (eg iron sulfide, [FeS]), which are often abundant con-stituents of freshwater sediments (Holmer and Storkholm 2001), can also be oxidized by such bacteria, but these compounds may not inhibit denitrification (Brunet and Garcia-Gil 1996). A similar process that couples the reduction of nitrate to the oxidation of methane was recently discovered in freshwaters (Raghoebarsing et al .2006), though it is not yet clear if this process is impor-tant to whole-ecosystem nitrate removal.The ability of bacteria to couple the reduction of nitrate to the oxidation of sulfur has now been estab-lished in a number of taxa with diverse metabolic charac-teristics (eg Dannenberg et al . 1992; Bonin 1996;Philippot and Hojberg 1999), including members of thegenera Thiobacillus ,Thiomicrospora , and Thioploca (Timmer-ten-hoor 1981; Jorgensen 1982; Kelly and Wood 2000). Bacteria with this capability include the “big bacteria” (eg Thioploca ) that are able to store nitrate,sulfur, or calcite in vacuoles (Schulz and Jorgensen 2001).This storage capability, in conjunction with their gliding motility, allows them to take advantage of steep biogeo-chemical gradients, for example by taking up nitrate from overlying oxic water and utilizing it to oxidize sulfur in sulfide-rich anoxic porewater (interstitial sediment water;Schulz and Jorgensen 2001).Figure 1.A conceptual diagram of the nitrate removal pathways discussed in this article.Respiratory denitrification Assimilation Sulfur-driven nitrate reduction FermentativeDNRA Iron-driven denitrification Anammox CO 2Organic CFe 2+Fe3+H 2S, S O SO 4–2N 2, N 2O NH 4+Biomass NO3–NO 2–N 2NO 2–NH 4+N 2N 2or NH 4+Figure 4:Hypothesized controls on predominant dissimilatory pathways of nitrate removal. This flow chart summarizes the conditions under which we would expect a particular nitrate removal pathway to be important. C inputs refer to labile organic carbon available to microbes. Sulfidic refers to the presence of significant amounts of either free sulfide (H 2S or S 2–), elemental S (S 0), or metal-bound sulfides such as FeS, all of which tend to be abundant in sediment environments with moderate to high sulfate in overlying water and high labile C inputs to support microbial sulfate reduction. Of these S forms,High C inputs Sulfidic Not sulfidicLow C:NHigh C:NLow CinputsLow FeHigh Fe H 2SFeS, S O Low C:NHigh C:N S oxidizersdominateS oxidizers:DNRA to NH 4+Respir denitrif to N 2FermentDNRA S oxidizers:denitrif to N 2Respirdenitrif toNO 2–thenanammox Respir denitrif to N 2Fe oxidation:denitrif to N 2。
英语作文评价环卫Title: Evaluating the Contribution of Sanitation Workers。
Sanitation workers, often unseen but indispensable members of society, play a vital role in maintaining the cleanliness and hygiene of our communities. Their tireless efforts contribute significantly to public health, environmental sustainability, and overall quality of life. Evaluating their contribution entails recognizing the challenges they face, acknowledging their impact, and advocating for their welfare.Firstly, it's crucial to appreciate the challenges sanitation workers encounter in their daily work. They operate in all weather conditions, sometimes in hazardous environments, facing risks to their health and safety. The physical demands of their job, including lifting heavy loads and exposure to potentially harmful substances, can take a toll on their well-being. Moreover, sanitation workoften lacks the recognition and respect it deserves, leading to social stigma and low morale among workers.Despite these challenges, sanitation workers make invaluable contributions to society. Their diligent efforts keep our streets clean, prevent the spread of diseases, and preserve the aesthetic appeal of our surroundings. By collecting and disposing of waste properly, they mitigate environmental pollution and promote sustainability. Additionally, sanitation workers play a crucial role in emergency response situations, such as natural disasters or public health crises, where their services are indispensable for maintaining public hygiene and safety.Furthermore, the contribution of sanitation workers extends beyond their immediate duties. They foster a sense of community pride and responsibility by demonstrating the importance of cleanliness and proper waste management. Through their work, they educate the public about environmental conservation and the significance of maintaining sanitary conditions. Additionally, sanitation workers often serve as frontline observers, identifying andreporting issues such as illegal dumping or infrastructure damage, thereby contributing to the overall maintenance of urban infrastructure.In evaluating the performance of sanitation workers,it's essential to consider various factors beyond the quantity of waste collected. Quality of service, efficiency, adherence to safety protocols, and interpersonal skills are all critical aspects of their work. Effective communication and cooperation among sanitation workers and with other relevant stakeholders, such as local authorities and residents, are essential for ensuring the smooth operationof sanitation services.Moreover, recognizing the contribution of sanitation workers involves advocating for their rights and well-being. This includes ensuring fair wages, providing access to healthcare and safety equipment, and implementing policiesto protect them from occupational hazards. Public awareness campaigns can help challenge stereotypes and promoterespect for sanitation workers, fostering a culture of appreciation for their vital role in society.In conclusion, sanitation workers make significant contributions to public health, environmentalsustainability, and community well-being. Despite facing numerous challenges, their dedication and hard work are essential for maintaining clean and hygienic living environments. Evaluating their contribution involves recognizing their challenges, acknowledging their impact, and advocating for their welfare. By doing so, we canensure that sanitation workers receive the respect, support, and recognition they rightfully deserve.。
A review on role of cleaning validation protocol inPharmaceutical manufacturing unitK. Harshavardhan*1, V.S.Thiruvengada Rajan 1, N. Amruth Kumar 1, S.Angala Parameswari 1,C.Madhusudhana Chetty 21Department of Pharmaceutical Analysis and Quality Assurance, 2Department of Bio-Technology,Annamacharya College of Pharmacy, Rajampet-516126, Andhra Pradesh, IndiaABSTRACTCleaning validation is must in order to identify and correction of potential problems previously unsuspected which shows effect on safety, efficacy and quality of subsequent batches of drug product with in the equipment. Manu-factures and authorities set high standards for the effective and reliable cleaning of production equipment in or-der to prevent cross contamination. Regulations, tight deadlines and increasing awareness of cost necessitate effi-cient and residue free cleaning processes. Residue free cleaning is a key factor in the life cycle of any chemical pharmaceutical product from research and development in the laboratory during scale up in the pilot plant and finally at the production site. An effective cleaning process takes all the individual factors in to account and is based on precise knowledge of the product mix and cleaning chemistry which results in greater efficiency and lower costs. The benefits due to cleaning validation are compliance with federal regulations, identification and correction of potential problems, previously unsuspected which could compromise the safety and efficacy of drug products.Keywords: Analytical testing methods; cleaning validation protocol; cleaning validation; validation. INTRODUCTIONCleaning validation provides documented evidence that the cleaning methods employed with in a facility are effective and consistent in cleaning pharmaceutical production equipment. Validation of equipment clean-ing procedures is mainly used in pharmaceutical indus-tries to prevent cross contamination and adulteration of drug products. The important task of performing a cleaning validation is to identify and correction of po-tential problems previously unsuspected which shows effect on safety, efficacy, or quality of subsequent batches of drug product produced within the equip-ment. Cleaning validation is important like that of pro-duction process and the process validation. It is there-fore deserves the same careful attention. The main rationale for requiring clean equipment is to prevent contamination or adulterations of drug products (Gala-towitsch S 2000). ObjectiveCleaning validation should be followed for prevention of interactions between active pharmaceutical ingre-dients. The cleaning of difficult to reach surface is oneof the most important consideration in equipment cleaning validation. It is necessary to validate cleaning procedure for the following reasons (Cleaning Valida-tion, 1999)1. Customer requirement-it ensures the safety and the purity of the product.2. Regulatory requirement in active pharmaceutical ingredient product manufacture.3. Assurance from an internal control and compliance point of view the quality of process.When the cleaning process is used only between batches of the same product the firm need to meet criteria of visible clean for the equipment. Residue free cleaning is a key factor in the life cycle of any chemical pharmaceutical product from research and develop-ment in the laboratory during scale up in the pilot plant and finally at the production site. An effective cleaning process takes all the individual factors in to account and is based on a precise knowledge of the product mix and cleaning chemistry (Mendenhall DW 1989). Various types of contaminants Contamination with active ingredientsCross contamination with Active ingredients may cause potential clinically significant synergistic interactions between pharmacologically active chemicals and it causes an unintended pharmacological activity so con-tamination of one batch product with residual active* Corresponding AuthorEmail: harshan17@ Contact: +91-9966981423 Received on: 04.07.2011 Revised on: 25.08.2011 Accepted on: 04.09.2011ISSN: 2231-2935 Review Articleingredient from a previous batch should not be tole-rated if the residues are more than the predetermined level.Contamination with unintended materials or com-poundsPrecursors to active pharmaceutical ingredients. Sol-vents and other materials employed during the manu-facturing process. Cleaning agent themselves and lu-bricants.MICROBIAL CONTAMINATIONThere is chance of microbial growth if the processing equipment is not properly maintained, cleaned and stored.It includes preventive measures rather than removal of contamination (Parentaral drug association, 1998; Cleaning validation, 1999).FDA RequirementsFDA expects firms to have written standard operating procedures (SOP) detailing the cleaning process used for various pieces of equipment. If firms have a specific cleaning process for cleaning between different batches of the same product and use a different process for cleaning between product changes, FDA expects the written procedures to address these dif-ferent scenarios. If firms have one process for remov-ing water-soluble residues and another process for non water soluble residues the written procedure should address both scenarios and make it clear when a given procedure is followed. It is required by the FDA, in the general validation procedure, that the personnel re-sponsible for performing and approving the study should comply with the acceptance criteria and the revalidation data. FDA expects firms to prepare specific written validation protocols in advance for the studies to be performed on each manufacturing system or piece of equipment which should address such issues as sampling procedures, and analytical methods to be used including the sensitivity of those methods. It is expected that firms conduct the validation studies in accordance with the protocols and document the re-sult of studies. Final validation report is to be approved by the regulatory board which states whether or not the cleaning process is valid (FDA guidelines 1993). Cleaning Validation PolicyThe main focus of this document will be to describe equipment and ancillary equipment/ process Cleaning Validation in an Active Pharmaceutical Ingredient manufacturing plant. However, it is appropriate to start by giving a brief introduction as to how the con-cept of Cleaning Validation should be approached in a facility. It is advisable for Active Pharmaceutical Ingre-dient manufacturing facilities to hold an Official Clean-ing Validation Policy. Specific department responsibili-ties should be outlined in this and it should be ap-proved by senior management. This policy should serve to provide a general guideline and direction for com-pany personnel, regulatory authorities and customers as to how the company deals with areas associated with Cleaning Validation. The policy should incorporate the following types of statements∙Definition of terms employed during validation i.e. rinse vs flush vs wash etc.∙A statement specifying what company policy is on validation of cleaning procedures related to equip-ment (including ancillary) and processes.∙Company policy re dedication of equipment in cer-tain cases (if products are deemed too dangerous and / or highly active to manufacture on multi-product equipment).∙Analytical validation policy.∙The policy should also state the rational for the me-thods by which acceptance criteria is determined.∙Revalidation policy (Health Sciences Authority,dec 2008).Acceptance criteria based on therapeutic daily doseThe principle for the requirement is that the standard Therapeutic Daily Dose (TDD)of the following sub-stance (contaminated. substance, in this case called "next") maybe contaminated by no more than a certain proportion (usually 1/1000 part) of the TDD of the sub-stance investigated in the cleaning validation (conta-minating substance, in this case called "previous"). This method only applies when the therapeutic daily dose is known. It is generally used for final product changeov-er API Process A to API Process B.ProcedureEstablish the limit for Maximum Allowable Carryover (MACO) according to the following equation.TDD previous x MBSMACO = ------------------------------SF x TDD nextMACO = Maximum Allowable Carryover: acceptable transferred amount from the investigated product ("previous")TDD previous = Standard therapeutic dose of the investi-gated product (in the same Dosage form as TDD next)TDD next = Standard therapeutic dose of the daily dose for the next productMBS = Minimum batch size for the next product(s) (where MACO can end up)SF = Safety factor (normally 1000 is used in calculations based on TDD)Based In Toxicological DataIn cases in which a therapeutic dose is not known (e.g. for intermediates and detergents), toxicity data may be used for calculating MACO.152 ©JK Welfare & Pharmascope Foundation | International Journal of Review in Life SciencesProcedureCalculate the so called NOEL number (No Observable Effect Level) according to the following equation and use the result for the establishment of MACO.LD50 (g/kg) x 70 (kg a person)NOEL = --------------------------------------2000From the NOEL number a MACO can then be calculated according to:NOEL x MBSMACO = -------------------SF x TDD nextMACO = Maximum Allowable Carryover: acceptable transferred amount from the investigated product ("previous")NOEL = No Observed Effect LevelLD50 = Lethal Dose 50 in g/kg animal.The identification of the animal (mouse, rat etc.) and the way of entry (IV, oral etc.) is important.70 kg = 70 kg is the weight of an average adult2000 = 2000 is an empirical constantTDD next = Largest normal daily dose for the next prod-uctMBS = Minimum batch size for the next product(s) (where MACO can end up)SF = Safety factorThe safety factor (SF) varies depending on the route of administration. Generally a factor of 200 is employed when manufacturing APIs to be administered in oral dosage forms. SF can vary depending on sub-stance/dosage form according to (suppose tox values from oral administration) as for example.Safety factorsTopicals 10- 100Oral products 100 - 1000Parentrals 1000 -10 000To calculate MACO values from tox data is frequently done when therapeutic dosage data is not available or not relevant. It is generally employed if the previous product is an intermediate and the following product an API.Establishment of limitsNMT 0.1% of the normal therapeutic dose of any prod-uct to appear in the maximum daily dose of the follow-ing product. NMT 10ppm of any product to appear in another product. No quantity of residue to be visisble on the equipment after cleaning procedures are per-formed(Fourman GL 1993; Vitale KM 1995; Brewer R 1996). CLEANING PROCEDURESStandard cleaning procedures for each piece of equip-ment and process should be prepared. It is vital that the equipment design is evaluated in detail in conjunc-tion with the product residues which are to be re-moved, the available cleaning agents and cleaning techniques, when determining the optimum cleaning procedure for the equipment. Cleaning procedures should be sufficiently detailed to remove the possibility of any inconsistencies during the cleaning process. Fol-lowing parameters are to be considered during clean-ing procedures (Quality assurance of pharmaceuticals: a compendium of guidelines 2006).Equipment parameters to be evaluated∙Identification of the equipment to be cleaned.∙Difficult to clean areas∙Property of materials∙Ease of disassembly∙MobilityResidues to be cleaned∙Cleaning limits∙Solubility of residues∙Length of campaignsCleaning agent parameters to be evaluated∙Preferable materials that are normally used in the process.∙Detergent available∙Solubility properties∙Environmental considerations∙Health and safety considerationsCleaning techniques to be evaluated∙Manual cleaning∙Clean in place∙Clean out of place∙Semi automatic procedures∙Automatic procedure∙Time consideration∙Number of cleaning cycles.Levels of cleaningThe manufacturing process of an Active Pharmaceuti-cal Ingredient (API) typically consists of various chemi-cal reaction and purification steps followed by physical changes. In general early steps undergo further processing and purification and so potential carryover of the previous product would be removed. Theamount or as we will call it here, level of cleaning re-quired in order to ensure that the API is free from un-acceptable levels of contamination by previous sub-stances varies depending on the step being cleaned and the next substance being manufactured in the same piece of equipment. API‘s and related interm e-diates are often produced in multi-purpose equipment with frequent product changes which results in a high amount of cleaning. During the course of this chapter the reader will be introduced to the concept of using different levels of cleaning, thereby giving the oppor-tunity to minimize the amount of cleaning and cleaning validation required without affecting the safety of the API. The CEFIC, APIC Guide to Cleaning Validation re-commends three levels of cleaning that may be imple-mented. This approach is outlined in the table 1 below, however should be mentioned that additional levels might be necessary depending on nature of the process and requirements of individual companies (Cleaning validation 2000).Table 1: Levels of CleaningSampling TechniquesFor all the methods the sampling points must be fixed in a manner that the true contamination of the equip-ment will be reflected. A combination of rinse sampling and swabbing is the effective method (James A 1992; Parentaral drug association 1998; Pei yang 2005; Hyde JM 1994; James A 1992; Philips GF 1989).Direct Surface SamplingIt will determine the material used for sampling and its impact on the test data since the material used may interfere with the test. For example adhesive materials used in swabs found to interact with the samples dur-ing analysis. AdvantagesAreas which are hardest to clean and reasonably ac-cessible can be evaluated that establishes the level of contamination or residue per given surface area.∙Residues that are not soluble and dried out can be sampled by physical removal.Swab samplingDuring swab sampling usually a small area of the cleaned equipment is swabbed with a pre-defined ma-terial and method (swab material, solvent and tech-nique). Subsequently the swab is extracted and the extract examined by a suitable analytical method. Then the quantified residue of the samples is extrapolated to the whole equipment It includes both physical and chemical forces.It is important:∙That the validation of the swab sampling is per-formed on the same surface (material, polish grade, area in dm2) and with the same materials as the rou-tine sampling of the equipment.∙To choose the swabb ing material such that it’s e x-tractable materials do not interfere with the ex-pected residue.∙To choose the sampling points such that they represent the worst case spots of the equipment AdvantagesIt is possible to sample insoluble residue as physical forces or action is associated with it. DisadvantagesBy this method it is not possible to swab difficult to reach area (e.g. sealing, slots, and condensers, piping). Rinse samplingIn this method the equipment is rinsed with the sol-vent after cleaned. If properly designed this method will probably give the best picture of the amount of the residue in the equipment (Leblane DA 1998). AdvantagesThis method covers the entire surface area of equip-ment even the difficult to reach area and which cannot be disassembled.DisadvantagesThe residue or contaminant may not be soluble or may be physically occluded in the equipment. An analogy that can be used is the dirty pot. In the evaluation of cleaning of a dirty pot, particularly with dried out resi-due, one does not look at the rinse water to see that it is clean one looks at the pot.154 ©JK Welfare & Pharmascope Foundation | International Journal of Review in Life SciencesStampsThis is not routinely used method. Stamps (coins) are placed on the appropriate sampling points in the equipment during the manufacture of product and cleaning. Then these coins are evaluated for contami-nation. From data obtained overall contamination of the equipment is calculated. For quantization the coins may be first swabbed and the samples further ana-lyzed.Routine production in process controlMonitoring indirect testing such as conductivity testing may be performed for routine monitoring once a clean-ing process has been validated. These are true in case of bulk drug substance manufacture where reactors, centrifuges, piping between large equipment can be sampled by rinse solution samples.TESTING METHODSThe analytical methods should be validated. The ana-lytical methods used must be specific towards the resi-duals or contaminants (e.g. product residue, detergent, residue and /or endotoxin). The analytical methods used should have predetermined specificity and sensi-tivity. If levels of contamination or residue are not de-tected, it does not mean that there is no residual con-taminant present after cleaning, it means that the le-vels of contaminant greater than the sensitivity or de-tection limit of the analytical method are not present in the sample. For detection of protein residue the product specific assay(s) can be used in addition to total organic carbon. A negative test may also be the result of poor sampling technique. The firm should challenge the analytical method in combination with the sampling method(s) used to show that contami-nants can be recovered from the equipment surface. There are many analytical techniques available but selection of appropriate tool depends on the parame-ters to be measured. Analytical methods are catego-rized in to specific and non specific methods(Kirsch RB 1998; Cleaning Validation 2000; Kaiser HJ 1999; Gavlick WK 1995; Jenkins KM 1994; Philips GF 1989; LeBlanc DA 1998; Fourman GL 1993; Swartz ME 1998). Specific MethodsIn this method a unique compound can be detected from potential contaminants. E.g. HPLCNon Specific MethodsIn this method any compound can be detected which produces certain response. E.g. Total Organic Carbon, pH and conductivity.HPLCEvery pharmaceutical company has an HPLC instru-ment, utilizing a variety of detectors. These include UV, fluorescence, electrochemical, refractive index, con-ductivity, Evaporate light scattering detector (ELSD) and many others. The vast majority of techniques de-scribed in the literature are for the determination of surfactants in concentrated products. Therefore, the limits of quantitation and the limit of detection are rather high. Analysis of anionic and cationic surfactants is done by HPLC and Capillary electrophoresis whereas amphoteric surfactants are analysed by HPLC, CD and ELSD (Lin W 2000; Heinig K 1997a, 1997b; Schmitt TM 1998; McPherson BP 1994).Capillary electrophoresisCapillary electrophoresis is used to separate, detect and determine sodium lauryl sulphate in cationic, anionic and non ionic surfactants (Kelly MA 1997) (Shamsi SA 1995) micellar electro kinetic capillary chromatography is used for the separation of non ionic alkyl phenol poly oxy ethylene type surfactants (Heinig K 1998; Heinig K 1999)LC-MS-MSCurrently liquid chromatography-ultraviolet spectro-metry is widely used because of its familiarity, robust-ness, ease of use and regulatory acceptability. This method will afford faster development and analysis time, potentially making the predominant tool of choice. This method is widely used for the detection of low dose compounds because of its selectivity and sen-sitivity (Kelvin J 2006)Total Organic CarbonTOC is determined by the oxidation of organic com-pound in to carbon dioxide. The oxidation can occur through a number of mechanisms depending on the instrument being used. TOC is used for the analysis of detergents, endotoxins, biological media and poly ethylene glycol (Jenkins KM 1996; Westman L 2000; Guazzaroni M 1998; Biwald CE 1997).Ion ChromatographyIon chromatography can be used for the analysis of inorganic, organic and surfactants present in the clean-ers. Most of the cleaners contain sodium and or potas-sium. The ion chromatography detection technique of suppressed conductivity is more sensitive to potassium ions than to sodium ions. Very low levels of cleaning agents can be detected by using this technique. Other techniques like TLC, AAS and Bioluminescence are widely used for the qualitative determination of surfac-tants as well as Inorganic contaminants and biological (Hoeft CE 1994; Pan N 1995; Takeda T 1992; Murawski D 1991; Nair LM 1998; Weston A 1998).Thin Layer ChromatographyTLC is useful in the determination in qualitative deter-mination of surfactants (Bosdorf V 1996; Read H 1985; Henrich LH 1992).Atomic Absorption SpectroscopyIt is widely in determination of inorganic surfactants (Raghavan R 2000)BioluminanceIt is widely used in the determination of biological (Da-vidson CA 1999).Optically Simulated Electronic EmissionIn some cases the limits of residue are very less that they cannot be detected by conventional methods. OSEE is very sensitive method that can be used for both qualitative and quantitative manner in this re-gard. Apart from the above mentioned techniques the biopharmaceutical industry utilizes a wide variety of techniques .these include enzyme linked immune sor-bent assay and limulus amaebocyte lysate technique (Inampudi P 1996; Rowell FJ 1998).Cleaning Validation ProtocolCleaning validation should be described in cleaning validation protocols, which should be formally ap-proved, e.g. by the quality control or quality assurance unit (Quality assurance of pharmaceuticals 2006).In preparing the cleaning validation protocol, the fol-lowing should be considered:∙disassembly of system;∙pre cleaning;∙cleaning agent, concentration, solution volume, wa-ter quality;∙time and temperature;∙flow rate, pressure and rinsing;∙complexity and design of the equipment;∙training of operators; and∙size of the systemCleaning Validation ReportA validation report is necessary to present the results and conclusions and secure approval of the study. The report should include the following information: Refer-ences to all the procedures followed to clean the sam-ples and tests. Any recommendations based on the results or relevant information obtained during the study including revalidation practices if applicable. Re-view of any deviations from the protocol. When it is unlikely that further batches of the product will be manufactured for a period of time, it is advisable to generate reports on a batch by batch basis until such time. The report should conclude an appropriate level of verification subsequent to validation (Parentaral drug association 1998; Lakshman Prabu S 2010). CONCLUSIONCleaning validation is required in the pharmaceutical field to avoid potentially clinically significant synergistic interactions between pharmaceutical components. 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