Embed Size (px)
Citation preview
CODETofflon News
Pharma Industry
Tofflon Insight
Tofflon Lab
Tofflon Service
Travel in China
Expertise In Pharmaceutical Industry
Contact us by [email protected]
Visit our websitewww.tofflon.com
The Tofflon Code teamEditor-in-ChiefMichael ChangDesign & Art DirectionTroy YanProduction & Marketing ManagerTroy YanAssistant editor Laura Luo
Editorial address2199,Fanghe Road,Duhui Road, Minhang District, Shanghai 201109 China
Opinions in this magazine do not necessarily represent those of Tofflon, and Tofflon accepts no responsibility for these opinions. While the information in this publication is intended to be accurate, no representation of accuracy or completeness is made.
Tofflon News
Pharma Industry
Tofflon Insight
Tofflon Lab
Tofflon Service
Travel in China
CONTENTS/ 01
/ 05
/ 06
/ 08
/ 09
/ 10
/ 12
/ 13
/ 14
/ 14
/ 18
/ 22
/ 25
/ 28
/ 31
When Christmas encounter 20th Anniversary-Appreciation, Cooperation, Breakthrough
Tofflon launched its inspection machine in P-MEC India, 2013
Tofflon offers automated and integrated pharma solutions to Indian markets
Tofflon Attended The 46th (2013 )China International
Pharmaceutical Machinery As the Largest Exhibitor
PDA Annual Trainings in China was Sponsored by Tofflon
Integration with global technology to provide service for pharmaceutical industry
Tofflon Attended the Conference of ISL-F
2013 Freeze-Dryer Process Seminars Successfully Held at Shanghai Tofflon
Tofflon in Pharma& Healthcare Vietnam Exhibition 2013
The 5th anniversary jubilation for Tofflon Russia in the 15th Pharmtech Exhibition
Monoclonal Antibody on Global and China
The advantages of LN2 Refrigeration
Methods of Pressure Rise Test at the End Point of the Primary Drying
Tofflon India-Customer Service Excellence(1)
Venice of the Orient- Zhouzhuang
When Christmas Encounter 20th Anniversary
Happy New YearHappy New Year
Appreciation, Cooperation, BreakthroughThe Christmas’s light halo and happiness have not faded, Tofflon’s 20th anniversary was coming。December 28, 2013 marked the Tofflon’s 20th anniversary. Mr.Anthony Zheng Tofflon with a single small factory in Shanghai, China. Today, this company owns 11 subsidiaries, and provide products and service for more than 1000 pharmaceutical companies in 30 countries.The whole celebration lasted almost 5 hours, 1800 employees were present in this event. More than 100 staffs prepared and presented their performance, shared their enjoyment with us.
Appreciation -For Having the Best EmployeesDuring the 5 hours celebration gala, we recalled the past 20 years of events. Tofflon rewarded more than 80 staff for their hard work and contribution to the company development. “appreciation for having the best employees, it’s the key to success for us. ”Anthony Zheng, the founder and the chairman of the board reviewed.“20 years past, from a common worker to a technical engineer, I appreciate this company providing big platform for me. I am thrilled to grow with this company. For me, it’s not only like work anymore, it’s like my family.” Ang Fang Yu, the engineer from freeze dryer division said, who already worked in this company for almost 18 years. Still, there are some engineers can not join in the celebration, due to the business travel. In order to share our pleasure, Mr.Zheng greeted the Tofflon India company staffs through Web meeting.In order to stimulate all of staffs’s intention of cost-saving, Tofflon rewarded the staffs who implemented the cost-saving projects with 10% of the saving cost amount. There are 20 more technical engineers were rewarded, the highest bonus is more than $20,000.
P02
Tofflon News
Cooperation-By Our Sincere, Grateful AttitudeThe clients Representative attended this celebration. “I started to cooperate with Tofflon since 1995, I never saw a company is so responsible for its clients, from ordering to SAT, all of the project participants, including service engineers, project manager, technical engineers, they focus on every details of the project. ”One of the client representatives recalled. Early the Ocotober, Tofflon held the grand dinner for the clients during the 46th (2013 )CIPM exhibition. Nearly 500 representatives presented the dinner.“We grow with our clients, we never stop exploring the way to serve the clients, satisfying the needs of pharmaceutical industry.” Li Zhong Ming, who was rewarded the “Best Service Engineer”prize said.
CooperationExpertise In Pharmaceutical Industry
P03
Breakthrough-the Solution of Freeze Drying System"The past 20 years have been a great journey for us, one that started with passion and a colorful dream," said Anthony Zheng,the founder and the chairman of the board, "and the journey becomes even more exciting as we continue to develop our solutions for pharmaceutical industry, even the medical facilities, because we are working on the human health, every day, we are contributing on this target."In 2013, Tofflon launched its solution preparation system, filling line and inspection machine, as so to provide better freeze drying system for its clients , earlier this year in an effort to expand product assortment beyond freeze dryer, automatic loading systems and barrier systems for which the company is most known. "By offering original designed solution preparation system, filling line and inspection machine with solid quality and advanced technology, we can really help consumers increase their efficiency and cut their cost fundamentally. " Michael Chang, the VP and Member of the Board said."Our Partners are having success with Tofflon’s development, and we look forward to adding more products and benefits in the future, We thank our Partners who have demonstrated the confidence to promote our new technology. "
Tofflon Legend-God will Bless Diligent PeopleTofflon story is special for many reasons, but none more important than the fact that it is our associates and staffs that continue to make everything possible.In honor of our 20th anniversary, we have put together a special book telling our story through the eyes of those who made it happen. The 20th anniversary commemorative book shared our stories and what they have stood for over the past 20 years.
Attitude
P04
Tofflon News
Shanghai Tofflon Science & Technology Co., Ltd, geared up for challenges in most well-known exhibition P-MEC 2013. During P-MEC 2013 Tofflon introduced new product, Auto Inspection System for Vials & Ampoules to Indian market. Tofflon enlistment of this TIVS F40 inspection machine in its product list, assured to provide total solution for freeze drying system. The whole design is based on “Automation, Isolation & Systematic Integration”. The launch of our new product in P-MEC 2013 gathered numerous attentions of many clients.
Auto inspection is most essential technology for evolving Pharma & Biotechnology industries, Tofflon dedicated services & work on high engineered innovation & automation, now enables the solution for Ampoule & vial inspection, which overcome tedious naked eye visual inspection methods. Along with Inspection machine Tofflon also exhibited Auto loading, Row by Row system to P-MEC visitors. Tofflon demonstrated its row by row working principal with simulating model of freeze dryer to many interested clients.Tofflon received many feedbacks and enquires regarding Row by Row & Auto Inspection system. P-MEC 2013 has given good platform for Tofflon new products in Indian market.
TIVS-F40 Inspection Machine
Expertise In Pharmaceutical Industry
P05
Tofflon Freeze Drying System India Seminar 2013
Tofflon Offers Automated and Integrated Pharma Solutions to Indian Markets
From 16th to 18th October, 2013, Tofflon held seminars in Ahmedabad and Hyderabad, India. 5 speakers from USA, Japan, Korea and Tofflon HQ presented comprehensively the trends of technology innovations and automated machinery solutions needed for the pharma and biotech industry.The Seminar, themed ‘Challenges and Solutions in Lyophilized injectables’ focused on the need for automation and integration of various technologies such as Freeze Dryers, Auto loading and Unloading systems, Barrier Systems and vial filling lines which include washer, sterilizing tunnel, filling, stoppering and capping machines. All these machineries are of significant for large-scale and high efficiency pharma and biotech manufacturing.
P06
Tofflon News
Over 100 representatives from all the leading pharma and biotechnology companies such as Mylan, Aurobindo, SMS, Virchow, Gland Pharma, Biological E Ltd, Indian Immunological Ltd, Gennova, Mab Pharma, Bharath Biotech, Dr. Reddy & Natco pharma etc were present during the seminar. Tofflon, the Chinese based leading pharma and biotechnology equipment solution provider is all set out to focus its energies to acquire major market share in India by offering highly automated and advanced integrated solutions to its pharma and biotech customers.On the whole the Company is initiating its focusing on the Indian markets to offer its customers not only top quality freeze dryers but also complete global lyophilisation solutions. To strengthen its core competence, Tofflon is making important investment from advanced innovation, facility expansion to organization restructure. To ensure its local presence, the company has established Joint venture and partnership with top quality companies from the USA, Europe and Japan, and has set up local officers and agencies all around the world.
“We are manufacturing freeze dryers since 20 years, now we are focusing on more automation and software integration. As India a is a vast country and the pharma companies here are looking at large scale production with high grade of efficiency at a lower cost, we at Tofflon are working on innovative automated solutions integrated advanced technology which would enable pharma companies to increase speed in their manufacturing, filling and packaging procedures. At the same time, we provide exclusive barrier system technology to ensure the aseptic environment” says Fengmin Wu, Assistant of Chairman, Tofflon. Speakers from South Korea, Japan and China took part in the seminar and gave elaborate presentations on Freeze dryers, process isolators, intelligent vision system, solution preparation system, power handling systems, barrier systems(oRABS/cRABS/isolators), auto loading systems, ALX derail ampoule filling line and automatic loading systems. While talking about the freeze drying system “Our freeze drying systems are designed by Italian and USA designers, the material is sourced from Germany, France and USA and assembling is done in China. We provide one of the world’s best high quality machinery at affordable price without comprising on the quality,” added Mr Wu.
Expertise In Pharmaceutical Industry
P07
The 46th China International Pharmaceutical Machinery Exhibition held in Chongqing, China on 26th to 29th, 2013. Tofflon participated this exhibition, with its freeze drying system and other new products including aseptic vial filling line, ampoule filling line, and HEPA system. At the night of 26th October, 2013. Tofflon held its 20 Anniversory Thanks Dinner in The Le Grand Large Hotel, located in Chongqing China World Trade Center. The representatives from China Pharmaceutical Associates and nearly 1000 Clients attended this dinner and exhibition. In this exhibition, Tofflon not only exhibited its freeze dryer, auto loading systems, barrier systems(production model and process isolator), automatic solution preparation system, vial filling line, ampoule filling line, but also demonstrated its new developed inspection machines(for powder and liquid ), aseptic API handling systems, pass box, rubber washer and API vibrator with isolator. Besides equipments, Tofflon also exhibits the lyophilized drugs from Tofflon Lyophilization Lab, this including Vaccine, Chemical Drugs, Traditional Chinese Medicine and Other new drugs. More than 30 technical engineers from product development departments introduced Tofflon’s new technology and various products. One visitor said“it’s a amazing, when I attend this exhibition and see new technology and equipments come out”. As the largest exhibitor with its 1100 square meters booth, Tofflon demonstrated its strength and development to visitors and its clients again.
Tofflon Attended The 46th (2013 )China International Pharmaceutical Machinery As the Largest Exhibitor
P08
Tofflon News
PDA Annual Trainings in China was Sponsored by Tofflon
The Parenteral Drug Association (PDA) is the leading global provider of science, technology and regulatory information and education for the pharmaceutical and biopharmaceutical community. Founded in 1946 as a nonprofit organization, PDA is committed to developing scientifically sound, practical technical information and resources to advance science and regulation through the expertise of its more than 9,500 members worldwide.In order to help Chinese pharmaceutical companies update the newest technology of risk control and validation during the process, PDA held its annual trainings in Beijing and Shanghai. The themes are “Quality Risk Management for Aseptic Processes” and “Process Validation: A Lifecycle Approach” . During the four days training in Beijing, 24 to 25 October, and Shanghai, 28 to 29 October. More than 120 professionals from 65 pharmaceutical companies attended the 4 days courses. Hal Baseman, the Principal of Valsource, and the Member of PDA Council who is the lecturer of the course “Quality Risk Management for Aseptic Processes”, shared his abundant experience of pharmaceutical industry and rich knowledge. Robert L. Dana, the Senior Vice President of PDA, who owned 40 years pharmaceutical industry experiences present his thorough understandings to the theme of “Process Validation: A Lifecycle Approach” .
“These courses are very inspiring, some of the validation approaches are very useful and practical for my daily works.” One of the attendees said, who are the QC Supervisor of a pharmaceutical company. Tofflon as the exclusive sponsor of this activities, shared its experience with the attendees regard of “freeze drying system in practice ” at the night of 24th , “Your course is very practical, you solved lots of problems we meet in the daily work”, one attendees commented. Chen Zhi ,who is the technical manager from Tofflon System&Solution Department, answered the attendees’ questions.
Expertise In Pharmaceutical Industry
P09
Integration with Global Technology to Provide Service for Pharmaceutical Industry
Tofflon 2013 Seminar in China
On September 24, 2013, Tofflon held a seminar themed “integration with global technology to provide service for pharmaceutical industry” in shanghai. The high number of over 500 specialists and visitors from 180 pharmaceutical companies were present in the seminar. It has impressed participants greatly. In 2013, it witnessed Tofflon’s 20th anniversary. It not only invited senior experts from SFDA to communicate with participants, but also experts from Italy and Sweden to share their sophisticated understanding of the technologies in pharmaceutical industry.
At the beginning of the seminar, Tofflon Chairman Mr.Anthony Zheng delivered opening speech and shared the latest trend in pharmaceutical industry worldwide. He said that nowadays pharmaceutical industry has been specialized worldwide accordingly ,such as ,United States is famous for its validation management and software engineering ,Italy is more specialized in mechanical design , Germany is well-known in mechanic control system ,Sweden is more in environment control system ,and Japan is specialized in environment conservation technologies ……Fortunately, Tofflon has already integrated the best resources in with world to provide service for the pharmaceutical industry and . All the customers were impressed and received positive feedback. One of the customers said: “Tofflon has already been far ahead of its competitors in China in integration of technology and resources. The seminar is very informative and valuable for me. It teaches me a great deal.”
P10
Tofflon News
After the seminar, all participants were invited to take factory tours in Tofflon headquarters and its several subsidiaries. It has demonstrated the whole picture of Tofflon manufacturing process, the quality control system ,company value and its corporation culture……etc. Especially, Tofflon has demonstrated the whole freeze drying system line and new products in workshop. It has fully illustrated Tofflon R&D and innovative capabilities. All customer witnessed and experienced Tofflon how to become the top brand of pharmaceutical machine manufacturer in China and how to expand its global markets with 20 years’hard work and persistence on the way.
As the proverb says: God rewards the diligent. In the seminar ,Tofflon have impressed customers by its image: advanced ,systematic ,reliable from the concept to vivid machine demonstration in workshop. It showcased Tofflon’s persistent commitment to provide its service to pharmaceutical industry.
Expertise In Pharmaceutical Industry
P11
P12
The International Society of Lyophilization held our International Conference on Lyophilization and Freeze Drying in Brazil at the Casa Grande Hotel Resort and Spa, located in a beautiful beach area of Guaruja, Sao Paulo.This year’s Conference took place October 2nd and October 4th.Michael Chang, Philip Zheng, Mike Stella, and Gerrard Yang attended the Conference. ISL-FD invited many scientists from all over the world, who are the experts in lyophilization, to Sao Paulo, and they all gave speech to share their latest results, including lyophilization technology improvement, new lyophilization equipment and its application in the area of pharmacy and food. Dr. Steven Nail of Baxter Biopharma Solutions was the Key Note Speaker. What followed was 3 days of well recognized scientists who shared advanced and novel papers on different applications of lyophilization.Micheal Chang, as the Board Member of Tofflon and Managing Director of International Business Division discussed how to transfer the latest technology to application, and shared his thought with the attendees.Cocktail lounge was held on the balcony of the Casa Grande Hotel. Following a banquet dinner was treated with exceptional entertainment by “Brazilian Style” musicians and dancers. Along with the Conference, a Table Top Exhibition was held by vendors who shared their company’s products and/or services with the attendees.
“International Conference on Lyophilization and Freeze Drying”—Tofflon Attended the ISL&FD Conference (2013), Sao Paulo, Brazil
In early September,under the full support of Agent Hanson Company, we Tofflon successively held 2013 Freeze Drying System Training for Korea Pharma&Bio Delegations in Shanghai. The training included several sessions ,which lasted about 15 days.This training specially invited Hanson's owner Mr.Y.J Bahng and veteran engineers who comes from famous Korean pharmaceutical companies to the seminars.At the begining of the training program, Mr.Michael Chang and Mr.Y.J Bahng gave the fascinating opening speech. During the training, experienced experts from Tofflon's different department made a fascinating and detailed speech on the history of Freeze-Dryer technology and System. Dr.Yang , who is senor manager from Tofflon Lyophilization lab, had given a wonderful speech. Tofflon established Lyophilization lab ,which has a professional team and advanced R&D equipments to optimize freeze-drying process. In the next few days, the experienced service engineer Mr.Max Xu ,who has many years services experience in the field for customers ,shared his expertise in service and professional overall solutions to problems on site. The training program was given in the process from concept to practice .It combined the concept and theory of Freeze-Dryer design, technology and how to apply them in pharmaceutical production manufacturing site.All the information was delivered from the view of pharmaceutical manufacture process. After the splendid lectures ,all of participants were impressed greatly. From the feedback ,this training was informative and valuable and it presented new technology for them. One of the customers said:”the speakers were knowledgeable and professional, all of them teach us a great deal, and the whole arrangement of the training is thoughtful and considerate ,which make us feel comfortable and enjoyable. Thank you!”
Expertise In Pharmaceutical Industry
P13
2013 Freeze Drying System Training for Korea Pharma&Bio Industry Delegations in Tofflon
The 5th Anniversary Jubilation for Tofflon Russia in 15th Pharmtech ExhibitionThe 5th Anniversary Jubilation for Tofflon Russia in 15th Pharmtech Exhibition
Tofflon in Pharmed & Healthcare Vietnam Exhibition 2013
Tofflon’s stand in Pharmtech 2013
In the past 5 years, Tofflon has been from nothing to well-known name in the Russian pharmaceutical industry. Since the market access, Tofflon has made many good friends, including strategy partner “Holding Pharmtech”, helpful and valuable customer “Petrvax”, “Microgen”, “Pharmstandard” and so on. Tofflon believe that globalization means localization.
Tofflon News
P14
On Sep. 18 to 21, 2013, Tofflon attended an exhibiton “Pharmaed & Healthcare Vietnam 2013”in Saigon Exhibition & convention Center(SECC), Vietnam. During exhibition, Tofflon showed its core product-freeze dryer and along with its new product: including vial filling line, ampule filling line, solution preparation system, barrier system and inspection machine. This exhibition has been organized 7 times successfully, during the 8th exhibition, more than 30 countries, 4,000 exhibitors attended presented this event. This exhibition is organized by Vietnam Central Health Communication & Education Center, Adpex J.S.C, VNPCA Vietnam Pharmaceutical Companies Association, Vietnam Medical Products Import Export Co. – Vimedimex VN, under the direction Ministry of Health of Vietnam. During 3 days of exhibition, exhibitors were brought closer to local users, distributors and dealers. This event provide a good occasion of face to face communicating with potential clients at their base in Vietnam. Meanwhile Vietnam shares international border with Laos, China, Cambodia and etc. It’s the economic gateway to a potential vast market owning 2 billion consumers. Vietnam’s investment value lays not only within the country itself but also on the regional linkages that it offers through its strategic geographic location. Living standard of people has increased steadily, and per capita health expenditure are dramatically increasing. The establishment of private owned hospitals, pharmacy and clinics has created a need for quality product.
One of exhibition guests - Mr. Basel, chief engineer of Microgen Allergen(Tofflon 2xLYO-5(SIP,CIP) user), said that he had to admit that Tofflon’s local technical support had the outstanding quick response, and sometimes the company does not count the service cost, in order to provide better service to the local clients.Every moment in the exhibition might have a major surprise. Friends from Ukraine, Belarus, Norway, Egypt, Germany and China joined the party in Tofflon’s stand as well. Conversation topics were GMP in different states, lyophilization process, modern factory and so on. The most often topic was the company future and the tendency of the industry. After many years deep in the market study and over one year preparation, a customized freeze dryer machine series “LYOSMART” was finally released for the Russian market and exhibited in the Pharmtech 2013. Tofflon LYOSMART was designed and manufactured under the principle of “just in time and just enough”. Its high cost-performance rate and customized size make it to be the replacement of TG-50 series machine, which was still widely used in Russia but were old model and near their original retirement ages. And its high practicability and high reliability would be proven in the following decade.
Tofflon attended the 15th Pharmtech Exhibition, last from 25th to 28th November, All-Russian Exhibition Centre, Moscow, Russia. Its stand in the exhibition hall was highly interested by old and new customers, friends and even competitors. It’s also the 5th anniversary of Tofflon Russia.In the past 5 years, Russian Federal is one of the most important markets for the company. As the world largest freeze drying system supplier, Tofflon has established stable distribution channel and quick response service center in Moscow Region. Dr. Alexander Didenko, head of lyophilization department of NPO Petrovax Pharm (Tofflon LYO-10(SIP,CIP) and 2xLYO-5(SIP,CIP) user), visited Tofflon’s stand for the second time since 2012. He expressed that Tofflon’s machines were working smoothly and expected Tofflon’s service team to maintenance another machine in his facility which is made by brand name manufacturer in USA.
After the new machine release and promotion presentation, made by Mr. Leo Li (Tofflon area sales manager) and Mr. Artemy A. Kirpichnikov(Director of “Holding Pharmtech”) during the exhibition, the speakers were surprised by the enthusiasm of the audience. After the rapid growth in the pharmaceutical industry over the last decade, the more sedate, stable development and growth being seen today is making companies slightly uneasy. Future growth of Tofflon in the Russian pharmaceutical market will be dependent on global cutting-edge technique, well experience in mass equipment production and customer-focused innovation.
Tofflon LYOSMART
LYO SMART release and promotion presentation
Friends in the exhibition
Expertise In Pharmaceutical Industry
P15
Здраствуйте, Tofflon
Namaste, TofflonHello, Tofflon
Hello, Tofflon
Bonjour, Tofflon
Guten Tag, Tofflon
你好, 东富龙
Tofflon, Your Global
P16
Pharma Industry
Headquarter:Shanghai Tofflon Science and Technology Co., Ltd.Address:1509, Duhui Road, Shanghai, China, 201108Tel: 0086 21 64901123 / 64906201�Fax: 0086 21 64905148 / 64906202 Email: Information: [email protected] Sales: [email protected]: [email protected]
Hola, Tofflon
Ola, Tofflon
Hello, Tofflon
P17
Expertise In Pharmaceutical Industry
Trusted Partner！
India office:Tel:080-41700254 Mobile:9900625836Fax:080-4127584Email:[email protected]. [email protected]
In recent years, the monoclonal antibody market around the globe has witnessed substantial growth, and the CAGR of market scale during 1997-2011 has reached 44% approximately. Meanwhile, monoclonal antibody is also a key major source of blockbuster drugs .Antibody drugs are usually generated from monoclonal antibody through genetic engineering, with the advantages of strong targeting, few side effects, etc. With rather promising application prospect in clinic treatment, antibody drugs are mainly applied in curing diseases like tumour, immune system and so on. In terms of the global market, antibody drugs account for over 40% of the entire biotech drug market and the market share still keeps increasing. Antibody drugs have become one of the most important parts of biotech drugs and monoclonal antibody drugs are even star products of antibody drugs. In 2011, the sales of six monoclonal antibody agents as Infliximab (Johnson & Johnson), Etanercept (Amgen), Bevacizumab (Roche), Rituximab (Roche), Adalimumab (Abbvie) and Trastuzumab (Roche) reached above USD5 billion around the globe, approximating 60% of global monoclonal antibody market. Among the top 10 best selling drugs in 2012, six of them were monoclonal antibody drugs with each annual sales value exceeding USD 5 billion. [1]
The market scale of monoclonal antibody drugs increased rapidly in recent years, In 2012, the global sales value of monoclonal antibody preparation exceeded USD 50 billion. Among that, Roche (plus Genentech) was the leading monoclonal antibody enterprises, which possessed seven products sold in the market including Avastin, Herceptin, Rituximab, etc. In 2012, its sales value of monoclonal antibody products reached USD 20 billion. Mono antibody drugs will become the main force promoting the development of biological drugs in the next few years.
Monoclonal Antibody on Global and China 2013-2017
Pharma Industry
P18
Pharma Industry
Unlike traditional small molecule therapeutics that are produced through chemical synthesis for less than $1 per gram, mabs must be produced in mammalian cells at a cost of $300-$5,000 per gram. Although simple proteins/peptides such as insulin, growth hormone, and G-CSF are produced in bacterial hosts such as E. coli with various advantages such as established regulatory track record, well characterized product and competitive cost; complicated proteins with glycosylation mostly can not be produced in E. coli because E. coli is unable to modify proteins after they are produced and it often makes misfolded and, thus, inactive proteins. For these reasons, monoclonal antibodies and fusion proteins can not be produced in E. coli but rather must be produced in mammalian cells. Compared to E coli system, the construction of the genetically engineered mammalian cells is more time-consuming, production is less efficient more expensive, and product launch requires an expensive commercial scale manufacturing capacity.Mab development begins with the construction of a master cell bank. This involves genetically engineering a host mammalian cell, typically a Chinese hamster ovary (CHO) cell, to produce the protein of interest. CHO cells are often used because they multiply quickly, are relatively hardy, and grow well in suspension culture. When a cell line is created that produces high levels of the desired protein and can be grown robustly in suspension cell culture, a master cell bank is created. It will serve as the source of all cells used in the production of clinical and commercial quantities of protein under development. The creation and characterization of the master cell bank typically takes 6-8 months.Once a master cell line has been created, the next step is bioprocess development. This covers 2 phases of activity: expansion of the cells
to a large volume and recovery and purification of the target protein.Once the clinical development is complete and the drug is approved, managing appropriate manufacturing capacity is extremely difficult. Too little capacity leads to lost sales while too much capacity results in unwarranted capital expense, low utilization rate of the facility, and high depreciation cost. Mab manufacturing took center stage in the late 1990s as a stream of monoclonal antibodies (e.g., Genentech’s Rituxan and Herceptin, and MedImmune’s Synagis) and antibody-fusion drugs (e.g. Amgen/Immunex’s Enbrel) achieved unprecedented success in the market. While this unforeseen success was welcome, the widely known Enbrel shortage as well as other manufacturing-related product delays highlighted the importance of adequate planning for manufactur-ing capacity [2] Enbrel’s shortage mandates that patients already on Enbrel had to wait in line to get their drugs and no new prescriptions were allowed for new patients. It is estimated that Immunex potentially lost billions dollar of Enbrel sales and also allowed faster uptake of a competitor product Remicade from Johnson & Johnson during launch.
In recent years, China bio pharmaceuticals industry develops rapidly, but antibody drugs lag far behind the average international level with sales value being less than 3% of biological drug share. At present, China antibody drug market is still in the initial stage.Mab development in China started mainly in academic research institutions in the late 1980s.
Challenges of mab manufacturing
Mabs in China
Expertise In Pharmaceutical Industry
P19
However, there is little progress since then. While all of the mabs entering clinical trials in the US and EU are humanized or fully human, most of the programs in China are still chimeric. Several of them are still mouse mabs. Lack of novel products and humanization technology are strong hindrance of the development in this area. Therefore Chinese players are mainly interested in biosimilar mab programs.However, with Shanghai CITIC National Health Pharmaceutical Co., Ltd. and Biotech Pharmaceutical Co., Ltd. releasing humanization products, product types of domestic antibody drugs will enter the upgrading stage. Although domestic full humanization products have not been released, humanization products and full humanization products will become the domestic trend of monoclonal antibody products in the future.
Although there are tremendous challenges in growing a sophisticated mab industry in China, there are also enticing opportunities to serve the large domestic market, to provide contract manufacturing service to reduce cost of mab therapeutics in the US and EU, and to develop high-quality biosimilar mabs for the global market. Returnees from the west who can bring a wealth of product development experience from the US and EU can play a significant role in expediting mab development and manufacturing in China.Monoclonal antibody still belongs to high end products in China market, which mainly depends on import. In 2012, the market scale of monoclonal antibody was only over CNY 2 billion, which accounted for less than 1% of the global market share but the growth rate was rather high. Roche is the largest winner in China monoclonal antibody market with the market shares of its Rituximab and Trastuzumab being the largest. Merck and Novartis also occupy rather large market shares. Take Rituximab and Trastuzumab that were produced and sold by Roche at an earlier time for instance, their sales values in sample hospitals were only CNY 17.70 million and CNY 2.70 million respectively in 2003, which increased to CNY 590 million and CNY 530 million in 2011.
In 2012, the sales value of Etanercept produced by China native enterprises exceeded CNY 400 million, with net profit approximating CNY 200 million and profit margin far exceeding that of other biological drugs. Currently, China domestic monoclonal antibody drugs are still in the initial stage and only nine kinds of drugs have been sold in the market. Most drug varieties that are in clinical study or have been sold are complete copies of products sold overseas with rather low production level and small scale, which restricts the domestic development of monoclonal antibody drugs. Facing huge market space, many pharmaceutical enterprises have already entered monoclonal antibody drug field, such as Shanghai CITIC National Health Pharmaceutical Co., Ltd., Zhejang Hisun Pharmaceutical Co., Ltd., Livzon Pharmaceutical Group Inc., Shanghai Fosun Pharmaceutical (Group) Co., Ltd., etc.
Opportunities of mab manufacturing in China
P20
Pharma Industry
Since 2011, Chinese government has issued many documents to support the development of biological drugs. In January 2012, China MIIT issued the "12th Five Year Plan" Development Plan of Medical Industry; in July 2012, Chinese State Council released the "12th Five Year Plan" Development Plan of National Strategic Emerging Industries; in January 2013, Chinese State Council launched the 12th Five Year Plan on Biology Industry Development. In terms of listed enterprises, the " industrialization of annually producing 3.2 million injections of Anbainuo" of Zhejang Hisun Pharmaceutical Co., Ltd. has already been listed in the special fund plan of emerging industry development, getting CNY 40 million subsidy from the government.Monoclonal antibody market develops rapidly in recent years with constant introduction of new varieties, so the market share of each drug is also changing constantly. CRI predicts that new varieties will constantly come to market and the market structure will be further adjusted in the next few years. Monoclonal antibody products will be more widely applied in clinic and the influence on cancer treatment and the markets of related fields will become increasingly obvious. CRI predicts that the annual market scale of China monoclonal antibody market will exceed CNY 10 billion by 2017.
Reference:
1. marketresearchreports 2013-20172. Birch et al., Advanced Drug Delivery Reviews 2006, 58, 671–6852. Thiel, K., et al. Nature Biotech. 2004, 22, 1365
P21
Lyophilization is one of the key processes in the production of many aseptic pharmaceutical and biological products. During lyophilization, water is removed from the products so that temperature-sensitive or unstable products could be transformed to stable products without changing their original properties. The lyophilized products can be transported and stored at normal environment conditions. Now this technology is widely used in biological engineering, pharmaceutical industry, food industry, material science and agricultural and veterinary products etc.The refrigeration capacity, flexibility of operation, operational reliability and performance of refrigeration system contribute to the successful lyophilization. However, the historical data show that 90%~95% of the lyophilizers have been adopting mechanical refrigeration. And 80% of the lyophilizers service have focused on refrigeration maintenance. In order to solve this problem and to improve the product quality and to shorten the lyophilization cycle, Tofflon successfully developed 10 m2 LN2 refrigeration freeze dryer in year 2006, then developed 20 m2 and 40 m2 LN2 refrigeration freeze dryers respectively in year 2007 and year 2008. The new type freeze dryers with advanced technology overcome many inherent problems which cannot be solved in the past, and better meet the requirements of modern freeze drying process. Cryogenic cooling system replaces mechanical refrigeration and transfers cooling energy from liquid nitrogen through special ly-designed cryogenic heat exchanger. The necessary auxiliary system includes a liquid nitrogen storage tank, a set of cryogenic valves, and piping from the tank to the refrigeration skid. All of these components are highly insulated to minimize the cryogen losses, e.g., by vacuum jacketing or super insulation. The cryogenic LN2/GN2 cools the HTF in an initial cooling circuit. Typically, a second LN2/GN2 cooling circuit cools the condenser by direct expansion in the coils. A more advanced cryogenic refrigeration system is a single nonfreezing cryogenic heat exchanger simultaneously cools both the shelves HTF loop and the condenser HTF loop.
The cooling capacities of LN2-based condensers are higher than compressor-based systems. It can readily achieve lower condenser temperatures. And more uniform and consistent condenser temperatures can be controlled throughout the entire process, including the peak load in primary drying. So the LN2 freeze dryer is more suitable for the drug dissolved in non-aqueous solvents.
Achieve lower temperature (For non-aqueous solvents)
The Advantages of LN2 Refrigeration Freeze Dryers
P22
Tofflon Insight
The freezing of a formulation solution starts with ice nucleation, followed by ice growth. In the freezing stage, most water separates into ice crystals through a matrix of glassy and/or crystalline solutes. To maintain the constant cooling rate can influence the microstructure of both ice and solute formed during freezing, further influences the characteristics of primary and secondary drying and ultimately the quality of the final product.
Maintain constant cooling rate (For better ice structuring)
Shown as the above, most of the lyophilizers service focuses on the maintenance of refrigeration. Compared with mechanical refrigeration, cryogenic cooling systems require minimal maintenance. Especially for the high value products, improving reliability means a big assurance of the quality of drugs.In addition to the above points, there are several other advantages, such as smaller footprint than mechanicals, environment friendly (no CFC) and quiet operation, and the nitrogen gas may be available for other uses.LN2 refrigeration freeze dryer as a high-tech product is not only using an advanced liquid nitrogen system. The other most advanced energy-saving designs are also using in the major components showing as below.
Improve reliability and requires minimal maintenance compared with mechanical refrigeration (For high value products)
The freezing of a formulation solution starts with ice nucleation, followed by ice growth. In the freezing stage, most water separates into ice crystals through a matrix of glassy and/or crystalline solutes. To maintain the constant cooling rate can influence the microstructure of both ice and solute formed during freezing, further influences the characteristics of primary and secondary drying and ultimately the quality of the final product.
Provide faster cooling and/or freezing rate (For vaccines)
Expertise In Pharmaceutical Industry
P23
Take advantages of longer service life, lower maintenance costs, stably running, and high product quality, the LN2 refrigeration freeze dryer will bring you huge direct and indirect comprehensive benefits.Tofflon has developed a great understanding of the pharmaceutical industry's needs in 20 years of engineering and manufacturing standard and custom lyophilizers. We have worked closely with our customers to manufacture cost-effective, reliable solutions to meet their specific freeze drying requirements. We look forward to working with you.
US Praxair NCOOLTM Heat ExchangerSamson®(Germany) LN2 control valveRosemount® (America) liquid level indicator and pressure sensor
◆
◆
◆
cGMP Lab Freeze Drye Production Freeze Dryers Tofflon freeze drying systems (two floors)
P24
The primary drying time is directly related to the ice sublimation rate and is determined by numerous factors, including chamber pressure, shelf temperature, heat transfer coefficient of vials, fill volume, and product resistance.The primary drying time can roughly be estimated from the calculation of heat and mass flow via Eqs. Primary drying time estimates for tubing vials as a function of Ts-Tb. These estimates are crude approximations, but can be used as an initial guess of the primary drying time with little input data required.The end point of primary drying can be detected by several different methods. At the end of primary drying, there is no ice present in vials (i.e., no ice sublimation and no heat removal by sublimation); thus, the product temperature increases to the shelf temperature, and the vapor composition in the freeze-drying chamber changes from essentially all water vapor during primary drying to mostly air or nitrogen. Thus, product temperature data indicate the end point of primary drying when the product temperature approaches the shelf temperature. Normally, the product temperature as a function of time shows a steep increase in temperature at the end of primary drying, followed by a plateau.
Methods of Pressure Rise Test at the End Point of the Primary Drying
Expertise In Pharmaceutical Industry
P25
Frequently, the vials containing thermocouples are not representative of the batch as a whole because of the bias in freezing behavior. Thermocouple vials usually have less supercooling, large rice crystals, and faster ice sublimation, and, therefore, shorter primary drying time. Drying differences between thermocouple vials and the rest of the batch could be a serious problem, especially for manufacturing where the bias in freezing behavior is more pronounced. Also, in manufacturing, Thermocouples are usually placed in front-row vials for maximum sterility as surance. Front-row vials finish primary drying far earlier than the interior vials due to atypical radiation heat transfer effects.
Thus, thermocouple vials are not representative both because of heat transfer effects and because of freezing-bias-induced mass transfer effects. Among the other methods that can be used, those methods that sense the transition in gas composition in the chamber from water vapor to nitrogen are perhaps easiest to use. Dew point sensors, which can detect the vapor composition change or the relative humidity in the freeze-drying chamber, shows a sharp dew point decrease at the end of primary drying due to the vapor compositions in the chamber changing from almost 100% water vapor to essentially 100% nitrogen. Comparative pressure measurement also works well. The thermal conductivity pressure gauge is calibrated against air and shows higher vapor pressure during primary drying because the thermal conductivity of water vapor is about 1.5 times that of air or nitrogen. At the end of primary drying, the pressure difference between the thermal conductivity pressure gauge and capacitance pressure gauge decreases and approaches zero. A variation of the classical pressure rise test, called the MTM method, is another very sensitive and promising method to indicate the end point of primary drying. The vapor pressure of ice determined by a fit of pressure rise data to the MTM equations approaches the chamber pressure when no ice remains .
Fig.1. The product temperature increases to the shelf temperature in the later period of the primary drying.
Fig2. The right position of temperature sensor to detect product temperature accurately.
Tofflon Lab
P26
The MTM method differs from the classical pressure rise test in that the MTM procedure removes the impact of water desorption from the freeze concentrate, and does not require “calibration” for each application to determine how much pressure rise is needed for a “not dry” decision. Experiments have shown that the MTM method can detect the pressure of only three vials with ice in a 50-liter laboratory freeze dryer.When thermocouple vials are used to indicate the end point of primary drying, an additional “soak time” or safety margin for primary drying time of at least 10% of the primary drying time of the thermocouple vials is helpful to make sure all ice has been removed. The soak time is the period of extended primary drying after the end point of primary drying as determined by thermocouple response. This soak time requirement is due primarily to the bias in primary drying behavior between thermocouple vials and the rest of the batch. Here we suppose the thermocouple vials are placed in the center of the array. The drying bias is larger if the thermocouples are placed in the front row, as is typical, and a longer “soak time” is necessary, at least 20% of the primary drying time for thermocouple vials. A soak time is not needed with the other methods of end point detection.The primary drying time is usually longer for manufacturing freeze drying due to greater supercooling in the sterile and “particle free” environment in manufacturing as well as less radiation heat transfer from the door and walls. If laboratory-developed processes that are based on a fixed time for primary drying are used without modification, there is a high risk of melt-back or collapse problems. The melt-back or collapse problem results from shelf temperature elevation before the end of primary drying, and the resulting increase in product temperature melts or at least collapses the product at the vial bottom. We suggest extending the laboratory drying time by at least 20% to scale-up processes that do not use annealing and thus have the potential for large freezing bias.
Fig3. MTM apparatus schematic.
Expertise In Pharmaceutical Industry
P27
Tofflon IndiaCustomer Service Excellence
Tofflon India Pvt Ltd is founded in 2010. It is a subsidiary of Shanghai Tofflon Science and Technology Co., Ltd. Tofflon India started its operation as a small firm, today it caters all Freeze drying services and supports across India.Tofflon India delivers productivity to customers seeking peak performance by providing innovative freeze drying solutions. This proven productivity is enabled through advanced pharmaceutical science and application knowledge. Today Tofflon India is a part of Indian pharmaceutical industry; it provides services to major pharmaceutical industries in India.
P28
Tofflon Service
1. We are where our customer needs to be
From past few years of strong, customer-focused approach and continuous quest for service quality have enabled us to attain and sustain leadership in all its major lines of business. Tofflon India employed many Indian service engineers. Company business strategies based on innovation and growth and our main source of innovation is our employees. Tofflon India involved in attracting, motivating and retaining talented people and helping them to perform at consistently high levels are all vital to our continued success. Tofflon offer many opportunities for professional and personal growth of the employees in a collaborative and stimulating workplace. A well trained and motivated workforce is the foundation on which our company is built. Tofflon want our employees to achieve their potential, further their careers and contribute to the continued success of the company. Continuous learning and development opportunities are an important part of our strategy to retain our best employees.
2.Employee Development Program
Every year on the contract basis one of the service engineers is migrated to our head office in shanghai for the training. During the training,
company provides technical knowledge of Tofflon products which intern develops the problem solving ability of the engineers at the customer site. During training Tofflon also guides the engineer about Tofflon new innovative technologies and products. A key focus of Tofflon development program is to identify and develop current and future leaders. As part of succession planning, Tofflon continually review and recommend for promotion of employees who show exceptional leadership qualities and strong performance. Employee retention rates give a good indication of employee satisfaction and ensuring the best employee remain at Tofflon India means our development program working successfully. By offering long-term job stability, development opportunities and a good working environment, Tofflon India aim to keep staff turnover to a minimum.
3.Our Engineering Culture
Tofflon India Professional Team is a knowledge based group which endeavors to provide best and wide spectrum of Freeze drying services & support at one stop. Tofflon India has strong foundations by which Tofflon wish to achieve robust growth. Tofflon diversified and dedicated team of
Expertise In Pharmaceutical Industry
P29
professionals has expertise in providing excellent services. The benefit of employing local Indian service engineer helps to solve the problems of customers at site by easy communication with local staff. Tofflon India in order to improve the service quality, conducts the investigation of customer satisfaction through customer feedback. And also to run the machine in healthy condition Tofflon Indian engineers conduct the training program to customer employees about machinery process of working & maintenance.
4. Tofflon India Vision
Tofflon India closely associated with many of the top pharmaceutical & biotechnology companies in India, like Strides (Mylan), Aurobindo, Gland Pharma, Gufic Bio-science, Intas, Bharath biotech, Gennova, Biocon, IIL, Nitin Life science etc. and provides most dedicated & valuable freeze drying service, support & supply of spare parts on turnkey bias. Tofflon India is an emerging company, at present Tofflon have registered offices at Bangalore and Hyderabad. In the future Tofflon planning to expand its branch offices & work force at various cities across India. It helps to provide the better services to customer during emergencies to carry out hazel free operation.
P30
Tofflon Service
Venice of the OrientZhouzhuang
Zhouzhuang, the "Venice of the Orient," close and small enough for a quick day trip from Shanghai. Although there are other towns in China such as Tongli, dissected by streams, rivers and canals, Zhouzhuang is the most famous such "water town" nowadays.The old town of Zhouzhuang is located in the "Golden Triangle" among Shanghai, Suzhou and Hangzhou. The stone bridges and flowing water of Zhouzhuang, the town that made CNN's list of the top-10 most beautiful towns in the world
More than 60 percent of Zhouzhuang's architecture has been well preserved from the Ming and Qing dynasties. Likewise, the town's 14 stone bridges, from the Yuan, Ming and Qing dynasties, embody a unique structure that mesh well with the old waterway infrastructure for which the town is famous.Ancient streets intertwine with waterways in Zhouzhuang's unique infrastructure. Known as "the best water village in China," the town was listed on CNN's top-10 most beautiful towns in the world.
Ancient streets well preserved from the Ming and Qing dynasties
P32
Travel in China
Water Lanes & Stone Bridges
The layout of the water lanes in Zhouzhuang resembles a Chinese character "#". Many stone bridges are built over them, linking houses on both sides of each stream. These stone bridges are very old. 14 of these were built in the Yuan, Ming and Qing Dynasties
Expertise In Pharmaceutical Industry
P33
Travel through Zhouzhuang's waterways on a Chinese-style gondola.Some of drivers c sang as they drove.
Gondola Driver in Zhouzhuang Water Village
2199,Fanghe Road,Duhui Road, Minhang District, Shanghai 201109 ChinaTel:+86 21 6490 1123 / 6490 6201Fax:+86 21 6490 6202 / 6490 6202Email:[email protected]://www.tofflon.com
Shanghai Tofflon Science and Technology Co., Ltd.
