Biocon clarifies on Methylcobalamin row
In the last few months, there has been a lot of controversy surrounding Biocon Ltd, one of the leading biotech companies in India, for allegedly violating certain norms of manufacturing Methylcobalamin. The controversy is that Biocon had requested the Union Government for a license to import the base material and manufacture Methylcobalamin (MeB12) in India.
The company had also obtained license from the Karnataka government to manufacture the drug in seven stages. On March 17, 2003, the Karnataka government had given license (No. 46 A-MF 668) to manufacture the drug in seven stages. However, on January 17, 2006, the office of the drug controller of Karnataka on a routine inspection found that Biocon was not manufacturing the product in its Bangalore facility and that it was importing the drug from China. The state government subsequently cancelled the license.
Speaking to CyberMedia News, Karnataka health minister, R Ashok pointed out, "The company has not manufactured the drug as per the seven stages. The government rule clearly states that if there are any changes in the manufacturing of the drug, which was not according to the license, then the company had to obtain permission from the government. Else it violates the Rule 18 (g) under Drugs and Cosmetics Act."
Following the state government's notice to Biocon, the company admitted that they were importing the drug without the government's permission. "The state drug controller, Rama Murthy has written a letter to Ashwin Kumar, chief drug controller in Delhi on March 28, 2006 on this issue to take action against the company. So far we haven't got any reply from the Central government. The state government cannot do anything in this matter," Ashok said.
Meanwhile, on February 10, 2006, Biocon got the license from the Central government to import Methylcobalamin. "It is true that the company has obtained the license in February this year, after the Karnataka government found out their illegal activity. But for three years, the company has violated the rule and done business. It is a punishable act," added Ashok.
BioSpectrum wrote to Biocon to understand the issue. Kiran Mazumdar-Shaw, chairman and managing director, Biocon Ltd informed, "Methylcobalamin is a form of Vitamin B12 and an internet search will indicate that it is available internationally as a dietary supplement or nutritional supplement and is not regulated as a drug in many countries.
The other common forms of Vitamin B12 are cyanocobalamin and hydroxocobalamin. However, in India, it has been regulated as a drug since 2002."
Biocon initially intended to manufacture the product starting from cyanocobalamin using a multi-step process for which it obtained a manufacturing license from the state drug controller's office. "However, competition from cheaper imports made this unviable. Hence, Biocon revised its manufacturing process to begin from an advanced intermediate with fewer manufacturing steps without compromising the quality of the final product. However, there was a regulatory oversight in not updating the manufacturing license to reflect the new manufacturing process. During a routine inspection, the state drug controller's office noticed this lapse and issued a show cause notice to Biocon. Biocon admitted the lapse and hence the manufacturing license for this product was cancelled," added Shaw.
Biocon immediately stopped manufacturing the product and also stopped importing the advanced intermediate. "Subsequently, Biocon made a fresh application to the Central and state drug controller's office and has obtained a fresh license from both. Hence the issue now stands rectified," informed Shaw.
According to Biocon, this is a minor product in Biocon's portfolio and is not central to its strategy of focusing on cardio-vascular, diabetes and oncology segments.
Srinivas R, CyberMedia News
Industry leaders urge for early clearance of biological materials
The third meeting of the Indian sub-group under the "Indo-US Joint Industry Working Group on Biotechnology" was organized in New Delhi recently. The event which was organized by FICCI, focused on issues related to clinical research, transfer of biomaterials and other concerns needing closer interaction with the various government departments. The meeting was chaired by Dr MK Bhan, secretary, Department of Biotechnology. Ashwini Kumar, Drugs Controller General of India (DCGI) along with other officials from the customs and excise also participated in the meeting.
Some of the prominent issues discussed included:
Exchange of biological material: At present, for importing live biological materials, clearance is required from the Ministry of Environment and Forests and the Drugs Controller, which takes about three-four months. Urging for early clearance of perishable biological material, the industry leaders suggested that the Drugs Controller may handle all the clearances as a single window.
In addition, they requested for process simplification for sending the clinical trial samples abroad for testing where the DCG (I) is given the authority for single window clearance of the clinical trial samples. Similarly for export of SCOMET items, a single window clearance mechanism was proposed.
New Drug Authority: The industry raised concerns regarding inadequate staff and other resources of the present Office of the Drug Controller General of India (DCGI). The biotech leaders discussed the proposed New Drug Authority, which is being considered by the Ministry of Health and Family Welfare on the lines of the FDA in the US. They suggested that the proposed authority should be an independent statutory body on the lines of TRAI, IRDA etc., headed by an officer of appropriate level and a scientific advisory board should be constituted for this with persons of eminence who can guide its functioning.
They were of the opinion that the New Drug Authority should be adequately staffed with trained scientists and should have enabling policies to attract the best brains in the country. The transition from old to the new drug administration should be smooth in order not to adversely impact the industry.
Samples for Pharmacogenomics: The industry representatives requested for a re-look into the requirement of ICMR permission before the samples can be shipped abroad. They suggested that only one regulatory authority should give clearance or opinion of experts may be requested.
Other suggestions: Clinical research expenditure be considered as R&D expenditure by the IT department; Need to expand training program on clinical research; Relief to the industry from the 12 percent service tax for clinical research; Customs procedural simplification to avoid delays in clearances; Removal of anomalies in duty structure between public and private sector; Strengthening the infrastructure at the ports including the cold room facilities; and Capacity building on airports and ports.
Responding to the industry concerns, Dr Bhan stated that the department will be taking up many of their concerns with the other ministries and in many cases help in developing a standard operating procedure.
AIBA recommendations for biofertilizers industry
The All India Biotech Association (AIBA) has come out with a set of recommendations emerging from a national level seminar on "Biofertilizers: Potential and Perspective", organized by it earlier this year. The day-long round of deliberations saw active participation from the agri research community.
The recommendations include: Establishment of a microbial consortium to ensure the quality of inoculants; urgent need for popularization of the existing mycorrhizal biofertilizers production technologies; micro enterprises be encouraged where they should be given the technology of increasing the shelf life of new products, development of different types of carriers and other innovations; and the industry take major initiatives for the quality control and standardization of the production technologies.
From the policy and regulatory issues perspective, the recommendations emphasize on: The evolution of a procedure to stop the production of biofertilizers by fake companies; Need for establishment of large number of decentralized production units and farmers be encouraged to produce blue green alga in their own fields; Exemption from customs duty on import of plant and machinery for production of biofertilizers and excise duty exemption, sales tax and other financial concessions/incentives be made available for the promotion of the industry; Testing facility, registration facility and a database needs to be established-the Kisan Vikas Kendras, state agricultural universities and deemed universities of the ICAR can be identified as important testing centers for this purpose. There could be at least six regional centers to act as referral centers.
The recommendations have also addressed other important issues like: Sale of spurious products, for which an appropriate legislation including the registration of the product and its certification is considered essential; A buyback agreement, especially with the farmers and the industry as also government agencies, i.e. a tripartite mechanism be evolved; and a minimum of 30 demonstrations of the new product to be used as biofertilizers must be conducted by the industry and the data scientifically evaluated.
The inaugural session of the seminar was presided over by Dr Manju Sharma, former secretary, DBT and it was inaugurated by Dr S Nagarajan, chairman, Protection of Plant Varieties and Farmers Rights Authority, New Delhi. There were elaborate discussions on the present status of biofertilizers use in the country, R&D, production technology and constraints in wider application of biofertilizers. Over 150 delegates had participated in the event.
"Medical equipment certification is a vast and rapidly evolving field"
- Manish Bhatnagar, director, sales and marketing of Underwriters Laboratories Inc.-India, South East Asia, Australia and New Zealand operations.
Manish Bhatnagar is responsible for business development, customer acquisition, branding and marketing initiatives, and customer service in these regions. Prior to joining Underwriters Laboratories, he worked for GE in various business leadership roles across India, Europe and North America. He is also a certified Six Sigma black belt. He holds an MBA from IIM Calcutta, and a BE from BITS Pilani. Bhatnagar shares his thoughts on regulation of medical devices.
What are your comments on the Union Health Ministry's recent decision to regulate quality of medical devices?
Asian countries, particularly, India is making vast industry improvements to attract more outsourcing business and also cater to the growing medical device opportunities in the Asian markets. It's a welcome move to introduce certification to regulate the quality of medical equipment. This provides a future road map for manufacturers to meet quality standards and also access and compete in international markets. At present, these regulations are confined only to in-vivo devices and probably could extend to electro-medical equipment also.
What is the current market trend in medical equipment certification in India and what does Underwriters Laboratories (UL) propose in this regard?
Medical equipment certification is a vast and rapidly evolving field that is often complicated by legal technicalities. In India, certifications are largely done for MNCs and few SMEs as they target at exports. Most of the devices are certified for CE mark, UL mark and some to FDA (510k) etc.
UL India is fully geared up to meet the requirements on regulatory, testing, evaluation and certification needs for India and international markets. We have our own independent test lab and also partner with various government labs for testing and evaluations. UL aims to provide Indian manufacturers a one-stop shop solution for all their global regulatory and certification requirements.
How will UL help the industry and regulatory bodies such as Central Drugs Standard Control Organization (CDSCO) towards formulating medical standards?
UL can provide technical inputs on requirements of the International Standards (IEC 60601-1, EMI/EMC), country deviations, providing test plans and compliance evaluation of medical equipment.
How different is UL from other certifications like CE or FDA?
UL mark is the world's most instantly recognized and trusted symbol and assures customers that the products certified by UL have been independently verified for safety, quality and reliability and are market driven marks. UL mark adds value to customers' products and helps entry in most demanding markets, be it Europe, North or South America, Asia or the Middle East. CE or FDA are regulatory in nature and are mandatory to enter markets such as Europe and the US. UL is also a notified body for medical devices and can certify and review products for CE, FDA and ISO 13485, a quality management system for medical device manufacturers.
What are UL's strengths?
UL's strength is in offering a full range of testing, certification, registration services and knowledge solutions locally that help customer's to meet national and international safety and regulatory requirements.
In how many countries does UL operate? Is the certificate applicable only in the US?
UL has presence in 96 countries with 62 laboratory, testing and certification facilities in the UL family of companies. UL is not only applicable in the US but also in demanding markets such as Europe, Asia and the Middle East and is also the notified body for medical devices.
What is the scenario in other countries with respect to regulation of medical devices?
Regulations of medical devices in this region is quite open and voluntary. However, manufacturers are required to register their products with the relevant health authorities prior to marketing their products. Most of the APAC regions accept international regulatory certifications such as CE and FDA.
What are your India plans as well as in other Asian countries?
UL India with its in-house test lab is also the regional hub for emerging markets such as South East Asia, Australia and New Zealand (ANZ), and the Middle East regions. We plan to double our headcount in the next two years.
How should one apply for UL? How long does it take to certify and what is the cost involved?
Any customer can apply to UL online (www.ul.co.in) or write to email@example.com, providing details of the product. Typically UL mark takes about 4-8 weeks in testing and certification and the cost depends on the type and construction of the product.
What are your views on the medical devices market and issues in India and the Asia Pacific?
The medical market size in India is close to $2 billion and consists largely of MNC players and SMEs. It is expected to touch $3.5 billion by 2010. The products mainly sold are active devices, inactive devices and implants. India is also one of the largest centers for development of medical software.
Asia Pacific is another growth market for medical devices with a strong domestic consumption as well as exports to the Europe and the US and most Asian governments are striving to improve their healthcare in order to meet these domestic demands.
The main issues faced by most of the manufacturers in this region are lack of clarity on regulatory requirements for medical devices and product standards such as IEC 60601-1, etc. Also there is a shortage of availability of local test facilities to test medical devices for quality. Also regulatory requirements in the AP region are voluntary and this could pose challenges whether the products manufactured and sold meet the required international standards on safety and quality.
With increased multinational medical companies outsourcing to Asia each year, not only can these companies reduce expenses, but they also benefit from Asia's fast growing economies and medical markets, but issues such as IP protection, manufacturing standards such as GMP, ISO 13485, etc. can present issues.
Ch. Srinivas Rao
India to offer a new effective typhoid vaccine soon
Mumbai-based USV Limited has entered into a license agreement with the Biotech Consortium India Limited ( BCIL) to upscale, manufacture and market a novel conjugate typhoid vaccine developed by a team of scientists at the All India Institute of Medical Sciences (AIIMS), led by Dr BL Jailkhani, Dr MK Bhan, Dr Ramesh Kumar, and Dr Sanjukta Sengupta and Shabirul Haque. The project was supported by the Department of Biotechnology (DBT), Ministry of Science and Technology, Government of India. BCIL is a company promoted by DBT for facilitating commercialization of biotechnology products and processes.
USV is an emerging force in biotherapeutics with products such as HGH, Nesiritide, PDGF, IL-2, interferons and erythropoietin in its pipeline. Eptifibatide, a platelet aggregation inhibitor, synthesized by its biotherapeutics division, has already been launched into the domestic market. The typhoid vaccine project could give USV a foray into the new niche area of vaccines.
Typhoid is still a very serious problem in developing countries of Africa and South America, several regions of former USSR, parts of South and East Asia and the Indian Subcontinent.
There are about 16-33 million cases of typhoid fever annually, accounting for nearly 6 lakh deaths. An earlier surveillance study conducted by AIIMS in a Delhi slum showed peak incidence in children between age 1 and 5 years and that the disease was as severe in children as in adults. With a rise in multi drug resistance, the disease has not only become difficult to treat but the cost of treatment also has increased over the years. Vaccination can help control the increasing morbidity and mortality, while reducing the expenditure of healthcare systems on disease control. Vaccination can also limit the spread of multidrug-resistant S. typhi to other geographic areas.
Currently available vaccines have several drawbacks. Though heat- and phenol-inactivated typhoid vaccines have shown 50-70 percent effectiveness in clinical trials, their frequent local and systemic side effects have limited their acceptance. The most widely used Vi capsular polysaccharide vaccine confers protection against typhoid in individuals between five and 45 years of age but is ineffective in eliciting protection in children less than five years who are at the maximum risk of getting the typhoid infection.
The present Vi conjugate vaccine developed by the team of scientists from AIIMS involves conjugation of capsular polysaccharide of S. typhi to a carrier protein obtained from the same organism through recombinant DNA technology and rendering the vaccine immunogenic in infants. It has the potential to prevent typhoid fever more effectively than Vi alone in infants, children and adults and can be administered along with other vaccines used for routine immunization of infants.
The vaccine under consideration has shown promising results in animal studies. It can induce a T-cell dependent immune response and thus may be effective even in children below two years of age. The results have shown more than 30 times higher immunogenic response with the conjugate vaccine than the Vi polysaccharide alone and thus is expected to give a longer protection period, may be even up to 10 years, as the immunity is T cell mediated.
There are several important potential uses of a well-tolerated typhoid vaccine especially if it is effective in infants. It could play an important part in controlling typhoid fever in endemic areas and should reduce the burden of implementation of school-based vaccination programs.
The Indian market for typhoid vaccine currently is approximately Rs 30 crore and is growing. At present, the global market is estimated at $50 million.
Panacea Biotec forays into measles vaccine segment
Panacea Biotec has entered into an agreement with Indonesia-based PT. Bio Pharma, a state-owned enterprise, to manufacture and market the measles vaccine. As per the terms of agreement, Panacea will procure the bulk vaccine from PT Bio Farma and formulate it into a finished product.
"Panacea Biotec plans to supply the vaccine to UNICEF, PAHO countries, countries in Africa region, LATAM countries, Asian region, CIS countries and countries in Middle East, in furtherance to the current WHO and UNICEF Global Measles Reduction Strategy," said Rajesh Jain, joint managing director, Panacea Biotec.
The agreement was signed in New Delhi by Rajesh Jain, JMD, Panacea Biotec and Marzuki Abdullah, president director, PT Bio Farma.
The demand for measles vaccine is estimated at 40 million doses annually in India. Currently there is a wide gap between the demand and supply of the measles vaccine, which Panacea aims to address through this tie-up. "The vaccine will be manufactured using a superior formulation technology and will be produced in a freeze dried form. It will be manufactured at the company's formulation plant at Baddi in Himachal Pradesh and it is expected to be commercially ready by the end of 2007," Jain said.
Panacea plans to produce about 30-50 million doses of the measles vaccine every year and in the long run the company will look at developing thermostable measles vaccine as well. Marzuki Abdullah, president director, PT. Bio Farma said, "Measles is a widespread disease worldwide especially in the developing countries. We are pleased to join hands with Panacea Biotec to enhance the global supply of measles vaccine thereby helping in combating the disease and saving millions of lives."
Delhi to get international biotech center
A UNESCO Regional Center for Education and Training in Biotechnology will come up in New Delhi with the Science and Technology Ministry signing an agreement with the world body for promotion of science.
A MoU was signed between Union minister for science and technology, Kapil Sibal and UNESCO director-general, Mciez Nalecz in New Delhi. The center will be promoted as a regional hub for research with the participation of countries like Japan, China and Australia, Sibal said.
According to the DBT secretary, Dr MK Bhan, Nobel laureates will be invited as visiting faculty to the center, which will have students from Asia. In addition to education and training, the center will have strong research program in areas like nano-biotechnology, stem cell research, biosensors, environmental biotechnology and agriculture biotechnology, Dr Bhan said.
The broad plan for the center, which will get an initial government allocation of Rs 50 crore, will be ready by February next year, Sibal said. The center will offer post-graduate degrees besides doctoral and post-doctoral training, Nalecz said.
DCGI approves Baraclude
Bristol-Myers Squibb has launched Baraclude (entecavir) for the treatment of chronic hepatitis B virus infection following its approval by the Drug Controller General of India.
Baraclude (entecavir) is indicated for the treatment of chronic hepatitis B virus infection in adults with evidence of active viral replication and either evidence of persistent elevations in serum aminotransferases (ALT or AST) or histologically active disease.
Baraclude is an oral antiviral therapy specifically designed to block the replication of hepatitis B virus (HBV) in the liver.
Chronic hepatitis B infection is a potentially life-threatening disease. More than half a million people worldwide die each year from hepatocellular carcinoma (HCC), and up to 80 percent of these cancers are caused by chronic hepatitis B.
India has intermediate endemicity for hepatitis B infection with prevalence for chronic infection of 4 percent. An estimated 36 million are chronically infected with the hepatitis B virus, most of which are established during early childhood. Hepatitis B infection is reported to be responsible for 80 percent of the cases of cirrhosis of the liver and 60 percent of HCC. It was estimated that 12,750 new cases of HCC were diagnosed in 2001.
Biocon registers hike in revenue
Biocon reported a net profit of Rs 39 crore for the first quarter-same as the corresponding period last fiscal-as the company said profits were static on account of higher spend on Biocon Park. The company said consolidated sales in the April-June quarter of 2006-07 grew 22 per cent year-on-year to Rs 212 crore. Biocon said in a statement that EBITDA (Earnings Before Interest, Depreciation, Taxes and Amortization) margins were at 26 per cent, down four per cent from Q1 of last fiscal, because of an adverse impact on foreign exchange movement and a 50 per cent increase in R & D spend, among other things. The company said its income from research services increased to Rs 29 crore, a 52 per cent growth over Q1 of 2005-06.
...gets DCGI nod for cancer drug
Biocon Ltd has said that the DCGI had granted approval to market its BIOMAb EGFR in India. The product will first be used in the treatment of head and neck cancers and later extended to other indications viz. colorectal, brain, breast, pancreatic and lung cancers.
Manipal AcuNova gets ISO Certification
Manipal AcuNova has received the ISO 9001:2000 certification by Underwriter Laboratories India Pvt Ltd. In a statement, Manipal AcuNova said that it was the first contract research organization in the country to be awarded this recognition for adhering to all the mandates of business processes as mandated in the scope of registration.
The scope of registration covers clinical operations, clinical data management, Bio availability/ bio equivalence, central reference laboratory and support services.
Venkitachalam, managing director, Underwriter Laboratories India Pvt Ltd formally handed over the certificate to Dr Ramdas Pai, chairman, Manipal Group in the presence of DA Prasanna, vice chairman and managing director, Manipal AcuNova.
Speaking on the achievement, Prasanna, said, "The achievement of the ISO 9001:2000 certification confirms to our customers that globally recognized and approved quality standards have been implemented in all our processes and operations facilitating better systems and cost effective management of the company. The ISO 9001:2000 certification also clearly establishes our long-term commitment to meeting and exceeding the needs and expectations of customers in a rapidly globalizing marketplace."
Wipro BioMed, CIphergen Biosystems form strategic alliance
Wipro BioMed, the healthcare division of Wipro Limited, has entered into an agreement with Ciphergen Biosystems Inc, to market the latter's ProteinChip Systems and Solutions.
The alliance empowers Wipro BioMed to market CIphergen Systems and Solution products in India, Srilanka, Bangladesh, Nepal Region.
Clinical trials highlight an emerging trend in R&D that uses smaller test volumes helped by sophisticated automated technologies like Ciphergen's ProteinChip Technology. Such technologies have redefined the process of drug discovery as it can identify and prioritize drug targets based on their ability to corroborate a multitude of gene expressions in parallel.
Varsha Anand, vice president, Wipro BioMed said, "With the industry witnessing changes, healthcare customers in India require more than a piecemeal selling approach. The service provider is required to value add and we are fully equipped to meet customer expectations through combinations of innovative approaches."
Avesthagen sowing 'Seed-For-Food' with Limagrain
Bangalore-based Avesthagen has entered into a strategic alliance with Group Limagrain ('Limagrain'), a French major in global seed business. This strategic alliance is a long-term, mutually beneficial agreement between Avesthagen and Limagrain, in which resources, knowledge and capabilities will be shared with the objective of enhancing each partner's competitive position.
"Alliances are becoming increasingly important in the agri industry to bridge the gap between the field experience and emerging technologies. This is because larger seed companies need to increase research productivity and biotech companies are representing one of the major sources of this cutting edge research. It is this symbiotic relationship that fuels an increasing number of opportunities. Pursuit of creative collaboration and partnership is a key requirement to success" said Dr Villoo Morawala Patell, CEO, Avesthagen.
Daniel Chéron, deputy CEO of Groupe Limagrain said, "With this global alliance, Vilmorin & Cie will have opportunities to speed up the development of new potential for growth already engaged in India by its vegetable subsidiaries. It will furthermore bring opportunities to operate collaborative R&D programs in biotechs, especially related to GMO's field plant trials. It will also provide development opportunities for Group Limagrain Ingredients division."
The current move in establishing alliances between Avesthagen and Limagrain, is to allow Limagrain strengthen its position in the Indian market. In turn Avesthagen will have access to Limagrain's expertise regarding elite germ plasm breeding and global seed marketing.
A Special Purpose Vehicle (SPV) is being created to jointly develop a seed business unit in India. This will help in marketing the improved plant varieties developed in collaborative R&D programs aimed to develop agrotechnologies that can add value to seed and food products.
Best Biotek Research Lab expands operations
Best Biotek Research Lab is opening its first training and research center at
Nagpur, Maharashtra. For Best Biotek, Nagpur center is the first to be operated
Nagpur-based Disha Institute of Biosciences which is involved in the bioservices business, have been appointed as the master franchisees for Maharashtra. Best Biotek plans to open centers in Hyderabad, Mumbai, Pune, Delhi and Kolkata by the end of this year.