Indian cos gearing up to embrace global GMP norms

Shardul Nautiyal, Mumbai Thursday, March 13, 2014, 08:00 Hrs  [IST]

In the wake of a spate of warning letters on Indian pharma companies by US FDA, the US-based online compliance and regulatory learning solutions company Underwriters Laboratories (UL) Eduneering, which trains drug regulators to ensure safety of FDA related pharma products is planning to equip leading Indian pharma companies on maximizing compliances related to consent decree, Form 483, data integrity and quality management systems. This would entail maintenance of electronic records for inspection readiness of Indian companies. This comes as a welcome change as US FDA commissioner Margaret Hamburg plans to hold multi-year capacity building workshops for domestic regulators to understand US FDA standardised processes of GMPs and cGMPs in drugs and medical devices segment. The workshops are planned to be held in Ahmedabad, Gujarat, Hyderabad, Chandigarh and Goa. FDA Commissioner had made a visit to India between February 10 and 18 for strengthening cooperation between the two countries on regulatory compliances. Informs Dr Kavita Mehrotra, global strategic alliances head, UL EduNeering, "Considering the fact that certain Indian companies have got critical global attention due to certain evasions, violations and avoidances during US FDA inspections, compliance is required for development of closed systems which captures electronic signatures, audit trails and any changes made in the system or content and also simultaneously offer, track, record and report at the same time. This is in accordance to 21 CFR Chapter 11 compliance of US FDA guidelines." To serve compliance and regulatory needs of the fast growing life science community in India, UL and US FDA have also extended their Cooperative Research and Development Agreement (CRADA) for five additional years, extending the agreement till 2019. US FDA’s CRADA with UL is the only learning technology agreement of its kind between US FDA and a private sector company. The extended CRADA agreement between US FDA and UL is designed to address training needs that include topics related to international inspections, import and export of products that fall under US FDA purview and intra agency and intra government co-operative agreements. It also involves access to the FDA’s Office of Regulatory Affairs online curriculum via ComplianceWire, which is UL EduNeering’s cloud-based learning platform. Designed specifically for Indian life science industry, the Learning Management System (LMS) called ComplianceWire is built on a cloud- based model which helps reduce IT and validation costs. Capable to cater globally in 34 languages, the system helps in audit readiness for training records while being fully secure and complies with US FDA’s electronic signature governance requirements. Equipped to provide SOP management, it adapts well to the strategic agility of the growing business needs of organizations. UL has trained over 30,000 US FDA inspectors till date. "As a statistical testament to our product leadership in this area, in 2013, we recorded 23 million training completions by our global audience, with 400 clients in pharma and medical device area and government agencies," Dr Mehrotra adds. With the coming of Obama Care and exports of generics, Active Pharmaceutical Ingredients (APIs) and finished drug products from India to the US projected to grow by 40 per cent, Indian life science companies are in dire need of achieving regulatory compliance to minimize organizational risk and improve quality and business performance through training on GMP compliance. Quality culture for patient safety The USFDA Commissioner, Dr Margaret Hamburg in her talks with Indian regulatory experts have advocated the need for a quality culture to be developed in Indian pharma companies. Ellen Leinfuss, senior VP, UL EduNeering and an expert on global regulatory compliance echoed sentiments of Dr Margaret and said that quality is linked to product safety and without focus on quality, the potential for patient harm increases significantly. In an email interview with Chronicle Pharmabiz, Dr Margaret said, "I am pleased that, as a global leader in the pharmaceutical sector, India will continue partnering with us to ensure that the companies exporting products to the US are adhering to established quality standards. On the home front, we at the FDA will also continue to increase our focus on quality. One way we are doing this is through the creation of a new office of pharmaceutical quality that will create one voice for drug quality at the FDA and improve our oversight of quality throughout the life cycle of a pharmaceutical product." Quips Leinfuss, "As the practice leader for UL EduNeering’s life science business, commitment of the US and India's pharmaceutical community is encouraging as it will help pharma companies foster a “quality culture.” Dr Hamburg stated, “In my talks with regulators and companies here in India, I have placed a great deal of emphasis on why quality matters.” Elaborating on the quality aspect, Leinfuss further says that the work done by compliance and regulatory learning solutions companies with the US FDA over the past 14 years can help develop training and educational programmes around cGMP and other key quality topics for safe delivery of drugs to global patients. Echoing his views Scott Barnard, quality, compliance and learning expert says, "Considering the demand and importance of meeting the quality and compliance expectations of the FDA, my experience of working with life science clients says that development of quality and compliance culture comes from education and training. We have had tremendous success helping clients use cGMP training and systems to build a strong quality foundation for their organizations." Reiterating the point that India pharma industry need to reclaim its position in a global market, Dr Kavita Mehrotra, global strategic alliances head, UL EduNeering concludes, "It is clear that India, the second largest exporter of over the counter and prescription drugs to the US is in the news because it is important to the global market." Proposal to reduce generic drug user fee In order to reduce the financial burden of around 300 US FDA approved pharma facilities in India, Indian Drug Manufacturers Association (IDMA) has asked the USFDA to reduce the annual fee on approved Indian pharma facilities by 50 per cent. This request was made during the discussions between the DCGI and the US FDA Commissioner during her recent visit to India. A proposal which is in the draft stage will be sent to the US FDA by IDMA following the request. The fee to be charged on an annual basis came into effect from October 2, 2012 under the Generic Drug User Fee Amendments (GDUFA). The US regulations require the exporting drug companies to pay user fees to supplement the costs of reviewing generic drug applications and inspecting facilities. Says S V Veerramani, president, IDMA, "We would be making a proposal to the US FDA following this request shortly which also aims at offering participation to around 100 small bulk drug companies who are planning to make an entry in the US market. The introduction of a facility fee of $230,000 annually for a US approved Indian facility in formulations and $60,000 for a bulk drug facility which did not exist earlier can be a deterrent for companies looking at regulated markets." Filing for an Abbreviated New Drug Application (ANDA) costs around $50,000 and a DMF Dossier costs $32,000, he further added. As per US FDA, these fees help it to reduce the backlog of pending applications, cut the average time required to review generic drug applications for safety and improve risk based inspections. With a spike in the frequency of US FDA's regulatory action and India accounting for 40 per cent exports of generics to the US, Indian life science companies are in dire need to achieve regulatory compliance through training on GMP compliance, consent decree, Form 483, data integrity and quality management systems. This would also entail maintenance of electronic records for inspection readiness and lead to additional costs in the form of training. "We are also planning to seek a role in offering our services and support to US FDA and Indian pharma companies on conducting mock audits and training workshops for audit preparedness of Indian facilities. We are awaiting a response on this subject from the US FDA," concludes Veerramani. Electronic data management In order to sensitise Indian companies regarding falsified, non existent or destroyed records which leads to violation of GMPs, regulatory experts recommend the need for developing and maintaining electronic data as paper records can easily be lost, damaged or cannot be validated for accuracy. As per the US FDA guidelines, effective documentation procedures must ensure not only the quality of the recorded data but also security of the records and the validity of the signature (electronic records must comply with 21 CFR Part 11). Pinpoints compliance and regulatory expert Scott Bernard, “The paper based records poses several risks in audit accuracy and also raises issues of security and validation.” According to experts, this has become more imperative with the implementation of new laws including the US Food and Drug Administration Safety and Innovation Act (FDASIA). Says S M Mudda, executive director, Micro Labs, “Dr Reddy’s have already started some electronic documentation in modular and phased manner. Micro Labs is also moving towards the same process with the introduction of an automated warehouse management system.” Taking note of compliance and scalability issue, many Indian companies, as well as global multinationals such as Teva Pharmaceutical Industries, Johnson & Johnson, are interested to move from manual system to an electronic system. Says Ellen Leinfuss, SVP, UL EduNeering, an online global regulatory learning solution provider, “We started the process of educating companies about electronic documentation a few months back and six to eight Indian companies have shown interest so far with us." The curriculum and the FDA authored suite of courses on GMP, cGMP, GCP and QSR, offered by UL EduNeeering, is designed to address training needs through services in India and include immediate and long- term relevant topics related to international inspections, import and export of products and global compliance etiquette. Sharing her views on electronic documentation, regulatory expert Dr Kavita Mehrotra explains, “I have had a chance to meet with several heads and leaders of large and mid-size Indian pharma companies in the past couple of months. Most Indian companies are struggling to understand the specifics of global compliance expectations, ranging from the need for appropriate documentation, to electronic records, to visibility and empowerment of QA groups.” Online regulatory and compliance solution is one very reachable way of offering consistent articulate electronically available training to all the employees regardless of their geographical location. Expertize on GMP norms and its accessibility comes as a much needed wake up call to the Indian pharma industry, which is ripe for standardizing training channels to meet the expected global standards. Dr Mehrotra concludes, "Global GMP processes are not only feasible and time tested but are also custom made to suit Indian pharma regulatory environment. There is a need to offer the Indian pharma companies effective, actionable training strategies, tools and content, to demonstrate and observe regulatory compliance.”

Dissolution testing gains ground in Indian pharma industry with new advancements

Shardul Nautiyal, Mumbai Friday, May 09, 2014, 08:00 Hrs  [IST]

In order to highlight the importance of dissolution testing in pharmaceutical industry as a tool in drug development and quality control, Society for Pharmaceutical Dissolution Science (SPDS) conducted its 2nd annual international convention DISSO ASIA 2014 between May 5th and 6th 2014 in Mumbai. Dissolution testing is required for all solid oral pharmacopoeial dosage forms in which absorption of the drug is necessary for the product to exert the desired therapeutic effect.  Disintegration was originally thought to be this characteristic. The United States Pharmacopeia (USP) introduced its disintegration test in 1950. With advances in methodology, the disintegration test was found to be too insensitive, and dissolution test methods were introduced in the USP in 1968. Experts deliberated that Dissolution is principally useful as a Quality Control test and is poised to gain importance as a research and development (R&D)tool for Indian academic institutions and pharma industry. Organised under the guidance of founder president of SPDS, Vijay Kshirsagar chief executive officer, of Track Consultancy,  Dr Nandakumar Chodankar, chief executive officer, A Solution Pharmaceuticals and the organizing secretary, Dr L Ramaswamy, managing director of Sotax India, the scientific sessions were programmed and executed under the chairmanship of Dr Mangal Nagarsenker, HOD, Pharmaceutics, Bombay College of Pharmacy, Mumbai. Speakers deliberated on new technology, innovation and issues related to dissolution. Around 150 delegates from industry and academia attended the event.  Sotax India was the platinum partner of the event. "Traditionally developed for solid oral dosage forms, use of dissolution testing has been widened to a variety of dosage forms such as semi solid, liposomes, nano particles, parenteral preparations in the last few years," explained Dr Ramaswamy. The event comprised of plenary lecture, poster exhibits, panel discussion and exhibits. Speakers drew the conclusion that a lot of progress has been made during the last three decades from the aspect of standardisation and harmonisation of regulations. Vijay Kshirsagar, director, TRAC Consulting, Mumbai spoke on the Relevance of Current Batch Centric BE Studies, Dr Vinod Shah, Ex. US FDA, Pharmaceutical Consultant, USA spoke on FDA/USP Perspectives on Dissolution Testing from Regulatory Filing point of view. Prof. Dr Jean Michel Cardot, Professor, Department of Biopharmaceutics, and Pharmaceutical Technology, Auvergne University, France spoke on In-Vitro Dissolution as in Vivo Surrogate; Samir Haddouchi, Managing Director, SPS Pharma Services, Clermont Ferrand – France spoke on Challenges and Solutions to Dissolution Testing of Non-Oral Formulations; Dr. Umesh Banakar, Professor and President, Banakar Consultancy Services, USA spoke on Biosimilars - The Emerging Frontier for Generics: Role of Dissolution Testing; and Michel Magnier, Product Manager, SOTAX AG spoke on Automation for Dissolution Testing. Bryan Crist, Manager, Scientific Affairs, Agilent technologies, USA spoke on Validation of Components and data of Automated Dissolution Methods; Prof. Dr. Sompol Prakongpan, Professor of Pharmacy, Burapha University, Thailand spoke on Biowaiver of Biopharmaceutics Classification System Class III Drug Products; Dr. Sid Bhoopathy, Chief Operating Officer, Absorption Systems, USA spoke on Strategies for Establishing Equivalence of Complex Drug Products and Dr. Flavian Stefan Radulescu, University of Medicine and Pharmacy “Carol Davila” Bucharest, Romania spoke on Correlation between rheology, in-vitro release and in- vivo performance of topical dosage forms. The International Symposium was inaugurated by Dr. GD Yadav, the Vice Chancellor of Institute of Chemical Technology (ICT), Mumbai. Dr.Vatlamudi Rao, who is the current President of IPA ( Indian Pharmaceutical Association) was the Guest of Honor. In his address he has expressed that IPA shall support SPDS and do collaborative programmes across the country. SPDS also launched a Desk Book of Pharmaceutical Dissolution Science on the occasion authored by more than 10 eminent authors and edited by Dr Sandeep Tiwari, Dr.Umesh Banakar and Dr.Vinod Shah. Dr. Vinod Shah and Dr. Umesh Banakar were awarded  with the SPDS excellence award for their immense contribution to the field of Dissolution Science by president Vinay Kshisagar and the Dr. Mangal Nagasenkar, Scientific Committee chairman and the organisers. There was also a Panel Discussion on “Handling dissolution Challenges” by eminent professionals from the Pharmaceutical Industry. Specifically designed for all the professionals from R&D, QA and QC as well as the Academia, SPDS is planning to organise DISSO America in USA next year.

FDA Nagpur takes action against retailers & wholesalers for non-compliance of norms

Shardul Nautiyal, Mumbai Saturday, May 10, 2014, 08:00 Hrs  [IST]

The Maharashtra Food and Drugs Administration (FDA)'s  Nagpur Division has cancelled 364 drug licenses of retailers and 12 drug licenses of wholesalers in the revenue year 2013-14.  The licenses have been cancelled for non -compliance to the Drugs and Cosmetics Act on the basis of inspections of 4,190 retailers and 1,265 wholesalers in Nagpur Division last year. According to official reports, FDA has gained an overall performance of 79.25 per cent in the previous year. There are 4,574 retail medical stores and 2,315 wholesale stores in Nagpur division.  Expressing satisfaction over the work of FDA Nagpur division, a state FDA official said that there has been a lot of awareness among common people and the department received about 3 to 4 complaints every day last year. Besides this, the division has 120 manufacturing units. FDA has completed inspections of all these units in the last one year. FDA has given show cause notices to 23 units and canceled licenses of five units, six licenses were suspended, warnings were issued to five units while eight cases are pending. Around 84 samples were declared sub standards on analysis by the government analysts out of the 521 samples of medicines collected by the FDA last year. Nine cases were filed on sub-standard medicines and eight cases were filed under other categories. The FDA has also taken action against two firms for violation of the provisions of Drugs Price Control Order (DPCO) and seized stock of medicines worth Rs. 1,48,675 and registered 10 FIRs under Drugs and Magic Remedies Act. Two firms were also fined Rs. 1,20,000 for selling sub standard medicines and ayurvedic medicines worth Rs. 50,000 were also seized.

Maha FDA cancels licenses of 5452 retailers, suspends 3178 for violation of D&C Act

Shardul Nautiyal, Mumbai Wednesday, May 14, 2014, 08:00 Hrs  [IST]

The Maharashtra Food and Drug Administration (FDA) has canceled licenses of 5452 retail pharmacies and suspended licenses of another 3178 retailers across the state in the year 2013-14 for violation of Drugs and Cosmetics Act like dispensing medicines without prescription and without proper bill. During the year, the FDA had conducted inspections on 48086 retail stores in the state. The FDA's crackdown is in line with the fact that there is irrational usage of around 65 per cent of antibiotics and cancellation of licenses is done based on the non-compliance like dispensing medicines without prescription and without bill. It has been reported that there is only five to six per cent billing on sales across Maharashtra. During the year, the FDA had inspected 5469 retail stores in Greater Mumbai, 7143 in Konkan, 11,801 in Pune, 6855 in Nashik, 4574 in Nagpur, 8097 in Aurangabad and 4147 in Amravati FDA divisions. Around 901 licenses were canceled and 693 suspended in Greater Mumbai alone. Maximum number of 1384 cancellations were done in the Konkan Division followed by Mumbai, Pune with 896 licenses, Aurangabad with 801, Nashik with 612, Amravati with 489 and Nagpur with 369. According to FDA officials, compliance to Schedule H1 is being pursued on a war footing by educating retailers.  Maharashtra FDA Commissioner Mahesh Zagade convened meetings in Nagpur, Nashik earlier and in Mumbai recently to sensitise retailers about the Schedule H1 compliance. The union health ministry had amended the D&C Rules to insert Schedule H1 to regulate the use of antibiotics in the country, and had placed 46 antibiotics under this category. Similar kind of actions have also been taken by FDA under the Drugs and Magic Remedies (Objectionable Advertisement) Act (DMR Act). Against the backdrop of several instances of violations to DMR Act last year, FDA has recently filed First Information Report (FIR) against a Mumbai based weight loss firm this year. FDA had served 1434 notices and filed 58 FIRs last year. Prosecution is going on for four cases.

http://www.pharmabiz.com/NewsDetails.aspx?aid=80244&sid=1  Need for coverage of mobile and migrant populations for prevention of polio

Shardul Nautiyal, Mumbai Friday, February 07, 2014, 08:00 Hrs  [IST]

With India being declared as a polio free nation on January 13, 2014 by the World Health Organization (WHO), experts point out that there is a need for coverage of mobile and migrant populations from countries like Burma, Pakistan and Afghanistan where polio cases have been detected. India can combat polio as Indian companies like Serum Institute of India and Bharat Biotech are capable of manufacturing polio vaccines of global standards. Informs Dr Sambhaji Zende, managing director, Haffkine Bio-Pharmaceutical Corporation, "India is on the way to make a paradigm shift from Oral Polio Vaccine (OPV) to injectables to make the vaccines more user friendly. Many European countries have adopted it and India would embrace the trend in the coming two years time." Though there has been a decline of 99 per cent in cases of poliomyelitis worldwide since 1988, India still needs to combat issues related to neglect of routine immunisation, immunity gap, lack of clinical and virological surveys and operational issues. Established in 1975 as a Government of Maharashtra undertaking to produce life saving vaccines, Haffkine Biopharmaceutical Corporation has a long history of indigenously manufacturing biological products. Since then, the company has come a long way and also set up a GMP facility that is pre-qualified by WHO for supply to United Nations Children's Fund (UNICEF). It was one of the first public sector vaccine manufacturing units to get a WHO accreditation for a trivalent OPV. It has three facilities in Maharashtra for different products. Located in the heart of the city, amidst various central and state research institutes and hospitals, the Mumbai facility manufactures the oral polio vaccine as well as the DPT vaccine.

FDA News

http://www.pharmabiz.com/NewsDetails.aspx?aid=79995&sid=1 Maha FDA files FIRs against pharmacists for doing dual employment

Shardul Nautiyal, Mumbai Saturday, January 25, 2014, 08:00 Hrs  [IST]

In order to deter pharmacists from selling their licenses to illegally run drug stores and taking up employment elsewhere, the Maharashtra Food and Drug Administration (FDA) has filed FIRs against 10 pharmacists in different cases of cheating and impersonation under different sections of CrPC of IPC across Maharashtra. Three pharmacists from Mumbai, two from Nanded, one from Pinjar, two from Thane and two from Nashik have been booked under section 416 for impersonation, 420 for cheating and 199 for violating the affidavit of oath (false statement made in any declaration which is by law receivable as evidence). The state FDA has also come across rampant violation of Drugs and Cosmetics (D&C) Act as several chemist shops in the state despite their licenses being canceled were found to be operating and dispensing drugs without any qualified pharmacist. Around 2500 cancellations and 1400 suspensions have been made across Maharashtra over a period of seven months due to absence of pharmacists at drug counters. Informs Sanjay Kale, joint vigilance commissioner, Maharashtra FDA, "We found that suspensions and cancellations have failed to make any impact as the drug store owners after getting penalised succeed in getting a stay on the matter from the appellate authority and continue with their illegal business.” "This is the outcome of the fact that there is a rising trend of qualified pharmacists selling their licenses to chemist shops and taking up dual employment either as a Medical Representative in a pharma company or as a faculty in an educational institution," he explains. Inspections done by the state FDA across Maharashtra over a period of seven months reported absence of pharmacists in 95 per cent of shops and in five per cent cases due to other reasons. Chemist shops across Maharashtra has been facing a massive crackdown by the state drug regulator in the past several months over absence of pharmacists and not maintaining proper billing records.