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.”