Department of Biotechnology
With Indian market benefiting from quick product regulatory approvals in bio-similars, the recent revision in guidelines by Central Drugs Standard Control Organisation (CDSCO) has made it more aligned with global regulations.
Besides this, regulatory landscape for biosimilars has been evolving with the global pioneer European Medicines Agency (EMA) also setting the trend, say experts.
Biosimilars are copy versions of already approved originator biologics that are marketed after patent expiry for the originator product. As the safety and efficacy of the innovator product is already established, copy versions are allowed to be developed and evaluated using an abbreviated pathway established on biosimilarity principles.
Since the first set of over-arching guidelines for biosimilars were released by the European Medicines Agency (EMA) in 2005, there has been much development in this space. The US Food and Drug Administration released its first set of draft guidelines in 2012, which have since been finalised. Additional guidelines were released in 2014-15. China FDA released its biosimilars guidelines last year.
However some experts like Dr Charu Manaktala, senior medical director, Biosimilars Centre of Excellence, Strategic Drug Development, QuintilesIMS Asia pinpoint, “The general principles of what the regulators expect, such as step-by-step development, focus on robust comparability and functional interests, pharmacovigilance – all of these are aligned with other guidelines.
She says that some points in the recent provision are contentious like the number of subjects required for different phases of development, but we need to have a more pragmatic view.
Compared to the pre-2012 era, she adds, “We have made significant progress. There is scope for revisions to further align our guidelines with the world view, but we are in a relatively good position.
“The basic regulatory framework for biosimilars registration has been established fairly well by 2016. The year also marked the 10th anniversary for approval of the 1st biosimilar in the EU. A number of regulatory guidelines are in place as well as a good amount of experience has been gained on a number of biosimilars ranging from simple proteins to complex monoclonal antibodies. Some of the other highly regulated markets such as Japan, South Korea, Canada, Australia among others have adopted EU biosimilar guidelines to a large degree,” Dr Manaktala concludes.
In addition to the revision of some of the earlier guidelines, the EMA published guidelines for pharmacovigilance of biologics in 2016. The US FDA has published a guidance on the labelling of biosimilars in March 2016.
The naming of biologicals and interchangability of biosimilars continue to be hotly debated topics. The EMA has approved biosimilars under the same non-proprietary name as for the reference product. In 2015, the US FDA issued draft guidance on the subject of non-proprietary naming of biosimilars. This guidance recommends that all biologicals should have non-proprietary names that includes a four-letter suffix to distinguish them from each other. The suffix would be composed of four lowercase letters and not carry any meaning.
The proposed approach is intended with a view to clearly identifying biological products to improve pharmacovigilance, and, preventing any unintended substitution. However, a number of industry stakeholders, including the USP have requested for alternative approaches to be considered.
While the interchangability guidance from the US FDA is awaited, Sandoz recently reported study findings that show lack of safety and efficacy impact from multiple back and forth switches between the it’s etanercept biosimilar and the originator product.
“We expect to see more products obtaining marketing approval on the basis of lean clinical data packages especially where validated PD markers are available, supported by strong quality comparability, in vitro biological activity evidence and clinical PK-PD studies,” adds Dr Charu Manaktala.
Asian manufacturers, especially from South Korea, continue to be key players in the current biosimilars landscape, with rich product pipelines as well as a number of approved products in both the EU and US.
South Korea is reported to have a goal of controlling 22% of the global biosimilars market by 2020. This goal is supported by the Korean government by way of providing capital as well as regulatory assistance to the domestic bioplharmaceutical companies.
Gujarat is laying stress on biotechnology after seeing states like Karnataka, Maharashtra and Andhra Pradesh reap benefits of investing in the sector. Its government is now working to persuade investors to its Biotech Park at Savli in Vadodara. The move is in sync with the bi-annual Vibrant Gujarat 2017 event to be held from January 10-13.
With the presence of over 180 biotechnology companies, Gujarat has established itself as one of the top five biotechnology hubs in India, stated Dhananjay Trivedi, secretary, department of science & technology, government of Gujarat.
The top five hubs for biotech are Karnataka Maharashtra specifically Mumbai and Pune, Tamil Nadu and Andhra Pradesh. The state is giving a push to biotechnology as a sector for promotion at the Vibrant Gujarat 2017 to be held at Gandhinagar. The eighth edition will draw attention to the fact about Gujarat’s prowess as a manufacturing hub in the country and bring the capability of biotechnology to the fore.
“This has been possible due to the presence of excellent physical and social infrastructure in the form of biotech parks, prominent academic institutions and clinical research organizations. Government of Gujarat has taken multiple initiatives to promote growth of biotech industry such as setting up a bio-incubator at Savli, technology facilitation cell, structured capacity building programmes, Gujarat Biotech Venture Fund etc.,” noted Gujarat S&T secretary Trivedi recently.
The Savli biotech park developed by the Gujarat State Biotechnology Mission (GSBTM) and the Gujarat Industrial Development Corporation (GIDC) spans over an area of 100 acres. The phase I comprises 38 acres of Special Economic Zone (SEZ) and 62 acres of non-SEZ area is now well developed with the basic infrastructure. The officials stated that the park would address the biotech industry’s need for specialized infrastructure. An area of 17.5 acre is earmarked for the Biotech Incubator and Common Equipment Library facilities and various laboratories.
“Adequate thrust has been given to promoting research and development through initiatives such as Gujarat Genomics Initiative, Marine Bio-resource Centre, Biodiversity Gene Bank among others. Going forward, biotechnology sector will remain a thrust area for Gujarat with the aim of making Gujarat the largest and most preferred biotechnology destination for investors,” he added.
Out of the total 1,797 Department of Scientific & Industrial Research recognized biotech companies in India, more than 10 per cent are in Gujarat. At least 50 per cent of the biotech companies in the state are located in and around Ahmedabad followed by 20 per cent companies in Vadodara region making them the major clusters of biotechnology industries, according to Gujarat’s department of Science & Technology.
Presence of a large number of international and domestic biotechnology companies, supplemented by biotech parks, academic institutions and clinical research organizations give it the much-needed impetus. Although a large chunk of companies are in the agricultural biotechnology segment, the contribution of the bio-pharma and bio-services is significant, stated DST.
The Department of Biotechnology (DBT) in collaboration with Department of Science & Technology, and the Department of Science & Technology, Government of South Africa, and South African Medical Research Council will soon embark on a collaborative research programme on HIV, TB and TB/HIV. The programme would be under the framework of bilateral Science and Technology Cooperation Agreement between the Department of Science and Technology, Ministry of Science and Technology, Governments of India and South Africa.
The thrust areas of the programme would be on development of preventive HIV vaccine by designing immunogens that can elicit potent and broadly neutralizing antibodies; isolation and characterization of neutralizing MAbs effective against clade C HIV-1 viruses for use in combination therapies, passive immunization, and/or for designing preventive vaccines; Creation of cohorts of TB patients with HIV-1 co-infection and formation of national biorepositories (for breath condensates, blood, tissue etc.)to facilitate immunological studies on HIV and TB; and identification of biomarkers and development of novel assays for diagnosis and management of tuberculosis and tuberculosis with HIV co-infection.
The DBT’s initiative in this regard is significant as the human immunodeficiency virus (HIV) and tuberculosis (TB) are the leading causes of death in adults and children in both India and South Africa, and the impact of the converging dual epidemics is one of the major public health challenges of our time. Development of effective biomedical tools and solutions for diagnosis, prevention and treatment of AIDS and tuberculosis is required to address challenges in disease management and control.
Interdisciplinary research in these areas will not only accelerate development of transformational technologies but also help to develop capabilities and solutions for these unconquered diseases. The proposal should be geared towards product development or have clinically useful applications. It should have intra country linkages and a strong collaborative component utilizing complementary expertise of both countries, and addressing regional needs.
Scientists in either country could also submit proposals in case they have an existing product or a proof of concept and they would like to access facilities in either country for a collaborative framework to help facilitate product development in an accelerated manner (e.g. manufacturing, preclinical testing etc.). The programme is aimed to facilitate partnerships between research institutions in India and South Africa. This programme will leverage upon existing scientific capacities, enable technology transfer and catalyze mentorship/training. Thus, this collaboration will synergistically advance discovery efforts towards development of new technologies and products for prevention and management of HIV/AIDS and TB by building scientific leadership capacity, fostering a sustainable environment for translational research and enhancing clinical capability/capacity. In South Africa, this call for proposal is open to researchers residing in South Africa and who are affiliated with a recognized higher educational or research institution such as a university, university of technology or science council. The South African applicant must be in possession of a PhD. Private sector companies are not eligible for this call. In India, the lead Indian applicants should be scientists/faculty members working in regular capacity in universities, academic institutes or national research and development laboratories/institutes. Private sector companies are not eligible for this call.
The Central government has to come out with appropriate strategy to overcome the trade barriers put up by the Vietnam government against Indian pharmaceutical exports in recent months. The regulatory authorities in Vietnam have been frequently finding fault with the quality of Indian pharmaceutical exports without much justification, according to some leading exporters.
This hostile attitude of the Vietnamese drug regulatory authority is resulting in issuing letters and blacklisting some Indian exporters citing compliance and quality issues. While the industry appreciated the pro activeness of the Indian government in reaching out to Vietnamese counterparts, the industry insisted that the government should take measures in interacting with the stakeholders as well to understand the ground realities.
Nipun Jain, chief executive officer, of Pharmachem stressed that Vietnam being a major export destination is an important market for the industry and thus pre-emptive measures should be taken to address the issue. To safeguard the interest of the Indian exporters, while maintaining a strong relation with the Vietnamese government, Jain who is also in the SME panel of Pharmexcil suggested that India and Vietnam should work together to collaborate on setting up a joint drug testing lab in Vietnam, which would ease up the tension and build the confidence among both the parties.
He also suggested that if not that the Vietnamese government can try to outsource the drug testing to a third party like SGS. If not that they can try adopting pre-shipment testing through a third party as being done for exports to Nigeria, where samples of drugs to be exported to the Nigerian market is tested through a third party testing laboratory in India itself before being exported.
“These are some of the practical solutions that can be adopted to address the issue. These steps will ease the exporters tension and uncertainity while exporting to Vietnam and will also help the Vietnamese authority in addressing their fears on quality issues, without affecting the exports,” Jain pointed out.
A highly placed source from the industry claimed that contrary to the claims made by the Vietnamese government, the fault does not lie with exporters alone, as the regulatory system in the country is equally to be blamed. On condition of anonymity a source revealed that there is a huge lacunae in the drug testing and regulatory system in Vietnam which is the main cause of concern for many. In fact, the source pointed that the testing labs and other facilities are not even updated and latest as per the internationally accepted guidelines.
“The ongoing situation cannot be sorted out without taking into cognizance of the deplorable state of the drug regulatory system in Vietnam, as well rather than playing the blame game they should take some constructive steps towards modernising their drug testing labs. May be then they will find out that the problem is not with the Indian drugs but is with their incapability in properly testing the products,” a source stressed.
Even as the academia and industries worldwide are actively involved in finding a solution to the growing Human Papilloma Virus (HPV) infection in terms of new screening/diagnostic tests, vaccines and therapeutic options, the Department of Biotechnology (DBT) will soon begin research on HPV prevention and control. The DBT’s initiative in this regard is significant as HPV infection is the leading cause of cervical cancer in the world. India bears 30 per cent of the burden of cervical cancer worldwide. The lack of awareness in rural areas and the lifestyle of women in urban areas worsen the situation of cervical cancer in the country. Low-cost, e?ective solutions are required for the prevention and treatment of HPV infections.
The DBT will conduct this research programme under its Biotechnology Industry Partnership Programme (BIPP). The DBT has invited proposals from eligible biotech companies to conduct research on HPV prevention and control.
Some of the indicative priority areas for submitting proposals include simple, sensitive, accurate and affordable screening tests (standard self-screening methods that are independent of individual interpretation); simple, sensitive, specific and acceptable diagnostic tests (cost effective and applicable to low resource settings); vaccines covering additional number of HPV types; process optimization for cost effective vaccine production; development of vaccines with specified duration of protection; and development of new therapeutic options including products of natural origin.
A single or consortia of Indian companies small, medium or large having in-house R&D units, alone or in collaboration with a partner from another company, institute or organisation are eligible to participate in the research programme. The main industry applicant should have DSIR recognised in-house R&D unit; alternatively, the applicant should be incubated at an incubation centre/biotech park which has a valid SIRO/DSIR certificate.
The last date for submission of proposals under this regular call is July 31, 2014. BIPP is a government partnership programme with industry for support on a cost sharing basis targeted at development of novel and high risk futuristic technologies mainly for viability gap funding and enhancing existing R&D capacities of start-ups and SMEs in key areas of national importance and public good.
DBT is operating this scheme through BIRAC, a not-for-profit public sector undertaking set up by DBT to promote and nurture innovation research in biotech enterprises specially start-ups and SMEs. Major thrust of the programme is towards funding technologies which address a major national problem and/or involves high level of innovation.