India-Japan Partnering Momentum: Regulatory Alignment Is Key
Executive Summary
Biopharma executives from India and Japan discuss the need for enhanced “alignment” on the regulatory front, including exploring the possibility of a mutual recognition agreement as the two nations seek to expand biopharma partnering efforts and also build supply chain resilience.
As India and Japan seek to build on long-standing diplomatic and strategic ties, biopharma executives at a recent event highlighted the need for greater “alignment” on the regulatory front and also certain partnering initiatives that have made an impact during the pandemic. Efforts for wider co-operation between the two nations to ensure supply chain resilience also appear to be building up.
Addressing the “India-Japan CEO Speak Series on Bilateral Economic Cooperation,” Ichiro Fujikawa, CEO of wholesaler/distributor Fujikawa & Co. Ltd., suggested that moving towards a mutual recognition agreement (MRA) in the pharmaceutical segment could be one way that India and Japan can “reduce the burden” of Good Manufacturing Practice (GMP) compliance reviews.
“I don't know when but I hope in the near future Japan and India conclude an MRA in the pharmaceutical field,” Fujikawa said at the session, referring to Japan’s MRA with the EU and its advantages.
Such MRAs typically, among other aspects, allow regulators to rely on GMP inspections in each other's territories, waive batch testing of medicines that enter from the partner nation and also share information on inspections and quality defects.
In 2015, Japan’s Ministry of Health, Labour and Welfare and India’s Central Drugs Standard Control Organization (CDSCO) had firmed up a memorandum of co-operation aimed at promoting the “exchange of information and cooperation in areas pertinent to medical products and the relevant administrative and regulatory matters” within the jurisdiction of both sides. Sharing best practices with a view to harmonize regulations “to the extent feasible” was also part of the agenda at the time.
While MRAs are typically complex and could involve long-running discussions to conclude, Fujikawa put forth that India could in the interim potentially consider participating in the Pharmaceutical Inspection Convention and Pharmaceutical Inspection Co-operation Scheme (PIC/S).
“If India can participate in PIC/S, the GMP-level is considered as same among the PIC/S countries. So, it can be a preparation for the MRA,” the executive added at the session on “Enhancing Collaboration between India and Japan in Healthcare and Pharma: COVID-19 and Beyond.”
PIC/S is a non-binding, informal co-operative arrangement between various regulatory agencies in the field of GMP of medicinal products for human or veterinary use. It aims to harmonize inspection procedures globally by developing common GMP standards and by providing training opportunities to inspectors. As of 31 December 2021, PIC/S comprised 54 participating authorities, including Japan's Pharmaceuticals and Medical Devices Agency (PMDA).
Wider Partnership Possibilities
Indian industry executives at the event mirrored similar views around the need for “greater alignment on regulatory requirements” between the two nations but alongside were upbeat about the prospects of collaboration across a gamut of activities between the "natural partners,” as one executive put it.
Deepak Sapra, CEO (active pharmaceutical ingredients and services), Dr. Reddy's Laboratories Ltd., referred to Indo-Japanese partnership possibilities beyond mere buying and selling to areas such as “co- creating, mutual recognition, co-development” and bringing solutions to unmet medical needs not just for people of the two nations, but globally. Areas such as contract research and development/manufacturing and clinical collaborations between Indian and Japanese companies are also growing at a fast clip, he indicated.
Dr Reddy’s had in 2020 partnered Japan’s Fujifilm Toyama Chemical Co. Ltd. and Global Response Aid (GRA) for the antiviral Avigan (favipiravir); the tripartite deal gave the Indian firm and GRA the rights to develop, sell and distribute Avigan in all countries other than Japan, China and Russia. (Also see "Can Avigan Bite Into Buzzing Indian Favipiravir Market?" - Scrip, 20 Aug, 2020.)
“This was a unique deal because the innovation happened in Japan. We partnered with them to take this drug global, jointly undertook developmental efforts, clinical studies in different parts of the world and as a consequence tens of millions of people around the world could get positively impacted,” Sapra declared.
The executive also referred to an ongoing project where the Hyderabad-based firm, in association with one of Japan's largest pharmaceutical companies, plans to manufacture and supply a key critical care drug to Japan. “It allows people at terminal stages of the disease to benefit and have a shot at living longer,” Sapra said, but provided no specifics on the deal.
The executive, however, also underscored the need for harmonization between the “way India and Japan view the regulatory setup” in both countries. “The harmonization of policies, the mutual recognition of PMDA activities with what is ongoing between the requirements for Japan and the systems and processes in India becomes very important to move collaboration forward into more areas,” Sapra asserted during the discussion.
Harmonization Of Pharmacopoeia
The CEO exchange came against the backdrop of the 70th anniversary of establishment of diplomatic relations between Japan and India and growing economic co-operation between the two nations. Japan’s Prime Minister Fumio Kishida was in India last month for the 14th India-Japan Annual Summit, which saw Japan pledge JPY5tn ($42bn) of public and private investment and financing to India in the next five years.
Fujikawa’s CEO also flagged up other nuances with reference to active pharmaceutical ingredients testing procedures and standards, noting that most Indian exporters comply with European Pharmacopeia and United States Pharmacopeia (USP) specifications, while supplies to Japan need to conform with Japanese Pharmacopeia (JP) specifications.
“If the pharmacopoeia could be harmonized, it would be easier to export for your side and to be more efficient,” he pointed out at the session, moderated by Panacea Biotec Ltd. managing director Dr Rajesh Jain.
Last October, the Pharmacopoeial Discussion Group (PDG), which brings together the European Pharmacopoeia, the JP and the USP, with the World Health Organization as an observer, said it was preparing a pilot to integrate additional world pharmacopoeias. Formed in 1989, the PDG essentially aims to harmonize pharmacopeial standards (excipient monographs and selected general chapters) in the US, Europe, and Japan, as part of efforts to maintain a consistent level of science across the three pharmacopeias, with the shared goal of protecting public health.
PMDA-CDSCO Discussions
Meanwhile, Mona Khandhar, Minister, Economic and Commerce, Embassy of India, Tokyo, who also addressed the event, said that regulatory symposia between the PMDA and India’s CDSCO have been “very robust,” including one held last year.
The fifth India-Japan medical products regulatory symposium was held in December 2021 and touched upon a range of issues including the CDSCO’s engagement with its overseas counterparts to ensure public health via formal memorandum of understanding and statement of intent. A specific roundtable of Indian firms and the PMDA has also been fruitful, Khandhar indicated.
“Generally the issues faced by Indian pharma companies in Japan such as selection of in-country caretaker, triplicate analysis, timelines for pre-consultation or consultation have been brought to the notice of PMDA, which is responding very positively,” she maintained.
Foreign manufacturers applying for drug master file registration are typically required to appoint an in-country caretaker for drug substances (active pharmaceutical ingredients (APIs)) in Japan.
Japan has traditionally been a tough market to crack for Indian firms and one where, experts say, business needs to get a good grasp of the cultural undercurrents as well have the right local partners before going in full throttle.
Khandhar, for instance, highlighted that Japanese business has a “specific culture/framework,” which depends a lot on trust and belief in long-term relationships. “They feel more confident when they are dealing with somebody who is aware about all these practices. So, it really helps if Indian companies have Japanese associates which have reputation and are reliable for the market.”
India’s top-ranked drug firm Sun Pharmaceutical Industries Ltd., which made its entry into Japan when it snapped up a portfolio of 14 established prescription brands from Novartis AG in 2016, is among those building its standing there. (Also see "ANALYSIS: Inside The Sun-Novartis Japan Deal" - Scrip, 4 Apr, 2016.) In 2018, Sun went on to acquire Tokyo-based Pola Pharma Inc.
Fujikawa also noted how some Indian firms hadn’t been able to penetrate the Japanese market in the past, referring to the impact of the National Health Insurance system there and quality thrust.
“The health insurance system is a universal system [in Japan]. The price of the medicine is not a big problem, just quality is a major issue. So they tend to select the Japanese domestic manufacturer’s products,” he remarked.
Supply Chain Resilience Efforts
Importantly, Khandhar also referred to collaborative efforts to de-risk supply chains, an area that saw massive turbulence during the peak of the pandemic.
Japan, she noted, was the first country to announce financial support for diversification of supply chains across critical sectors including healthcare and pharma for Japanese companies. One such program will provide support to Japanese companies for building new plants/facilities for critical products and materials within Japan.
“With this, there is also a trilateral supply chain resilience initiative between India, Japan and Australia and the recent announcement of a JPY5tn investment during the prime minister-level summit in March. We expect close business-to-business collaboration next on the strength of very strong government-to-government co-operation and especially more so in this critical sector.”
Last year, the trade ministers of India, Japan and Australia formally launched the Supply Chain Resilience Initiative, which aims to initially share best practices and steer investment promotion and “buyer-seller matching” events to provide opportunities for stakeholders to explore the possibility of diversification of their supply chains. Much of these efforts are aimed at countering the supply chain sway of China, especially dominant for APIs and key starting materials in the pharmaceutical sector.
India, for instance, imports over 60% of its API requirements from China, though the country has initiated medium- to long-term measures by way of a large-scale Production Linked Incentive (PLI) schemes to shrink this dependence.
In 2020, India outlined details of a PLI scheme for manufacturers of certain critical APIs and drug intermediates in the country, while last year another such scheme sought to enhance broader manufacturing capabilities and facilitate “product diversification to high value goods" in the pharmaceutical sector.
In addition to APIs and key starting materials, the second scheme covers a range of segments including complex generics, orphan drugs, repurposed therapies and even cell-based and gene therapy drugs. (Also see "India APIs Incentive Scheme: Will It Galvanize Local Firms, Bridle The Dragon?" - Pink Sheet, 8 Jun, 2020.) (Also see "Will The $3bn Stimulus Amid COVID-19 Place Indian Cos Among Goliaths?" - Scrip, 12 Mar, 2021.)
Fujikawa’s CEO also acknowledged how COVID-19 exposed the wider supply chain weaknesses in Japan for essential drugs. ‘In the current two-three years, diversification of the supply chain is one of the key issues,” Fujikawa said, also noting that he hopes the India’s PLI scheme can help avoid “over dependence” on a specific country.