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Approved antibiotics and those under clinical development are insufficient to arrest AMR: Rex Clements, Centrient Pharmaceuticals

Flagging off World Antimicrobial Awareness Week from November 18-24, Rex Clements, CEO, Centrient Pharmaceuticals, in an email interaction with Viveka Roychowdhury suggests that since it does not make business sense for the pharma industry to continue investing in the R&D of new antibiotics, governments and innovative solutions like insurance can come in to steer and fund antibiotic discovery. On India’s National Action Plan for AMR, he says they can be further sharpened if stringent antibiotic residue limits are prescribed for the pharma industry and responsible manufacturing is rewarded while discouraging pharma emissions

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What has been the fallout of the pharma industry’s lack of interest and investment in antibiotics?

The last class of antibiotics was discovered in 1987. Despite this, a number of new chemical entities in the antibiotic space have been synthesised. However, the lack of commercial case for these molecules has resulted in development being discontinued by private companies. As a result, antimicrobial resistance (AMR) continues to grow and could account for 10 million deaths every year by 2050[1]. Calling the situation alarming would be an understatement, the World Health Organization’s (WHO) annual Antibacterial Pipeline Report in April 2021 had revealed that the recently approved antibiotics and those under clinical development are insufficient to arrest AMR[2].

The scenario of drugs failing to prevent infections is no longer theoretical. Increasingly, the doctors are being confronted with drug-resistant infections in patients across the world; WHO’s AMR surveillance networks have found high rates of AMR in the bloodstream, gastro-intestinal and urinary infections among most of the countries surveyed[3]. The spillover of these developments will adversely affect development and push millions into poverty[4].

What has and can be done to incentivise R&D in new antibiotics?

While the pharma industry needs to take a more pronounced role in the R&D of new antibiotics, incentives driven by the government are equally important. Most of the pharma industry has shied away from the R&D of new antibiotics because of the risks involved. Antibiotic R&D requires a heavy investment of time and money. We are talking about a time frame of around ten years, and investments of over $1.5 billion to bring a new antibiotic to the market[5]. The annual revenue that a pharma company can generate from the sale of an antibiotic is estimated to be around $46 million[6], and that is where the problem lies. It does not make business sense for the pharma industry to continue investing in the R&D of new antibiotics. That is where the governments and innovative solutions can come in to steer antibiotic discovery. A lot of these incentives would have to be tailored to local contexts, but theoretically, a share in the funding of R&D programmes between the industry and the government can be the first step. Alternatively, the insurance model for funding new antibiotics, where the healthcare systems and the healthcare providers pay a fixed annual fee to the manufacturers can be deliberated[7].

The world witnessed the extremely inequitable distribution of key medicines, including antibiotics, during the COVID-19 pandemic. How can the supply chain risks be mitigated to prevent such disruptions in the future?

Even before the COVID-19 pandemic, the issue of inequitable distribution of therapeutics had persisted. During the 2009 influenza A(H1N1) pandemic, the supply of therapeutics and vaccines to low- and middle-income countries were crowded out by wealthier nations[8]. This is a systemic and complicated issue whose resolution is dependent on harmonisation between different institutions, funders, governments and pharmaceutical companies. Additionally, disruptions should be prevented by strengthening supply chain resilience. There is a need to diversify the geographical base from where the raw materials for antimicrobials are sourced.

AMR has been termed the silent pandemic. How effective have the One-Health Approach and global and national action plans on AMR been? Your comments on India’s national action plan on AMR, which have not been as effective?

Even though termed as a ‘silent pandemic,’ the importance of the issue has resonated with almost 2/3rd of the countries in the world. As of May 2021, 145 countries have calibrated their National Action Plans (NAP) with the Global Action Plan on AMR[9]. AMR is a complex problem, it cuts across sectors and transcends international boundaries. Multi-lateral agencies like the WHO have done well to emphasise inter-governmental and intra-governmental coordination. Countries must continue to strengthen multi-sectoral coordination, improve the data monitoring and reporting on the spread and emergence of AMR, and catalyse awareness regarding the critical nature of AMR.

Keeping the diversity of the country in mind, I think, India has done quite well on many fronts. While states like Madhya Pradesh, Kerala and the Union Territory of Delhi have already localised the NAP-AMR, Andhra Pradesh, Telangana and Karnataka, among others, are in the process of activating their state action plans. The AMR Surveillance Network of the Indian Council of Medical Research (ICMR) continues to expand[10]. The research capacity of institutions like ICMR has been further strengthened by international collaborations. The banning of colistin and the limitation on the use of antibiotics for the meat industry will help bring down the misuse of antibiotics in the livestock sector. However, the NAP-AMR can be further sharpened if stringent antibiotic residue limits are prescribed for the pharma industry. A policy can be adopted that rewards responsible manufacturing while discouraging pharma emissions.

The pharma sector has only recently tried to cut down on harmful effluents polluting the air and natural water bodies. This has already taken a toll on the environment. Antibiotics are prime environment polluters, so how has Centrient Pharmaceuticals (Centrient) addressed this problem? What are the environmentally sustainable practices in place currently and those planned for the future?

The production of antibiotics is only detrimental to the environment when untreated effluents are released by manufacturers into the soil and water bodies. In line with our organisational mission of quality, reliability and sustainability, Centrient has leveraged R&D for cleaner methods of production. I say this with pride, that whether it is Romaz Arizpe in Mexico or Toansa in India, our internal measures for pollution control across sites are as stringent. Our environmental stewardship is informed by a regular life-cycle assessment of our manufacturing processes. Centrient’s innovative technologies have helped us champion the cause of AMR stewardship in the pharma industry. Since 2016, we have had systems in place that can detect antibiotic levels as low as 50 parts per billion at all our production sites. Our largest portfolio, the SemiSynthetic Penicillin API range meets the AMR Industry Alliance’s Predicted No-Effect Concentrations (PNECs) target values. By the end of 2021, we are striving to meet Predicted No-Effect Concentrations (PNECs) target values for all wastewater streams including the supplier sites[11].

How will the recent acquisition of Astral SteriTech by Centrient Pharmaceuticals impact the end consumer in India as well as globally?

Through the acquisition, Centrient will expand its finished dosage form portfolio with sterile injectable Semi-Synthetic Cephalosporin and Semi-Synthetic Penicillin antibiotics. These are critical life-saving medicines for the infection treatment of patients in hospitals but face increasing risks of supply shortage. Centrient can now supply generic pharmaceutical customers with a focus on this institutional sector and through them reach more end consumers (patients).

Moreover, with Centrient’s global reach, it can bring Astral Steritech’s products to new geographies beyond Astral Steritech’s current largest markets of the US and South Asia. This will increase access of these life-saving products to patients around the world, which is at the heart of the company’s purpose.

Centrient Pharmaceuticals is wholly owned by Bain Capital Private Equity, a leading global private investment firm. What does the PE fund look for in an acquisition target in this space?

Bain Capital Private Equity and Centrient look for the transformative value that such an acquisition brings.

This particular acquisition is an important step on Centrient’s journey to become the leading, diversified and fully integrated partner to generics marketers. It further strengthens Centrient’s position as the global business-to-business industry leader in beta-lactam antibiotics. Being close to Centrient’s core products of beta-lactam antibiotics, the acquired product portfolio provides Centrient a diversification opportunity within the attractive growing niche segment of sterile injectable antibiotics.

With the broadened product portfolio, Centrient can further meet the needs of its customers in Semi-Synthetic Cephalosporin and Semi-Synthetic Penicillin finished dosage forms and become the preferred partner in these segments. This broadened product portfolio as well as Astral SteriTech’s advanced in-house manufacturing capabilities and two US-FDA approved production lines, allow Centrient to further strengthen the delivery of its value proposition of quality, reliability and sustainability in finished dosage forms.

[1] https://www.who.int/news/item/29-04-2019-new-report-calls-for-urgent-action-to-avert-antimicrobial-resistance-crisis

[2] https://www.who.int/news/item/15-04-2021-global-shortage-of-innovative-antibiotics-fuels-emergence-and-spread-of-drug-resistance

[3] https://www.who.int/publications-detail-redirect/9789240027336

[4] https://www.worldbank.org/en/news/press-release/2016/09/18/by-2050-drug-resistant-infections-could-cause-global-economic-damage-on-par-with-2008-financial-crisis

[5] https://www.sciencedirect.com/science/article/pii/S0168851017302002?via per cent3Dihub

[6] https://www.nature.com/articles/d41586-020-02884-3#ref-CR1

[7] https://www.sciencedirect.com/science/article/pii/S0168851017302002

[8] https://jamanetwork.com/journals/jama/