Anyone who has ever tried spicy food knows the feeling: what once seemed unbearably hot can become easier to tolerate over time. Bacteria can adapt too—but to become more resistant to drugs that combat them, resulting in far more dangerous consequences.

As bacteria are repeatedly exposed to antibiotics, some evolve ways to survive them. This phenomenon, known as antimicrobial resistance (AMR), is a major global health threat and could cause 1.91 million deaths by 2050 ^[1]. Yet in Asia, drug-resistant infections cause a particularly heavy burden, and access to newer and effective antibiotics remains alarmingly low.

A global team of researchers, including collaborators from Duke-NUS Medical School’s Centre for Regulatory Excellence and ADVANCE-ID at the National University of Singapore’s Saw Swee Hock School of Public Health, set out to understand why.

Their findings, published in Clinical Infectious Diseases and The Lancet Regional Health, draw on a review paper and a qualitative study involving stakeholders such as policymakers, regulators and pharmaceutical companies.

“We wanted to understand why pharmaceutical companies are not registering newer antibiotics in Asia despite there being a high demand for them. Existing research and new insights from key players revealed concerning ground realities, including disjointed and inefficient systems for approval, supply and use of newer antibiotics,” said co-author Dr Rathi Saravanan from Duke-NUS’ Centre for Regulatory Excellence.

 
Regulatory roadblocks

Before a new antibiotic can reach patients in any country, it must first be reviewed and approved by regulators. This process is essential to ensure that drugs are safe, effective and manufactured to the right quality standards.

But across low-and middle-income countries (LMICs) in Asia, different requirements and approval timelines can make the process fragmented and unpredictable. Regulated clinical trials by pharmaceutical companies need to demonstrate how a new drug works in the body and how the body processes the drug. Other requirements include scientific evidence for marketing authorisation as well as compliance with applicable manufacturing, labelling and distribution standards for respective countries that would be selling the drug. When differences in requirements and processes across the countries disincentivise manufacturers from entering the Asian market, they choose to prioritise US and Europe, where regulatory processes are more streamlined and transparent, instead.^[2]

As manufacturers also need to consider their commercial interests when registering a drug in a new market, they prefer entering high-income countries (HICs) with robust regulatory frameworks and clinical trial infrastructure as well as greater purchasing power. The higher predictability in market approval timelines also helps manufacturers to justify the financial feasibility in the HICs. Meanwhile, LMICs that urgently need new antibiotics are deprived of them.

The delay in getting the drugs to these regions is compounded by the weak health system infrastructure in LMICs, where small, poorly equipped regulatory teams have to sift through large backlogs—some stretching over five years—of clinical trial data for various drugs. In addition, the capacity to adequately evaluate novel and complex antibiotics is a challenge.

As a result, countries that urgently need newer antibiotics may be among the last to receive them.

 
Making access safe, faster and more equitable

Regulatory challenges are only one dimension of the multifaceted challenge. More efficient, affordable and predictable regulatory approval processes could alleviate the burden of unmet need for newer antibiotics by strengthening manufacturers’ confidence in the region.

Establishing a consensus for drug-approval requirements across the region and combining antibiotic procurement efforts could reduce the time, cost and commercial uncertainty that manufacturers face when registering new antibiotics. Similarly, building regulatory capacity by investing in the training of larger teams of regulators as well as bolstering support for regulatory filings could reduce the barrier to entry into new markets.  

“The solutions to making access to newer antibiotics more equitable may sound straightforward on paper, but in reality, policymakers, regulatory bodies, global health organisations, manufacturers and other key stakeholders must make a concerted effort to achieve public health goals in a timely manner,” said co-author Assistant Professor James Leong from Duke-NUS’ Centre for Regulatory Excellence.

By identifying the stakeholder and barriers that delay access to newer antibiotics, the researchers hope their work will provide a starting point for improving how healthcare innovations are developed, commercialised and delivered to patients across the region.

As AMR continues to rise, that work is becoming increasingly urgent. New antibiotics can only save lives if they reach the patients and health systems that need them most.