Antimicrobial resistance: MPs call on UK government to maximise potential of bacteriophages

Phage biobanks

The report recommended structural changes in terms of getting the Medicines and Healthcare Products Regulatory Agency and the Department of Health and Social Care to work more closely with phage researchers and clinical practitioners, along with new infrastructure such as phage biobanks and manufacturing facilities. It also proposed establishing a government “catapult” or innovation centre to produce phages.

The committee noted that, in the UK, phages are not manufactured to required good manufacturing process (GMP) standards and therefore cannot be used in clinical trials. The problem is that investment in compliant manufacturing plants will be justified only after successful clinical trials. The committee called on the government to build a GMP facility with shared facilities for use by phage innovators, the NHS, and companies seeking to produce other personalised medicines.

Greg Clark, committee chair, said that the mothballed Rosalind Franklin Laboratory in the West Midlands, which appeared for sale on the Rightmove website in November, should be considered for the manufacture of phages “rather than be lost to the nation and to science in a fire sale.”

He said that the laboratory had already received over £1bn of public funding and consisted of modern, secure laboratory facilities. It was set up by the government to end the inadequacy of testing capacity in the covid pandemic and was meant to be an important source of national resilience against future pandemics.

“Phages offer a possible response to the increasing worldwide concerns about antimicrobial resistance,” said Clark. “But the development of phage therapies is at an impasse, in which clinical trials need new advanced manufacturing plants but investment requires clinical trials to have demonstrated efficacy.”

The Rosalind Franklin Laboratory is owned by the UK Health Security Agency (UKHSA). A spokesperson said, “Options are being explored for the best use of the site going forwards while ensuring the best value for taxpayers’ money, and an update will be provided in due course. Where necessary, specialist equipment at the Rosalind Franklin Laboratory will be retained to support UKHSA’s ongoing pandemic preparedness work.”

Potential lifeline

Martha Clokie, professor of microbiology and director of the Centre for Phage Research at the University of Leicester, agreed that a much tighter connection was needed between phage researchers and the Medicines and Healthcare Products Regulatory Agency, the Department of Health and Social Care, and practising doctors to help progress phage treatment to the point where it can be used in the NHS.

She told The BMJ, “Phages have huge potential to save lives, but it is important to carry out the fundamental research on phage biology to ensure that the best phages are identified and developed within the new ecosystem that still needs to be defined. So, with suitable phages and with phage-antibiotic combinations, and with structural changes to ensure that regulation and production are carefully considered, phages may just provide the lifeline needed to help mitigate against antimicrobial resistance.”

The committee’s report noted several weaknesses in using phages to tackle bacterial pathogens. For example, it can be difficult and time consuming to identify which phage is needed and at what dose. There is also the possibility of bacteria developing resistance to phages.

Simon Clarke, associate professor of bacteria in cellular biology at the University of Reading, said, “Bacteria develop resistance to [phages] easily, meaning that new, expensive treatments might become useless pretty quickly; and they are one of the ways nature uses to move around genes which cause a bacteria to become resistant to traditional antibiotics, so the widespread use of phage could lead to even more antibiotic resistant infections.

“Perhaps most worryingly, they can also transfer genes which give bacteria different disease causing properties, potentially leading to the development of novel, virulent pathogens.” He said that he favoured other approaches to tackling antimicrobial resistance, such as better stewarding of antibiotics and exploring different combinations of drugs.

Another recommendation in the committee’s report is for the Medicines and Healthcare Products Regulatory Agency to consider allowing the compassionate use of non-GMP phages that have been produced in the UK for last resort medical cases where other medical approaches have failed. It also called on the government to review the status of phages in its plans to tackle antimicrobial resistance.

A Department of Health and Social Care spokesperson said that the department would publish a response in due course. “We are committed to tackling the global threat of antimicrobial resistance both at home and abroad,” they said. “Our current five year national action plan is helping protect patients from deadly infections by reducing the need for antibiotics, optimising use of antimicrobials, and investing in innovation. We are also in the process of developing our new five year national action plan for 2024 to 2029, which will capture learning from the covid pandemic.”

Mark Sutton, scientific leader at UKHSA, told The BMJ, “We have an active programme of work aiming to understand how phages can be manufactured and used for clinical treatment, as well as investigating the impact of phage resistance as it emerges and exploring rapid phage susceptibility test methods to support future clinical use.”