Euro Roundup: UK government orders review of commercial clinical trials landscape

Against a backdrop of falling investment in commercial clinical trials, the UK government will undertake an independent review under Lord James O’Shaughnessy to find and clear potential barriers.
 
Data collated by pharma trade group ABPI show the number of industry clinical trials initiated in the UK has fallen each year since 2017, the year after the vote to leave the European Union. The steepest fall in activity happened during the pandemic years. By 2021, the number of clinical trials initiated by the drug industry had fallen to 394, down from 667 in 2017. Declines affected all therapeutic areas, with oncology study starts dropping most dramatically, from 234 in 2017 to 139 in 2021. Research on cardiometabolic and immune diseases is down too.
 
“The UK has traditionally been a strong global location for trials. However, our life sciences sector has reported a 44% fall in recruitment of patients to commercial clinical trials between 2017 and 2021 — so it is vital that we act to rebuild competitiveness,” according to George Freeman, Minister for State at the Department for Science, Innovation and Technology.
 
The review is intended to “offer recommendations on how commercial clinical trials can help the life sciences sector unlock UK growth and investment opportunities” and “advise on how to resolve key challenges in conducting commercial clinical trials in the UK.”
 
The government expects to publish the findings in the spring and wants O’Shaughnessy, a Conservative Party member of the House of Lords, to provide both priority actions “to make progress in 2023” and longer-term ambitions. ABPI called the ordering of the review “an important recognition that we need to act decisively to reverse this negative trend.”
 
Press Release, ABPI Response
 
MHRA outlines response to EU MDR extension
 
The Medicines and Healthcare products Regulatory Agency (MHRA) has outlined its initial response to the European Parliament vote to extend the transition period for the Medical Devices Regulation (MDR).
 
Late last week, the Parliament backed the European Commission’s proposal for a longer, staggered move to full enforcement of MDR in response to concerns that a shortfall of notified body capacity will disrupt the supply of medical devices. The new timeline has implications for the UK, which remains tied to the EU’s regulatory framework almost seven years after the Brexit vote.
 
MHRA addressed the ties in a statement published after the Parliament vote. Because Northern Ireland remains subject to EU regulations, the updated MDR timeline will automatically apply in that part of the UK. The situation for the rest of the UK is different.
 
As it stands, manufacturers can place medical devices with valid CE marks on the market in England, Scotland and Wales until 30 June. That pathway is open to devices with certificates that are valid under the EU’s new transitional arrangements. MHRA plans to extend the acceptance of devices with CE marks. The changes should be put into law “in the coming months” and MHRA will publish guidance as soon as possible.
 
Laura Squire, chief healthcare quality and access officer at MHRA, welcomed the revised EU transition period for MDR, stating that it “will help mitigate the risk of shortages of medical devices available on the market.”
 
MHRA Notice
 
EMA seeks feedback on ICH immediate-release oral dosage form bioequivalence guideline
 
The European Medicines Agency (EMA) has released a draft guideline on running bioequivalence studies of immediate-release solid oral dosage forms for consultation.
 
Officials at the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) have prepared the M13A guideline to provide recommendations on performing bioequivalence studies during development and after approval. The guideline covers dosage forms such as tablets, capsules, and granules and powders for oral suspension. It is the first text in the series to describe the scientific and technical aspects of study design and data analysis to support bioequivalence assessment of the dosage forms.
 
ICH notes that the acceptance of comparator products across regulatory jurisdictions “could reduce the burden of multiple clinical trials demonstrating bioequivalence against local comparator products,” but that acceptance is dictated by the local laws. Even so, the group has included study designs to lay the groundwork for that approach.
 
A section describing the general principles in establishing bioequivalence dominates the draft. Within that section, ICH discusses the design of pharmacokinetic endpoint bioequivalence studies, covering topics such as the population, sample size and comparator products, before addressing data analysis for non-replicate study design. A subsequent section covers specific topics such as endogenous compounds and how to handle orally disintegrating tablets, chewable tablets and oral suspensions.
 
EMA is accepting feedback on the draft until 26 May. ICH is preparing two more guidelines in the series, M13B and M13C, that will describe biowaiver considerations for strengths beyond those investigated in bioequivalence studies and cover products with specific requirements, such as highly variable drugs.
 
Draft Guideline
 
EFPIA rebuts criticism of transferable exclusivity voucher fix for antibiotic R&D crisis
 
Big pharma trade group EFPIA has joined with antibiotic biotechs to correct claims in a comment piece that called the transferable exclusivity voucher (TEV) a “flawed incentive to stimulate antibiotic innovation.”
 
Earlier this month, experts including Jim O'Neill, the economist who performed the UK’s antimicrobial resistance review, published a comment piece in The Lancet that found fault with the TEV proposal. The EC is considering giving TEVs to companies that bring new antibiotics to market. The voucher would extend the market exclusivity of another drug to incentivize antibiotic development.
 
The idea has proved controversial, with member states reportedly pushing back against it late last year, but EFPIA and BEAM Alliance, a group of smaller companies working on antimicrobial resistance, have defended it against the latest attack. 
 
EFPIA argues that TRV is the “policy solution most likely to replenish the antibiotic pipeline,” adding that it will accelerate price negotiations and market access by decoupling “the incentive for the antibiotic from payment.” The trade group recommends limiting the use of TEVs to products with two years left on their existing protection to minimize detrimental effects on the development of off-patent therapies.
 
O'Neill and his co-authors proposed a revenue guarantee in every member state as an alternative to the TEV program. However, EFPIA argues the scheme “is complicated, would take many years (which we do not have) to set in motion and is likely to be inadequate to effectively direct greater R&D efforts in antibiotics.”
 
EFPIA Statement
 
Other news:
 
EMA has decided against updating the clinical and nonclinical sections of its scientific guideline on the use of adjuvants in human vaccines. Other documents have superseded the sections. Applicants can still use the quality section of the EMA guideline. EMA Notice