European Regulatory Roundup: EMA Adopts Revised First-in-Human Trial Guidance; UK Appoints Industry Veteran Ahead of Negotiations with Pharma (27 July 2017)

Posted 27 July 2017 By Nick Paul Taylor

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Welcome to our EU Regulatory Roundup, our weekly overview of the top regulatory news in Europe.

EMA Adopts Revised Trial Guidance to Account for Rising Complexity of Study Protocols

EMA has adopted revised guidance on first-in-human clinical trials. The revised text is intended to address the rise in the complexity of study protocols that happened following the adoption of the earlier version in 2007.

The agency is set to publish the feedback it received on a draft version of the guidance later this year. That will give a fuller picture of any reservations the industry had with the direction taken by EMA, but the changes made between the draft and final versions show where the agency felt compelled to tweak the guidance.

New additions to the final guidance include a section on selecting a starting dose. The draft version had one section that covered how to select a dose for patients and healthy volunteers. For the final version, EMA has created sections dedicated to patients and healthy volunteers, enabling it to go into more detail about the differences between the two groups. In healthy volunteers, EMA is advising sponsors to start lower than the pharmacologically active dose. In patients, sponsors have the flexibility to go up to a dose that has "a minimal pharmacological effect and is safe to use."

EMA has also removed a section on dose escalation schemes from the final version. The section covered the criteria sponsors should include in the protocol to dictate what data are needed to support a decision to move up to the next dose.

While these and other changes mean the final version differs from the draft, the adopted version still includes the big amendments EMA wanted to make to the current text. That earlier 2007 text runs to just 12 pages, compared to 22 for the new, final guidance. EMA lengthened the document in response to the expansion of what sponsors are trying to achieve in first-in-human trials, which now feature single and multiple ascending dose stages and assessments in different populations.

EMA Statement, Final Guidance

UK Appoints Chief Commercial Officer Ahead of Negotiations with Pharma Industry

The UK Department of Health has appointed a chief commercial officer (CCO) ahead of negotiations with the pharmaceutical industry. Industry veteran Steve Oldfield has taken on the newly created post with a brief to prepare a strategy for negotiations with commercial suppliers.

Officials specifically want Oldfield to ready the health department for "key engagements with the pharmaceutical industry in particular over the PPRS scheme." The current version of PPRS — the Pharmaceutical Price Regulation Scheme — came into force in 2014 and has a five-year term. That means the government is approaching the point at which it must renegotiate the voluntary drug pricing initiative.

To strengthen its hand going into the negotiations, the government has appointed a CCO with more than 25 years of experience in the healthcare industry. Oldfield is current chief operating officer at PGT, a consumer health joint venture set up by Procter & Gamble and Teva. Earlier in his career, Oldfield worked at companies including Sanofi and Teva.

The government sees that industry experience as vital as it enters negotiations that are critical and sensitive given its healthcare budget constraints and already strained relationship with parts of the industry.

"[Oldfield] brings deep knowledge of the pharmaceutical industry, which will be very valuable as we start to work with them on the next iteration of the £8 billion ($10 billion) per annum medicines pricing scheme," Gareth Rhys Williams, government chief commercial officer, said.

Press Release

EMA Recommends Actions to cut Risk of Antimicrobial Resistance in Animals

The European Medicines Agency (EMA) has proposed actions to cut the risk of animals developing resistance to antimicrobials. EMA set out its current thinking in draft reflection papers on the use of aminoglycosides and the off-label use of antimicrobials in animals in the European Union.

The lengthy reflection papers set out why EMA thinks the two topics are important and what changes it wants to implement. In the case of off-label antimicrobial use, the situation is complicated by the lack of data on what products are used off-label and in what quantities. EMA wants such data but thinks a formal information-collecting system would burden veterinarians and regulatory agencies. Instead, EMA is proposing to run a limited research initiative.

That is one of seven recommendations made by EMA in the paper on off-label use. The other recommendations cover the need to perform full diagnostic investigations before prescribing drugs for off-label use, the development of evidence-based treatment guidelines and ways to encourage companies to develop products that cut the need for off-label prescriptions.

The second reflection paper covers the use of aminoglycosides, a specific class of antimicrobial medicine. EMA wants to place veterinary-authorized aminoglycosides in category two because of their importance in human medicine and the risk resistance will transfer from animals to people. Aminoglycosides not authorized for veterinary use will remain in category three, pending risk assessment.

Officials also used the reflection paper to outline considerations for marketing authorizations, summaries of product characteristics and the need for further research. Points raised by EMA include the questionable value of combinations containing aminoglycosides. EMA singled out combinations involving (dihydro)streptomycin as particularly problematic given the degree of resistance to the molecule.

EMA is accepting comments on the aminoglycosides paper until the end of October. The comment period on the off-label antimicrobial paper closes at the start of next year.

Press Release, Antimicrobial Paper, Aminoglycosides Paper, More

MHRA Rules no Patients Harmed by Software Fault at Major Supplier of Plasma Products

The United Kingdom regulatory agency has found no evidence a software fault at a major supplier of plasma products harmed patients. Officials performed the assessment after an inspection of Bio Products Laboratory (BPL) found a problem with software the company uses to ensure the safety of the products it sells.

As BPL is a major supplier of plasma products to the National Health Service (NHS), the discovery of the problem raised concerns its products may put patients at risk of harm. However, a review of the available information has found no evidence NHS patients were harmed or put at risk by the products. A government representative communicated news of the findings of the Medicines and Healthcare products Regulatory Agency (MHRA) review in a statement to parliament.

MHRA initiated the review to assess the impact of a problem with software used by BPL during the manufacture of plasma products. The software controls the first of the three steps BPL uses to ensure the safety of its products. This step relates to the selection of healthy donors and the traceability of the materials they provide.

BPL and MHRA took the fault seriously enough to initiate a manual review of whether the software failings enabled inappropriate donations to make it through the first of the safety controls. There is no evidence this happened. With the second two safety controls — pre-production tests of plasma safety and inactivation of viruses during manufacturing — working as intended, MHRA thinks the products BPL shipped were safe.

The issue is yet to be fully resolved, though. MHRA told the government BPL has adopted interim measures. The agency thinks these measures provide the necessary assurance of safety while BPL works to adopt a long-term fix.

Government Statement

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