Napoleon once allegedly described England as a nation of shopkeepers, but if he were around today, he would say the U.K. is a nation of small and medium enterprises (SMEs), according to U.K. clinical research expert Dr. Ignazio di Giovanna.
Jonathan Brenton, minister counsellor (prosperity) at the British Embassy in Moscow, speaking at the opening of the two-day conference on Tuesday. Photo: Sk.ru.
Such a description is music to the ears of the Skolkovo Foundation, which is tasked with developing a culture of entrepreneurship in Russia. Many of those SMEs work in the field of pharma and biotech, where there is great potential to build on existing cooperation between the U.K. and Russia, participants of the Future of Pharma: U.K. & Russia conference organised by the Skolkovo Foundation, U.K Trade and Investment and the British Embassy in Moscow heard on Tuesday.
The opening sessions of the two-day conference – which is being held at the Skolkovo innovation centre and is aimed at exchanging experience and finding new ways of cooperation between the two countries – focused on clinical research. The U.K. has turned its clinical research around in the last few years, di Giovanna said, offering plenty of food for thought as to how Russia can make its market more attractive to foreign drug developers.
The U.K. government’s Medicines & Healthcare products Regulatory Agency is “the envy of the world,” according to di Giovanna, CEO of the CCA Clinical Research company, and a former president of the U.K.'s Clinical and Contract Research Association (CCRA), which represents companies providing services to the pharma industry.
Among the factors that make the U.K clinical research market attractive to foreign companies – not least Russian ones – are its speed in reviewing and approving studies, its standardized contracts with hospitals and strong government support, di Giovanna told the conference.
This was not always the case, however. Ten or 15 years ago, some trials were being cancelled because they took too long to set up and not enough participants could be found, prompting the research to be moved outside the U.K., said di Giovanna.
He attributes the start of the U.K. market’s turnaround to 2001, when a group of companies went to then-Prime Minister Tony Blair to complain that the country was losing its clinical research. A series of changes were introduced to battle back the country’s market share, including setting up the National Institute for Health Research in 2006, and introducing standard contracts for signing with hospitals, as well as uniform costing templates.
Dr. Ignazio di Giovanna, CEO of the CCA Clinical Research company. Photo: Sk.ru.
“What’s really important in the U.K. is that we have huge political support,” said di Giovanna, citing investment of half a billion pounds a year into health infrastructure in the U.K.
“In the last five years alone, the research networks have been responsible for recruiting 3 million patients into clinical studies,” said di Giovanna.
Many of the improvements he cited occurred in the past five years.
In 2010, the median time to obtain NHS permission for a study was 115.5 days. Last year, that figure had fallen to 20 days, he said. Likewise, the number of studies has soared from 94 in 2010 to 448 last year, and 63% of studies now recruit their target number of patients on time, compared to 21 percent in 2010-2011, he added.
“It’s almost a complete reversal of what it was five years ago,” he said.
Russian regulations
At first glance, a comparative overview of the Russian clinical research market presented by Svetlana Zavidova, executive director of the Association of Clinical Trials Organisations (ACTO), an NGO, looked less rosy.
Russian regulations on clinical research were dramatically changed in 2010 with the passing of a new law on the circulation of medicines. It was this law that introduced a requirement for clinical trials of foreign-made drugs to be conducted in Russia before they can be registered and sold here.
In order to analyse how closely the new Russian regulations corresponded to European ones – particularly regarding clinical research – the Russian Health Ministry and European Commission produced a report on the subject in September 2012. The report concluded that the new legislation in general corresponded to that of the EU, but identified nearly 20 places in which it did not.
Since then, changes have been made to eliminate some of the exceptions, but many issues addressed in the report remain today, said Zavidova, including a ban on foreign companies performing testing on healthy Russians in phase one trials (only Russian sponsors are allowed to do this), and criteria set for the lead researcher that has reduced the pool of research teams available for sponsors.
By far the most contentious change to the law is the requirement to carry out local research, even when it has already been completed abroad, she said.
“The requirement to carry out local trials has been criticized since the introduction of this law, but it remains in force. The requirement to repeat the research is unethical,” said Zavidova, adding that amendments have since been made concerning generics and orphan drugs, as medication for rare diseases is known.
While the law provides an exception to the requirement if a mutual agreement on recognizing the other country’s research exists, this is purely theoretical, said Zavidova, since the EU doesn’t have such agreements, and simply refers to the Good Clinical Practice (GCP), an international quality standard.
The effect of the 2010 legislation was a steep drop in the proportion of international multi-centre clinical trials from 59.6 percent of the Russian market in 2004-2011 to 35.9 percent in 2015, according to data compiled by the ACTO. The proportion of both locally sponsored and foreign sponsored bioequivalence studies – in which two drugs, such as a brand product and potential generic, are compared – has grown.
The average time needed to get approval to conduct trials and permission to import and export, which is also needed in order to conduct the trials, is 117 calendar days, said Zavidova.
“Time is not the biggest strength of the Russian clinical research market, but we have other advantages, such as the speed with which patient groups can be assembled,” she said.
“Unfortunately, we have a lot of patients, so what we lose in time waiting for permission, we make up in assembling patients.”
Svetlana Zavidova, director of the ACTO NGO. Photo: Sk.ru.
Zavidova said her organization was witnessing international trials held successfully in the U.S. and Europe attracting more critical comments and refusals from regulatory authorities in Russia when they applied for permission to hold the trials here.
“We want to release the data on all these refusals in the past five years since the law was passed – and on the international research that was successfully carried out in other countries, but was cancelled here at the stage of the expert opinion, either due to long delays or baseless recommendations – and show what Russia has lost in terms of the trials and the future drugs that our patients could be receiving if not today, then tomorrow,” she said.
The tone of the conference was, however, far from gloomy. The aim of the event was precisely to establish what areas of improvement there are and what each country can learn from the other. Russian approval times of 117 days are almost identical to what the U.K.’s were six years ago.
Di Giovanna said there were certainly similarities between the U.K. and Russian markets.
“The U.K. saw a decrease in clinical studies at the same time, about 2008-2010, and that coincided with the increase in clinical studies placed elsewhere in the world: in particular South America, India and China were starting to take much more of the portion of clinical studies, and some of that has now been reversed,” he said.
“We experienced the same downturn in clinical trials, and we’ve worked very hard to try to reverse that with all the procedures we’ve put in place,” he said.
First-hand experience
The conference also gave a platform to Russian pharma entrepreneurs with practical experience of working on the U.K. market, such as Maxim Kholin, business development director and co-founder of Gero, a resident company of Skolkovo’s biomed cluster.
One of Gero’s projects is, in Kholin’s words, “to be politically correct, [aimed at] prolonging healthy life expectancy. To be less politically correct, it’s a drug for slowing down the ageing process.” In developing the drug, the company’s scientists are analysing genome data to find biomarkers in individuals, based on which they issue lifestyle advice accordingly.
“We needed the blood and data of people who’d died. Because we’re studying ageing, we need to understand, could we have predicted when these people would die,” Kholin explained. The company found the data it needed at University College London, which had collected several blood samples from 1,000 people and recorded how long they lived for and what they died of.
“We were able to obtain this data. We had to go before an ethics committee, but now we have a unique advantage that will enable us to develop an ageing biomarker,” said Kholin, adding that his company had also gained access to the U.K. Bio Bank, which holds blood, urine and saliva samples from half a million people.
Kholin’s advice for other Russian companies was to be ready to demonstrate the scientific value of any research before an ethics committee.
Maxim Kholin of Skolkovo resident Gero said access to U.K. resources gave his company a "unique advantage." Photo: Sk.ru.
Two-way process
While the first day focused mainly on U.K. opportunities for Russian companies, the second day was aimed at presenting the Russian market to the British participants of the conference. Representatives on both sides were quick to point out that the U.K. and Russia already have a strong history of cooperation in this area.
“It’s incredibly important to us that we are growing our cooperation in healthcare, in bio pharma, not just in business but in the science that underpins that business. We have a great existing cooperation and we want to build on it,” said Jonathan Brenton, minister counsellor at the British Embassy in Moscow, opening the conference on Tuesday.
“Mutual cooperation already exists, when Astra Zeneca, for example, is working with Yandex, when GSK is actively carrying out clinical trials here,” he said, referring to a joint data project between the U.K.-based pharma giant and Russian Internet company.
“We want more cooperation. Why? Modernity has brought to us new global challenges, whether they be Ebola virus … or antimicrobial resistance. Innovations in bio-pharma, new approaches to developing drugs, exchange of experience in the sphere of medical education and healthcare, improving the quality of our clinical trials: these are the answers to these challenges,” said Brenton, adding that the U.K. has cooperated with the Skolkovo Foundation since its creation in 2011.
His words were echoed by Kirill Kaem, head of Skolkovo’s biomed cluster.
“Currently, the challenges we face are not Russian or related to any specific company; they are global,” said Kaem, adding that he expected the conference to lead to concrete results.
“For Russians, it’s very gratifying that in our everyday cooperation [with the U.K.], we see a practical and pragmatic approach characteristic of the U.K.,” he said.
“We expect this approach to allow the discussions at the conference to result in practical projects that will lead to the development of new medicines and their successful launch on the market,” said Kaem.