Stephanie Sutton was an assistant editor at Pharmaceutical Technology Europe.

Stephanie Sutton

Last week, I looked at a consultation in the UK concerning access to unlicensed medicines. The 12-week consultation, launched by the UK’s Medicines and Healthcare products Regulatory Agency (MHRA), seeks opinions on giving physicians the option to prescribe seriously ill patients certain medicines that are still progressing through Phase II and Phase III clinical trials. The blog is available 

		The scheme forms a key part of the UK government’s Strategy for UK Life Sciences, which aims to support innovation and give the UK a leading role in life sciences globally. Included in this is a provision to provide patients with better access to innovative medicines.

		The MHRA has conducted a lot of research on the subject of early access to medicines and claims there is broad support for such a scheme. One of the main points emphasised in the agency’s research is that the potential risks of taking an unlicensed medicine will need to be fully and honestly communicated to the patient. There were some concerns that desperation may cloud decision making, but it was generally felt that earlier access to medicines would benefit those with “little else to lose.”

		For patients with debilitating or chronic conditions, such as rheumatoid arthritis, views were mixed on the idea of early access. In cases where patients are not in immediate danger, such as suffering from high-blood pressure, it was felt that early access to medicine should not be given.

		One of the big questions if the scheme is implemented will be what happens if something goes wrong? For example, what if a patient dies from severe side effects? Participants in the MHRA’s research felt that liability should lie principally with the pharmaceutical company and the clinician who offered the treatment. At the same time, though, no one person or body can be made fully liable as patients must personally accept the risks of taking an unlicensed drug.

		Another question will be how early access to medicines will be funded, and how it could affect other care needs. In general, the research showed that funding could be justified if early access delivers long-term cost savings for the NHS. However, the brunt of the cost should be the responsibility of the pharmaceutical manufacturer, which will be benefitting from patients volunteering for the medicines.

		I wonder what the pharma industry will think of that? Companies will have to pay to submit their medicines to the scheme but it seems as if the benefits of getting medicines to patients earlier may outweigh the costs. However, competition may be tight as the MHRA expects only one or two medicines a year to be approved for early access.

		The scheme has been welcomed by several industry associations, including the UK’s BioIndustry Association (BIA), although BIA hopes that more medicines will be approved under the scheme.

		“This is a step towards facilitating the availability of promising medicines to patients at an earlier stage in their development lifecycle,” said Steve Bates, BIA Chief Executive Officer, in a 

. “However, the proposal to limit the scheme to only one or two medicines a year, targeted at the end of phase III trials, does not, in the BIA’s view, meet the ambition the UK government set out in its Strategy for UK Life Sciences. This included an option to fully discuss the review of innovative medicines at an earlier stage of development, where supported by suitable data.”

		The proposed scheme is open for comments until Friday 5 October. Comments can be posted or emailed to the MHRA. Full details are available on the 

		The agency is aiming to make a decision on implementing the scheme by the end of this year.

Articles

Last week, I looked at a consultation in the UK concerning access to unlicensed medicines.

UK Examines Earlier Access to Medicines

 its first set of finalized guidelines concerning good pharmacovigilance practices (GVP). The guidelines are a key deliverable of Europe’s 

, which will come into effect on July 2, 2012. 

Several modules make up the GVP package. Seven modules have been finalized so far concerning pharmacovigilance systems and their quality systems, pharmacovigilance systems’ master files, risk-management systems, management and reporting of adverse drug reactions to medicinal products, periodic safety update reports, postauthorization safety studies, and signal management. 

Each module was released for consultation between February and April 2012 and the final versions reflect some of the comments received. Each module was developed by a team of experts from the EMA and EU member states. 

More modules are also under development, including modules for pharmacovigilance inspections and additional monitoring, and will be released for consultation later in the year. 

The European Medicines Agency has published its first set of finalized guidelines concerning good pharmacovigilance practices.

EMA Finalizes Pharmacovigilance Guidelines

The European Medicines Agency (EMA) has launched an investigation into Roche after an inspection found that thousands of potential safety reports connected to Roche medicines, including reports of 15,161 deaths, had not been evaluated to determine whether they should be reported to regulators as adverse drug reactions.  

According to the inspection, which was conducted by the UK’s Medicines and Healthcare products Regulatory Agency (MHRA) as part of a coordinated European program of routine inspections concerning safety-reporting systems, Roche identified around 80000 reports that had not been evaluated. The reports were collected through a Roche-sponsored patient support program and relate to products marketed by the company in the US. As well as deaths, suspected adverse reactions were also unevaluated, including approximately 23000 reports gathered through Roche’s reporting systems and 600 from clinical trials.

It is unclear whether any of the reports have already been submitted to authorities through other channels, such as healthcare professionals, whether the deaths or suspected adverse effects have any causal link to Roche’s products. In addition, the EMA explained in a 

 that more recent information from the company indicates that there may be a smaller number of deaths, although this has yet to be verified by regulatory authorities.  

The EMA will work with national medicines agencies, including FDA, to investigate the deficiencies and will also examine whether the safety reports have any impact on the overall benefit-risk profile of the medicines involved. In the meantime, Roche have been told to submit a revised comprehensive action plan for evaluating and reporting all outstanding cases, as well as plans for corrective measures to ensure adequate reporting by Wednesday 27 June.

The EMA also reiterated that Roche must ensure that all known reportable events are immediately flagged to the appropriate authorities, both for products in clinical trials and for marketed products.  

 released by the MHRA, Sir Kent Woods, chief executive of the MHRA, said: "Patients should continue to take their medicines because our investigation into Roche has currently found no evidence of a safety risk to patients. Roche’s actions are unacceptable and our investigation has identified that Roche’s reporting systems are inadequate. We are taking urgent action to ensure that these are rectified by Roche as a matter of priority.”

The European Medicines Agency has launched an investigation into Roche after an inspection found that thousands of potential safety reports, including 15161 deaths, connected to Roche medicines had not been evaluated to determine whether they should be reported to regulators as adverse drug reactions.

EMA Investigates Roche for Deficiencies in Safety Reporting

A coordinated European programme was recently carried out involving routine inspections of pharmaceutical companies’ safety reporting systems. Whether regulators suspected deficiencies or not is unknown, but they certainly found them when the UK’s Medicines and Healthcare products Regulatory Agency inspected one of Roche’s UK sites. During the inspection, the company identified around 80000 reports, including 15161 deaths, connected to Roche medicines marketed in the US that had not been evaluated to determine whether they should be reported as adverse drug reactions. The reports were collected through a Roche-sponsored patient programme.

		At the time of writing, Roche had not published an official statement on their website in response, perhaps because the company has more important matters to attend to than press statements at the moment. The European Medicines Agency has asked the company to submit a “revised comprehensive plan” for the evaluation and reporting of all outstanding cases, as well as plans for corrective measures, by tomorrow (27 June). This includes evaluation of each of the 80000 reports and appropriate follow up. As well as the deaths, other unevaluated reports included around 23000 concerning suspected adverse reactions collected from Roche reporting systems and another 600 form clinical trials.

		Of course, it is not yet known whether any of the deaths or other reports have causal relation with Roche medicines or not. No doubt all pharmaceutical companies receive thousands of reports every year, but these must all be evaluated to monitor a product’s benefit–risk balance throughout its lifecycle. The safety of a medicine is not set in stone once it has been approved by regulators as side effects or safety concern may often arise when a medicine is used in a wider population. In a 

, the EMA reiterated to Roche that the company must ensure that all known reportable events are immediately reported to the appropriate EU authorities, for both marketed products and those in clinical trials.

		The EMA will be working with national medicine agencies and the FDA to investigate the deficiencies in Roche’s safety-reporting system. This includes looking at whether any of the 80000 reports impact the overall benefit–risk balance of the medicines involved.

A coordinated European programme was recently carried out involving routine inspections of pharmaceutical companies’ safety reporting systems.

Deficiencies in Roche Safety Reporting

Merck Serono has revealed its “final efficiency 

” for operations in Switzerland, which includes confirmation of the closure of sites in Geneva and Coinsins and their associated job cuts.

The restructuring was first announced in February 2012, but in April, in accordance with Swiss law, Swiss-based employees were given the opportunity to provide alternative proposals to avoid the job cuts, to reduce their number or to minimize their impact. The majority of proposals received from employees focused on maintaining all or some of the company’s activities in Geneva, developing a biotechnology cluster in Geneva or were measures relating to the company’s social plan. Several aspects of the received proposals relating to the social plan have been incorporated into the final program, including lowering the minimum age for early retirement from 58 to 56 years of age. In addition, employees who resign before the expected end of their contract will retain the right to part of their severance payment, under certain conditions.

However, Merck explained that it could not retain proposals advocating the maintenance of its activities in Geneva given the need to eliminate existing job-function duplications.

"The restructuring of Merck Serono's activities in Switzerland is part of an extensive program concerning all regions and all businesses of the Merck Group, necessitated by the unprecedented market shifts and the competitive environment facing the Group," Stefan Oschmann, Executive Board Member of Merck and CEO of Merck Serono, said in a press statement. "This restructuring process involves tough measures, but these are essential to safeguard the future of Merck Serono.”

As part of the final efficiency program, the company is also offering to facilitate the creation of start ups from employees using a fund of EUR 30 million ($38 million). Employees who proposed ideas for developing service companies targeting the biopharmaceutical industry are being encouraged to apply for start-up support, which may include capital investment, granting of intellectual property licenses and/or cessation of material assets. Employees can continue to submit project for consideration until 30 September 2012. Several proposals are already at advanced stages of discussion.

The majority of job transfers and cuts as part of the restructuring are expected to be completed by the second half of this year. Closure of the Geneva site is planned for mid-2013 and for 2014 for the Coinsins site. 

The restructuring plan includes consolidating all headquarter functions on a Merck Serono campus in Darmstadt, Germany. Out of the 1250 positions currently located in Geneva, roughly 750 will be transferred to other sites and 500 will be eliminated.  Approximately 80 positions in the Canton of Vaud will be made redundant while manufacturing operations based in Coinsins will be relocated to Aubonne.

Merck Serono has revealed its final "final efficiency program" for operations in Switzerland, which includes confirmation of the closure of sites in Geneva and Coinsins and their associated job cuts.

Merck Serono Announces Final Restructuring Plan

The European Federation of Pharmaceutical Industries and Associations (EFPIA) has called for the German government to take “urgent action” regarding its pricing system, which is perceived as hindering the market entry of new, innovative medicines in the country. In particular, EFPIA has become concerned by the fact that some global companies are choosing not to make certain new medicines available in Germany because of the current pricing measures.

At a recent meeting in Berlin, Richard Bergström, director general of EFPIA, explained that although it was appropriate for Germany to carefully control its healthcare budget, early experience with the system was “disappointing.” The measures imposed by the system have been described as “punitive” and include actions such as a 16% rebate system and the use of Greece (currently in the midst of a debt crisis) as a reference market for the price of pharmaceutical products. The assessment also uses generics for reference pricing.

“We have found the set-up very rigid,” said Bergström, in an EFPIA 

. “Unfortunately, many of our member companies have been forced to announce that several new medicines will not be made available in Germany, because the model seeks to base the price for new medicines on what is paid for much older, generic medicines.” EFPIA believes that price comparisons should be made with patented products, not generics, and that there should also be more “meaningful” discussions. In addition, EFPIA adds that the inclusion of Greece as a reference country for pricing may not be appropriate. Several pharmaceutical companies have lowered the prices of medicines in Greece because of the debt crisis, and EFPIA claims that it is important to acknowledge that some countries need to pay more in order to sustain innovation.

With reform still in the “learning phase,” EFPIA added that it is important for stakeholders to work together. Bergström said, “The original intent was good, but some things were lost in translation to the practical model.... The pharmaceutical industry, as EFPIA and its national association in Germany, vfa, remains constructive, and wishes to work with the German government and sickness funds to find a pragmatic solution.”

The European Federation of Pharmaceutical Industries and Associations has called for the German government to take "urgent action" regarding its pricing system, which is perceived as hindering the market entry of new, innovative medicines in the country.