Posted 08 December 2016
By Nick Paul Taylor
Welcome to our European Regulatory Roundup, our weekly overview of the top EU regulatory news.
EC Appeases Some SMEs With Revised Advanced Therapy GMPs but Objections Remain
The European Commission has received some favorable feedback on its draft good manufacturing practice (GMPs) guidelines for advanced therapy medicinal products (ATMPs). However, while small and medium-sized enterprises (SMEs) were broadly supportive of changes proposed in the draft, the commission is still a long way from satisfying all groups affected.
Officials published the draft in June after spending several years gathering feedback on the needs of manufacturers of gene therapies, somatic cell therapies, tissue-engineered products and other ATMPs. The consultations led the commission to draft a guideline designed not to burden academic centers, hospitals and SMEs with regulations mandating quality systems reminiscent of those found at conventional production plants. Instead, the commission proposed a flexible approach intended to support the evolution of quality systems as manufacturers gain more knowledge about an ATMP.
Having reviewed feedback to the draft, the commission thinks it has largely succeeded. In a summary of the 53 sets of comments submitted, the commission said the document “was supported by the majority of the respondents,” adding that “support was particularly strong among academia and SMEs.” The claim is backed up by some individual submissions from SMEs and academic groups, such as Belgian biotech Promethera Sciences, which praised the “flexible approach” taken in the guideline.
However, the commission also received responses from multiple people and organizations that, to greater and lesser extents, object to the guideline. A significant number of respondents called for the GMPs to be incorporated into Volume 4 of EudraLex, as opposed to existing as a standalone text. Some of the strongest criticism of the current model came from academic and hospital groups in the UK, several of which said they could not support the document because of the belief it will create uncertainty. Overall, some see the document as causing more harm than good.
“We consider that the document proposes a diluted form of GMP which will unnecessarily pose additional risk to patients and practitioners whilst failing to advance the speed of approval of novel ATMPs,” organizations including the NHS Advanced Therapy Medicinal Products Working Party and Newcastle Cellular Therapies Facility wrote in their responses to the commission.
The commission refers to the range of concerns the ATMP sector expressed regarding the standalone status of the document, without hinting at whether it plans to make changes in response to the criticisms. A clearer picture of how the commission will change the document will emerge once it has discussed the feedback with the European Medicines Agency (EMA) and other groups.
Other topics likely to be discussed include the need, or otherwise, for dedicated ATMP production areas, aseptic process validation requirements and certification by the Qualified Person. Commenters mentioned concerns with the guideline’s approach to each of these areas. The commission singled out aseptic process validation as the topic that received the most comments.
EC Summary, Industry Responses
PRAC Warns Sovaldi, Other Hepatitis C Drugs Can Reactivate Hepatitis B
The EMA’s Pharmacovigilance Risk Assessment Committee (PRAC) has warned direct-acting antivirals such as Gilead Sciences’ Sovaldi can reactivate hepatitis B, prompting it to recommend all patients are screened for the virus before starting treatment. PRAC made the recommendation following a review that also assessed a possible link the liver cancer.
PRAC began looking into links between direct-acting antiviral hepatitis C drugs and reactivation of hepatitis B after physicians began reporting cases of it happening. To date, approximately 30 cases have been reported, a figure PRAC describes as suggesting the frequency of reactivation is “low.” However, given reactivation of hepatitis B can be fatal, PRAC is recommending physicians take steps to cut the risk of it happening.
This will entail screening patients for hepatitis B before starting treatment and then monitoring and managing anyone found to be infected with both viruses. By following clinical guidelines, PRAC thinks the risk of reactivation can be managed.
PRAC thinks the risk is a result of the speed at which Sovaldi and its competitors reduce levels of the hepatitis C virus. As the presence of hepatitis C suppresses hepatitis B, the sudden removal of the virus is thought to affect the balance and lead to reactivation.
Officials looked into the risk of reactivation as part of a review that also assessed reports linking the hepatitis C drugs to liver cancer. This cancer review was inconclusive. PRAC wants to see data from further studies before reaching a position and potentially making a recommendation.
UK Imposes Record Fine on Pfizer for 2,600% Price Hike
The UK has fined Pfizer £84.2 million ($106 million) for “charging excessive and unfair prices” for an anti-epilepsy drug. Pfizer marketed the drug as Epanutin (phenytoin) until September 2012, at which time it sold the rights to Flynn Pharma and precipitated the events that led the Competition and Markets Authority (CMA) imposing a record fine.
Flynn debranded the product, continued sourcing it from Pfizer and increased the price by up to 2,600%. Packs that used to sell for £2.83 cost £67.50, CMA found, resulting in NHS expenditure on the product increasing 2,400% year on year. CMA attributed some of the increase to Pfizer charging Flynn more for the product than it used to demand from the National Health Service. Flynn bumped the price up further still, resulting in the dramatic rise and ultimately fines for both companies.
“Businesses are generally free to set prices as they see fit, but those holding a dominant position should not abuse this situation and set prices that are excessive and unfair. There is no justification for such rises when phenytoin sodium capsules are a very old drug for which there has been no recent innovation or significant investment,” Philip Marsden, chairman of the Case Decision Group for CMA’s investigation, said.
The fine comes at a time when politicians are seeking to revise the law to prevent drugmakers with dominant positions from exploiting the situation. A briefing document to support the legislative proposal identified 10 cases of the price of a generic drug increasing by 1000% or more from 2005 to 2015.
Pfizer plans to appeal the decision.
CMA Statement, BBC News
EC Asks EMA, Other Regulators to Create Antimicrobial Resistance Outcome Indications
The Directorate-General for Health and Food Safety has asked the heads of EMA and other regulators to create a list of harmonized outcome indicators member states can use to track the effect of action plans against antimicrobial resistance.
With the commission making the tackling of antimicrobial resistance a priority, efforts to control the spread of hard-to-kill bacteria are taking off across Europe. Some initiatives will work better than others, but without ways to accurately compare their impact policy makers may struggle to identify effective and ineffective schemes.
To address this concern, Xavier Prats Monné, the directorate-general, has written to EMA Executive Director Guido Rasi and the heads of the European Centre for Disease Prevention and Control and the European Food Safety Authority. In the letter, Monné asks the organizations to collaborate on the creation of harmonized outcome indicators. The indicators should support surveillance of resistance in humans, food-producing animals and food. Monné also wants to track the use of antimicrobials in humans and food-producing animals.
The Directorate-General has given the executive directors until 30 September 2017 to propose a list.