EUCRAF News updates July 2015


Update to Chapter 1 Notice to Applicants

The European Commission has published a revised version of Chapter 1 – Marketing Authorisation of its Notice to Applicants (Volume 2A Procedures for marketing authorizations). This update is Revision 5 of the essential reference and guidance document that is intended to facilitate the interpretation and application of the EU’s pharmaceutical legislation as set out in Regulation (EC) No 726/2004 and Directive 2001/83/EC.


Revised rules on fees payable to the EMA

Please note that the EMA has published a new explanatory note on fees payable for procedures at the EMA applies, which came into effect on 1 August 2015. The changes to the implementation of the “fee Regulation” (Council Regulation (EC) No 297/95) introduced with this note concern the definition for distinct good-clinical-practice (GCP) inspections as well as an extension of fee reductions for pharmacovigilance-related variations to marketing authorisations to veterinary medicines. The currently payable fees apply since 1 April 2015.


Fast track routes for medicines that address unmet medical needs

The EMA has published for consultation revisions of its guidelines on the use of accelerated assessment and conditional marketing authorization. While both tools are not new, the agency is updating the existing guidelines in order to clarify the intended scope and criteria of both procedures and to optimize their use, with the overall goal to get promising new drugs to patients faster. The revisions also take into account discussions had at the European Commission Expert Group on Safe and Timely Access to Medicines for Patients (STAMP).

The consultation period is scheduled to end on 30 September 2015.

Revision of Guideline on the scientific application and the practical arrangements necessary to implement Commission Regulation (EC) No 507/2006 on the conditional marketing authorisation for medicinal products for human use falling within the scope of Regulation (EC) No 726/2004

Revision of Guideline on the scientific application and the practical arrangements necessary to implement the procedure for accelerated assessment pursuant to article 14(9) of regulation (EC) No 726/2004

Biosimilar rhG-CSF guideline

The Biosimilar Medicinal Products Working Party (BMWP) has published for consultation a concept paper for the revision of its guideline on the development of biosimilar recombinant granulocyte-colony stimulating factor (rhG-CSF). As one of the first product-specific biosimilar guidelines, the previous guidance was already published in 2006. Since then, extensive experience with biosimilar versions of the originator drug Neupogen has been gained in scientific advice procedures and marketing authorization applications. In addition, the proposed update is intended to align the rhG-CSF guideline with the “overarching” biosimilar guideline, e.g. regarding the introduction of a risk-based approach for in vivo animal studies. The prerequisites for waiving confirmatory clinical trials for rh-G-CSF biosimilars will also be specified. The consultation ends on 31 October 2015.

Revision of the Guideline on non-clinical and clinical development of similar biological medicinal products containing recombinant granulocyte-colony stimulating factor (rhG-CSF)


21st Century Cures Act

The US House of Representatives has passed new legislation that is intended to speed up the discovery, development and delivery of scientific innovation and to expedite patient access to new drugs and devices (the so called “21st Century Cures Act”). The bill covers a broad range of topics, starting from the discovery of new biomedical advancements (e.g. NIH budget and the promotion of paediatric research or the creation of a “NIH and Cures Innovation Fund”); the development (including modern trial design for drugs and biologics, expedited patient access, antibiotic drug development and enhancing combination products review) as well as the delivery of health care (e.g. via telehealth services for Medicare patients).

Many provisions of this bill, which still needs to pass the US Senate before it can be signed into law by President Obama, are expected to have a significant impact on the development and delivery of medical innovation. However, the legislation is not uncontroversial and critics have raised concerns about its potential impact on patient safety.

Corporate news


The British pharma giant GSK received a positive CHMP opinion for their malaria vaccine MosquirixTM (Plasmodium falciparum and hepatitis B vaccine, also referred to as RTS,S/AS01) for children aged 6 weeks to 17 months. This scientific opinion is significant in that it recommends the first vaccine for the prevention of malaria caused by the Plasmodium falciparum parasite, as well as hepatitis B. The clinical development of MosquirixTM consisted of a large Phase III clinical program including more than 16,000 children from seven African countries. While the CHMP determined only a modest protection, the committee still concluded that the benefit of the vaccine outweighed its risks.

Of note, the positive outcome of the CHMP’s scientific assessment will not be forwarded to the European Commission for granting of a EU-wide marketing authorization. Rather, the evaluation was made under the so called Article 58 procedure (of Regulation (EC) No 726/2004). Based on the EMA’s positive scientific opinion WHO may include the vaccine in its public health recommendations for national immunization programs; furthermore, it may support GSK’s marketing authorization applications for MosquirixTM in countries outside the EU.

Novo Nordisk

The Norwegian drug maker Novo Nordisk announced on 1 July 2015 that the company will discontinue sales of its new diabetic drug Tresiba® (insulin degludec) in Germany by the end of September 2015. The company’s “opt-out” resolution is a reaction to the outcome of the AMNOG pricing procedure. Following a decision of the German Federal Joint Commission (G-BA) that Tresiba® does not offer any additional benefit over available therapies, the reimbursement price determined by the arbitration board was set at the level of human insulin.


On 17 July 2015 Amgen’s received EU marketing authorization for RepathaTM (evolocumab) for the treatment of adults with hypercholesterolaemia. The human IgG2 monoclonal antibody inhibits the proprotein convertase subtilisin kexin 9 (PCSK9), an enzyme that is involved in the control of blood levels of cholesterol, especially LDL or “bad” cholesterol. With this EU approval, Repatha is the first PCSK9-inhibitor to be approved world-wide. A week later, on 24 July, Sanofi received the FDA’s nod for its PCSK9-specific monoclonal antibody alirocumab (Praluent) for the same indication.

Amgen also released positive Phase II trial results of it bispecific CD19xCD3 antibody Blincyto® (blinatumomab) in patients with relapsed/refractory Philadelphia chromosome-positive (Ph+) B-cell precursor acute lymphoblastic leukemia (ALL). Blincyto® (blinatumomab) was initially approved by FDA end of 2014 for treatment of patients with Philadelphia chromosome-negative (Ph-) relapsed or refractory B-cell precursor ALL. The BLA was reviewed under the FDA’s breakthrough therapy designation program and received approval 5 months ahead of the agency’s review goal date.