Biosimilars in the EU – what have we learned so far?

NDA Group Advisory Board member, Steffen Thirstrup, has written an article in Scrip Regulatory Affairs Magazine Sep 2013 on ‘Biosimilars in the EU – what have we learned so far?’

With the EU set to approve its first two biosimilar monoclonal antibodies, Steffen looks back over the past seven years since the first biosimilars were approved and examines the lessons learnt and the outlook in the EU.


Biosimilars by Steffen Thirstrup

This article was published in Scrip Regulatory Affairs September 2013


Dr Steffen Thirstrup

Dr Steffen Thirstrup, MD, PhD
Medical Advisor, NDA Group

Previously Head of Division, Medicines Assessment and Clinical Trials at the Danish Health and Medicines Authority. During his 9 years with the regulatory agency in Denmark, Steffen held several significant roles including 5 years as CHMP member, 1 year as a member of the Committee for Advanced Therapies (CAT), Chairman of the CHMP Respiratory Drafting Group and Co-Chair of the EC Working Group on Market Access of Biosimilars under the EU Platform on Market Access of Medicines in EU. Steffen is a medical doctor, has a PhD in pharmacology and has a broad clinical background in general internal medicine with a special interest in respiratory medicine combined with an in-depth knowledge of clinical pharmacology and therapeutics.

He is Board Certified Specialist in Clinical Pharmacology and Therapeutics with the National Board of Health in Denmark. He is also adjunct professor at the School of Pharmacy, Faculty of Health Sciences at the University of Copenhagen.

NDA Group attends RAPS 2013 – The Regulatory Convergence, Boston 28th September – 2nd October

NDA Group are going to be attending this year’s RAPS 2013 – The Regulatory Convergence, held in Boston between 28th September to 2nd October.

We are attending one of the foremost global regulatory events to meet with US pharmaceutical companies and discuss what’s needed when introducing new products in the EU. This includes everything from regulatory strategy and the needs of regulatory Agencies in the EU, through to advice on HTA and pharmacovigilance requirements to get a drug to market and then keep it there.

If you are interested in meeting us, please email

Professor Beatriz Silva Lima runs ATMPs workshop

Further AB Office Image

Professor Beatriz Silva Lima, PharmD, PhD, Non-Clinical Expert for NDA’s Regulatory Advisory Board, is running a workshop on ATMPs at 2013 PDA Europe Conference on Advanced Therapy Medicinal Products.

Beatriz will specifically talk about ‘iPS cells, can they replace (some) preclinical studies’ as part of a broader session on Pre-Clinical Studies.

The PDA Advanced Therapy Medicinal Products Conference provides an opportunity to exchange information and thoughts between the industry and regulators of different areas with the aim to improve the understanding of ATMP development and the regulatory expectations in this new and emerging field of medicinal products.

The event takes place in Florence, Italy, on 25-26 June 2013.

For further information, please see:

Making a success of new drug development

Frustrated with the high rate of new drugs failing to pass the regulatory requirements, Dr Lars-Helge Strömquist founded the NDA Group in 1997. In this article, that was published in the September/October 2011 issue of Pharma Magazine, he describes some of the core reasons for this high failure rate and also some of the solutions to counter the trend.

Wasting $60 billion on failed drug development programmes is unacceptable. But just how does the industry improve its strategy in getting new drugs to market quicker? NDA’s Dr Lars-Helge Strömquist, comments on the state of the industry.

In 2009, the failure rate of new drug applications (NDAs) in the European centralized procedure peaked again at 40% – a trend that is showing no sign of declining (1). The cost for the industry of failed drug development programmes is estimated to be $60 billion worldwide (2). These combined failures of pharmaceutical companies, of all sizes, to get new drugs to market is placing a huge toll on society.

Is it acceptable that a large number of patients are put at risk in trial programmes that have no chance of ever delivering a product to market? Is it acceptable that investigators and their sites are involved in studies of limited medical value? Is it acceptable that regulatory agencies are bogged down in assessing applications that cannot be approved? Finally, is $60 billion spent every year on drugs that fail to get approved really sound business? The industry needs to change this trend, to reduce the failure rate and to get new drugs to market quicker. In addition, there is a need to generate solid facts to encourage the termination of inferior drugs that are in development as early as possible.

Why do so Many NDAs Fail?

The European Medicines Agency (EMA) is transparent with the reasons drug applications fail and statistics are presented regularly that show why. The majority of failures are not because of poor molecules or therapies; they are the result of suboptimal clinical programmes and the resulting data that fails to demonstrate whether the treatment’s benefits outweigh the risks to patients.

Usually, such deficiencies can be caught much earlier than is currently the case. Many of the programmes that have failed in late Phase III had sufficient signals to justify terminating the programme much earlier. Yet, because development was allowed to continue, patients were put at risk, agencies had to engage in activities that were predestined to result in refusals, and the companies in question spent huge amounts of money on trial programmes that would never succeed. In addition, the time spent on a failed programme could have been channeled into other scientific or business-related activities to create true value to the organization, patients and society as a whole.

Solving the Puzzle

To get to grips with these issues it is important to understand that any company will first and foremost look to its own survival. Indications that a company’s single product is predestined to fail will not be appreciated by anyone with a vested interested. Expecting people within an organization to step up and deliver this bad news at such early stages is perhaps not entirely realistic. This fact is also reflected in the statistics from EMA where external scientific advice was primarily requested by the bigger companies, who understand that engaging with regulators early in development will provide a roadmap to approval and are prepared to take the consequences in those cases when the news is bad.

Successful drug development is all about ‘doing the right things right first time’ and, to ensure this, drug developing companies should seek qualified third-party opinion before putting their plans into practice. Securing early third-party input and second opinion on the drug development programme is the only way to ensure that it is in line with external requirements and avoids internal bias.

According to research by the EMA, “obtaining and complying with scientific advice appears to be a predictor of outcome” (for a successful marketing authorization application) and “obtaining scientific advice early in development and at major transition points, as well as compliance with the advice given by the CHMP are recommended”(3). Today, such impartial and qualified advice can be delivered through four main sources: FDA in the US; the EMA Scientific Advice Committee in Europe; the European National Competent Authorities; and through the NDA Advisory Board, an independant third party. The earlier this external advice is sought, the more value it will deliver to the development process, by providing intelligence on, for instance, clinical end point selection, trial design and regulatory strategy.

The most natural stages of drug development optimal for third party assessment are

  • Non-clinical plan
  • Phase I plan
  • Phase II plan
  • Phase III plan

At each of these stages, external advice can provide practical, strategic, economic and societal benefits. It is of outmost importance to secure health economic and reimbursement requirements are covered no later than in the Phase III plan. This will ensure that the drug being developed is likely to be widely marketable once it obtains approval.

For the industry, as well as for society, the end goal has to be to get good medicines to patients faster. The pharmaceutical industry can, therefore, not afford to ignore the benefits of seeking external scientific and regulatory advice during their drug development programmes. Failing to do so risks them spending significant sums of money, resources and patients on studies that will not deliver regulatory success.

This article was published in the September/October issue of Pharma Magazine


Athersys is a US-based clinical stage biopharmaceutical company with a growing pipeline of therapeutics to treat significant and life-threatening diseases. To ensure the global success of its drug, it was necessary to broaden this clinical trial programme to include Europe. However, the company recognised the need for specialist regulatory support to advise how to best approach this region.

Top 10 Pharma

To get its drugs to market faster and reduce the cost of developing new medicines, the company recognised the need to change the way it was approaching its whole development and approval processes for new medicines. The company had traditionally always addressed the regulatory and HTA requirements separately, and over two stages. However, it realised this was no longer an effective way to work. Having worked with NDA Group for a number of years on the regulatory side, the company was interested in NDA’s consulting service to provide joint advice on gaining regulatory and HTA approvals in Europe, called NDA Joint Advice.

Impact of the Paediatric Regulation on existing medicinal products – a review

This article, written by NDAs Jill Challis and published in the Regulatory Rapporteur in October 2011, reviews the impact of the Regulation over the last five years on improving the likelihood for safer and more effective use of existing medicines in children.

Children are not simply young adults when it comes to medicines. Factors affecting growth, metabolism and development may result in adverse paediatric events even though the drug is safe for use in adults.

The aim of the EU Paediatric Regulation was to better protect the health of children in the EU by increasing the availability of medicines intended for children, making information on those medicines widely available and stimulating high quality paediatric research. For currently authorised medicinal products, Articles 45 and 46 of the Regulation have resulted in the ongoing review of existing paediatric data, followed by updates to the product information for a number of medicines.

The requirement for patent-protected products to have a paediatric investigation plan (PIP) in place has also resulted in an increase in research into innovative ways of delivering medicinal products to the different age groups from birth to <18 years in adaptable, age-appropriate dose forms. One aspect of the Regulation which combines both the provisions of an age-appropriate dosage form and paediatric updates to the product labelling is the introduction of the Paediatric-Use Marketing Authorisation (PUMA).

This article reviews the impact of the Regulation over the last five years on improving the likelihood for safer and more effective use of existing medicines in children. Specifically, it reviews the changes which have been introduced to product labelling in terms of paediatric dosing and safety information as a result of the Article 45 and Article 46 assessments, and discusses the increasing availability of licensed medicinal products in dosage forms suitable for use in the different paediatric age groups from birth through to adolescents.







Jill Challis BSc (Hons)

Jill has worked as a consultant in Regulatory Affairs since 1993 and has worked in industry for Synthelabo and Sanofi Aventis since 1997. She joined NDA in 2006.

She specialises in the EU Paediatric Regulation, assisting clients with PIP applications, defining PIP/PIP waiver/deferral strategies and taking many applications through the PIP procedure on behalf of clients to successful completion.