Mandatory use of eCTD in 2019 – Are you ready?

Mandatory use of eCTD for all submission types and procedures by 1 January 2019
From January 2019 all submissions in CP, DCP, MRP and NP, related to authorisation and regulatory maintenance (variations) of human medicinal products, must be submitted in eCTD format.

Baseline dossier
Submission of a baseline CTD Module 3 serving as a start of an eCTD is highly recommended by the agencies, as the baseline dossier facilitates the review and assessment of future applications. A baseline submission is a compiled submission of the current status of the dossier, i.e. resubmission of currently valid documents that have already been provided to an agency but in another format. The sections provided to make up a baseline can be defined by the applicant, but any omissions should not render the submitted content to be misleading. A baseline would typically consist of the Module 3 documents that tend to change over time during the lifecycle of the product.

NDA Service
NDA´s well experienced team may assist you with publishing of variations in eCTD format as well as with conversion of your current documentation to eCTD format.
For more information about eCTD publishing and NDA´s other services, please contact



Shelley Gandhi Chairs the 2nd Annual Biosimilars Europe Congress

Shelley Gandhi, Strategic Advisor Pharmacovigilance & Drug Safety NDA Group, has been invited to Chair the 2nd Annual Biosimilars Europe Congress Nov 23 – 24, 2017 at Hilton London Olympia, London.

The conference will bring together industry experts to explore the strategies to gain insight into new biosimilar development strategies, different characterization and analysis methods, clinical advancement and successful case studies.

This conference offers a rare opportunity to its participants to understand and learn from top experts in the biosimilars field and to share experiences. The conference will also provide a platform to discuss the current vital issues, regulatory issues, market assessment and commercialization and globalization.

Key themes:

  • Current status of Biosimliars market
  • Monoclonal antibody Biosimilars
  • Challenges faced when moving towards globalization
  • Opportunities in emerging markets
  • IP issues, naming and labelling issues related to biosimilars
  • Partnership, new investment and business models
  • Challenges and opportunities for biobetters and monoclonal antibody biosimilars
  • Clinical trials strategies and new guidelines for biosimilar clinical trials
  • Benefits and concerns of interchangeable and biosubstitutes and post authorization monitoring
  • Bringing biosimilars closer to patients and healthcare professionals
  • New solutions to demonstrate similarity and different characterization methods

To find out more about the event click here.







Shelley Gandhi, Strategic Advisor Pharmacovigilance & Drug Safety NDA Group

How do we value drugs? Reforms for better decisions and use.

Within the framework of SNS, Centre for Business and Policy Studies, and the research project Value of new drugs, a number of researchers at the SNS initiative examined a number of issues of great importance for health care. The final report presents overall conclusions and policy suggestions for how we can improve today’s decisions on the use of drugs, both for the drugs that are available today and the new drugs coming on the market.

Authors are NDA’s HTA Advisory Board Chairman Bengt Jönsson and Katarina Steen Carlsson. The report was presented at a conference in Stockholm, Sweden, 22 November 2013, and was discussed by leading decision makers in the Swedish health-care and pharmaceutical policy, for example Christina Åkerman Director General of the MPA and Anders Blanck CEO LIF, the Swedish life science industry organisation. NDA’s Thomas Lönngren, who also contributed to the report, participated in a couple of the panel discussions as well.


Professor Bengt Jönsson






Professor Bengt Jönsson
Chairman, HTA

Professor in Health Economics at Stockholm School of Economics. Founding director of the Centre for Health Technology Assessment (CMT) at Linköping University. Member of the Editorial Board of the European Journal of Health Economics and the International Journal of Health Technology Assessment in Health Care.  Former President of the international Health Economics Association. Advisor and consultant to WHO, OECD and the World Bank.

Prof. Steffen Thirstrup co-chairs biosimilars at EU DIA Biosimilars Workshop November 21-22 in Dublin, Ireland

Medical Advisor and NDA Advisory Board Member, Steffen Thirstrup (MD, PhD) is taking part in a DIA event titled “Biosimilars workshop – European experiences and challenges” in Dublin on 21-22 November. Steffen Thirstrup has been the chair of the organizing committee of this workshop.

This 1.5 day workshop will focus on the European experience with biosimilar medicinal products, giving an overview of the current regulatory and market-access situation, lessons learned, together with the challenges faced by two classes of products, Erythropoietin (EPO) and Granulocyte-Colony Stimulation Factor (G-CSF).

For more information, please click here

Prof. Steffen Thirstrup speaks at DIA Biosimilars 2013 November 13-14 in Bethesda, Maryland, USA

Medical Advisor and NDA Advisory Board Member, Steffen Thirstrup (MD, PhD) is attending and speaking at the DIA Biosimilars Conference on 13-14 November in Bethesda, Maryland, USA. Steffen will run a session on ‘Market experience in EU’, which will address the EU’s approach to biosimilars and his experience of how this works in practice. Steffen was co-chair for the project group on Market Access for Biosimilars under EC’s Platform on Access to Medicines in Europe. To find out more, please click here.

Dr. Markku Toivonen talked at EURORDIS Summer School on Medical Research and Clinical Trial Methodology

Dr. Markku Toivonen, Scientific Director at NDA Group, held a talk at this year’s EURORDIS Summer School on Medical Research and Clinical Trial Methodology. EURORDIS is committed to empowering people living with rare diseases and set up its annual Summer School to provide training and hands-on experience on clinical trials, drug development and the EU regulatory processes. Around 40 participants took part, selected dependent on their English language skills, experience in rare disease advocacy, and their willingness to be involved in drug development and regulatory affairs at the European level.
During Markku’s session on clinical research, he discussed the need for greater evidence-based medicine, the lifecycle of drug development from pre-clinical (specifically of orphan medicinal products) and the stages of drug development. After, Markku followed with a session on clinical trials, specifically looking at the ‘Gold Standards’.

This year’s school was held between 17-21 June 2013 in Barcelona. For more information, please see:

ATMPs workshop at 2013 PDA Europe Conference on Advanced Therapy Medicinal Products

Professor Beatriz Silva Lima, PharmD, PhD, Non-Clinical Expert for NDA’s Regulatory Advisory Board, is contributing towards 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:

A structured approach to assessment of product suitability for switch to OTC status in the EU

The EU non-prescription market represented 14.5% of total pharmaceutical sales in 2009, equating to 26,062 million Euros (source AESGP). Estimated figures for 2010 are that the EU market will account for 36% of the global non-prescription market (1). This market deserves consideration for established prescription products in the EU Community and can be accessed via a process of ‘switching’ legal status, either at a national or European level. Several articles have highlighted the impact on the business of switching a product to non-prescription status and the growth of the OTC market (2, 3). This article will outline the structured approach used by NDA’s dedicated Switch Team to assess the multiple facets to be explored, when considering a change in legal status of a product.


The categorisation of a product is determined according to national criteria. These national categories drive whether the product can be advertised to the patient, reimbursed and whether they are available only via a pharmacist or freely available for self-selection by the patient. There are differences across the EU Member States in categorisation of non-prescription medicines and the impact of these differences should be assessed taking into account the target markets of interest for non-prescription EU sales, for example in France and Italy, the Regulatory Agency may prohibit advertising of certain self-medication products.

For a product approved via the EU Centralised procedure, the legal status is defined at a high level at time of approval, e.g. for the product alli ‘medicinal product not subject to medical prescription’. However, the appropriate national categories are still applied e.g. alli is sold as a P or Pharmacy product in the UK.


The interest of the Pharmaceutical Company in consideration of a switch in legal status may be driven by the desire to expand their product portfolio, as an end of patent life strategy or to reach a potentially wider patient population for conditions which are undiagnosed or untreated in a considerable percentage of the total patient population. There is also the potential for an additional 1 year’s data exclusivity if new significant data are generated to support the switch application. The type of data which could trigger the additional data exclusivity is defined in the EU switch guideline (4) and includes ‘significant pre-clinical / clinical studies, new dosage strengths/indications/ pharmaceutical form or Actual use studies which support safety and efficacy in the non-prescription setting.

In terms of the switch climate and receptiveness of Regulatory Agencies to switch applications, this is again very Member State specific. Public Health needs and cost savings to National Health Authorities if products are switched, facilitate a positive switch environment in some EU countries. The UK stands out as being particularly proactive in encouraging switch considerations and has worked with other key stakeholders to produce a list of possible therapeutic areas and medicines that could be switched (5).

Appropriate self-medication is also in the interest of the patient, since it leads to easier availability of treatments for self-diagnosable conditions and saves time (and money) needed for a visit to a physician to obtain a prescription. Identification of key EU and national patient organisations covering the relevant therapeutic area, who could help in providing the patient’s perspective on the proposed OTC development, also forms part of the assessment.

Finally, the role of the pharmacist needs to be considered, since they can be critical in successful use of a non-prescription medicine. Depending on the product concerned, pharmacists may be called on to establish a patient’s suitability to receive the product via a structured questionnaire or ‘screening’ type questions.


There are multiple regulatory pathways available for switching legal status depending on the initial route of approval, i.e. national or European basis. Legal status of an existing licence can be changed by submitting a variation or a new application may be filed. It is also possible to file a pan- EU application via the Centralised procedure on the basis of ‘interest of patient health at community level’. An assessment considers the pros and cons of the different regulatory strategies.


The EU switch guideline referenced above is pivotal to consideration of switch suitability. It must be demonstrated in the switch application that the product does not meet any of the criteria below:

“Medicinal products shall be subject to medical prescription where they:

are likely to present a danger either directly or indirectly, even when used correctly, if utilized without medical supervision, or

are frequently and to a very wide extent used incorrectly, and as a result are likely to present a direct or indirect danger to human health, or

contain substances or preparations thereof, the activity and/or adverse reactions of which require further investigation, or

are normally prescribed by a doctor to be administered parenterally.”

The Clinical section of the NDA assessment therefore provides a detailed analysis of whether any of the above criteria would be triggered, by consideration of the safety and efficacy profile of the product together with an assessment of the current approved labelling. Potential posology options for the OTC product are proposed. A detailed review of existing competitor products in specific EU countries is also part of the assessment. This has been useful to provide details of switch precedents and compare potential labelling of the proposed switch product with existing competitors.

The Regulatory assessment, in addition to description of potential regulatory filing options , also reviews precedents or concerns raised previously by Agencies, impact of on-going product commitments and the impact of multiple presentations or duplicate licences on the Regulatory pathway. Critical issues for discussion with Agencies are identified.


Since national legal basis categories and switch procedures have such an impact on switch consideration, the core NDA Switch Team works with consultants in all major EU countries to ensure that the switch assessment provides this national focus in addition to the overall assessment.

The NDA Switch Team has combined experience of working on over 60 OTC switch assessments or switch applications to agencies, for multi-national pharmaceutical companies, in a variety of therapeutic areas including Central Nervous system, Genito-urinary and Cardiovascular.

Dr. Toivonen talked at EURORDIS Summer School

Dr. Markku Toivonen, Scientific Director at NDA Group, held a talk at this year’s EURORDIS Summer School on Medical Research and Clinical Trial Methodology. EURORDIS is committed to empowering people living with rare diseases and set up its annual Summer School to provide training and hands-on experience on clinical trials, drug development and the EU regulatory processes. Around 40 participants took part, selected dependent on their English language skills, experience in rare disease advocacy, and their willingness to be involved in drug development and regulatory affairs at the European level. During Markku’s session on clinical research, he discussed the need for greater evidence-based medicine, the lifecycle of drug development from pre-clinical (specifically of orphan medicinal products) and the stages of drug development. After, Markku followed with a session on clinical trials, specifically looking at the ‘Gold Standards’. This year’s school was held between 17-21 June 2013 in Barcelona. For more information, please see:

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

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