NDA speaks National Pharmacovigilance & Risk Management Conference

Shelley Gandhi, NDA’s Head of Pharmacovigilance services, has been invited by the United Arab Emirates government to speak at their 3rd National Pharmacovigilance & Risk Management Conference on 29th and 30 May, titled: “New Pharmacovigilance Legislation, Implementation and Risk Management Assessment Industrial Perspective”.

The main objective of the conference was to inform the pharmaceutical companies to report ADR and submit their PSUR to the national authority in UAE in order to minimise medication error and adverse drug reactions.

Shelley spoke on a number of topics, including ICSRs & MedDRA, Signal Detection and Management, PSUR (PBRERs) and co-chaired shared panel sessions, to an audience that included physicians, pharmacists and Pharmacovigilance officials and specialists.

Managers ignore PV at their peril

The implementation of Europe’s new pharmacovigilance legislation is currently ongoing, creating ripples as each step forward makes the day-to-day effects more tangible. Since July 2012 a new committee at the European Medicines Agency, the Pharmacovigilance Risk Assessment Committee (PRAC), has started to establish itself as a major influence and stakeholder in the system for regulating medicines.

From a strategic perspective the implementation of the new legislation brings with it several critical aspects that the leadership and management of every pharmaceutical company must take into account as it creates plans to develop new pharmaceuticals. In this article I will summarise three of these aspects: accountability, transparency and perpetual development.


The new legislation puts increased accountability on the management of companies to ensure that their processes are used in a safe and efficient way. For example, companies are now required to include with their marketing authorisation dossier a risk management plan that is proportionate to the risk of the product. This plan must describe the pharmacovigilance activities that a company has prepared in order to minimise risks.

High profile cases around the world illustrate that no-one in a decision-making position is untouched by these new measures. Demonstrating a robust safety and monitoring system is essential. Failure to do so threatens not only the safety of patients and the company’s good reputation and share price, but also the freedom of individual decision makers.

The new law and supporting guidance documents emphasise the central role of the qualified per son for pharmacovigilance. This person is appointed by management to oversee compliance with the new legislation and must be fully integrated into management with oversight of all business functions. Only this way can a company be sure that it has control over all of the post-marketing events that may have an impact on the safety of patients.


For many years the EMA has been promoting a culture of transparency. This means giving healthcare professionals and the public access to regulatory documents and to the work of the agency’s committees. With the coming into force of the pharmacovigilance legislation, transparency has taken on a new meaning: it has become a whip for driving companies into adopting a more risk-based approach and to focus more on patient safety.

The minutes from PRAC meetings are now being made available on the agency’s website; their content could easily become a company’s worst nightmare. The committee is currently examining products already on the market for evidence of previously undetected safety signals. It is asking probing questions that are subsequently being published on the agency’s website within days of the actual meeting.

The PRAC also has been given a mandate, in certain cases,to hold public hearings. It intends to exercise this right in 2013; to date it is unclear under what circumstances the clause would be invoked.

Society, patients and the financial markets are now being given information about medical products that could shape public opinion about the products and ultimately determine their success.

Perpetual development

By introducing the concept of benefit/risk in the pharmacovigilance legislation, the burden of proof for a product’s beneficial effects has been extended way beyond the point of initial approval. It seems that the Committee for Medicinal Products for Human Use (CHMP) no longer holds total exclusivity over the evaluation of a treatment’s efficacy. Reading the PRAC minutes highlights how the new committee involves itself in this aspect of its remit.

The implication for a company’s development strategy is that all initial approvals in effect are conditional- in the broadest sense of the word. The new legislation requires that companies increase the evidence of a drug’s benefit/risk over and above what is required for marketing authorisation. This means gathering more data after authorisation about how a medicine works in clinical practice. Broadening the evidence base with patient outcomes data will improve future drug research and help health technology assessment bodies decide whether or not to recommend a new drug for reimbursement. Conversely, a drug’s reimbursement status, and indeed its authorisation, could be called into question if its benefit/risk profile changes as a result of the patient outcomes data. The requirement to continually assess benefit/risk will also affect a company’s applications for new indications and its decisions on whether or not to apply for over-the-counter status.

In conclusion, the new pharmacovigilance legislation means that managers of pharmaceutical companies will be held responsible for a drug’s performance to an even greater extent than before. Indeed, missteps by management could lead to public disclosures by the EMA. The development phase of a product is now explicitly extended beyond the agency’s initial opinion and the European Commission’s approval of a product, effectively extending it into the marketing phase. Management must ensure that systems are in place to t rack a product once it is in clinical practice. This will be essential if a product is to stay on the market and be assessed for its true value to patients.

Rosalind Cox comments on new EU Medical Device Legislation

Rosalind Cox, Scientific Advisory at NDA Group, writes an article for the December issue of Regulatory Rapporteur on the new EU Medical Device Legislation. She reviews the key impacts of the proposed legislation, referencing that they are still up for review before gaining EU Parliament agreement.

This article was Published in Regulatory Rapporteur – Vol 9, No 12, December 2012.

Dr. Panos Tsintis shortlisted for TOPRA Lifetime Achievement Award

Dr. Panos Tsintis, a member of NDA’s Regulatory Advisory Board, was shortlisted for a Lifetime Achievement Award at the TOPRA Awards 2012. The award recognises an individual who through his or her life’s endeavours has demonstrated a significant and lasting contribution to Regulatory Affairs – over and above what might have been expected from the professional role the individual was employed to do.

Dr. Panos Tsintis has spent over 20 years working in regulatory affairs and pharmaceutical medicine, across industry, consultancy and with a substantial contribution within EU regulators, from drug development to post-marketing. Today, Panos provides strategic advice to a number of international pharmaceutical companies – including risk management, regulatory support in MAA and orphan drug designation, paediatric plans, through to scientific advice and crisis management.

Getting good medicines to patients and keeping them there

In this article, published in Regulatory Rapporteur, September 2012, Thomas Lönngren, strategic advisor to NDA Group reflects on the hurdles to overcome and roadblocks still to be negotiated in Drug development – particularly in measuring the “value” of new medicinal product.

We live in a world where it is tougher than ever to get new medicines to patients. There is far greater scrutiny of new drugs, more processes, greater differences in decision criteria between countries when making a drug available to a patient, and new monitoring across the lifetime of a product. This uncertainty has not always been the case, and there is renewed hope that greater collaboration between industry and governing bodies will reverse this trend to bring a greater focus on what’s right for the patient – access to good medicines.

Dr Lönngren has over 30 years’ experience in the regulatory field. Currently an independent strategic advisor to the NDA Group. Prior to this, Dr Lönngren was Executive Director of the European Medicines Agency (EMA). He has also held positions at the Swedish Medical Products Agency, the Swedish National Board of Health and Welfare and the Swedish International Development Agency’s health cooperation program in Vietnam. Dr Lönngren is a qualified pharmacist from the University of Uppsala, Sweden, and holds an MSc in social and regulatory pharmacy. In 2008, Dr Lönngren was awarded Drug Information Association’s Distinguished Career Award.

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.

Medicines for older people and the need to get on track

In this article, published in the February 2013 issue of Regulatory Affairs, Markku Toivonen discusses the need to consider the elderly in global drug development. The reasons for the mis-prescribing in this fast growing population are discussed, highlighting the importance of adequate representation in clinical trials, pre and post authorisations studies. Shortcomings in current regulatory guidance, recruitment problems and lack of specific information for older people are cited among the myriad of factors that need to be redressed. Markku discusses the way forward and steps that regulatory bodies are taking to address these challenges.


You can find the article here.



Dr Markku Toivonen






Dr Markku Toivonen MD, PhD.
Scientific Director, 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 22 November 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.

You can read the report here.


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.

European mid-sized pharmaceutical company

The company had no paediatric expertise and limited understanding of the requirements of the EU Paediatric Regulation. They required help in understanding the requirements of the Regulation and its implications on development of their compound. They needed support in to developing a strategy for the paediatric investigation plan (PIP) and so approached NDA because of our extensive paediatric and regulatory expertise in this area.

Biosimilar Monoclonal Antibodies approval across Japan, EU and US

The client is developing a pipeline of biosimilar monoclonal antibodies for approval in Japan, EU and US. While the regulatory pathway is well-defined in the EU, the pathway to approval of biosimilar products is at a much earlier stage in US and Japan. Although some requirements appear to be aligned across most phases of development, there are still are still major differences in the regulatory requirements from the different regions.

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: http://www.eurordis.org/content/eurordis-summer-school-patient-advocates.

NDA invited by United Arab Emirates government at PV Conference

Shelley Gandhi, NDA’s Head of Pharmacovigilance services, has been invited by the United Arab Emirates government to speak at their 3rd National Pharmacovigilance & Risk Management Conference on 29th and 30 May, titled: “New Pharmacovigilance Legislation, Implementation and Risk Management Assessment Industrial Perspective”. The main objective of the conference was to inform the pharmaceutical companies to report ADR and submit their PSUR to the national authority in UAE in order to minimise medication error and adverse drug reactions. Shelley spoke on a number of topics, including ICSRs & MedDRA, Signal Detection and Management, PSUR (PBRERs) and co-chaired shared panel sessions, to an audience that included physicians, pharmacists and Pharmacovigilance officials and specialists.

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 info@ndareg.com