Integrated product development for ATMPs

By: Claes Buxfeldt and Dr Paula Salminkangas

In this article, published in the September issue of MedNous, Claes and Paula discuss why an integrated product development strategy for ATMPs is essential to meet both regulatory and HTA requirements.


Advanced Therapy Medicinal Products (ATMPs), which include cell and gene therapies and tissue engineered products, are a group of innovative products targeting diseases and conditions for which there are few, if any, effective treatments. The success of the first CD19 chimeric antigen receptor T cell (CAR T) products Kymriah and Yescarta against B-cell malignancies has raised the awareness of the high potential of ATMPs, but also shown the several challenges relating to their clinical use1. One of these challenges is the high prices asked by the manufacturers of these products, which are not always supported by national pricing and reimbursement bodies2.

In such cases, the discrepancy between a regulatory approval and a negative decision from a health technology assessment (HTA) body has raised concerns and questions from industry about how to ensure that an approved product also gets to the market and to patients. Many jurisdictions have created early access schemes and ways to communicate with regulatory and HTA bodies early on to ensure successful outcomes of both reviews3. However, the ATMP industry is facing challenges in both aspects.

The development of ATMPs has substantially increased with a focus on clinical trials in recent years. Several cell and gene therapy products have been authorised worldwide, most recently the CAR T product Tecartus from Kite Pharma Inc.4 in the US and Zolgensma for spinal muscular atrophy (SMA)5 in the EU.

Today there are more than 980 developers globally, the majority (78%) of whom are in North America and Europe.6 Over 1,000 clinical trials were underway worldwide at the end of 2019, two-thirds of which (64%) were in Phases 2 and 3. There has been a clear shift from early to late phase trials, as only four years earlier the majority of trials (> 90%) were in Phases 1 and 27. Since beginning of 2015, the overall number of ATMP clinical trials and ATMPs in Phase 3 has doubled, suggesting multiple new ATMPs will be approaching the marketing authorisation application stage in the next few years.

Today, the focus of ATMP development is heavily in gene therapy and genetically modified cells which constitute three-quarters of products in clinical trials. This is most probably due to the fast development of novel vectors and technologies, including genome editing. In addition, a lot of safety data has accumulated for certain gene therapy approaches (e.g. adeno associated virus vectors, AAV and lentivirus vectors, LVV), which reduces the regulatory burden before first clinical trials.

From an indication perspective, the majority of ATMP clinical trials (657/1066, 62%) 6 are in oncology, including leukaemia, lymphoma, and solid tumors, which may be explained by the great interest towards novel immunotherapies using genetically modified cells. In 2019, genome edited cells using the CRISPR/Cas9 approach proceeded to clinical trials both in the US and the EU8 and the first results from a trial studying an induced pluripotent stem (iPS) cell-derived product were reported in the EU 9.

Click to the full article
 

Contact us to learn more about how our integrated team can provide advice and support into your drug development plan.

 


References :

  1. Mohty M., Gautier J., Malard F., et al. CD19 chimeric antigen receptor-T cells in B-cell leukemia and lymphoma: current status and perspectives. Leukemia 2019, 33: 2767–2778
  2. Jönsson, B., Hampson, G., Michaels, J., Towse, A., Graf von der Schulenburg, JM. and Wong, O. Advanced therapy medicinal products and health technology assessment principles and practices for value-based and sustainable healthcare. Eur. J. Health Econ. 2019, 20(3): 427–438
  3. Jörgensen, J. and Kefalas, P. Reimbursement of licensed cell and gene therapies across the major European healthcare markets. J Mark Access Health Policy 2015, 3: 10.3402/jmahp.v3.29321.
  4. FDA approved Cellular and Gene Therapy Products, https://www.fda.gov/vaccines-blood-biologics/cellular-gene-therapy-products/approved-cellular-and-gene-therapy-products
  5. EU public assessment report for Zolgensma https://www.ema.europa.eu/en/medicines/human/EPAR/zolgensma
  6. Alliance for Regenerative Medicine: 2019 Regenerative Medicine Sector Report, available from https://alliancerm.org/sector-report/2019-annual-report
  7. 7.Alliance for Regenerative Medicine: Q1/2015 Regenerative Medicine Sector Report, available from https://alliancerm.org/wp-content/uploads/2018/04/ARM_Q12015_Data_Report_Web_Version.pdf
  8. CRISPR Therapeutics and Vertex Announce Progress in Clinical Development Programs for the Investigational CRISPR/Cas9 Gene-Editing Therapy CTX001, available from https://investors.vrtx.com/news-releases/news-release-details/crispr-therapeutics-and-vertex-announce-progress-clinical
  9.  Cynata Completes Clinical Study Report for Phase 1 Trial of CYP-001 in GvHD, available from https://www.globenewswire.com/news-release/2018/12/18/1668688/0/en/Cynata-Completes-Clinical-Study-Report-for-Phase-1-Trial-of-CYP-001-in-GvHD.html

 

 

Leveraging Expedited Regulatory Pathways to Optimize Drug Development

A Pharmafocus webinar

Join us on Thursday 24th September 2020, 15:00 BST | 16:00 CEST | 10:00 EDT, when Dr Frank Casty, Judith Plon and Professor Steffen Thirstrup will guide you through the expedited regulatory pathways available in the EU and US and discuss how to effectively leverage these to accelerate and optimize your drug development program.

A timely market introduction is a critical component of any drug development strategy – not only from a commercial standpoint, where an earlier market entry can lead to a competitive advantage, but also for patients awaiting better treatment options.

Regulators worldwide have developed specialized pathways to expedite review and approval of new drugs. Navigating these pathways can be a daunting task for sponsors.

Partnering with experienced regulators both in the US and EU is critical to achieving expedited reviews since getting the strategy right, developing effective documentation, and preparing for regulatory interactions can make the difference between a standard regulatory review and a successful expedited review

Our panel will discuss:

  • Which pathways are available
  • When to apply for specific designations
  • What data are required and what to expect if the designation is granted
  • Best practice to create a successful strategy

Click here to book your place today!


About the Panel

Dr Frank Casty: Senior Clinical Regulatory Advisor, NDA Group

Frank works with small and large companies across several therapeutic areas including cardiovascular, respiratory, inflammation, oncology and rare diseases.  He has led numerous FDA interactions, IND and NDA filings as well as presented at successful FDA Advisory Committee Meetings.

Before joining NDA, Frank worked for more than 25 years in small and large pharmaceutical companies leading Global Clinical Research and Medical Affairs organizations as well as serving as technical consultant for Business Development activities.

Judith Plon: Principal Consultant, NDA Group

Judy works with small and large companies across multiple therapeutic areas. She serves as a US Agent for clients leading the submission of their INDs, NDAs, and special designation requests (i.e. Orphan Drug Designations).

Prior to joining NDA Judy spent over 25 years in the Biopharma Industry, primarily working in the discipline of regulatory affairs. She held positions of increasing responsibilities and last served as a Vice President of Global Regulatory Affairs.

Professor Steffen Thirstrup: Director NDA Advisory Board, NDA Group

Steffen excels at advising companies on their development strategies to meet expectations of regulatory agencies around the world. He applies his skills to a broad range of therapeutic areas and have successfully helped numerous clients interact with regulatory agencies throughout the stages of development and during regulatory review.

Prior to joining NDA in 2013, Steffen was employed as the head of Division for Medicines Assessment and Clinical Trials at the Danish Health and Medicines Authority where he also acted as Danish member of the Committee for Human Medicinal Products (CHMP) at the EMA.

 

 

Market access for immune-oncology products in the EU

By: Claes Buxfeldt, HTA Director at NDA Group

In this article, published in Volume 22 September 2020 of Pharmafocus, Claes Buxfeldt discusses key considerations in early development to succeed with market access for immune-oncology products in the EU.


Integrating market access considerations early into your development program saves money and the chances that your product will reach the market, or a premium at exit.

At NDA we work closely with development teams covering many disease areas. Reflective of the global pipeline, a large part of our time is spent helping clients with immune-oncology portfolios. Here we cover what activities should be considered in early development of new immune-oncology (IO) drugs to ultimately secure reimbursement or optimise the asset’s value. We also explore how IO treatments are different compared to other treatment options and important attributes to consider.

Background

Achieving regulatory approval by demonstrating your product’s appropriate benefit/risk profile is only one step to reach and treat patients. In many countries pricing and reimbursement bodies have additional requirements to be fulfilled. This includes demonstrating comparative effectiveness and value for money.

Immune-oncology (IO) therapies

Instead of targeting tumours directly, IO therapies engage the patient’s own immune system to stop them. This approach may offer a more effective treatment for some patients. Important characteristics of IO therapy include full tumour regression, often a more sustainable clinical outcome and improved health-related quality of life compared to standard chemotherapy. IO therapy often has a different side-effect profile and durability of response.

The development of targeted immune checkpoint inhibitors resulted in the first FDA approval in 2011 of Yervoy (ipilimumab – CTLA4 antibody) for melanoma. Additional studies of PD1/PDL1 antibodies have led to regulatory approval both as single agents and in combination with other agents. IO therapies are now approved by EMA and FDA in treating melanoma, lung, kidney, bladder, head and neck cancer.

Key distinctive features of IO therapies:
  • Immune-mediated mechanisms of action,
  • Significant and increased durability of response,
  • Unique kinetics enabling delayed response,
  • Potential for shorter treatment period,
  • Possibility of being “cured”,
  • Different, often more manageable, side-effect profiles,
  • Sometimes severe and systemic adverse effects,
  • Better health-related quality of life,
  • Flattening of the Kaplan Meier survival curve suggesting durable responses,
  • Administrated often in unique combinations of IO drugs.

Critical questions in developing IO therapies include targeting of those patients most likely to respond, combining IO therapies with other treatment options, mitigating related side-effects and reducing the resistance to therapies. How to practically use these therapies in an evolving health care environment and when to stop treatment are also important.

Click to the full article
 

Contact us to learn more about how our integrated team can provide advice and support into your drug development plan.

 

 

 

Optimising the path to market for ATMPs

A two part webinar series

Together with Cirio Advokatbyrå would like to invite you to our two-part interactive webinar series, Optimising the path to market for ATMPs.

ATMPs, Advanced Therapy Medicinal Products, are an increasing and diverse group of innovative products. They are complex  products with unique development challenges, and several have shown very promising efficacy results in treating highly debilitating diseases and conditions. However, the prices of the first approved ATMPs have been high and not always supported by the national pricing or reimbursement bodies or other payers.

This interactive webinar series will focus on the challenges of ATMP development and market access with case examples of approved products. The option of an integrated product development to cover both regulatory and HTA expectations will be presented, together with information on regulatory, HTA and market access support available for ATMP developers.

Session 1: Integrated Product Development for ATMPs to meet Regulatory and HTA requirements

Date: 22nd September

Time: 11am – 12pm CET

Session 2: Models for realizing ATMP- value

Date: 29th September

Time: 11am – 12pm CET

Our panelists are available to answer questions at the end of each session. You can ask your questions during the webinar or send them in advance to denise.stromquist@ndareg.com


Click here to book your place today!



Panelists 

Paula Salmikangas: Director of Biopharmaceuticals and ATMP, NDA Group

Paula joined NDA in 2017 from her position as a Research Professor at the Finnish Medicines Agency (2003-2017). She has served as a member of the EMA Committee for Advanced Therapies (CAT) from 2009 to 2017 and as the Chair of the CAT 2014-2017. She has also been the Chair of EMA CPWP and a member of the BWP. Her main areas of expertise are biological medicinal products, especially advanced therapy medicinal products and CMC aspects of biopharmaceuticals.

Steffen Thirstrup: Director NDA Advisory Board, NDA Group

Steffen joined NDA in 2013 from his position as head the Division for Medicines Assessment and Clinical Trials at the Danish Health and Medicines Authority where he alos acted as Danish member of the Committee for Human Medicinal Products (CHMP) at the EMA. Steffen excels at advising companies on their development strategies to meet expectations of regulatory agencies around the world. He applies his skills to a broad range of therapeutic areas and have successfully helped numerous clients interact with regulatory agencies throughout the stages of development and during regulatory review.

Anders Burén: Senior Counsel, Cirio Advokatbyrå

Anders specialises in strategic collaborations in the pharmaceutical industry and in regulatory law. He advises on Swedish and international aspects of agreements of all kinds governing research, development and commercialisation in the pharmaceutical industry and on product approvals, marketing and other regulatory considerations. Anders has previous experience as Assistant General Counsel for the AstraZeneca Group’s transaction lawyers based outside the US. Before that he was Assistant General Counsel for the Group’s lawyers based in Sweden.

Per Hedman:  Partner, Cirio Advokatbyrå

Per Hedman is head of Cirio’s Life Science, Health and Food practice – the Biological team. Per advises companies in all aspects of their business and legal affairs, including regulatory advice, R&D arrangements (such as non-disclosure, material transfer, clinical trial and joint development agreements), commercial relationships (such as manufacturing, supply and distribution agreements), M&A (such as product acquisitions and spin-outs, domestic and cross border), capital-raising transactions (debt and equity), and IPO:s and other capital market transactions.


To learn more about NDA’s ATMP capabilites click here


The challenges to overcome age-related disease

Through the lens of COVID-19

By: Tom Hughes, CEO Navitor Pharmaceuticals & Johan Strömquist, CEO NDA Group 

In this article, Tom Hughes and Johan Strömquist discuss the challenges facing longevity research and the adoption of health span as a viable target for medicines in the future.


Over the last few years the field of longevity and health span research has exploded and our understanding of the processes underpinning ageing and age-related disease has expanded greatly. In spite of this there are several challenges facing researchers, drug developers and society in general that must be overcome before we start seeing broader treatments that can fundamentally change the underlying pathology of ageing.

In the age of COVID-19 the need for progress has never been more urgent. The disparity in mortality rates we are seeing during the ongoing crisis is a stark reminder that age greatly impacts health. According to statistics shared by the CDC, age is a strong determinant of mortality in patients with COVID-19. There’s little doubt that people fall into a high-risk category for death from infection with this virus once they reach middle age.

A similarly notable finding was reported recently in The Journal of Infection that age-related comorbid conditions also represent a major risk factor for severe morbidity and death from COVID-19, including type 2 diabetes (OR 3.68), hypertension (OR 2.72), and underlying respiratory disease (OR 5.15). Whether directly associated with co-morbid conditions of aging or biological aging itself, it is clear that age and age-related diseases are in the spotlight as accelerants for serious complications of COVID-19.

The excess morbidity and mortality associated with aging, apart from COVID-19, comes with staggering implications for healthcare costs. This is driven in part from the fact that over 80% of people 65 years and older suffer from multiple comorbid conditions, and that over 70% of healthcare spending is allocated to the ~32 percent of people with more than one chronic condition.

To learn more about NDA’s  services and how we can help you, click here.


Click to the full article


About the Authors

Thomas E. Hughes, PhD, President and Chief Executive Officer,
Navitor Pharmaceuticals
Dr. Hughes currently serves as a member of the Board of Directors of miRagen Therapeutics, Inc., is an advisor to Atlas Venture, and is a member of several scientific and strategic advisory boards, including Broadview Ventures, HotSpot Therapeutics, and Nimbus Therapeutics. Dr. Hughes holds a Ph.D. in nutritional biochemistry from Tufts University, an M.S. in zoology from Virginia Polytechnic Institute & State University and a B.A. in biology from Franklin and Marshall College

Johan Strömquist, Chief Executive Officer,
NDA Group
As CEO of the NDA Group since 2013, Johan has worked to expand the NDA’s capabilities across the continents working with a team of exceptional skill and expertise. Johan has a background as serial entrepreneur in the IT and technology industry, serving the life science industry for over 20 years. His main focus remains on developing NDA’s unique ability to provide world leading advice and a client experience second to none.


 

Are you attending the Virtual DIA Europe 2020 Conference?

We would love to connect with you during the DIA and discuss how we can support you to optimise your path to market approval.

Working together we can:

  • Accelerate your drug development program to reduce your time to approval
  • Optimise the management of the regulatory process to provide accurate and predictable outcomes
  • Reduce your risks and increase the probability of gaining Market Authorization

Don’t miss our  great speakers sharing their knowledge in different forums throughout the conference:


Brian Edwards – Principal Consultant

Wednesday, July 1st, Oral Poster Presentation -#CHR 102: Skills, Communication and information in Pharmacovigilance – Oral Poster Presentations

 

 


Dr Mira Pavlovic – HTA Expert, NDA Regulatory Advisory Board member

Tuesday, June 30th, 13:00 – 14:00, Session title:#S0407 L: Drug Assessment for Regulatory and HTA Purposes: Similarities and Differences, the Way Forward. Track:04: Value-Access.

This session will explain similarities & differences about regulatory and HTA requirements to support product authorization and access to market, as well as the concept of added therapeutic benefit both from regulatory and HTA points of view.


Prof. Beatriz Silva Lima – Non Clinical Expert, NDA Regulatory Advisory Board member

Wednesday, July 1st, 18:00 – 19:15, Session title:#DL04 SL: Industry – Regulator Dialogue: Tailor-made Regulatory Guidance for Non-clinical to Clinical Development. Track:01: Clinical Trials.

i) First in human programs
Since the implementation of the new revised EMA Guideline on strategies to identify and mitigate risks for first-in-human and early clinical trials with investigational medicinal products, there has been an interest as to the response by the Pharmaceutical Industry. Would the guideline be interpreted as too conservative and force companies to conduct FIH studies in non-EU geographies? EFPIA conducted a survey among 12 member companies with 54 FIH studies.

ii) Programs in Severe Diseases/Conditions
For a small number of severely debilitating or life-threatening (SDLT) diseases/conditions, regional guidance’s exist encouraging the use of “ICH S9-like” approaches. A lack of incentives for drug developers to engage into costly development may lead to unclear prospective. This session item will address a harmonized and focused approach on development options for SDLT indications to reduce resources to start early clinical development, to bring innovative medicines to patients faster.

Panellist: How has the New EU Guideline Changed the Conduct of First in Human Trials in Europe

Speaker: Beatriz Silva Lima, NDA Group, Advisory Services


Click here to download the Preliminary Programme.


Pre-book a meeting with one our team, via the DIA App or simply
contact us meet-us@ndareg.com

Preparing for the Medical Device Regulation

An interactive webinar

On Friday the 3rd July 2020, 9:00 BST | 10:00 CEST , Dr Tina Amini, Medical Device Division Director, NDA Group will guide you through the key points to consider in your efforts to become Medical device regulation (MDR) compliant and focus on the implementation of MDR Article 117.

During this interactive seminar Tina will clarify the requirements applicable to medical devices under the new Regulation, highlight the major changes and provide an understanding of the impact on the industry. She will also highlight the impact to the manufacturers of integral drug-device combination products as the result of MDR and provide guidance on documentation to be submitted to the notified body.

Highlights:

  • Understanding the new regulatory requirements under MDR
  • MDR Article 117
  • Notified Body expectations for Device aspect of Combination products Drug/Device (regulated as medicinal products) or Device/Drug (regulated a medical device)

To learn more about NDA’s Medical Device division and services click here


Click here to book your place today!


About the Speaker

Dr Tina Amini, a pharmacist with a PhD in Pharmaceutics, is Director of Medical Device Division at NDA Group.

She has over 30 years’ experience in Pharmaceutical and Medical Devices. She previously held the positions of Head of Notified Body and Senior Technical Specialist at LRQA Notified Body and Pharmaceutical & Medical Device Expert at BSI Notified Body, where she was responsible for device/drug combination products, Conformity Assessment of a wide range of medical devices and onsite assessments of Quality Management Systems (QMS) as the lead auditor.

Tina has extensive experience of regulatory expertise for CE marking of medical devices, and has been involved in the classification of borderline products and consultation process with several EU competent authorities and EMA for device/drug products. Prior to joining Notified Bodies, Tina worked in the pharmaceutical industry in a variety of disciplines.

 

 

Interview with Kurt Stoeckli, President NDA Advisory Services

Driven by the desire to understand the human nature, and eventually seeking to understand the physics that construct it all. Kurt Stoeckli’s road to becoming the new President of NDA’s Advisory Board may seem as long and winding as any rising mountain road in the alps in his native Switzerland, but just like them, it does follow a coherent logic and destination.

“It’s all about being curious, asking the right questions, staying passionate and being open to new inspiration”, says Kurt Stoeckli, the new President of NDA’s Advisory Board. “Because knowledge is changing rapidly, and the life cycle of innovation is shorter.”

Growing up in a rural area in Switzerland, between Basel and Lausanne, he dreamt to become a farmer and wanted to drive trucks as a schoolboy and then he became fascinated by climbing

high mountains in the alps; a seemingly unlikely background for someone who would move on to become a leader in the pharmaceutical industry. On his way there, the study of philosophy caught his attention.

“It was more of a hobby and an inspiration”, he says of his early academic career.

“In high school, I was engaged in literature and theater. I wanted to learn more about what drives humans.”

However, when the time came to aim for a professional career – “reading Kierkegaard, Wittgenstein or Heidegger can be fascinating, but epistemology is not a profession”, he points out – he was inspired by a teacher to turn his focus towards chemistry, and later on, biology..

“I loved experiments. You can set up a hypothesis and you can verify or falsify your hypothesis under defined conditions. I like it. Moving from chemistry to biology was a natural evolution in my scientific career. You start by understanding the structure of molecules which is incredibly useful to then understand their function.”

Becoming increasingly interested in physiology and pathophysiology, Kurt Stoeckli worked his way down towards the basics of immunology, fascinated by the immune system’s fundamental importance in keeping a multi-cellular organism, like the human body, in balanced and healthy state; unlike any other organ system of the body with a defined place, the immune system is more like a mobile organ system, doing its job effectively – regardless where it is needed.

When eventually entering the pharmaceutical industry, his leadership skills turned out to come in handy. He headed up the Biologics Division at the French pharma company Sanofi, later becoming the CEO of Glenmark Switzerland and the global CSO of the group.

“It’s all about being curious, asking the right questions, staying passionate and being open to new inspiration”

What are you most proud of during your career?

“Two major things. Having critically contributed to the development of at least two marketed drugs, dupilumab (Dupixent) and sarilumab (Kevzara); they are approved for multiple indications like severe asthma and RA; right now, sarilumab is also used in clinics to dampen excessive immune reactions associated with COVID-19. The other important achievement concerns the development of key talents. High potential people that could unfold their talents and grow into leadership positions, taking major decisions today, and developing next-generation talents for tomorrow. In that way, the cycle continues.”

What about your biggest challenges?

“The shutdown of entire research sites and separating from people that were completely committed to the company and gave their best. Yet I had to go through this twice during my 18 years at Sanofi, based on the company’s strategic direction. That was tough for me.”

Growing up on the border between the German- and French-speaking areas, Kurt Stoeckli speaks German, French, and a little Italian – as well as English, of course. Has the time come for a new challenge – Swedish?

“Hopefully, I will get more familiar with it. My son, who studied in Uppsala, told me it’s not so difficult.”

He calls himself an entrepreneurial scientist because entrepreneurial scientists make use of scientific innovations and must deliver results that make sense from a business perspective.

“While I was within big pharma, I learned how to work with start-ups, how to help them. I have been a co-founder of some companies as well as an investor. I built my own consultancy for start-ups, so my new role as an advisor at NDA isn’t completely new to me.”

What are your intentions for this job and for the Advisory Board?

“The NDA Advisory Board thrives on being proactive and understanding the big areas of growth and innovation. Let us take the Advanced Therapy Medicinal Products (ATMP) as an example. Gene therapies are emerging. Today’s approaches will further innovate, and fully targeted gene delivery along with controlled and precise repair mechanisms will offer new ways of treatment. It will require new regulation and development strategies. We need to know how to bridge emerging sciences and related regulatory challenges, so that new treatments can bring the benefit to patients and value to the healthcare system without delay. That is what we strive for, and that is why we have scientists, physicians and ex-regulators working together at NDA. This is what drives me.”

Where do you see yourself and NDA in the coming years?

“I see NDA offering unique value to clients by understanding the value chain for innovative medicines and providing differentiated premium services that are composed of expertise in translational sciences, integrated development, perhaps companion diagnostics, and definitely innovative regulatory sciences. My role is to set up a strategy and bring in my network to make sure we deliver on this promise.”

Are you looking for deep regulatory and strategic knowledge to support your drug development program?

Learn more about NDA Advisory Board and its members here.

Enhancing Pharmacovigilance

To give oncology products the best possible opportunity

By: Dr Brian Edwards, Principal Consultant, NDA Group 

In this article, Dr Brian Edwards follows on from his very successful webinar, Opportunities to enhance Pharmacovigilance in Oncology, to argue that to maximise the benefits of innovation in our products we need innovative pharmacovigilance.


We are witnessing a tremendous expansion in oncology products with great opportunities that will benefit patients. Regulatory agencies have responded with expedited review pathways and schemes to enable early access. Data sources such as patient reported outcomes and real-world evidence are being adopted, especially once the product is marketed. The products may often be dependent on biomarker kits which have arisen from the exciting progress in genomic and stratified medicine.

Throughout healthcare and the life sciences, technologies such as machine learning or artificial intelligence are being introduced with great expectation about increased cost efficiency and productivity. With this greater importance of pharmacovigilance (PV) within a changing environment, we need to adapt to recognise limitations of certain data so that the quality that can be reasonably expected will differ if we are to strengthen current standards of PV.

However, we put all this progress at risk if we do not respond effectively to warning signs about medical quality, timely follow up and completeness of adverse drug reaction (ADR) case reports that could undermine confidence in novel oncology products by impairing the ability to make informed decisions.

For that reason, in their 2015 Guidance, the FDA urges sponsors not to report all serious adverse events, including those where there is little reason to consider them suspected adverse reactions.* Study investigators agree. There seems to be misinterpretation of what should be sent to sites resulting in examples where all reported adverse events are sent to every site that conducts a trial that uses that agent, regardless of relevance.

The full article was published in Volume 69 Spring 2020 of Pharmafile – Therapeutic areas in focus. 

Click to the full article
 

To learn more about NDA’s Pharmacovigilance services and how we can help you, click here.

*Safety assessment for IND safety reporting guidance for industry, Food and Drug Administration, 2015, https://www.fda.gov/files/drugs/published/Safety-Assessmentfor-IND-Safety-Reporting-Guidance-for-Industry.pdf

Potential Consequences of SARS-CoV-2 to ongoing clinical programs

The FDA Perspective

By: Laurie Smaldone, CMO/CSO, NDA Group 

In this white paper, NDA’s Laurie Smaldone discusses the potential impact of COVID-19 on on-going clinical trials.


Laurie Smaldone
CMO/CSO

The virus SARS-CoV-2 and the resulting COVID-19 disease have created devastating impacts around the globe on lives and livelihood, including major disruption of ongoing research and development activities for innovative therapies. From many perspectives the spread of SARS-CoV-2 has impacted and will continue to impact ongoing global registrational programs for a variety of disorders especially those not directly addressing the treatment or prevention of the SARS-CoV-2.

This disruption impacts all facets of the drug development process, from the Sponsor company, to the supply chain of investigational treatments to the productivity of study sites. The FDA has issued guidance to address the challenges that may arise from a range of disruptions that could impact the validity and integrity of clinical programs.

The FDA has noted that the spread of the virus may lead to GCP violations and protocol deviations, including impact on trial endpoints and safety collection.   FDA’s Center for Drug Evaluation and Research Director Janet Woodcock stated that “trials may be able to shift to tele-outcome assessments”, but others “may be damaged and may have to halt and not start up again until we can interact more freely”.

FDA’s recent guidance, “Conduct of Clinical Trials of Medical Products during COVID-19 Pandemic”  addresses the potential impacts to ongoing trials.  The guidance provides stakeholders in the drug development and approval process with critical considerations for ongoing trials.

Potential COVID-19 impacts

Trials may be impacted in a variety of ways. Some sites have had to close down or have witnessed significant recruitment delays due to the inability of patient travel, illness, or redeployment of study personnel to address COVID-19 patients or trials.  These limitations can greatly impact study continuity and procedures to maintain study integrity.  In making decisions on trial continuity, Sponsors will need to do a robust   assessment of  trial conduct that may impact patient safety, GCP, drug storage and administration, and protocol procedures .

 

Click to read the full white paper

What did we learn from the 2009 pandemic?

By: Thomas Lönngren Strategic Advisor, NDA Group

In this commentary, NDA’s Thomas Lönngren discusses the regulatory learnings from the 2009 pandemic and how these are applicable to the current pandemic.


In April 2009 we were in the middle of an ongoing influenza pandemic and as the Executive Director of the European Medicine Agency I was ultimately responsible for the Agency’s response.

EMA’s responsibility was to ensure that we could get a vaccine approved as soon as possible and evaluate potential antivirals for the prevention and treatment of the infection. We also set up a robust surveillance system monitoring the safety of vaccines and antivirals when they were put on the market. All of this had to be done while ensuring that staff and experts working at the agency could continue to operate and deliver advice to developers of vaccines and antivirals while maintaining their own well-being.

One of these proposals was the idea to create what became known as the Mock-up vaccines. Specific guidance was developed by the Agency for an assessment procedure for pandemic influenza vaccines

 

It was an intense period with many meetings, ensuring the operation of the agency as well as daily teleconferences with European Commission, WHO, other regulators such as the FDA, and the industry. Luckily there were preparations in place.

When the pandemic broke out in April 2009 we were not taken by surprise. Warning signals came from WHO as early as the beginning of 2000. The SARS outbreak in 2002 had also served as a wakeup call. The outbreak of bird flu caused by H5N1 virus was an additional indication that a pandemic was imminent.

Click here to read the full commentary
 

To learn more about our how our advisors can support your drug development program click here

 

Related article: What do we need to know before the next influenza pandemic: by Vaccines Expert Peiter Neels

Medical Device Regulation: Key Changes and what it means for Combination Products

A Pharmafocus webinar

On Thursday 4th June 2020, 15:00 BST | 16:00 CEST | 10:00 EDT, Dr Tina Amini, Medical Device Division Director, NDA Group will guide you through the key points to consider in your efforts to become Medical device regulation (MDR) compliant and focus on the implementation of MDR Article 117.

The EU MDR continues to provide challenges for the medical device industry and pharma/biotech companies.

Medical device manufacturers must meet new obligations under the new regulations such as correct classification of devices, general safety and performance requirements, UDI systems, new vigilance reporting timescales, sufficient clinical evidence, a person responsible for regulatory compliance and other obligations as per Article 10 of MDR. To date, only a few devices have been certified under the new MDR.

The regulation also impacts pharma/biotech companies. MDR Article 117 amends the medicinal product directive (Directive 2001/83/EC) and requires that marketing authorisation applications for medicines with an integral medical device must include the results of the device’s assessment of conformity by a notified body depending on the device classification.

Manufacturers who are developing integral DDCs need to consider this change in requirements and assess the impact on their development programmes. Companies must identify a notified body to provide an opinion on the conformity of the device to the MDR. For some, this is a new and unknown process with no defined timelines.

Topics covered will include:

  • Medical Device Regulation key changes
  • Possible bottlenecks
  • The requirements of Article 117 as it applies to new drug/device combination marketing applications and variations
  • Notified Body selection and interaction process
  • Submission requirements to facilitate Notified Body review and the latest guidance with respect to Notified Body Opinions

To learn more about NDA’s Medical Device division and services click here


Click here to book your place today!


About the Speaker

Dr Tina Amini, a pharmacist with a PhD in Pharmaceutics, is Director of Medical Device Division at NDA Group.

She has over 30 years’ experience in Pharmaceutical and Medical Devices. She previously held the positions of Head of Notified Body and Senior Technical Specialist at LRQA Notified Body and Pharmaceutical & Medical Device Expert at BSI Notified Body, where she was responsible for device/drug combination products, Conformity Assessment of a wide range of medical devices and onsite assessments of Quality Management Systems (QMS) as the lead auditor.

Tina has extensive experience of regulatory expertise for CE marking of medical devices, and has been involved in the classification of borderline products and consultation process with several EU competent authorities and EMA for device/drug products. Prior to joining Notified Bodies, Tina worked in the pharmaceutical industry in a variety of disciplines.

 

 

Medical Devices and their growing regulatory challenges

By: Tina Amini, Division Director Medical Devices, NDA Group 

In this article, NDA’s Tina Amini explains what companies need to look out for in the growing area of device regulation.


Tina Amini

Recent scientific advances and improvements in enabling technologies have opened new avenues for convergence among medicines, diagnostics, and devices. The medical technology industry continues to be one of the most diverse and innovative sectors.

Major shifts in the health care environment including regulatory requirements make it increasingly difficult for medical technology companies to sustain traditional growth and profitability.

Why can we say that the regulatory challenges in the medical device field are growing?

With the introduction of the new Medical Device Regulation (MDR), and the pending In Vitro Diagnostics Regulation (IVDR), the regulatory landscape in the EU has undergone tremendous change. The new situation gives rise to uncertainties and unknowns and it will take time before it settles and becomes predictable again.

 

Why was the new regulation introduced?

“The new regulation aims to boost patient safety and effectiveness of all the medical devices that are commercialised but also to increase transparency to make the process clearer to everyone involved.”

“Shortcomings in the Directive in divergent interpretations also resulted in different output from the Notified Bodies. The new regulation attempts to address this as well.”

 

How does the new regulation change the European device market?

“The situation is currently uncertain. The delay in the database EUDAMED, an insufficient number of designated Notified Bodies, and lack of sufficient Guidance documents are all causing challenges. There is a lot of guess work awaiting official decisions and guidance. It is however certain that the new regulations will bring substantial change to how medical devices are brought to and maintained in the market.”

“The regulation also impacts the Notified Bodies as they have to be re-designated under new regulations. The time and cost associated with this has actually resulted in some Notified Bodies not applying for designation under the new regulations.”

“Up until now only eleven Notified Bodies have been designated under MDR, and three under IVDR and not all with full scope, compared to about 80 Notified Bodies that were operating under the MDD in the early 2010s. Today there are not enough Notified Bodies to pick up all the work. For companies this means longer timelines as you queue to have your product reviewed. We’re already seeing the manufacturers struggling to find a Notified Body to take them on.”

 

Article originally published in the April 2020 issue of Pharmafocus

Click to read the full article

How we can help?

NDA’s Medical Device Division has extensive experience with both medicines and medical devices. We can support you with your interactions with Notified Body  and assess your product from a scientific, technical, and regulatory perspective to be adequately prepared to meet the requirements. We also have the expertise to help manufacturers to implement the requirement of the MDR and IVDR regulations.

To learn more about how we can support your company, click here to see our full range of services.

Kurt Stoeckli joins NDA as President NDA Advisory Services

We are happy to announce and welcome Kurt Stoeckli to the team as President NDA Advisory Services.

Kurt brings significant experience from leadership positions in the pharmaceutical industry and has extensive expertise in the areas of immuno-oncology, autoimmune diseases and tolerogenic vaccination. His experience also spans medical devices and advanced digital e-health platforms.

As President of NDA Advisory Services Ltd, closely supported by Prof. Steffen Thirstrup, Director NDA Regulatory Advisory Board, Kurt will manage the operations, strategy and development of the NDA Advisory Board, including business development, sales, marketing and service development. His intimate understanding of the working conditions in large pharmaceutical, as well as small biotech companies, will enable him to ensure close interactions and a rapid response to the shifting conditions that these companies are facing.

The NDA Advisory Board comprises some of the most well-known names in the industry, many of whom have been involved in designing the regulatory and HTA systems in place today. Together, they provide strategic advice and unbiased second opinions to pharmaceutical clients during part of, or the complete end-to-end drug development life cycle. This also includes support and advice during interaction with regulatory agencies, be it at scientific advice, during review of a marketing authorisation application or at any stage post-authorisation.

 

Johan Strömquist, CEO of NDA Group, commented on the appointment:

“The NDA Advisory Board is one of a kind – no other professional body comes as close to reflecting the current opinions and practices of the world’s regulatory and reimbursement agencies. I am delighted to welcome Kurt to our team. His experience, extensive network and industry reputation will break barriers and help us ensure that the best products get the attention they deserve. I very much look forward to working with him to help bring more good medicines to people all over the world.”

Kurt is joining NDA from Glenmark Switzerland where he was CEO and the groups global CSO. Prior to this he headed up the Biologics Division at Sanofi as Group VP & Global Head.

 

Steffen Thirstrup, Director NDA Advisory Board:

“Having Kurt on board is very exciting. He brings exactly the right blend of expertise and connectivity that is so important for us to have maximum impact on development of important therapies. His leadership experience and track record of launching new and bold initiatives will also be very welcome to our Advisory Board as we prepare to take the next step in our evolution.”

To learn more about the how the NDA Advisory board experts can support you and your drug development challenges click here

 

Webinar – Opportunities to Enhance Pharmacovigilance in Oncology

On Thursday 23 April 2020, 15:00 BST, 16:00 CEST & 10:00 EDT,  Dr Brian Edwards Principal Consultant, Pharmacovigilance & Drug Safety, NDA Group, will discuss current best practices and opportunities for future improvement in oncology safety processes.

Oncology has seen tremendous advances in treatments with impressive results for some previously incurable solid cancers. This is best illustrated by immunotherapies such as immune checkpoint inhibitors. In addition, the use of predictive biomarkers helps identify patients who may truly benefit from treatment.

To maximise benefit of these therapies, we need to enhance pharmacovigilance. We are all keen to ensure pharmacovigilance work transforms from volume-based operations to value-based work through effective use of technology to allow automation and machine learning without comprising quality and early risk detection.

The use of accelerated procedures for regulatory approval means more and more that real world evidence gathering and assessment is deferred to the post-authorisation phase, putting more responsibility on pharmacovigilance professionals.

The webinar will focus on:

  • How best to increase operational efficiency using technology and the consistency of data quality when processing ICSRs, including applying severity grading and collecting patient reported outcomes
  • Novel approaches to signal detection when faced with large amounts of data
  • How best to manage off label use and medication errors
  • Planning for risk management of immunotherapy-related toxicity, which can be variable, occurring at any time throughout treatment or even after completion of treatment

To learn more about NDA’s Pharmacovigilance specialists and services click here


Click here to book your place today!


About the Speaker

Brian has a BSc (Hons), M. B. B.S., MRCP, MD.  and is a GMC registered physician with previous experience in hospital, renal medicine and clinical research, as a pharmacovigilance assessor in the UK regulatory authority (MHRA), clinical trials and post-marketing pharmacovigilance in a global CRO, deputy QP for pharmacovigilance at Johnson & Johnson. He joined NDA in 2007 and specialises in PV quality management and all aspects of safety compliance, risk management, QP for pharmacovigilance services, clinical trial safety.

In addition, Brian is Director of ISoP Secretariat Ltd and co-chairs the ISOP Medication Error Special Interest Group, Vice President Pharmacovigilance & Drug Safety in the Alliance Clinical Research Excellence and Safety (ACRES) and Chair of the UK Pharmaceutical Human Factors group.