Design and optimisation of a quality target product profile for ATMPs

The quality target product profile (QTPP) is an inherent part of product development and provides an overview of all the elements that have an impact on the quality, safety and efficacy of the product in a given clinical indication. The concept is defined in the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use guideline Q8 and may be more familiar for those developing conventional pharmaceuticals.

However, it also provides an excellent tool for advanced therapy medicinal product developers and should be used to consider all elements that have an impact on the ultimate quality of the product and, consequently, the safety and efficacy in clinical and commercial use. Building up the QTPP should start at the research phase and continue up to the marketing authorisation application (MAA) phase; if it is put together properly and regularly updated, it provides the skeleton for the entire chemistry, manufacturing and control module of the MAA.

To find out more read the full article written by NDAs Director of Biopharmaceuticals and ATMPs Paula Salmikangas. The article is also featured in Regulatory Rapporteur – Vol 16, No 2, February 2019.



By Paula Salmikangas – Director of Biopharmaceuticals and ATMPs, NDA Advisory Board






Effective presentation of immunogenicity related data in regulatory dossiers

NDAs Paul Chamberlain, Biopharmaceuticals & Immunogenicity Expert and NDA Advisory Board member, provides practical advice about how to present immunogenicity-related information in regulatory dossiers, with a particular focus on a model for an Integrated Summary of Immunogenicity to be submitted in the marketing authorization application for novel biopharmaceutical products in ICH regions (EU, USA and Japan) in the latest publication of Bioanalysis.

A format that links the analysis of potential risk factors to a justification of the methodology applied for risk evaluation and conclusions for riskmitigation is presented as a model that can be adapted according to the weight of evidence to be submitted in support of the assessment of impact on overall clinical benefit versus risk for the particular situation.




If you are interested in hearing more from Paul he will be presenting at the following events in March:

DDF Summit on; Biosimilars – Regulatory Primer for Formulation Scientists 12th March in Berlin. To learn more click here.

NDAs breakfast seminar; Immunogenicity for investigational biopharmaceutical products – Start with the goal in mind, 14th March in Munich. To learn more and to sign up for the event click here.



Maximising value in early development

Capture1Selecting product candidates with the highest probability of success and applying rigorous risk-based management in development maximises the value of biopharmaceutical products and increases speed to the clinic and registration.

Due to the high costs for product development, few small and medium sized pharmaceutical companies will take their product to the market on their own. Therefore, the goal is often to develop the product to a stage where partnering becomes feasible. However, the aim should be to add as much value as possible to the product during early development, as this will maximize the likelihood of a successful deal with a corporate partner and provide alternative exit opportunities for the company.

Read the full article written by Niamh Kinsella, Principal Consultant, VP Early Stage Development, Paul Chamberlain Biopharmaceutical and Immunogenicity Expert and Josefin-Beate Holz, Clinical Strategy Expert, to learn how you can maximise the value of your product by having an early development strategy.






Niamh Kinsella
Josefin-Beate Holz
Josefin-Beate Holz
Paul Chamberlain







Europe vs USA: new drug product approvals in 2016

TereseBy Terese Johansson PhD, Consultant, NDA Group

For the past four years, expert consultants at NDA have analysed new drug approvals across the EU and US and published our findings. This year we continued to review the publicly available data on drug product approvals for 2016 as it has been reported on the FDA and the EMA official websites in January 2017. As it is challenging to pull together data from two regions with different classification and reporting styles some general inclusion and exclusion criteria to create consistent indicators of the yearly trends in the EU vs the US have been applied.

The following summary provides an overview of the key findings and an analysis of what the data (i) means for the industry. The data is visually represented in an infographic below.



Drop in US approvals but no similar trend seen in EU yet

Last year there were a total of 74 new drug approvals granted in the US and EU together that meet our selection criteria. Of these new products, 19 were approved only in the EU, 19 only in the US, and 36 were granted in both regions during 2016. We found that 17 drugs that were approved in the EU 2016 had already received approval in 2015 or earlier in the US, while only six products registered in the US in 2016 were approved in the EU before 2015 or earlier. This indicates that applying for approval in the US prior to registration in the EU still remains as regular praxis. Compared to 2015 there is an overall drop in approvals for US in 2016. In the EU, this decrease is not yet observed, but it’s likely to expect a similar trend for the EU in 2017 year’s approval figures. Of the new drug approvals 35 products were classified as novel drugs (e.g. NAS, NME or BLA), nine of these were approved only in the EU, nine only in the US and 17 were approved in both regions. For the EMA, the number represents the fewest NASs approved since 2011, while the FDA has not approved this few NMEs/BLAs since 2010.

Expedited drug development and nonstandard review approval pathways are the new norm in the US, but in the EU special approval procedures are not as common. During 2016, special approval procedures like conditional and accelerated approval pathways were issued for seven of the new approvals in the EU, the majority in oncology and in the orphan field. To support early drug development and speed up the evaluation and approval process, EMA have encouraged the industry to seek early interaction via scientific advice with the regulatory and health technology assessment (HTA) bodies, as well as interactions with the committee for advanced therapies (CAT). The intention is to enable early and continued interaction and dialogue between pharma industry and regulators. In the first quarter of 2016, EMA launched a scheme for PRIority MEdicines (PRIME), to optimise development plans and provide accelerated assessment to medicines of major public health interest. Furthermore, in the last quarter of 2016 EMA also launched a new pilot for tailored scientific advice for biosimilars. The result of the efforts is still to be seen.

In the US the continued dialog with companies throughout development offered by the FDA enables familiarity with the product already at the time of registration. In 2016 special approval procedures and designations like Fast Track, Breakthrough, Accelerated Approval and Priority Review were used for 18 of the new approvals, in many cases more than one of these pathways was granted per product. Interestingly, the drop in the US approvals seen in 2016 could possibly be explained by the increased use of the shorter nonstandard approval pathways since there has also been a significant increase in complete response letter (CRL). During 2016 FDA issued 14 CRLs, compared to just two in 2015 (iv). The increase of CRLs seen in 2016 indicates that the use of speedier nonstandard approval pathways in the US may not be so speedy after all, at least not for 2016 as some companies have discovered. It also suggests that the choice of approval pathway is of significant strategic importance for the drug review process. However, it should be noted that the FDA has a higher rate of granting special approval status compared to EMA and that the measures taken by the FDA with the introduction of shorter nonstandard approval pathways has clear overall effect on shortening the mean approval timelines.

Oncology and big pharma dominate the approval statistics

Looking at the therapeutic areas, the far busiest was oncology, among the noteworthy approvals are Lartruvo (for the treatment of soft tissue sarcoma, approved in the EU and US), Rubraca (for the treatment of ovarian cancer, only approved in the US), Tecentriq (for the treatment of urothelial carcinoma, only approved in the US), and Venclexta (for the treatment of chronic lymphocytic leukemia, approved in the EU and US). Oncology is followed by metabolic and neurological disorders.

In the US, five biosimilars was approved in 2016. In the EU, eight new approvals for biosimilars were recommended for approval by the CHMP in 2016, four of these were still pending approval by the European Commission (EC) in Jan 2017 (compared to no biosimilars gaining EU approval in 2015).

Altogether 39 orphan drugs were approved in the US during 2016 and 14 in the EU (a mix of NME, BLA, NAS or old substances with a new use for an orphan disease). Among the noteworthy orphan approvals are Exondys 51 (for the treatment of Duchenne muscular dystrophy, only approved in the US), Darzalex (for the treatment of multiple myeloma, approved in the US 2015 and in the EU 2016) and Spinraza (for the treatment of spinal muscular atrophy, only approved in the US). We expect the strong overall trend for more orphan drugs submitted to and approved by the FDA and EMA to continue. The last ten years both FDA and EMA have received orphan drug designation requests at record rates for each following year and this trend is reflected in the drug approvals from the agencies.

Furthermore, two Advanced Therapy Medicinal Products (ATMP) Strimvelis (for the treatment of severe combined immunodeficiency due to adenosine deaminase deficiency) and Zalmoxis (for the treatment of certain types of high-risk haematological malignancies) were approved in the EU.

The pooled statistics show that big pharma represented 53% of the new drug approvals in 2016 vs 47% of the new approvals originated from small and medium sized pharma (v). For big pharma this is a decrease compared to previous years when they contributed with 72% of the new approvals in 2015 and around 64% in the two previous years. In addition, in the US several big pharma companies which did well in 2015 and the years before did not receive any drug approvals in 2016. Both the EU and US show an increase in drug approvals from small and medium sized pharma compared to previous years but big pharma still dominates the drug approval statistics; implying that big pharma are continuing their efforts to acquire small and medium sized pharma with promising portfolios but without adequate resources to pull through the costly late stage drug development (vi). One of the factors contributing to cost challenges for small and medium sized pharma lies in the two agencies’ sometimes divergent approach in assessing benefit/risk profiles, causing the need for larger clinical trials, label differences and some drugs not reaching certain markets in the end.

NDA supported over 40% of the approvals in the EU during 2013-2016 and over 20% of the approvals in the US in 2016

As reported for 2014 and 2015 our analysis for 2016 shows that NDA kept a strong position in supporting the new drug products that received approval in Europe. Over the last four years NDA has supported over 40% with a great breadth of services. Through NDA’s expanding activities in the US the company also supported over 20% of new drugs that achieved approval by the FDA during 2016.

In summary

The FDA has had a significant drop in drug approvals in 2016 compared to 2015 but continues to grant more expedited and nonstandard review approval status compared to the EMA. The US drop in drug approvals for 2016 is not observed in the EU but is likely to be more prominent during 2017. The trend that many companies first seek approval in the US persists. Big pharma continues to dominate the drug approval statistics, with oncology being the most common therapy area represented, followed by metabolic and neurological disorders.

NDA had a strong presence in the EU regulatory arena and supported over 40% of the new products approved from 2013 to 2016. NDA have also increased our presence in the US and supported over 20% of the new products that were approved by the FDA during 2016.


To read the statistics of new drug product approvals from last year click here.

To read the Press Release click here.

Disclaimer: This report is based on preliminary research figures distilled from the FDA and EMA websites. As experience tells us, the final number of approvals reported normally fluctuates for some time after the end of the year, as the Agencies go through their house keeping processes. There could therefore be some slight changes to the findings outlined in this report before the data is completely finalised.


(i) The data was gathered from the EMA and FDA official websites, concerning the drug approvals for new active substances (chemical, biological, biotechnology or radiopharmaceutical substance), new molecular entity, new biological entity, new drug combination, biosimilars and vaccines, excluding only generic and duplicate applications from the data.

(ii) FDA Novel Drug Approvals for 2016

(iii) CHMP: Agendas, minutes and highlights 2016

(iv) FDA blog

According to John Jenkins, retiring director of FDA’s Office of New Drugs, the primary deficiency in several of the applications was the failure to comply with FDA’s current Good Manufacturing Practice (cGMPs) regulation. “2016 may serve as a reminder to sponsors that all of their manufacturing facilities must be in compliance with cGMP regulations if they wish to ensure approval of their application. Failure of manufacturing facilities to pass FDA inspection can unnecessarily delay patient access to novel new drugs”.

(v) The list of the top 50 pharma companies in 2016 was obtained from

(vi), New drug NMEs approved by FDA 2003-2016, and Lincker H, Ziogas C, Carr M, Porta N, Eichler HG; Regulatory watch: Where do new medicines originate from in the EU? Nat Rev Drug Discov. 2014 Feb;13(2):92-3

Strategies for Success in Global Development

NDA-Icons-2016-CS4This article will consider the rationale and benefits of identifying global development and commercialization needs early in the product life-cycle and then discuss some strategies for framing the global development.

Careful planning and assessment will permit the needs of the major countries and regions to be incorporated into a single global development program which will meet the needs of the major pharmaceutical markets.

Although a company may potentially only wish to commercialise their products initially in a single market, inclusion of the needs of the other regions within the development plan will generate a roadmap
for future registration opportunities that can be used for partnering or out-licensing strategies.

Read the full article written by Rosalind Cox, Principal Consultant, for insights on strategies for framing global development.









By Rosalind Cox – Principal Consultant, NDA Group


Immunogenicity: anticipating and avoiding issues for biopharmaceutical development

NDA Advisory Board member, Paul Chamberlain, has just had an article titled Immunogenicity: anticipating and avoiding issues for biopharmaceutical development, published in Drug Target Review.
All biopharmaceutical products are associated with an intrinsic potential to induce immune responses in treated subjects. Regulatory agencies expect sponsors to evaluate and mitigate these risks during product development, applying a strategy that addresses product- and patient-related factors. Overall, understanding and controlling immunogenicity-related risks are attainable objectives, and approvability should not be compromised if these risks are suitably evaluated from the earliest stages of development.