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Who we are

Xendo is a leading consultancy and project management organisation in the fields of (bio)pharmaceutical products, medical devices, and healthcare. Thanks to our multi-disciplinary, knowledge-driven approach, Xendo can deliver a broad palette of services to the life sciences industry, applying the right colour to projects we participate in. For over 25 years we have successfully completed thousands of national and international assignments for start-ups as well as for the largest, established multinational companies and organisations. Over 230 experienced and highly educated professionals offer their expertise ranging from strategic advice and project management to auditing, operational support, and training; providing a full-colour spectrum.

Our clients

The spectrum of our fields of expertise is as broad as the range of clients we work for, enabling us to cater to the varied needs and wishes of the Life Science industry. We bring our palette of services to companies, ranging from start-ups to multi-national organizations, to provide them with robust solutions. Whether they are a (bio)pharmaceutical or medical device company, a hospital or a pharmacy, a manufacturer or a laboratory, we match their colour.

14-11-2017
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#Xendo awarded for the third time in a row as FD Gazelle

Xendo was named an FD Gazelle 2017 again, meaning we belong to the fastest growing companies in the Netherlands for the third time in a row. The Gazelle Awards, an initiative of the ‘Financieele Dagblad’ (Dutch Financial Times), are awarded annually to the fastest growing enterprises, where the main criterion is a turnover growth of at least 20% per year during a three-year period.

André van de Sande (CEO, Xendo) says:

Our clients increasingly know how to find us for our expertise and support in all phases of product development and we are very grateful for the trust they place in Xendo.

Based on this trust, we have been able to grow our organization from 60 to over 240 employees. We plan to further expand in the Netherlands as well as internationally and as such we are always open to getting into contact with new potential colleagues. Please visit our website to see an overview of our most recent vacancies.

14-11-2017
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#COMPLETE PV SYSTEM: READY IN 1 MONTH

Bringing new products to the market while managing all pharmacovigilance (PV) requirements within a reasonable timeframe can be challenging, especially now that the technical requirements of a PV system are becoming increasingly complex. Getting it right the first time will help you off to a good start.


A high-quality and cost-effective solution

This is exactly what we can provide you with regarding the necessary support. Our PV experts provide cost-effective solutions in compliance with all regulatory requirements while you focus on what matters to you: the quality and safety of your product.

To assist in achieving a fit-for-purpose PV system and to safeguard your responsibilities as a Marketing Authorisation Holder, we offer an end-to-end solution for small and medium-sized companies who are about to bring a product to the market in the EU and need a fully functional pharmacovigilance system. We can provide the planning, implementation, and maintenance of any or all of the essential parts of your PV system. The complete set-up of your global PV system can be realised in 1 month, which includes:


State-of-the-art Safety Database - Argus

Our dedicated case processing team makes use of the industry acclaimed standard Oracle Argus Safety Database for Adverse Event Management; including Safety Database Hosting & PV Query Tool. By applying a multi-tenant approach and lean processes with a focus on first-time-right we’re able to offer this software as part of a cost-effective solution.  And with this state-of-the-art database, line listings and reports for case processing can be generated independently of the size of a corporation.

Have a look at the schematic overview.


Other PV services

After setting up your basic PV system, we are also fully equipped to provide you with all other PV services like:


Xendo - A trusted advisor

So why Xendo? Taking your product to the market requires experience and solutions beyond pharmacovigilance. This is why we aim to offer a complete spectrum, including all the expertise you’ll need to be successful.

Introducing our palette of services that complements our pharmacovigilance department and sets us apart as a full-service provider:

With many, effectively cooperating consultants in different fields of expertise at your disposal, we’re able to offer you a complete package and peace of mind.

Please contact us to find out more!


10-11-2017
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#Posters ESGCT 2017

At the ESGCT 2017 conference, we presented two posters on CMC development and comparability strategies.  Afterwards, we received several requests for the posters and additional info, so we have decided to put them online! Have a look and leave us a message if you'd like more info as well.

Comparability Exercise

CMC Development

08-11-2017
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#BIO Europe Berlin

Xendo CEO André van de Sande and Xenia Freifrau-von Maltzan brought one of our customized VANMOOF bikes to this years' BIO Europe in Berlin. Several hundred participants showed that the raffle we organised with Berlin Partner was a huge success and attracted a large crowd. We wish to congratulate this years' winner and we are very much looking forward to another successful BIO again next year!

31-10-2017
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#Brexit: Picking a new Reference Member State. How?

In our previous Brexit blog we gave a broad overview of consequences that are on the horizon for the (bio)pharmaceutical industry. Especially professionals in Regulatory Affairs, Quality Assurance and Pharmacovigilance will be affected besides those working at EMA headquarters. Though nothing is certain yet we stipulated that, for the moment, the best advice may be to prepare for the worst: a hard Brexit. An important item on the list is to select a new Reference Member State (RMS).

Reference Member State

A reference member state is like a marriage; you stick with it for life; at least your product does. There are only two reasons to request a change of RMS. Usually, the Marketing Authorisation Holder (MAH) can request a change of RMS under exceptional circumstances, as described in the procedural advice by the CMDh. The other reason is (you probably saw this one coming) Brexit; or more specifically, the triggering of Article 50 by an RMS. To whom would this apply? All companies that have a marketed product for which the RMS for a Mutual Recognition Procedure (MRP) or Decentralised Procedure (DCP) is currently the UK. Seeing as how the UK is in second place (right after the Netherlands) for the total amount of new applications (MRP/DCP) and in third for finalized procedures (2017), a large number of companies will be affected.

Below you can see the new applications (started and finalised) from January 1st to June 30th this year as reported by the CMDh; click here for larger image.

So just a quick summary of an RMS’ role. They act as:

  • scientific assessor of a dossier
  • regulatory advisor to the applicant
  • moderator between applicant and CMS

The RMS provides regulatory and scientific advice as well as assessment reports, they decide on timetables, evaluate responses, organize and chair break-out sessions, refer to the CMDh, inform the EMA if there is no consensus after referral, inform applicant and Concerned Member State (CMS) after positive conclusion and prepare the final assessment report as well as the public assessment report.

It’s clear there’s ample motivation to do some research on the different Health Authorities (HA). What should you look for in a new RMS?? Some of the items to investigate prior to your selection could be.

Things to consider when picking a new RMS

Know your RMS

Previous experiences with an HA can be of major advantage. These connections often make sure procedures move along according to the set timetables without any unforeseen trouble because you understand their point of view, they speak the same language so to speak.  These professionals look out for and mitigate unforeseen delays due to their experience with that RMS; they are familiar with their workload, approach and the way they communicate.

Differences among Health Authorities

Although we’re all in the EU, every member state is responsible for their own day-to-day business. Though not limited to just Health Authorities, this is certainly the case here as well. Some might be better communicators, others more prone to act in a timely matter and others more inclined to be open to more pragmatic approaches. Companies are especially recommended to check the pass-through times and a backlog of a possible new RMS and are required to contact the Health Authority in advance to check their availability to take over as RMS for existing procedures. Besides there is also a difference in not every HA has extensive experience acting as an RMS at all.

It’s also worthwhile to see which of the current Member States are actively preparing for Brexit like the MEB in the Netherlands.

The Medicines Evaluation Board (MEB) is preparing for the partial takeover of extra work which arises due to Brexit. In this context continuity is paramount. For that reason, the Dutch government is investing € 2 million in extra capacity for the MEB in the coming years. Investments are also being made in reinforcing the European network by facilitating extra training opportunities.

 

Initiatives like these will most likely help assure a smooth transition to a new RMS.

RMS has experience in a therapeutic area

Some RMS have more experience than others in certain therapeutic areas. Are you a generic, you might want to check the originator’s RMS; which is often also the RMS for other generics. This is noticeable when an originator product goes off-patent because almost all generics manufacturers will tend to apply with this same RMS with which the original was registered. Or does a Health Authority have a special focus regarding specific therapeutic areas? Have they been involved in the development of certain guidelines? If the new RMS is going to be one of the current CMS, recall what the attitude towards the product was during a previous application. These are all questions worthwhile to investigate before making a final decision.

Location of the company

Though it might seem like an open door, avoiding language barriers and having the proper infrastructure in place is always a benefit to the daily business. As a matter of fact, the EMA itself is currently in the process of deciding on a new location for its headquarters (deadline 22nd November) and in a technical report by the agency they name several aspects that are deemed to be important factors weighing into the final decision.

It’s also strategic to choose your RMS according to your company’s EU affiliates; opening up the possibility of direct communication with the HA. Increased contact and the ease of face-to-face counsel can contribute positively. This is especially useful considering we’re working in a regulatory universe that seems to thrive mainly on communication through elaborate documents. Besides these advantages, it also allows affiliates to join the strategic conversation with HQ and to increase their visibility and experience.

Commercial reasons

Last but not least: financial gain. There are several commercial reasons to interact with a certain RMS; straight-forward aspects like fees charged by HAs, the market size of the RMS and are there key opinion leaders available?

Practicalities and recommendations

Some practicalities to keep in mind:

  • there can be no change of RMS during an ongoing procedure (of importance for timing/planning);
  • it is the obligation of the MAH to ensure that both the current RMS and the future RMS accept the change of RMS;
  • it is the responsibility of the MAH to supply to the new RMS if any dossier/ assessment reports or other relevant materials are missing or for any reason not already in possession of the new RMS.

And some summarizing recommendations:

  • an organisation should map their situation and set up reasonable timelines for the upcoming changes
  • budgets need to be adapted to higher (or lower) costs; HAs charge different fees for procedures
  • investigate possible RMS to your best ability or attract external advice
  • contact your HA of choice well in advance to prevent any unwelcome surprises

RMS overview

Finally, remember that these changes are imminent, possibly causing a rush on popular HA’s and thus proper planning is well-advised, to say the least.

Below you’ll find all possible member states that can be chosen as an RMS. There are, of course, differences in the amount and nature of applications these states have handled in the past and it would be far too elaborate to discuss all possible differences. So to this purpose, we’ve highlighted the ones that we’ve personally worked with up until today. Should you have any questions we invite you to contact us for some additional specific information.

And we always welcome any new topics regarding Brexit that you’d like to hear more about!

Blog by: Nick Veringmeier - Xendo

Austria

Belgium

Bulgaria

Croatia

Cyprus

Czech Republic

Germany

Denmark

Estonia

Spain

France

Greece

Hungary

Ireland

Italy

Latvia

Lithuania

Finland

Luxembourg

Malta

Netherlands, The

Poland

Portugal

Romania

Sweden

Slovakia

Slovenia

Iceland

Norway

26-10-2017
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#25 years of Gene Therapy: Advances and Challenges

Xendo was exhibiting at the yearly conference of the European Society for Gene and Cell Therapy (ESGCT) in Berlin, where the society was celebrating its 25th anniversary. This update shares the major advances and the challenges that currently being faced in the field.

THEN AND NOW

In the early days, gene therapy was mainly investigated in academic research centers. Currently, the number of marketed ATMPs (including gene therapies) is still limited, but as there are over 900 ongoing ATMP trials you can expect that gene and cell therapies are well on their way to become an important treatment modality with a high potential to deliver new and improved treatments to patients. Currently, most development is still seen in indications where there is an unmet medical need but its expected that ’the focus on common diseases will also increase.
Since the inception of the European Society for Gene and Cell Therapy 25 years ago, it took 20 years for the first gene therapy product to gain market approval. And during this time we’ve seen the field mature; following the common lifecycle development of any medicinal product. Does that mean it’s already fully developed? Probably not, we could say it’s now in its teenage phase. Still young and full of energy but definitely on its way to adulthood.


Besides academic institutions, biotech startups are now also contributing significantly to gene therapy development. The approval of Glybera (uniQure) in 2012 was a major milestone for the entire field and may have initiated major biopharmaceutical companies to increase their involvement in Gene Therapy. The approval of Strimvelis (GSK) in 2016 was an example of a collaboration between start-up and big pharma and surely there are more to come as we know some multinationals are partnering with pioneers in the field.

ADVANCES

At the conference, impressive progression was reported throughout the major fields within Gene Therapy:

  • Ocular and central nervous systems Gene Therapy;
  • Cancer Gene Therapy;
  • Muscle and pulmonary Gene Therapy;
  • Metabolic and lysosomal storage diseases;
  • Blood Disorders.

In these fields, scientists presented their progress and companies their pipelines, both addressing the technical and scientific advances in gene therapy. Significant effort is being put into research and early development to overcome the many challenges that still lie ahead.

To be able to apply different treatments, new strategies are under development. Though gene replacement is still prominent in the field, technical advances are made to allow for a switch towards gene repair; with CRISPR/Cas9 as a well-known example. Nevertheless, it will remain challenging to assure the absence of off-target effects using this technology. In addition, RNA inhibition strategies add another mechanistical approach to the gene therapy repertoire. An elegant strategy was presented during the conference, where a single vector was used including both a transgene but also inhibiting shRNAs which nicely demonstrates that combinations of different approaches are currently filling the pipeline. In cancer therapy development, combinations of immunological cancer vaccines with oncolytic vectors illustrate how different fields in molecular medicine can come together to boost future development.

CHALLENGES

For some the sky may be the limit, still, there are serious challenges that need to be resolved before any major breakthrough of Gene Therapy in medicinal practice can be achieved. In general, these challenges show a high similarity between different fields and vectors.

Therapeutic Dose

Firstly, one should be able to provide a sufficient therapeutic dose to the target tissue and cells. This may be solved by increasing the manufacturing capabilities, allowing the manufacture of highly concentrated vector doses. However, when doses become too high this may also impact the safety profile of the vector and its use. In general, improving manufacturing platforms may not be the easy solution for this challenge. A different challenge is to improve delivery of a vector to the appropriate tissues and cells. A great deal of research is currently going on to improve vector platforms but also work on new vector types was presented. However, if you’re able to efficiently target the right tissues and cells at an appropriate dose, the transgenes would need to be expressed at a suitable expression level, which means not too low but definitely not too high.

Long-term effects

Another technical challenge is how to achieve a long-term effect which is especially relevant in areas where the mechanism of action relies on gene replacement or repair strategies. As is the case when a mutated gene is the underlying cause of a disease and needs to be replaced by a functional gene, which would (of course) need to be present throughout a patients entire life. Though only a marginal subfield within the gene therapy community, long-term effects of epigenetic modifications could definitely put a new perspective on things and will surely raise the regulators’ attention given the potential impact of epigenetic inheritance.

Prevention or intervention

The question whether you need to intervene in the development of a disease was argued both ways. In some cases, disease progression may be too far along in order to be able to effectively cure patients with gene therapy and early screening of patients may become more relevant in order to intervene in early stages of disease development. An issue here might be to demonstrate the efficacy of a treatment because the onset of disease symptoms in a non-treated patient may also take a significant time. Following this strategy you would need extensive follow-up, prolonging development and approval timelines.

Developmental Roadmap

The transition from a relative small lab-table to the larger industrial environment is one of the most commonly underestimated pitfalls. During the transition phase, a product and its manufacturing processes should be defined and controlled after which internal and external requirements are integrated and guide further development. Ideally, these changes and lot-to-lot variations of a product shouldn’t hamper pre-clinical and clinical studies. Many iterations and a creative problem-solving attitude are therefore required to build in sufficient robustness. Since quality cannot be tested into the product but only verified, the quality should be built into the process from the start.

Considerations

Given the numerous technical challenges, it’s paramount to integrate a solid regulatory strategy into your technical and clinical development strategies. If gene therapy development is conducted by SMEs and academics, it is often seen that these parties struggle with the regulatory path also because of lacking resources and an undervalued importance of implementing regulatory strategies in product development.

At the conference, a recurring topic during our conversations was related to the application and need of a product development mindset, which differs significantly from the academic mindset that is still dominating. Product development requires a multidisciplinary approach to achieve the required synergy between research, product and process development, regulatory, quality, analytics, non-clinical and clinical experts. A rule of thumb is that successful product development would need a backward strategy. In other words, start with the end in mind, define your stage gates and milestones and develop a strategy that bridges science with development and manufacturing and make sure it’s included from the very start. Obviously, there’s the funding issue that many of the startups are facing, usually resulting in a strong drive to cut corners during development. But if doing so you should understand the impact and risks that are involved in order to weigh the possible consequences.


blog by: Harm Hermsen and Christian Maasch

23-10-2017
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#XENDO CEO SPEAKER AT EMBASSY IN JAPAN

Xendo CEO André van de Sande was the keynote speaker at a seminar in Japan about the possibilities that the Dutch Life Sciences industry offers. This event was organized by the Dutch embassy prior to the BIO Japan expo where Xendo participated to increase our exposure as a leading consultant for Japanese companies looking to enter the EU market.

 If you are interested then please check out our Japanese service pages:

Pharmacovigilance Regulatory Affairs Quality Management & Lean Six Sigma
ファーマコビジランス 規制関連業務 品質管理 & リーンシックス・シグマ

10月10日、パシフィコ横浜で開催される Bio Japan 2017 を前に、大使館にてオランダ・ライフサイエンス・セミナーが開催されました。オランダはレンブラントの時代から医薬学でのイノベーションを担っています。

 

NLinJapan

NL Life Science Seminar was held prior to #biojapanexpo. NL has been the forerunner of life/medical technology since the times of Rembrandt.

 

18-10-2017
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#Pharmaco- & Medical Device Vigilance. What's the difference?

Are Pharmaco- and Medical Device Vigilance the same?

The European Medical Device Regulation 2017/745 (MDR) is published on May 5th, 2017 in order to replace the current Medical Device Directive 93/42/EEC; meaning that from 2020 onwards only MDR will apply and before that time both the MDR and MDD apply. Medical device vigilance (MDV) is a key element that is significantly reinforced in the new MDR. The European database on medical devices (Eudamed) will be revised to include vigilance data. These changes make the procedures similar to the Eudravigilance database and the pharmaco-vigilance (PV) process.

The MDV requirements affect the entire medical device (MD) industry with products in the EU. They will need to adjust and upgrade their quality management systems, and implement the required organisational elements and staff to comply with the MDR. The MD industry ready themselves to handle adverse events and incidents, including activities such as evaluating, trending and reporting as specified in articles 87-90 of the MDR.

Because of similarities, it might be tempting to follow PV procedures and systems in order to meet MDV requirements. However, this might not be the right approach because there are distinct differences. In this presentation, we will look at similarities and differences: what can we share and where do we need to pay attention to, in order to ensure compliance with the new regulations.

Recently Xendo colleague Jan Bart Hak presented on this at PhV Day 2017 and below you can find the slide

DOWNLOAD SLIDEDECK

&

INFO: New pharmacovigilance system (Argus)