Subscribe to newsletter



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!

Posters ESGCT 2017

#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

BIO Europe Berlin

#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!

Brexit: Picking a new Reference Member State. How?

#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






Czech Republic















Netherlands, The









25 years of Gene Therapy: Advances and Challenges

#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.


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.


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.


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.


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



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。



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


Pharmaco- & Medical Device Vigilance. What's the difference?

#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



INFO: New pharmacovigilance system (Argus)



It’s an exciting time for companies joining the Biosimilar race.

As we get more experienced to apply more advanced technologies, as well as new production processes for biologics, the regulatory landscape and recent strategies for the development of Biosimilars are rapidly evolving at the same time. In Biosimilar development, it isn’t easy to keep track of best development practices and regulatory expectations. Additionally, trends can be observed within leading health authority agencies to become more open for discussions and accept new scientific- and product-tailored development strategies to establish and demonstrate Biosimilar comparability. As usual, it´s all about risk assessment, impact evaluation, and scientific-based justifications, but agencies are actively paving the way for Biosimilars with new regulatory procedures and guidelines. In general, biological manufacturing processes show an inherent variation in terms of process and product. It’s important to look at the development of Biosimilars from an integrated standpoint that includes the essential quality, non-clinical and clinical elements. Obviously, there is a high demand for Biosimilar CMC development as it plays a critical role in demonstrating comparability to the reference product.

What is it about

In our latest update, you'll read more about:

  • the wave of biosimilars at the horizon
  • development challenges and biosimilar comparability
  • best practices and orthogonal approaches
  • the rapidly evolving landscape

Download the whitepaper and feel free to contact us if you have any questions regarding Biosimilar development

NEW: XPure Systems website

#NEW: XPure Systems website

Our XPure Systems team recently launched their new website to better serve new customers who are looking for a downstream processing solution using SMB technology. We invite you to have a look at #SMB #downstreamprocessing

All you need to know about the EU & US MRA

#All you need to know about the EU & US MRA

All you need to know about the EU & USA MRA

March 2017 was a historical month for the pharmaceutical industry and for EU and US. The amended mutual recognition agreement (MRA) on “Pharmaceutical Good Manufacturing Practices” between the EU and the US was signed. Best case scenario, it could lead to significantly reduced inspection pressure of the FDA EU inspectorates and we might be done with re-testing of imported batches and batch certification. So let’s hope this amended MRA will actually be implemented and history doesn’t repeat itself.

Mutual Recognition Agreement

In the broadest sense of the word, a mutual recognition agreement is a bilateral trading agreement to facilitate trading between nations or regions. It facilitates market access while safeguarding consumer health, mutual acceptance of reports, and certificates, exchange of information, and encourages harmonization. An MRA covers various economic sectors including Pharmaceutical Good Manufacturing Practices. The sectoral annex of “Pharmaceutical good manufacturing practices” mentions for instance; recognition of GMP regulation, exchange of reports of inspections of manufacturers, and the possibility to rely on foreign test results for batch release, the so-called re-testing. The EU has MRAs with several countries; Australia, Canada, Japan, New Zealand, Israel, Switzerland and the US and all with different terms and conditions. All these MRAs are in force, except the one with the US. Which was first drafted in 1998, but was never actually implemented. So, what happened?


History of MRA events so far (link)

  • In 1994, MRA negotiations began between the EU and the US.
  • After numerous difficulties, (disclosure of inspection reports to the public and differing opinions on how to focus on post approval inspections or on post- and preapproval inspections) the negotiations finally resulted in an MRA in 1998, which already contained a “Pharmaceutical good manufacturing practices” annex.
  • Apart from the usual 18 months, the implementation period was extended to 3 years. In this period, it was recognized that legislation and implementation of this legislation were too different, to be able to mutually accept GMP inspection information at that moment. The MRA came a bit too soon. Hence, it was never implemented.
  • Despite the apparent failure of the MRA, it was recognized something should be done. The FDA expanded its reach beyond US borders by opening offices in Europe, China, India, and Latin America and conducted significantly more foreign inspections to gain more insight into the GMP compliance level of foreign companies.
  • Together with the Food and Drug Administration Safety and Innovation Act. In 2012 (FDASIA), stating that FDA cannot and should not monitor the world’s drug inventory by itself, this resulted in 2014 in Mutual Reliance Initiative (MRI). Which aims to increase strategic collaboration between the FDA and EU member states through the exchange of information.
  • Additionally, in September 2014, the FDA was invited to observe the EU’s Joint Audit Program, in which two EU nations audit the inspectorate – the regulatory authority – of another EU country.
  • These combined initiatives eventually resulted in an amended MRA on a sectoral annex of “Pharmaceutical good manufacturing practices” in March 2017.


Amended MRA EU and US 2017

The signed amended MRA is a major achievement, but euphoria should be tempered. Although this MRA could probably significantly cut costs for (bio) pharmaceutical companies enormously, it still contains a lot of terms and conditions. Aspects like an FDA assessment of the EU member states, an EU assessment of the FDA, and not all products are included in the annex. Depending on all these terms and conditions and assessment outcomes, parts of the MRA will come into force in time.

EU assessment of FDA

The EU’s assessment of the FDA started in September 2015. EU officials visited three FDA district offices, FDA headquarters complex, and an FDA laboratory. The EU team inspected with the same criteria that apply within EU. In late 2016, EU also observed FDA conducting an inspection as part of its evaluation. The progress in collaboration, negotiations, and assessments was found positive and finalization of the assessment in 2017 should be achievable.

FDA assessment of EU member states

  • FDA assessment started a year earlier in September 2014 with their presence at the Joint Audit Program of EU.
  • However, this is just a small part of the full capability assessment that the FDA will perform in all member states. In 2017, the FDA had already attended 14 audits of different EU member states and expects to be present at the remaining 14 before the end of 2017.
  • For this full capability assessment, the FDA requires each member state to provide a capability assessment package to FDA containing e.g. a finalized Joint audit program audit report, completed conflicts of interest questionnaire, four inspection reports including the report from the inspections observed during the Joint Audit Program audit, standard operating procedures (report finalization, training and inspector qualification, etc.) and an inventory of manufacturing facilities.
  • Eight of these packages should be assessed by FDA, before the MRA comes into force on 1 November 2017. Subsequently, the FDA and EU can and will rely on each other’s GMP inspections.
  • FDA intends to complete all of the 28 (27 after March 2019 depending on Brexit negotiations) full assessments by 15th of July 2019. After completion of all assessments, re-testing of imported batches and batch certification is no longer required. Until that moment, each imported batch and each batch to be certified is to be re-tested. The fact that delivery of capability assessment packages and their assessments are already planned and documented in the MRA, provides confidence that these milestones will be achieved.

NOTE: Not all Pharmaceutical products are included!

A wide variety of the pharmaceutical products are included in the amended MRA, but medicines derived from blood or blood plasma, human tissues and organs, immunologicals,  and veterinary products are not. for now, Medicinal products for veterinary use are expected to be included in July 2019 and Vaccines and plasma derived medicinal products in July 2022.


The signed amended MRA is an important step forward. Nonetheless, it contains a significant number of terms and conditions, but it does provide a roadmap. If a positive attitude is maintained and the challenging timelines are respected, both parties will mutually accept GMP inspection information from 1 November 2017 onwards and omit the further need for import testing and batch certification after 15th of July 2019.

Until then, it is business as usual.

Blog by: Jeroen Ottens MSc, PharmD - Consultant 

Lean Deviation Management

#Lean Deviation Management

Within Good Manufacturing Practice (GMP), we both love and hate them. On the one hand, they are a valuable source of information on how we should arrange our processes, on the other hand managing them can be quite a challenge. More specifically: deviations. Often seen as something negative and probably one of the biggest burdens within the quality system. But what if you could increase the quality of deviation reports and reduce the time you spend resolving them? Let’s have a look at some examples on how we can apply Lean Six Sigma in achieving these goals.

Deviation Reduction

Reoccurring deviations are amongst the leading causes of losing control of a deviation management system, resulting in a build-up of deviations that are not closed in time, ultimately putting your processes, products or even patients at risk. It sounds easy: stop deviations from reoccurring. But, for example, identifying and preventing reoccurring deviations is easily forgotten in the daily routine of closing them. This is where a Green or Black Belt can help. By analysing deviations, grouping them and using Pareto charts, for instance, it becomes clear what the reoccurring issues are. To do so, besides Lean and GMP knowledge, you will need the knowledge of the Subject Matter Experts (SME), especially those who actually perform the process on a daily basis. This is where the Kaizen becomes an essential tool. The Kaizen is a multi-day workshop in order to improve a process or to solve a problem. Identifying the most reoccurring issues and solving them can be done with a multi-disciplinary team during a Kaizen of a few days, making this investment in time well worth it.

Improved root cause analysis

In order to prevent deviations from reoccurring, we need to address the underlying problem causing the deviation. This is what is called the root cause. After the root cause is identified, defining corrective and preventive actions (solving the problem) is often straight forward. However, putting CAPAs in place that aren't addressing the true root cause can result in losing control even further. Just think of a boat with a leak: pumping out the water is a great short term solution, but meanwhile, the leak is probably getting worse. In the end, the pump won’t be enough anymore to keep afloat, so we need to install a bigger pump. This is called ‘tampering’, and this also often done solving deviations. In order to improve the quality of root cause investigations and thus prevent tampering, a vast array of the 150 Lean Six Sigma tools is at your disposal. Depending on the issue just think of applying Lean group exercises with your SMEs like Process mapping, making a SIPOC,  performing Kaizens or Gemba walks (shop floor visits) in order to increase your understanding of the problem.  You can support your findings with aspect from the Six Sigma spectrum: data gathered from sampling or test runs. So defining metrics and detailed data collection plans in order to investigate the extent of the problem and identifying process variation can boost your investigations.  By applying such an approach, the quality of investigations will improve, lead times will reduce and (maybe most important) teamwork will be improved.

Backlog reduction

So what if you already have a build-up of deviations and a large backlog? Where to start? How to get activated again? Instead of looking at an endless list, we need to find a starting point. Compare it to a shop floor. If it is one big mess with lots of equipment in a room, execution of work in there won’t be efficient. Here we can apply the lean concept of 5S

  • Sort: Sort out everything that is really needed in that room and what is not (take these out of the room).
  • Set: Arrange all items at the place where they are needed
  • Shine: Clean the place since we made room to do so
  • Standardize: define a process/best practice in order to maintain the improved situation
  • Sustain: Ensure the new standards are met.

But, why not apply this to your deviation system?  One thing we have learned is that there is plenty of low-hanging fruit within most deviation systems, investigations that are almost finished or a bunch of relatively easy deviations to solve. Sorting deviations, stratifying them and giving them a place (priority/group) will give you a good starting point to reduce the backlog. Also here, by applying a Kaizen approach you will be able to achieve much in a short period of time. It can be helpful to use visual management in such a case:  for example, develop an overview of all deviations to be closed in the Kaizen and apply colour coding (red, yellow, green) to show statuses,  priority’s or deadlines. This way, you always know the status of a project and you remain in control. For a long term solution, think of a best practice to improve the process including a thorough definition of roles and responsibilities within the process. By applying these concepts, solving a backlog will be like a walk in the park.

Deviation process improvement

Altogether, a deviation handling process that is fit for purpose is what you need. Not just a procedure, but especially how it’s done in practice. It often happens that in practice we are doing additional steps compared to what is required according to a procedure. This is what we call a ‘process around the process’.  But why do we end up with such a waste in the system? Practical limitations compared to the theoretical procedure, or even tampering to make a process more efficient in the short term is what we often see as causes. This is one of the biggest causes of excessive workloads and increased lead-times related to deviation management. Situations like these can be addressed by applying the DMAIC process, which means:

Define the problem

Measure the extent

Analyse the data gathered

Improve the process

Control (check/sustain) the new situation.

Truly understanding current deviation processes facilitates working towards a much leaner situation. Standardization and visual management can prove to be your best friends in order to solve problems in a sustainable manner.

So where to start?

In the end, having deviations is not the problem in GMP.  It’s part of a healthy, working quality system. The way we handle the deviations determines whether it becomes a challenge or not.  This is where you can make a real difference by applying the basics of Lean Six Sigma on both the system as well as individual deviation investigations. See deviation management as ‘a problem’ itself: the system will only work if you really know the process behind it. Map the process, define the essential process steps, apply clear roles and responsibilities with those involved and from that, proceduralise it. Next, incorporating the DMAIC structure in your root cause investigations will leverage them and definitively solve the deviations. Finally, applying visual management will give you the edge in keeping control of your deviation management system once and for all.

If you want to learn more about applying Lean Six Sigma principles in the Life Sciences, please contact Xendo or take a look at the courses we provide together with the Biotech Training Facility (Yellow Belt & Green Belt).

Blog by: Stefan van Dam - Consultant & Green Belt






You have been redirected.

In 2013, Vigilex has merged with Xendo. In addition to the full spectrum of pharmacovigilance services, together we offer a broader palette of services and are able to take on larger projects in the Life Sciences industry.

We invite you to have a look at the different services that we have to offer. Also, don't hesitate to contact us regarding the merger of Vigilex and Xendo.