How to start a Biosimilar development – a risk-based approach

Daniel AmstutzKnowledge, NewsLeave a Comment


Participants of the biologics and biosimilar conference.
Our MD Karlheinz in the second row towards the center.

Following the Biosimilar conference in Boston a few weeks ago, we would like to share our presentation on how to properly start a Biosimilar development project.

We don’t think our approach is unique, in fact far from it, as we refer to Juran’s Quality by Design concept and subsequently to the ICH guidelines Q8, 9 and 10. And we certainly don’t believe that it is the only approach to go forward.
Yet, we believe that our way of looking ahead and be prepared for obstacles is more practical, efficient and economical (in the long run) than the eyes-wide-shut-and-hope-for-the-best approach, which seems to be surprisingly more common than we have thought.

Don’t get us wrong, we understand very well that Biosimilar development is new territory for most organizations wanting to enter the increasingly growing field, and it is only understandable that mistakes happen, that knowledge is incomplete or insufficient and that unforeseen events occur. Yet, the Quality by Design approach as a well-proven tactic to plan ahead and be prepared is not something that is exclusive for Biosimilars, so why is it not more common?

We can’t tell.

We do know, however, that our presentation was met with genuine interest and positive feedback. So, here is the presentation with the commentary on each slide – free of charge.

Biosimilar development in short

All throughout development and production, we can assist and help you with your project, either directly through consultancy services or hands-on work with your specific documents and data, or we may provide you with one or several of our products ranging from customizable molecule manufacturability or CDMO selection guides to fully fledged Quality Management solutions, such as TEMIS (controlled management of digital documents) and METIS (laboratory/experimental data database).
Biosimilar development is one of our core competency.

Analysis and assessment of project

Biosimilar development always starts with being as certain as possible about your own starting position. What is the intention for going the biosimilars route? How high is the budget for the project and what is the assumed financial goal? Which product do we have in mind? Do we need additional infrastructure, is the existing facility sufficient, can we redesign parts of it, do we need to build an entirely new one, or do we need or want to outsource certain project parts?
All these questions should be answered as thoroughly as possible, yet for most, additional research is required and they cannot be resolved immediately.

Once the initial setup is defined and jotted down, a project needs to be outlined with timelines and deadlines, milestones, investments costs, potential risks and pitfalls. In a Quality by Design approach, all considerations should include proper risk assessments which allow to categorize and grade risks by priority, impact and other factors; and they need to be repeated and or updated when circumstances change.

QBDC has performed many project risk assessments and assisted companies in initial and ongoing project management considerations

Selection of molecule

Around the same time or even prior, you should come to a decision on the most suitable molecule or molecules, as the numerous characteristics vary significantly. The factors are production-related, such as mode of action, glycosylation, chromatographic steps, cell line, fermentation method etc., but also market-related, such as date of market introduction, competitor(s) local and worldwide, sales (if currently marketed) and many more.

Be aware, while the gathered information is publicly available and may be gathered by anyone, it is not processed to allow in-depth comparisons or to include company-specific factors such as available facility infrastructure, manpower, scientific knowledge. Even the geographical location of the facility and the targeted market and, thus, governing regulations change the outcome over which is the most suitable molecule.

QBDC has developed a manufacturability risk assessment for a number of potential monoclonal antibodies, based on publicly available information (taken from US FDA, European EMA and other regulatory bodies), which we provide as a structured and refined spreadsheet. Along with this worksheet, we provide a specifically built decision matrix which takes your company’s preconditions into account and supports your decision-making.

molecule manufacturability assessment

Exemplary molecule manufacturability diagram. (Note: most molecules are redacted for confidentiality reasons)

Selection of CDMO

Similar as the molecule manufacturability assessment, we have also developed a structured guide for finding the right CDMO for your project, in the likely event of outsourcing one or several project steps to a third party.

The strength of our CDMO Selection Guide is the combination of both factual and social factors. Not only is it necessary to know the facts and numbers of a CDMO such as annual revenue, number of employees, experience with similar projects, available facility infrastructure, but also the interpersonal impression of your future business partner.

You want to ask yourself: Do I trust this potential business partner to deliver the quality I demand from them? Does the project team on-site seem competent enough? Does the facility on-site meet my expectations? Does the collected information from before the visit hold up to the actual state of affairs on-site or are there discrepancies (e.g. clean room procedures do not conform with the assumed standard, GMP documentation has obvious flaws etc.)?

These and many other questions can be processed gradually and systematically with our Selection Guide, to eventually find the optimal business partner.
In addition, we may assist you in preparing and customizing the questionnaires of the CDMO guide, or – at a later stage – perform or accompany the audits at potential candidates.

CDMO Selection Guide Phases 0-6

Phases 0 to 6 of the CDMO Selection Guide by QBDC; a structured approach for finding the most suitable project partner.

Comprehensive services and solutions

While the above services and products mostly apply to specific project parts, QBDC is also experienced and capable to support you in a more comprehensive role such as with project management during one or more of the initiation, design, analysis or execution phases, or even all of them throughout.

Last but not least, QBDC also offers two software solutions for the controlled management of digital documents and data, TEMIS and METIS.
TEMIS is a GMP-compliant and part11-validated electronic document management system (eDMS), which allows the user to administrate and manage their digital documentation. Observing the market and competitors, we detected a severe lack of software solutions for small and medium-sized enterprises. Either the software is too expensive at 6 digit US$ prices (including implementation and training) or it does not comply with the required regulatory standards. More often than not, small and medium-sized businesses are forced to either invest more than necessary, work with insufficient means, or revert entirely to a paper-based documentation system. All three way are less than ideal in our almost completely digital world.

With TEMIS we can fill this gap and help small and medium-sized companies to regain their deficit in comparison to those businesses who can and want to invest in a massive documentation system.
Read more about TEMIS here.

METIS, our other software solution, fills a similar gap, which is the ability to provide a data history for digital data. If there isn’t a sophisticated system in place, companies usually collect their data either in paper form or file them in simple spreadsheets. The former is inconvenient and inflexible, the latter is risky and in some circumstances no longer accepted by the authorities. An example for this, is an FDA warning letter to BBT Biotech GmbH in May 2016 (see No. 4 of the letter).

With METIS it is possible to collect laboratory/experimental data in a secure environment, protected with a password protected user role assignment, and it allows to compare current with past data or against predefined experiment limitations, to quickly act and react, before it is too late.
Read more about METIS here.


Entering the Biosimilar market and succeeding in it is no “Zuckerschlecken” as we say in German, it is no “piece of cake”. All of our clients work with us for this exact reason. No one knows everything – including us –, but working with us will allow you to benefit from our experience and knowledge with Biosimilars and help you to be better prepared for all eventualities.
Being aware of your own limitations is the first step to eventually succeed.

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