2023-05-26 07:24:00
Industry Pharma : What exactly is the biotesting ? What are the major types of analytics and technologies behind it?
Ludovic Burlot : The biotesting is a generic term taken up by Polepharma as part of its congress, which refers to the global analytical sphere surrounding the development of biotherapies. Under this name, without being exhaustive, we will thus find as themes the structural characterization of biomolecules, the conduct of bioassays to determine their activity and their mode of action, the evaluation of their interactions, either with other biotherapies or with small molecules, the search for impurities and the analysis of sterility.
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To do this, we must have ever more efficient analytical systems, such as mass spectrometry, spectrophotometry, separation methods (chromatography and capillary electrophoresis), Elisa tests and many more… but also the coupling of these methods. In addition to this subject of analytical development and the specific equipment associated with it, we will include in this theme the biotesting strategies related to pharmaceutical quality and regulatory requirements.
Since when the biotesting has it imposed itself in the world of pharmacy as a key subject?
L.B. : The boom in the analytical development of biomolecules dates back to the 1960s, with the arrival of the first recombinant proteins. During the development of these new proteins, it was necessary to be able to define their structure, which is intrinsically linked to their mode of action and their activity. Certain proteins purified from animal samples, such as insulin, or human plasma, such as certain coagulation factors, have today been replaced by recombinant proteins. The laboratories had to demonstrate that these proteins had structures close to those of the human protein and that the impurities coming from these new processes did not present a risk for patients. Indeed, whether in cell culture or by animal transgenesis, these new expression systems generate contaminants that are specific to them, impurities that need to be identified and quantified.
How is the game changing in analytical development?
L.B. : Several factors contribute to the evolution of analytical development. First of all, drug regulatory agencies have increasingly high expectations regarding the demonstration of the safety and efficacy of these biotherapies. We must also reduce the development cycle of these drugs and, here again, analytical development must contribute to this. The arrival of innovative therapy drugs (ITMs) brings new challenges and, in particular, the need to provide analytical answers in ever shorter times.
Beyond the pharmaceutical sphere, knowledge of the “living” also boosts its development, such as, for example, genome sequencing, characterization of emerging viruses… In 25 years, I have therefore been able to see, on my scale, the evolution of certain technologies, such as mass spectrometry and chromatography. Mass spectrometry, born to characterize small molecules, is now suitable for the characterization of large complex proteins, while being more sensitive for the search for impurities. The trend today is to characterize proteins in their native forms, without going through digestion steps to analyze them. More traditional methods, such as Raman spectrophotometry, for example, have been adapted to meet the needs of conducting on-line industrial processes, such as cell culture. Today, biotesting is a central activity in the process of developing biotherapies, which explains all these advances or technological adaptations.
What is the maturity of this subject today? biotesting ?
L.B. : On recombinant products, the state of the art is well known in terms of analytical development. On the other hand, on the subject of ATMPs, we are at the beginning of the implementation of analytical development strategies, as twenty or thirty years ago, for recombinant proteins.
And do we have all the necessary analytical tools?
L.B. : That’s hard to answer. We want to be always more sensitive, more precise and faster, which always requires new tools. For MTIs that I know less well, we will find the same analytical tools as those used for recombinant proteins, but they are not always used for the same purpose.
For example, flow cytometry and qPCR are traditionally used for the production of recombinant proteins to better characterize their activity and for the search for impurities. In the field of Car-T cells, these technologies are now used for immunomonitoring, once the cells have been injected into humans. In conclusion, for innovative drugs, even if some existing analytical technologies are adapted to their needs, it is likely that new tools are essential for their development.
At what stage of drug development is the greatest need for biotesting ?
L.B. : We need analytical development throughout the life cycle of a biomedicine: from start to finish, without interruption. In the early phases of development, it is essential to properly identify the structure of the candidate biotherapy. Then, when the product has been selected, it will be necessary to develop its production/purification process and its formulation. Analytical development will accompany all these phases, making it possible to provide a finished product for the clinical development phases and meeting regulatory requirements. At the marketing stage, a control strategy must be defined and implemented, making use of all the knowledge accumulated throughout its analytical development, demonstrating that the product meets the quality requirements to ensure its effectiveness and safety.
Are all these analyzes carried out internally by the laboratories or are they outsourced?
L.B. : In general, the organization of analytical development is highly dependent on the size and structure of the pharmaceutical company. As for start-ups, they define and organize the development of molecules and subcontract analytical development because they do not have the critical size to set up laboratories. Investments in equipment are often heavy and require rare skills, as in the case of mass spectrometry. As far as LFB is concerned, like many medium-sized or large companies, we carry out almost all of the analytical development in-house. We will have to outsource the development of certain methods, if we occasionally lack resources or specific skills/tools.
Why keep all of these analytical capabilities in-house rather than outsourcing?
L.B. : An analytical laboratory will always be challenged by its management to know whether to keep skills in-house, which represents a cost, or whether to outsource the activity. If we want to go faster and faster in the development of drugs, it is clear: it is better to carry out the analytical development in-house. This provides more speed and agility. Nevertheless, it is very hypothetical to believe that all of these complex methods can be internalized. A good mix between subcontracting and internalization is certainly the best strategy to deploy according to these means.
What are the challenges today biotesting ?
L.B. : Two major issues arise in the pharma sector: how can we speed up the development of drugs, and in particular, how can we go faster in the clinical phases? How to ensure reliable production? And all this, while meeting pharmaceutical and regulatory requirements. For this, analytical development must allow us, with the right tools, to develop the production/purification process more quickly and to define a formulation adapted to its use, while ensuring the quality of the drug and the safety of the patient. This limits the risk of adverse effects during clinical studies. THE biotesting is today an integral part of what can be called the drug control strategy.
Today, the contribution of biotesting allows to have a better characterization of the drug throughout its production/purification, which allows us to better characterize its manufacturing process, and therefore, to better define the critical process parameters with respect to the quality of the product. Like what could be practiced 25 years ago, this synergy between biotesting and characterization of the manufacturing process makes it possible to control the quality of the product throughout its manufacturing process and to ensure its liberality. Without setting up an analytical control strategy, too cumbersome at the end of manufacturing. Through this strategy, drug availability to patients is improved, which is all the more important for ITDs.
Why did you agree to support the Polepharma Days of Biotesting ?
L.B. : In the field of analytical development, we often find ourselves alone in the face of our challenges and the requirements of drug regulatory agencies. A congress such as this one makes it possible to benefit from the experience of other laboratories in order to discuss the approaches and strategies that have been implemented. It allows us to compare our understanding of the regulatory need and to discuss the new texts which have just been promulgated. It is also an opportunity for equipment manufacturers and scientists from the academic world to present new scientific and technological advances that can meet our challenges. These days on the biotesting are a unique opportunity for all of us to enrich each other.
This interview is an advertorial produced on behalf of the Polepharma cluster
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