The rise of the awareness of biotechnology in recent years is accelerating the emergence of new drug candidates of biological origin. But, we also know that, among all the projects that start, only a few end up developing an effective and safe medicine.
But completing drug development is by no means the end of the road. Both for companies with experience in pharmaceutical production and for those projects that emerge from a start-up, there is a common denominator that poses a real challenge: moving from a non-GMP development environment to a GMP production environment. Compliance with Good Manufacturing Practices is mandatory and indisputable for the production of any drug. GMP ensures that a drug will have consistent quality levels and that it will be safe for the final patient.
At Klinea, as an engineering company specialising in the biopharmaceutical sector, we are aware of the obstacles involved in this transition. Our experience allows us to advise our clients in the best possible way, to help them along this difficult path, and to make the launch of a new biopharmaceutical a success. Here are some of the challenges of the transition to a GMP environment, and how Klinea proposes to overcome them.
The first challenge faced by this type of project is the scale up of the process. Producing on a laboratory scale may be relatively affordable. But starting to produce on a larger scale may cause the first problems to arise. For example, some of the techniques used at laboratory scale are not easily reproducible at industrial scale. This can be due to two factors:
- The equipment does not exist or cannot operate on a large scale. This would be the case, for example, with a sonicator. This equipment is used in the laboratory for lysing (membrane rupture) of cells. Its main disadvantage is that it causes an increase in the temperature of the solution on which it is used, which can lead to the denaturation of some proteins, and therefore to a decrease or elimination of their activity and consequently to the loss of their therapeutic function. A sonicator could be replaced, for example, by a high-pressure homogeniser, which, although it can also cause increases in temperature, can be counteracted in a simpler way. Enzymatic lysis of the cells could also be possible.
- The scale-up of some production operations does not follow a linear relationship. In many cases, it is not sufficient to increase the size of the equipment in a linear fashion to increase the process volume. The logic: “I want to increase the amount of product I purify 10 times -> I increase the size of my equipment 10 times” does not always work. It is also very likely that it will be necessary to change the operating conditions of the equipment to obtain the same result. We cannot agitate a 1000L tank at the same speed as a 10L tank.
In addition to the problem of process scale-up, there is uncertainty about the process. “I am going to start producing something that no one has ever produced before, where do I start, how many stages should I purify, what is the ideal size for my batches?
At Klinea we have a unit specialised in biotechnology and bioprocesses applied to the biopharmaceutical industry. We know the equipment manufacturers on the market very well, and we can accompany and advise our clients to choose the suppliers that can best meet their needs, while recommending configuration and customisation methods that can add value to the production process. We are also experts in bioprocesses. We can advise – among others – on process design, the definition of the different stages or the choice of batch sizes, depending on production needs.
Another major challenge to overcome during the transition to the GMP environment is uncertainty. We know that uncertainty is inherent in almost any project. But in the case of bioprocesses, it is even more evident. As we have said before, we start the path towards the design of a production line with some doubts about some details of the process. But this cannot be used as an excuse to delay the design of the layout of the installation and all the other elements that are not explicitly part of the production line, such as auxiliary equipment areas, quality control, changing rooms, etc.
Another type of uncertainty is that of the process itself. When dealing with cells and other biological agents, the consistency of the process is not the same as in chemical processes. Sometimes we will have to deal with processes in which the amount of product or the activity that we will obtain in each fermentation batch will not be exactly the same (always within limits that allow us to demonstrate robustness and reproducibility). This will inevitably affect the subsequent stages of purification, formulation or filling.
To combat this uncertainty, at Klinea we propose flexibility. Flexibility in the design that allows spaces to be adapted to the final stages and equipment of the process, once these have been defined. Let’s say a customer is still not sure what type of chromatography they will need to purify their product. We can allocate a room that is flexible enough for the different types of chromatography to accommodate the different scenarios that may arise.
But we also value flexibility in the operation of the plant. So that, even if there is a certain variability in the process, it can be adapted to the needs of each batch and achieve the most optimised production possible. For example, we could choose a support for single use microfiltration equipment, so that it is possible to place filters of different sizes depending on the amount of product to be purified.
In addition, we work using agile methodologies, also known as agile. Our Project Managers have the necessary knowledge and experience to work as agile and efficient as possible. So it is easy for us to adapt the direction of the project as decisions are made.
Finally, there is one of the most difficult and important challenges: adapting to the GMP environment. Nothing you can achieve in a project counts if you don’t achieve compliance with GMP regulations and the medical agency at the end of the day. This is especially difficult for start-ups with no previous production experience beyond lab scale.
Our team members have more than 20 years of experience in GMP environments in all areas: design, production, quality, compliance, etc. Our cross-functional team works together to ensure that our clients’ objectives are met.
This is how at Klinea we can accompany you through all the steps of the GMP transition to make it a success. If you would like to know more about the transition to a GMP-compliant production environment, contact us at email@example.com
- Posted by Klinea
- On 27 January, 2022
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