A Biotech Talk with Nadège Grabowski, Healthcare team leader at ZAZ ventures
Shortages in raw materials have a big impact on the manufacturing process and unavoidably as well on the end-user, in this case, the patient. Raw materials can be anything used in the process ranging from pipets over bioreactors, as well as organic materials. We interviewed Nadège Grabowski, who worked for several years in cell & gene therapy.
France-Emmanuelle Adil - Tiamat CEO
Do raw material shortages happen often?
I can’t make a statement as to the entire market, but in my experience, in the last 3 years, I had to deal with shortages twice for 2 different raw materials.
How do you react when this happens?
Unfortunately, there is not much you can do when this happens. You can check whether the supplier can procure the materials from a different production site. The best thing you can do is to plan for shortages before they happen because you can’t just start using new materials in your process. Shortages thus imply that manufacturing has to be stopped.
Are any specific raw materials more sensitive to shortages?
Some lab consumables are less critical, for instance, if it is a pipet it can be replaced without any issue. But if it is your bioreactor, for example, it is an issue. These are referenced in IMPD and IND, so they need to be qualified and validated before use.
What does that imply for you and your end-customer, the patient?
If it leads to a change that implies modification to all the batch records, it will require several validations and final approval from quality assurance, so that takes quite some time. The changes have to be analysed, to be sure that the equivalents are understood and managed. For instance, for the pipets, is supplier A the exact same as supplier Z? We need to be sure that it will not impact the end product. If it is the exact same, you still have to modify the batch records, because you have to be sure you take the right reference. You might even ask for the deviation to be validated. If it is something that you cannot change, You can’t do anything, it stops the manufacturing activities.
"If it is something that you cannot change, You can’t do anything, it stops the manufacturing activities."
So, stopping a manufacturing process not only costs you money and time, but it also impacts your end-user, the patient?
To treat patients with an autologous therapy you generally have a little window of time to harvest the starting material (patient apheresis) and manufacturing the product for the injection. If you have to delay the harvesting of two weeks because of a raw material shortage, you are not sure that the patient is still unable to undertake the apheresis procedure because of the advancement of the disease.
What alternatives do you have in case of shortages?
You need to plan for it upfront, if you don’t validate your raw material, if you don’t include them in IND/IMPD you don’t have any alternatives.
Do you usually have backup suppliers?
It is a requirement, but unfortunately, for small companies, it is unusual. It costs a lot of money to validate alternative suppliers, and you have to use them regularly to manufacture clinical/commercial batches. To validate them you have to show that the final product is exactly the same with the two references though complete comparison studies. For raw materials, in vivo studies are required. Then the regulatory dossier should be amended and approved. It takes several months.
What about animal-based raw materials specifically, are they sensitive to shortages?
We don’t have more shortages of animal-based raw materials than others, because mainly the problem is when we have contamination of the manufacturing lines, the animal-based raw materials are not more impacted than the others. Animal-based raw materials are very well checked before usage, the regulations are very strict. This does mean that when we have to replace them we need to go through the validation process again and are delayed significantly.
What do you need that doesn’t exist yet?
We need all backups that give the exact same results as the initial raw materials.
Do you have anything to add?
Raw material shortages are very stressful, especially if you are producing an autologous solution because you can’t treat patients in a high need for treatment.
Raw materials are definitely a critical part of the cell & gene therapy manufacturing. Shortages can be a catastrophe when the deadlines are short, and the patient is always the one who suffers from it.
How do you manage raw material shortages in your field? Share your good practices to avoid critical production delays with us: comment below.
Thank you Nadège for your insights, this talk is intended to explain the complexity of shortages in Cell & Gene therapy industry, quoted words by France-Emmanuelle Adil, Founder & CEO of Tiamat Sciences.