Why was utilising CRO services for freeze drying, so vital in response to Covid-19?

Interview by Aimee Blakemore, June 2021.

Earlier in 2021, we published our technical review on freeze drying in relation to the COVID-19 pandemic. As a follow-up, Dr. Mattia Cassanelli, Technical Manager of Biopharma Group’s consultancy division, has been interviewed to delve further into the benefits of freeze drying during this time, what was learned and what trends he expects to see for freeze drying in the future.

About Mattia

Mattia joined Biopharma Group in February 2018 and is the Technical Manager of the consultancy division, providing support through desktop study, cycle audit, characterisation of the material pre- and post- process, formulation development, optimisation of the freeze-drying cycle and tech transfer/scale-up.

Mattia’s background includes a PhD focussed on drying mechanisms of hydrocolloids in the food industry from a microstructural point of view at the University of Birmingham. He also gained a Master’s degree in material engineering, and a Bachelor’s degree in industrial engineering completed at the University of Trento, Italy.

For those unfamiliar with the process, what is freeze drying and why is it so important?

Freeze drying, or lyophilisation, is a drying process which consists of the sublimation of ice crystals into vapour. Rather than using a heat treatment, samples are frozen, then the pressure is decreased, and at that point sublimation occurs. That way, as a process based on negative temperatures, the activity and stability of the product, along with any active ingredients, are better retained whilst limiting any damage to the product and avoiding degradation of the molecules. This is why freeze drying is especially popular in the pharmaceutical and diagnostic sectors.

2020 was a very strange and unique year, how was it for Biopharma Group?

It was a very different and unusual year indeed. We noticed a significantly increased demand in terms of diagnostics applications along with pharmaceutical applications such as vaccines, and as Biopharma Group is a CDMO, we constantly evaluate the freeze drying industry market. At the beginning of 2020, there was a noticeably higher demand for diagnostic products and applications and towards the end of the year it was all about the development of potential vaccines.

When it comes to diagnostic products, how have you coped with the large market demand? 

As you can imagine, due to the pandemic and for other applications, we noticed a huge demand for In-Vitro Diagnostic (IVD) Testing products. These products are the tests used to determine whether a person tests ‘positive’ or ‘negative’ by taking a sample from the person and applying to the test product. It was a busy year, and to keep up with demand, we increased capabilities and production capacity within Biopharma Group. We noticed that this was something that happened industry wide.

To meet the demand for the products required, there were two main approaches; regular freeze drying of in-situ liquid contained in vials or well plates, which are then freeze dried, kitted, and placed into packaging to be distributed. The alternative was to use lyo beads, also known as freeze dried spheres, which use a different preparation process but will provide the freeze-dried products required to help sustain the huge demand.

How important are the product formulations to the freeze drying process?

When you develop a formulation for a diagnostics application, what is good for liquid is not necessarily good for lyo. It is very important to formulate a product in such a way that it can be suitable for freeze drying. This involves the inclusion of cryo-protectants to protect against freezing injuries, and some lyo-protectants to protect against drying stresses, so having a well formulated product is essential. Depending on the application and the method chosen for freeze drying of the product such as liquid vials, well plates or lyo beads, having a bespoke, high-quality formulation can help to enhance the properties of the material and retain the activity and stability of the reagents, whilst ensuring that the formulation does not interfere with the test itself.

How has the growth in vaccine development impacted the freeze-drying industry?

Currently the main focus has been on vaccines for COVID-19, which is a liquid product, and everything has been dictated by this. When it comes to freeze drying, you can store the material for longer, the shelf life will be extended, and you can also avoid, and/or limit, cold chain supply issues, which is highly beneficial. What we are doing currently, for example, is working with the companies developing the vaccines, in trying to develop a formulation that can be suitable as a liquid form for the short-term, and in a lyo form for the mid to long term. When talking about vaccines such as mRNA, that contain liposomes and lipid nano particles, it would be better to have storage that did not rely on very low or minus 80-degree temperatures. By increasing the storage temperatures, it would make transporting the products easier to those countries where the cold chain is not so available.

What are the main technical challenges for vaccines? 

» retaining activity of the vaccine

» minimising any damage that drying could cause to the product

» ensuring a ‘good’ shelf life

» ensuring storage is possible at room temperature

…and for freeze drying we also need to ensure that cryo-protectants and lyo-protectants are included in the formulation of the product to protect against further damage from the processing, as mentioned earlier. These added excipients also need to be compatible for injection and for the specific applications that the product is designed for. A study must be developed for the formulation and freeze-drying process, as well as a good protocol for the freeze drying that will help to maximise the quality of the product.

What other products/applications could you support with your expertise in freeze drying?

The great thing about freeze drying is that it can be utilised across multiple sectors, not only pharmaceutical but also diagnostics, biotech, and food, for example. A popular trend currently, is the production of pro-biotics which involves freeze drying micro-organisms and bacteria. This is also used for bio-therapeutics, human cells, and human tissues for tissue engineering such as collagen scaffolds. Not only can small molecules be freeze-dried, but also large molecules like those found in molecules and anti-biotics. Something that is currently in the design and development stages at Biopharma Group, is a formulation for mono-clonal antibodies therapies, focusing on treatment rather than prevention. One of the great things about working for Biopharma Group is that you never get bored! Each day deals with different products and projects.

What has been learned from 2020?

Diagnostics applications are very important. Not just for COVID-19 but for other infections and diseases.

What could be the freeze-drying trends in future? 

I am expecting something very similar to last year. It is expected that the diagnostics sector will continue developing and that the pharmaceuticals sector will continue to develop new drugs, APIs and blood products at a steady pace. Freeze drying will become even more popular as a means to accomplish this. Diagnostics will be especially important for specific applications such as seasonal infections but also for things such as cancer and tumours.

Where can people go to if they want to find out more about how Biopharma Group can help them? 

Visit the Contact Us page to submit an enquiry form. Alternatively, you can drop Mattia a message directly on LinkedIn to arrange a call to discuss your project requirements and to find a tailored solution to suit.