Incubators, Freezers & Cooling Equipment
Advancements in Freeze Drying Production & the Impacts on Scale, Sustainability and Compliance
Aimee Blakemore for Biopharma Group,
bps@biopharma.co.uk
Freeze drying, also known as lyophilisation or simply ‘lyo’, 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. As a process based on negative temperatures, the activity and stability of the product being freeze dried, 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 sector.
A strong factor that is driving the increased need for freeze drying in the pharmaceutical industry is because it stabilises a product and its ingredients for distribution, makes the product lighter, more compact and increases shelf life. This is a useful, cost effective and effi cient way to optimise transport of large quantities of products, no matter the industry. In terms of pharmaceutical applications, it also allows products to be shipped to countries where temperature may affect the stability of a product and a cold chain is not available or where product may need to be stored for long periods.
Another strong factor underpinning the need for freeze drying for pharmaceutical applications is that freeze drying technology has adapted for scalability, allowing larger batches of products to be produced more quickly, more effi ciently and more cost effectively, with much less error.
What Has Infl uenced Advancements in Freeze Drying Production?
Recent advancements in freeze drying over the past year have allowed for faster processing, scalable adaptability, optimised sustainability and legislation compliance within the sector. The Covid-19 pandemic has played a part in the advancements of newer technology for lyophilisation, due to the sheer scale of production requirements for vaccines and diagnostics alongside the extremely tight time scales to take products from conception to delivery.
Formulation Considerations Can Affect Production
It is important to remember that when a formulation is developed for freeze drying, there are many factors which can affect the production and manufacturers will often see up to 20% of samples being rejected due to various things that can go wrong.
At the start of the lyo process, products must be formulated in such a way that they 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 product itself.
During the freeze drying process, vials can freeze at different rates and temperatures, moisture content is varied and some vials could even show evidence of collapse which means product homogeneity and yield can be inconsistent. This results in time lost, deviations or contaminated products which cannot be used, further time needed to correct the errors and all of this also costs money.
Not only is it now possible to ensure that a freeze dried product is of the highest quality, but the latest innovations have now made it possible to reduce room for error during the freeze drying process, which leads to higher effi ciency, quicker production and higher cost savings.
By utilising the latest R&D insights from Biopharma Group such as ControLyo, SMART and TDLAS, which work on the principle that the more information and control one has over a process, the less likely issues are to occur with product moving beyond their design space and thus, needing to be rejected. ControLyo, for example, has many benefi ts whilst enabling scalability for manufacture for products such as sterile injectables. The product benefi ts include achieving improved inter and intra-batch product quality, with the QbD (‘Quality by Design’) approach ensuring that all vials have the same nucleation temperature and timestamp, including those with a thermal couple. In addition to this, manufacturers can now also reduce freeze drying stress on biologicals, work with larger ice crystal sizes to minimise dry layer resistance, have a shorter reconstitution time, reduced protein aggregation, reduced pH shift, better cake appearance and can often require no change to the users existing formulation.
Another trend to consider is how patient treatments have started to move away from broad population therapies in favour of targeted treatment of smaller and more personalised patient populations. For this reason, the biopharmaceutical industry has transitioned to smaller aseptic batch manufacturing. A potential reason for this shift toward small scale batches could be due to the fact that API can sometimes be scarce, so test quantities may be limited and very expensive. There are also new oncology drugs and live viruses needing to be handled carefully. This trend has become pronounced over the past decade, increasing the importance of freeze drying within biopharmaceutical research and development (R&D) and manufacturing environments, which continues to rise. Some key infl uences on this change are due to at least 41% of biological drug products requiring freeze drying/lyo processing and because continual growth is expected due to development and availability of more complex drugs. It is also because a high number of large molecule drugs, for example Antibody Drug Conjugates (ADCs), may be unstable unless freeze dried, driving forwards the necessity of freeze drying within the marketplace.
Page 1 |
Page 2 |
Page 3 |
Page 4 |
Page 5 |
Page 6 |
Page 7 |
Page 8 |
Page 9 |
Page 10 |
Page 11 |
Page 12 |
Page 13 |
Page 14 |
Page 15 |
Page 16 |
Page 17 |
Page 18 |
Page 19 |
Page 20 |
Page 21 |
Page 22 |
Page 23 |
Page 24 |
Page 25 |
Page 26 |
Page 27 |
Page 28 |
Page 29 |
Page 30 |
Page 31 |
Page 32 |
Page 33 |
Page 34 |
Page 35 |
Page 36 |
Page 37 |
Page 38 |
Page 39 |
Page 40 |
Page 41 |
Page 42 |
Page 43 |
Page 44 |
Page 45 |
Page 46 |
Page 47 |
Page 48 |
Page 49 |
Page 50 |
Page 51 |
Page 52 |
Page 53 |
Page 54 |
Page 55 |
Page 56
