Aseptic spray drying may be a better alternative to traditional lyophilisation for some products, thanks to its tight control over particle characteristics. It also offers gentler process conditions, high throughput and batch processing and requires lower capital investment to set up. It is also compatible with innovative stabilisation technologies.
Lyophilisation and low-bio burden spray drying methods have been around for some time; Nova Laboratories’ Sam de Costa highlights new techniques that are meeting the demands of a changing healthcare landscape.
Downward cost pressure on the world’s largest pharmaceutical companies has undoubtedly created a fragmentation of the drug development industry, evidenced by the continued proliferation of ‘virtual’ companies and the increased use of contract manufacturers to help deliver cutting-edge new drug delivery methods in a more cost-effective way. Nova Laboratories has had aseptic lyophilisation capabilities for almost seven years and offers this service to a wide range of clients, from large pharma to small biotech firms. Increasingly, however, clients have sought alternative processes to lyophilisation to reduce costs and other associated problems.
While lyophilisation is currently the leading method in the manufacture of small molecules and biologicals (peptides and proteins), Nova believes it has limitations that restrict its further development for drug delivery. The company predicts that the next five years will see greater uptake of aseptic spray drying as a more viable alternative to traditional lyophilisation – particularly with the number of blockbusters due to come off patent in therapy areas such as pain management, osteoporosis and mental health.
Aseptic spray drying is a truly enabling technology; its tight control over particle characteristics opens many avenues for drug delivery and presentation. Where new drug development is concerned, Nova is witnessing increased demand in therapy areas such as oncology, especially where clinical trials demand repeat dosing. It believes spray drying will offer companies greater efficiencies, quicker processing and greater flexibility.
The company recently undertook a number of projects in which spray drying, under truly aseptic conditions was not only beneficial, but in some cases also essential to meet certain criteria for quality and delivery.
Aseptic spray drying in progress
(c) Greg Harding Photography
One of the primary benefits of aseptic spray drying is that it subjects the product to gentler processing conditions. Lyophilisation exposes active ingredients to freezing temperatures, which can cause irreversible damage to their composition. During spray drying processes, sensitive ‘actives’ within the product are not subject to high temperatures for any prolonged period of time, which minimises in-process damage to the product. The evaporative cooling effect during drying further minimises any potential damage to the product by heat. Because of this, Nova has been able successfully to manufacture temperature labile material using aseptic spray drying.
One of the company’s largest spray drying customers is Dutch company ProFibrix, which has developed a new haemostat product based on a blend of spray dried micro-particles containing the clotting factors Fibrinogen and thrombin. Crucial to this product is the fact that the spray-dried active clotting proteins can be mixed in the final presentation and stored at room temperature without initiating coagulation – an outcome that is not possible if the product is formulated as a liquid.
Nova has manufactured late stage clinical trial material at commercial scale to supply the ProFibrix pivotal trial FINISH-3 and is preparing for commercial supplies in the future that require kilogram quantities of powder. Due to the volumes required, high-capacity spray drying capability is essential for product realisation.
From an economic standpoint, spray drying requires lower financial investment and operational time than a similar scale lyophilisation plant. The efficiencies it generates have benefited clients in a number of ways.
When high throughput is required, a significant cost reduction is achieved, because aseptic spray drying is a reliable continuous process that facilitates high-volume manufacturing, such as when large volumes of a vaccine or drugs are required for stockpiling under emergency situations. Lyophilisation’s ability to meet such demands is limited because it is a batch process: the quantity of product that can be manufactured is restricted to the size of the lyophiliser.
Aseptic spray drying
(c) Greg Harding Photography
Until now Nova has aseptically spray dried pharmaceutical biologics continuously for up to five days to manufacture large (kilogram) quantities of powder. Once spray dried, the product can be filled aseptically into various presentations including vials, medical devices and capsules. Furthermore, the spray dried powder can be aseptically blended, filled and finished under the same roof, giving further cost savings.
Through particle engineering, spray drying enables further development of the product – giving improved characteristics that can result in greater bioavailability, rapid dissolution or improved flowability. Companies have also approached Nova for proof of concept trials to demonstrate compatibility. Using aseptic spray drying, the separate components of the vaccine can either be jointly or individually spray dried – under conditions unique to each separate element – before being combined in the final delivery method.
Aseptic spray dying is compatible with a number of innovative new stabilisation techniques developed to remove problems associated with refrigeration and to increase bioavailability.
Nova’s VitRIS (Vitrified Readily Injectable Suspension) platform uses spray drying as a basis. The pharmaceutical product is mixed with water-soluble glass formers and dried as a solid, non-crystalline, amorphous glass using spray drying. The outcome of this first part of the process is spherical, highly polished microspheres in which the product is immobilised and stabilised.
The powder containing the stable product can then be converted into a ready-to-inject format by suspension in an inert anhydrous liquid, typically medically approved fluorocarbons, hydrofluroethers or low-density metabolisable oils. This second step requires the ability to match the density of the powder with the density of the liquid to prevent the powder either floating or sinking. The result is a stabilised liquid suspension that does not require refrigeration storage.
The platform is currently being evaluated by a number of global pharma firms who are making early feasibility enquiries. Nova is currently working on a project to produce a pentavalent vaccine against childhood diseases.
Further processes can be combined with aseptic spray drying to improve the dissolution rate of the resulting powder. The company’s Aerosphere technology, for example, allows the manufacture of temperature stable powder that dissolves rapidly compared with conventionally dried powder. Biological ‘blowing agents’ are added during the spray drying process to create larger, hollow spheres with increased surface area that improves the dissolution rate.
The HydRIS platform enables products to be stabilised in a ready-to-inject format
(c) Greg Harding Photography
The breakthrough has the potential to speed up medical care delivery in emergency services and can even be used in military applications. It cuts the need for refrigeration and liquid storage facilities. It has applications for vaccines, a range of therapeutic proteins and nucleic acids.
Using the same sugar-glass stabilisation technology as VitRIS and Aerospheres, Nova has also developed the medical device HydRIS, which has been shown to stabilise highly labile novel delivery platforms based on live organisms – live viral or bacterial vector vaccine.
To meet the increased demand for large-scale production, the company is currently drawing up plans to expand manufacturing capabilities to cater for full-scale commercial manufacturing volumes.
Conversely, it has also experienced increased demand for much smaller volumes of powder – often from start-ups in the very early stages of drug development. In instances like these, it is not economically viable to use the company’s main manufacturing facility. To meet this demand for smaller test batches of aseptically manufactured powder, the company has recently installed a series of scaled-down spray dryers operating under aseptic conditions. The hope is that this capability will enable smaller companies to undertake feasibility studies that would previously have been financially unachievable.
Nova predicts that the adoption of aseptic spray drying by the pharmaceutical industry will increase exponentially. When it comes to manufacturing innovative drugs using novel delivery systems, it may be the only process capable of doing the job.