Making Better Medicines

Enabling Technologies - Prosonix, the leading company in proprietary pharmaceutical ultrasonic particle engineering technologies and added value ultrasonic process chemistry solutions leverages its intellectual property and sonoprocessing equipment to deliver sustainable value to customers. Based in Oxford, UK, a team of chemists and engineers combine to give Prosonix a multidisciplinary approach to solving complex problems of customers in pharmaceuticals, fine chemicals and minerals processing by employing the technology for the "Complete Crystallization Control" of products, processes and unit operations. CHEManager Europe spoke with David Hipkiss, Prosonix CEO, about this emerging niche market, the developments of the company and the business climate.

CHEManager Europe: Who are your main customers, what companies typically apply your technologies?

D. Hipkiss: The business has changed a little bit over the years. We are working with all people in pharma actually; ­innovator, speciality and generic. We have a number of opportunities working outside of the pharma industry in the likes of cosmetics, energy and natural products. But they only tend to be considered, if the technology is a slam-dunk, a good fit.

You said that business has changed. What was it like in the past?

D. Hipkiss: Historically some of our very biggest projects have been in minerals processing. We haven't done anything like that proactively for a very, very long time. Although I will say that one of our current projects involves catalysis. And instead of using the equipment and the technology for crystallizing, we are actually using process intensification via aiding dispersion and in-situ wet milling. The applications of the technology are still broadening, and where there is good opportunity to make money, we will follow them.

Do you also work with fine chemicals companies?

D. Hipkiss: Through choice we have tended not to work with the typical fine chemical companies. Number one, we have enough business with our core customers elsewhere, whereby we can construct long term business relationships and can get reach-through arrangements such as royalties and licensing, which is very difficult to do with the likes of a fine chemical company. Furthermore, uncontrolled exploitation of your technology can lead to its value becoming a little bit commoditized; we need to make sure we have an element of control over that.

Prosonix technologies can be applied across the pharma life cycle, particularly emergent into two discrete segments. Can you give us a brief overview of the main areas?

D. Hipkiss: The first segment, standard particle engineering is largely based around the use of the Prosonitron reactor for controlled crystallisation of pharmaceutical API. This is a simple retrofit technology typically for large-volume drug production. And yes, we believe it can become the preferred standard for manufacture. What are people interested in there? Reducing cost of goods, improving process robustness and improving reliability. The second segment, the advanced side is really where we are looking at the other types of technologies, which we call DISCUS, SAX, UMAX, and particle rounding technology (PRT), etc. That is where we are engineering performance enhancing features into the crystals themselves, such that they have a transformational benefit in the formulation. Thus, one is cost saving, one is enabling. On occasion we deliver both.

What are the key process benefits of sonocrystallization?

D. Hipkiss: The key benefits of sonocrystallization include control of particle size, shape, crystallinity, and polymorphism directly from solution, as well as an improved robustness in batch consistency, filtration, isolation and drying. We can also eliminate the need to use physical seeds and critically, milling and micronsisation. As a consequence of that the drug product, which is subsequently formulated, is better and more reliable, more stable, and critically GMP is improved. It also meets the definitions of the ICH Q8, the PAT and the new QbD directives emergent from the FDA.

Recently, you announced collaborations with Pfizer and Sandoz. What is the subject of these agreements?

D. Hipkiss: We have worked with Pfizer for many years. Pfizer has successfully demonstrated our technology at small scale, kilo scale, pilot scale and they have now bought a commercial scale system for installation in their key new product introduction facility in Ireland. The system we have provided is a multiple, mobile system capable of working on reactors up to 4000 litres which is full commercial scale.
With Sandoz Aeropharm we have a public arrangement to assist them in the manufacture of difficult to make inhaled products. The generics opportunity is one of growing and significant interest to Prosonix.

Are there more such partnerships on the horizon?

D. Hipkiss: We probably have seven or eight others right now, but we are not allowed to talk about those, but we have several similar relationships already in place in pharmaceuticals. I hope to be able to announce a couple later this year. Our inhalation segment is growing very rapidly across the pharmaceutical life cycle.

How has your product pipeline developed in recent years?

D. Hipkiss: Well, I think, now we are close to a hundred feasibility projects in total. We have conducted more than 20 successful pilot scales around the world. Two have gone to full commercial scale so far, and we are planning for several of those successful pilot projects to go to full scale some time in the next two to three years. Mostly they are involved with sonocrystallization. Though, as I have mentioned, there are other opportunities in general particle size reduction or dispersion or indeed some energy products. People are becoming more interested in sonochemistry and sonoprocessing and they usually come to us in the first instance. To-date we have not done too much work in sonochemistry at scale, though we see a great growth opportunity to use the identical Prosonitron reactor systems and to affect many, many different chemical operations.

Prosonix entered a partnership with Syrris in December 2008 to market the SonoLab lab-scale sonocrystallization and sonoprocessing equipment. Why did you decide to have this equipment line marketed by a partner?

D. Hipkiss: Very simply, firstly they are an excellent company and secondly they have what they call the Atlas Platform, which is a very cost-effective multipurpose automated ­reactor platform, which is increasingly becoming standard in many of our pharmaceutical customers. The Atlas Platform was originally a synthetic chemistry platform and it did not have a crystallization module. Naturally we believe that sonocrystallization is the best thing to do, so we teamed up with them. We have developed a small scaled down version of our equipments called the SonoLab SL10, that bolts on to the side of the Atlas automated reactor, and you can begin to do small scale sonocrystallization in your own laboratories. Syrris have a worldwide service and distribution network and over 200 Atlas systems already in place around the world, we very much hope to be able to migrate our technology into those existing customers, never mind, the new ones, which they are beginning to convert. So it is a very good symbiotic relationship.

Last year, you intended to form key CMO partnerships with a few Indian-based API manufacturers in order to meet the demands of your pharma customers. What has become of these plans so far?

D. Hipkiss: Our business has changed a little bit. We recognize that India is still a key player for API supply, though our development activities in that regard are on hold at the moment, but it is still a nearer term objective. However, what has gone forward very rapidly is our inhalation technology program, it has been very successful over the last nine months. Currently we have over 20 customer driven inhalation programs, and based on this success we are now taking two inhalation products to GMP manufacture in an FDA approved European facility of a leading CMO, and that will happen in the next six months. That will provide material suitable for trials. We expect to further our relationship into a formal partnership, such that we will be in the supply chain and the key supplier for the engineered particles for a couple of leading products on our pipeline. Perhaps most importantly the other key benefit is that we can say that we are doing GMP for our inhalation particle engineering technology at scale; that really does de-risk the perception very strongly in the eyes of new customers in showing that we have backed ourselves and we have our other customers backing us showing that the technology is scalable. We are very pleased with that.

How is the business developing?

D. Hipkiss: In terms of people and floor space here in Oxford the company has quadrupled in size. If we want to grow the company in the way that we envisage we may not be able to do this solely by organic means. We finished our fiscal year on March 31. Our results have not yet been published for this year, but I can tell you that we have more than doubled our revenues again. We have trebled our order book and we have delivered a very strong P&L and Balance Sheet performance. This is around 18 months ahead of business plan, and we plan to make a further doubling of our order book and probably another 50% increase in revenues on this year. Going into this year we trebled our forward order book, so we are full, pretty much right the way through to the end of August on service projects. That does not include all of the other equipment projects and licensing opportunities that we have on as well. We plan for it be another very good year for Prosonix and I think, given the team's performance last year in what is a very challenging economic climate that we can stand proud and say that Prosonix is here to stay.

Sounds pretty unique in the current financial situation.

D. Hipkiss: Yes and thank you. We have done very well. But you know Prosonix couldn't have achieved last year
a) without the utmost dedication of its people, and b) without the support of our clients, delivering significant new and repeat business.