Quality First - As the trend of specialized medicine continues to grow, so does the development of highly potent active pharmaceutical ingredients, better known as HPAPIs. Handling these highly potent substances is a challenge, and there is no universal framework regulating them. That means it's up to each company to ensure the highest standards of safety and quality themselves. Swiss-based Cerbios is one such company. The privately owned API manufacturer is active in both small molecules in its chemical division and large molecules and probiotics in its biological division. Brandi Schuster spoke with CEO Gabriel Haering on the company's role as a service provider for HPAPI development as well as the company's work with monoclonal antibodies (mAbs) and recombinant proteins.

CHEManager Europe: Cerbios offers third-party services for HPAIs in your chemical division. What developments have you noticed in this area of APIs?
Gabriel Haering: The trend in HPAPIs has been developing positively over the last several years, thanks in part to a heightened interest in the development of more selective compounds with high pharmacological activity and lower dosages. This goes for both new chemical entities and future generics.

What are the challenges in HPAIs?
Gabriel Haering: The challenge is not only related to the proper handling during production, but also to the cleaning of the facility. For the cleaning to be fully validated, it must be done under cGMP and very strict health and safety guidelines have to be enforced for our operators and maintenance staff.  In some cases, the cleaning of the plant can take longer than the production time itself, and this is an important cost factor.

At the present, there's no official guidance for handling these compounds? What does Cerbios do the ensure quality and safety? 
Gabriel Haering: We have invested significantly in state-of-the-art facilities capable of handling category 4 HPAPIs in line with the Safebridge system. Safebridge is a consultancy that provides health, safety and environmental services to companies developing and manufacturing potent pharmaceutical compounds. Paramount to all of that are our well-trained and experienced personnel. We also have large pharma companies as partners that also have a history of experience in handling and manufacturing very potent compounds who have attested to Cerbios' high level of quality.

How important is innovation for an API manufacturer?
Gabriel Haering: Over the past years, we have pushed innovation internally at all levels. Without continuous improvements and innovation at all levels, it will be more and more difficult to grow or even to survive. Four years ago, the perception within the company was that innovation was an R&D task; now everybody is more conscious of the contribution they can make to the company. 

Under Cerbios' biological division, you offer CMO services for development and supply for clinical trials. Many companies shy away from early-phase molecules because of the costs, risks and long-time to market.  What's in it for you as a company?
Gabriel Haering: You have to start early and follow the clinical trials for biotech projects. Changing an API supplier during the clinical phase for biologics is definitely more problematic than it is for small molecules, where batches for toxicology studies and Phase I can be made from one supplier and cGMP production for later clinical phases can be made in a different manufacturing site with another partner.

With biological mAbs or recombinant proteins, we work with cells that are sensitive to different parameters than small molecules. Water for example, despite being of best quality, is very different in different regions or areas. And traces of certain components can influence the "quality-of-life" of the cells that will be more or less "happy" and thus produce more or less - also better or worst - of the new biological entity, or NBE, of interest.

Cerbios is getting ready to start production in its new biologics plant dedicated to the production of monoclonal antibodies and therapeutic recombinant proteins. What was the strategic reasoning behind building this plant?
Gabriel Haering: Development of NBEs based on CHO mammalian cells remains that largest area for future modern medicines. In addition, antibody drug conjugates are also a fast growing development area. Having both capabilities under one roof — small molecule HPAPI manufacturing and biotechnology - Cerbios will be able to offer development and manufacturing as integrated services. Of course, there are also big players having these capabilities under one roof, but several pharma companies prefer to work with small and medium companies that have a different approach and advantages.

Thanks to internal know-how that has been acquired for the development and manufacturing of non cGMP material in the past based on CHO mammalian cells, and since Cerbios is a cGMP API manufacturer, this was the next logical move: a state-of-the-art plant for cGMP production for clinical trials and later commercial supply, by completing the plant with a second production unit.

How much of a delay was caused during the detailed design phase? What were the reasons for the delay?
Gabriel Haering: As in many complex projects, delays are not forecasted but can happen.

In our case, it was mainly due to the decision to show the plant layout to Swissmedic and to our U.S. FDA consultant prior to beginning the main activities.

Based on their feedback - and considering that our goal was to have a production unit suitable for making and selling cGMP material worldwide - we had to make some important changes to the detailed design that inevitably delayed the commissioning and construction start.

In conclusion, it was our decision to delay the project in order to have a really state-of-the-art production unit that can serve our partners for all geographic areas, including the U.S., Europe and Japan.

In what other areas is Cerbios currently investing?
Gabriel Haering: We are investing in both our chemical and biological business areas. In our chemical division, the investments are primarily in technologies for HPAPIs where we can generate new IP. This is of great interest for both the originator during the development phase or for life-cycle-management as well as for the generic companies, enabling them to be able to launch the generic version with non-infringing chemical processes and crystalline forms as soon as possible.

In the biological division, of course, we have the investment in the cGMP plant for CHO based mAbs or recombinant proteins with the option to add an additional production line shortly or larger manufacturing plant at a later stage.

We are also investing in our infrastructure; this includes the detailed design of a new R&D building that should be operative in the second half of 2015. We also invest in continuous training and external courses to improve technical and management/organization skills of our employees.

What regions of the world are most interesting for your business?
Gabriel Haering: Cerbios is a global player. Historically, our markets are the highly regulated ones, such as the EU, the U.S. and Japan. Over the last years, we are also growing in the emerging BRICS markets. This growth has partly come about thanks to innovation on older chemical processes, which has allowed us to be competitive with different APIs with different drug master files in these countries.

We see advantages in every region; the U.S., for example, is very important for new chemical and biological entity development and manufacturing. This is because it has the largest amount of originator companies, from small biotechs to large pharma. Japan, on the other hand, is also very important for us: there we have several long-term partnerships with companies for our products. Europe is our home, and this is where we have been stable historically. And last but not least, the BRICS countries have a lot of potential for high-quality medicines.

What are the advantages and disadvantages of being a Swiss-based API manufacturer in a world where many companies are moving east to cut costs?
Gabriel Haering:  My answer today is very different than it would have been a few years ago. Pharma companies who want to save on cost end up losing millions of dollars due to delayed clinical trials and, as a result, delayed product launches. A very simple example: if you consider a drug that can generate $350 million a year, every day of delay in the launch means a $1 million loss to the company. For a month, the lost turnover is $30 million!

The final balance is in any case negative: $29.7 million lost considering that the company made a $0.3 million initial cost saving.

We are also observing a reverse trend with pharma companies and CMOs that have invested in east; many are selling their plants and moving back west. The signals on the market now are contradictory and must be further observed. I think Warren Buffett said it best: Price is what you pay; value is what you get. I think this is something everyone does in their private lives, but it gets forgotten in business.

Our goal is to provide a higher value than expected.

Visit Cerbios at the CPhI 2013 in Frankfurt Oct. 22-24 in hall 3.1, booth H20.