HPAPIs And Bioconjugates

On an industry level, how would you characterise the overall market for HPAPIs?

The market is growing rapidly—probably the most aggressive growth rate that we see in the pharmaceutical market today. There is real emphasis on oncology; it is becoming increasingly clear that many potent compounds are more highly effective in this area and an increasing number of our clients are consequently developing such compounds. Success with being able to better target HPAPIs and increase their effectiveness has also increased demand and helped grow the market. I expect this trend will continue.

What would you identify as the key trends influencing the market for HPAPI bioconjugates?

Several different delivery mechanisms are currently being developed, including antibody–drug conjugates and liposomal formulations. They are beneficial because they help the potent drug to target a particular site, which typically results in being able to dose the patient with smaller quantities of highly cytotoxic drugs. Smaller quantities of drugs mean fewer side effects, so patients usually have a better quality of life; for example, hair loss and nausea can be reduced. The targeted delivery approach also allows more of the drug to get to the target area more quickly, so treatment can be shortened.

A key trend here is antibody–drug conjugates (ADCs); we see more highly potent compounds being conjugated to antibodies than probably any other targeted delivery platform.

Have there been any recent developments at SAFC with HPAPIs or bioconjugates that you think have been significant?

Recently, we have been expanding our capacity for HPAPIs. We brought a facility online in January 2011 to produce highly potent compounds by bacterial and fungal fermentation in Jerusalem (Israel). Demand is definitely increasing. Within the past year, we also built a large-scale manufacturing facility in Verona, Wisconsin (US) which enables us to manufacture HPAPIs at a 200kg scale, which is at the higher end of production scale currently available.

We also have plans to build commercial antibody-drug conjugate capability in addition to our conjugation facility in St Louis (US). That capacity is filling up very well, hence our plans to create a further facility to carry out conjugation at commercial scale.

What challenges lead some pharma manufacturers and contract manufacturers to shy away from HPAPIs or bioconjugates? How is the industry overcoming these issues?

It is extremely important to create a safe environment to manufacture them in and this requires a lot of investment to build and maintain. With that said, it is not just the initial capital investment, but the continuing costs to operate in a safe and compliant manner. The pharmaceutical companies that are looking to develop these drugs put the emphasis on the CMO to be responsible for ensuring that the proper infrastructure is in place to operate things correctly. As such, there have been companies that have looked at the HPAPI market as an easy one to get into, until they recognized all that would be involved in order to operate safely.

As the industry further realizes the importance of protecting their workers and the environment as well as the product, a number of CMOs are now making sure they put the proper controls in place to become Safebridge certified. SAFC has already established this and it is a major differentiator of our business.

Do you think the growth opportunities in HPAPIs and bioconjugates justify the expensive investment required in specialised containment and manufacturing technologies?

Yes, we do. We have recently made quite a number of investments, so as an organization we absolutely do believe that the opportunities justify the expenditure. We are already working with a number of technology innovators in that space which is an important part of justifying the long term commitment and investment. We have also seen that our smaller scale capacity is already filling up nicely which furthers this justification.

Looking ahead five years from now, how do you see the market for HPAPIs and bioconjugates evolving?

I see nothing but upsides. The bioconjugate area, in particular, is in the early stages of technology development, so it is going to be critical that over the next few years we start to see some successes in that area. Seattle Genetics has submitted a biologic license agreement for brentuximab vedotin, and this could be one of the first potent drug–antibody conjugates on the market.

I believe the next few years will be very telling; there is a high degree of confidence that these conjugates are going to be successful. I think that almost every major pharmaceutical company has taken a licence to, and invested in, this type of technology. That is a pretty strong endorsement that the major pharmaceutical companies believe ADCs are going to be an important technology over the next few years.