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PrepLC eNews

A Look into the Trends happening in Contract Manufacturing Organization's from Corden Pharma Colorado

Dr. Brad DeHoff is the Director of Technical Development and Process Support (TDPS) for Corden Pharma Colorado. With a PhD in Synthetic Organic Chemistry from the University of South Carolina and additional post-doctoral experience from the Université de Montréal, Dr. DeHoff began his career with Syntex more than 22 years ago as a Senior Chemist working in process research. Dr. DeHoff advanced to the level of Distinguished Scientist and assumed increasingly responsible assignments as Global Supply Leader for Fuzeon, Small Scale Production Manager, Technical Manager of Chemistry and Head of Development and Supply Projects before becoming R&D Director. As the Director of R&D, Dr. DeHoff oversees a technical staff of approximately 35 organic chemists, analytical chemists, process engineers with responsibility for Corden Pharma Colorado’s process development, process optimization and process support activities.

Phenomenex:
Could you please explain the various preparative chromatography techniques that Corden Pharma is able to offer its customers?

DeHoff and Staff
Our expertise lies in reverse phase chromatography, but we also use ion exchange and normal phase chromatography at Corden. Implementation of other techniques such as HILIC or embedded polar phases awaits a project requiring these techniques. Corden Pharma Colorado has both high and low pressure systems for purification and concentration/capture steps at some of the largest scales available in the peptide industry.

Phenomenex:
In which technique do you see most interest and growth?

DeHoff and Staff
At Corden Pharma Colorado, large scale preparative reverse phase chromatography is the most requested technique. However, the ability to perform large scale chiral separations is an area that has been getting a lot of attention in the recent years.

Phenomenex:
Often chromatography is considered the "last resort" after all other purification approaches have failed. Which role does preparative chromatography play in your strategy planning when you start a new project?

DeHoff and Staff
This is dependent on the type of target molecule that a customer has requested. If it is a peptide, then preparative chromatography is an integral part of the synthetic design, while in small molecule projects, crystallization for purification is the preferred strategy. At the end of the project analysis, the most cost effective strategy which yields high quality becomes the route of choice.

Phenomenex:
Presumably as a response to the economic recession some major pharmaceutical companies have closed some sites or labs with preparative chromatography capabilities for cost saving measures. Do you think that will lead to an increased outsourcing trend for chromatography services and how will this affect companies like Corden Pharma? Is there a shortage of prep chromatography capacity available for outsourcing?

DeHoff and Staff
This is an excellent observation. We have seen an increase in requests for prep chromatography services. Corden Pharma Colorado believes there is a shortage of very large scale industrial purification capacity.

Phenomenex:
There are a limited number of companies in America and Europe offering preparative chromatography services under cGMP conditions. Do you see cGMP competition increasing from countries like China?

DeHoff and Staff
We do not see competition from India or China for large scale chromatography services, particularly under cGMP. In fact, a large company based in India approached us for large scale chromatography services.

Phenomenex:
Which industry are you seeing the most growth, Pharma, BioPharma or Food and Bio-industries?

DeHoff and Staff
For Corden Pharma Colorado, our growth is in the Pharma area with BioPharma as an up and coming sector.

Phenomenex:
What do your customers expect from a stationary phase manufacturer in terms of availability, choice of phase, delivery time and financial stability?

DeHoff and Staff
Our customers expect us to manage the sourcing of the stationary phases so our expectations are as follows: 1. We prefer that the phase be kept in stock at the manufacturer. 2. We choose high quality phases that we expect to last for multiple batches/campaigns. 3. Minimal delivery time is preferred. 4. We prefer to deal with financially robust suppliers who are capable of handling the vagaries of the market and have the production capacity to respond to large orders. 5. We want our suppliers to continue manufacture existing products going forward as this minimizes the need for us to redevelop a process which occurs when a phase is discontinued.

Phenomenex:
Compared to reversed phases, there are relatively few chiral chemistries in use at preparative scale. Do the chiral stationary phases which are available on the market satisfy the customer needs in terms of variety?

DeHoff and Staff
In our experience, it isn’t necessarily a lack of variety but the high expense associated with chiral phases due to their specificity. Having said that, we have seen examples where the throughput of a chiral separation was not as high as needed for commercial viability. As more companies get involved in the chiral chromatography business, perhaps the prohibitive cost will come down.

Phenomenex:
What major purification cost cutting efforts do you think corporations will employ in the coming years?

DeHoff and Staff
The longevity of stationary phases will become more critical as a way to cut costs while performing large scale chromatography. Regeneration of phases is already part of our development process in an effort in increase the life of a packed column. Solvent recycling and recovery also plays an important role in keeping costs down. There will be a greater push toward using the highly automated chromatography systems to reduce labor costs.

Phenomenex:
Phenomenex has recently put a lot of resources into a new group called “PhenoLogix” which offers phase screening and method development. How do you rate the significance of such services to a company like Corden Pharma?

DeHoff and Staff
Phase screening services simply makes sense. It gives companies like Phenomenex the opportunity to show the selectivity and advantage of their many column phases, while providing much information to the customer about potential chromatography options. Phase screening is an efficient way to improve turnaround on a new project to give CMO/CROs the head start in their development. By using a service like “PhenoLogix”, it frees up valuable development time early on in a project to spend on other critical aspects of the project.

Phenomenex:
If you were to write a wish-list to manufacturers of the various types of stationary phases used in different modes in preparative chromatography, where do you see the most potential for improvements and which new phases would help you achieve your purification goals?

DeHoff and Staff
Most new peptides possess significant hydrophobicity and may be aggregation prone during processing. Because of this we would like to see more phases with reduced hydrophobicity as these phases induce less aggregation of hydrophobic peptides. In addition, having pH range flexibility and the ability to regenerate the phases to improve the lifetime of the column would be helpful in large scale preparative chromatography.