In any industrial fermentation process, it is vital to carry out strain improvement in order to maintain a competitive edge. It is well-established that the best way to reduce production costs is to increase the titre of the fermentation product, which results in space and cost-savings (no need to build additional fermenters) and improved extraction and down-stream processing efficiency due to having a more concentrated broth.
A certain amount of titre improvement can be achieved by process development alone, but eventually the genetic limit of the microorganism is reached (maximum level of expression) and further improvements can only be achieved by increasing its genetic potential by mutation and selection.
CONTRACT OUT OR WORK IN-HOUSE?
Strain improvement is not a trivial activity and to carry it out efficiently involves the application of a wide range of techniques which need to be carried out by trained specialists. The decision whether to do the work in-house or to contract it out depends on a number of factors.
If a company has a trained, in-house group of scientists and technicians, with experience of working on similar projects previously, then it is probably most cost-effective to do this work in-house. However, even if such a group exists, there may be an argument to contract it out if the group is already fully-committed to other projects.
If the company does not have such a group, then it seems on the face of it that the work should be contracted out. However, even if the work is contracted out, the results eventually have to brought in-house for implementation and at so least a small in-house group with relevant training will be required.
CONTRACTING OUT – ADVANTAGES AND DISADVANTAGES
One obvious advantage of contracting out the strain improvement work is that it will (hopefully) be carried out by specialists who are trained in the field. However, there is often a problem of communication if the contract research company (often academically-based) does not understand or appreciate the industrial aims of the client. To overcome this problem frequent liaison between the contract research company and the client company is required, at the bench level (not at the managerial level).
Another advantage is that the contract research company will or should have all the necessary equipment and facilities for carrying out the work. But herein lies the second problem. The contract research company, by its very nature, has to use generic platforms to accommodate the requirements of a variety of clients and therefore they are unlikely to be able to replicate the exact conditions of any one client. As I have pointed out in other papers in this series, if mutants are not screened under the same conditions in which they are intended to be used, this will result in the selection of false positives i.e. strains which show improvements under the specific limitations of the screen, but not under industrial production conditions. This leads to the problem of what I call horizontal transfer (scale-up being vertical transfer) and which also occurs when established processes are purchased from technology suppliers. This problem is made worse by the fact that the raw material medium ingredient supplies and the water of the contract research companies and technology suppliers are likely to be different from those of the client company.
ON-SITE CONSULTING IN HOUSE – MAINLY ADVANTAGES
Strain improvement using an on-site consultant eliminates these problems. If the strain improvement work is carried out at the site where it is intended to use the improved strains commercially, there will be no problems of horizontal transfer and (if the proper advice is given) minimal problems with vertical transfer (scale up).
Even if the client company does not have an existing in-house group, it should l give consideration to creating one. As I pointed out above, at least a small group will be required anyway for in-house implementation of outsourced work. Given this, it makes sense to create a slightly larger group which can carry out all the work themselves. This group need not be composed of highly qualified or fully-trained strain improvement experts, because they will receive on-the-job training as consequence of the consultancy.
Hiring an on-site consultant will be very much cheaper than using a contract research laboratory, as the consultant will have minimal overheads. The only additional costs incurred by the client will be some equipment costs, if it does not already have suitable facilities, and as I mentioned above, hiring some additional staff.
My experience has shown me that although there may be occasions when an argument can be made for contracting out strain improvement work, on balance, on-site consultancy is much cheaper and more effective, as well as providing additional benefits such as staff training.