Downstream Processing

6.5.3. Downstream Processing

The downstream processing is solely related to the extraction and purification of the desired end-product from the bioprocess based on the skills of bioscientists, chemists, chemical engineers, and process engineers.

The very design and absolute efficient operation of downstream processing methodologies es- sentially include two important aspects, namely :

(a) Vital elements in getting the required products into viable commercial usage, and (b) Reflect the need to lose more of the desired product than is absolutely necessary. Example : Humulin (R) [Eli Lilly, USA] ; Insulin : More than 90% of the 200 staff members are actively

engaged in the various recovery processes. Obviously, downstream processing of biotechnological processes truly represents a major portion of the overall costs directly involved in most processes, but at the same time is also the least glamorous aspect of biotechnology. Summararily, any improvements rightly afforded in the downstream processing would certainly benefit the overall efficiency and exhorbitant costs of processes.

The various stages of ‘downstream processing operations’ are as stated below : Stage I : Separation — Filtration — centrifugation — flotation — disruption ; Stage II : Concentration — Solubilization — extraction — thermal processing — membrane

filtration — precipitation ; Stage III : Purification — Crystallization — chromatographic methods ; Stage IV : Modification — Structural analogs ; Stage V : Drying — Under vacuum — spray drying — freeze drying — fluidised — bed drying ; Salient Features : The salient feature variants of the downstream processing are as enumerated

under : (1) Initial separation of the bioreactor broth into a liquid phase and a solid phase, and subse-

quent concentration and purification of the product. (2) Processing comprises of at least five stages as described above. (3) Methods either proposed or in use usually range from two extremes i.e., conventional to

almost mysterious that may predominantly comprise of such well-known techniques as : distillation, centrifugation, filtration, ultrafiltration, solvent extraction, adsorption, reverse osmosis, molecular sieves, selective membrane technology, electrophoresis, and affinity chromatography.

ANTIBIOTICS

225 Special Note : In fact, it is in this particular domain wherein a plethora of reasonably

potential industrial applications of latest developments in biotechnology have virtually come to grief or rendered problematic by virtue of the following two important draw- backs, namely :

(a) extraction failed to achieve the ingenuity of the designers, and (b) extraction procedure has virtually consumed so much excessive energy-input as to render it

almost uneconomical. It has been a practice to ascertain the final product of the ensuing downstream purification stages

to possess some degree of stability for the ultimate commercial distribution. However, stability may be best accomplished for a wide range of products by affording some form of drying, for instance : freeze- drying, spray-drying, fluidised-bed drying. The method of choice is solely dependent on product quality and cost-effective measures.

Dry-form products : include — antibiotics, amino acids, organic acids, polysaccharides, single- cell proteins, enzymes etc.

Liquid-form products : include — products which cannot be dispensed conveniently in a dried form. Proteinacious products : to avoid possible changes of ‘denaturation’.

In general, special precautionary measures need to be taken 80 as to avoid any scope of either deterioration or microbial contamination.

Highlights of Downstream Processing : Operations indulging in downstream processing do possess quite a few outstanding features, namely :

(1) It gives rise to several challenging and demanding aspects of a wide spectrum of biotechnological processes.

(2) Hallmarks of most high value biotechnological products are solely based upon their purity and stability.

(3) Ultimate success of a wide range of biotechnological processes shall entirely depend upon the correct well-defined area of choice and modus operandi of such established systems.

(4) The commercial-scale operative measures will solely depend upon the economic viability/ feasibility without the least compromise on the final end-product ; and for this the utmost understanding and cooperation should always prevail between the ‘bioscientist’ and the

‘process engineer’.