- 29 March 2007 -

Fine chemical filtration: Defining filtration processes

Where does filtration fit into the production of fine chemicals and pharmaceuticals? Ken Sutherland looks at the various processes available.

Life science applications for filtration and other separation equipment are a category of the fine chemical sector, as far as the Standard Industrial Classification is concerned. The SIC is rather quiet about what the modern world regards as life science applications, with no reference to "biochemicals" even in the 2007 revision (which is not intended for use until 2008).

The "fine chemical" classification is not easily made. The manufacture of basic pharmaceutical products and pharmaceutical preparations must be included (this has an SIC Division to itself, number 21), but what to include from the previous Division, "Manufacture of chemicals and chemical products" is less clear. Taking "fine chemicals" to mean chemical materials made in smaller quantities, then the further coverage in this article is of the manufacture of:

. dyes and pigments;

. pesticides and other agrochemicals;

. paints, varnishes and similar coatings, printing inks, mastics and sealants;

. soap and detergents, cleaning and polishing preparations, perfumes and toiletries;

. essential oils;

. explosives;

. glues and adhesives, and gelatine and its derivatives;

. photographic materials and chemicals; and

. other specialty and performance chemicals.

Industrial gas production should probably be included, but is not, because the main process is a bulk one. Still (incorrectly excluded, obviously incorrectly, are the wide range of processes, many as yet mainly experimental, which come within the realm of biotechnology. These include the large and rapidly growing production of ethanol and similar products, as fuels or raw materials, by the fermentation of starch and other substrates, together with the vast and continually expanding range of fermentation processes for other products. The manufacture of genetically modified food and crop materials is an important, if contentious, component of this sector, as are the legion of special biologically active materials, and the biological routes to established products.

In all of these processes, the great majority of them carried out in the liquid phase, the process use of filtration (and, to a much lesser extent, sedimentation) is widely found, as a solid recovery step, or in purifying ingredients, intermediates or final products, and in the recycling or treatment of waste streams.

The equipment market

The total chemicals market - bulk, fine and pharmaceutical - will make up about 16.4% of the global filtration and related separations market in 2007, of which the fine and pharmaceutical component will be close to 40%, or an estimated US$1435 millions. This is one of the fastest growing sectors of the global marketplace for filtration equipment, employing a very wide range of production processes, from simple chemical syntheses to complex drug production. The range of process needs for filtration equipment is similarly wide, and in many cases vital to the manufacturing process.

Growth rates have been high in all parts of the sector, and especially the pharmaceuticals industry, and are expected to continue, thus making it a good market for filters and related equipment. The fine (or speciality) chemicals component is a strong one, with many major chemical companies moving into the business. Much of the component's sales volume is in niche markets, with strong demands, so that this part of the sector presents a good and growing market.

Equipment characteristics

Working with relatively small production quantities has already been identified as a characteristic of the fine chemical and biotechnology sector. Largely as a result of this, the fine chemical and pharmaceutical industry is a major user of batch processes, with their need for accurate transfer of liquid reagents and products, and thorough cleaning between batches. The equipment needs in this sector combine the wide range of processing conditions found in the bulk chemicals sector with the high production standards of the food and beverage sector, if not higher. The suppliers of this equipment have developed systems well able to meet these needs, but the development process needs to be a rapid one to keep pace with the developments in the sector.

Many pharmaceutical and biochemical processes handle quite toxic materials and need very clean work spaces for the production facilities. This creates a need for ultra-clean inlet air, but also for very good vent air filters to prevent the escape of toxic materials into the external environment. These may be just to separate dust particles, but may also be combination filters to remove gaseous impurities as well.

The key equipment developments needed here are the achievement of very fine degrees of filtration in both liquid and gas processing or containment. Much of the sector is strongly controlled by regulatory bodies, and better filtration of liquids and gases is a major component of such regulations.

Biotechnology

The biotechnology sector (the manufacture of chemicals and other products by biotechnical means - but excluding the production of beverages by fermentation) has two components: the steady production of a range of speciality chemicals by fermentation methods, and the very high profile bioengineering industry, which has invested huge amounts of money, but which, as yet, has made very little in the way of profits. When this component does start to produce profits, then the filtration equipment industry in general, and the membrane separation component in particular, will have a very exciting new sector to consider. Although biotechnology is included in the above numerical estimates with the pharmaceutical sector, it is worth noting separately, because of that future prospect, and because of its very distinct characteristics.

Biochemical production has at least the manufacturing standards of the food and beverage or pharmaceutical sectors, and usually higher ones. Its filtration processes can require exceedingly delicate handling, the quantities involved can be quite small, and the unit value of its products may be exceedingly high - such that absolute care in production and packaging is essential.

Many production processes, especially those producing the recently developed genetically engineered products, have not only sophisticated separation processes, but also vital need to be protected from invasion from the external environment - and for that same environment to be protected from the products of the contained process. All of this adds significantly to the tasks that require filtration equipment.

Among the more important developments in biotechnology are the production of enzymes as reaction promoters, and the use of enzymes in an immobilised state, using membranes as supports.

Biotechnology provides one of the major uses for pervaporation systems, which can be employed in the concentration of delicate by-products such as amino acids and enzymes, or the removal of volatile by-products.

Hygienic operation

One of the most important characteristics of the separation equipment used in the pharmaceutical sector especially is the need for it to be able to operate in a state of scrupulous cleanliness. Contact surfaces will normally be of polished stainless steel, and the whole equipment should be easily cleaned, preferable by some kind of clean-in-place process. The cleansing processes must allow sufficient residence time for the cleaning solutions to do their job. Design and fabrication must ensure the absence of square (rather than rounded) corners, dead ends and threaded joints in contact with process materials, while contact surfaces should be sloped so that liquids may drain from them. Care must be exercised for process materials that involve salt solutions, as these can attack stainless steel, so plastic or glass-lined equipment may be preferred.

Most of the operating processes in the pharmaceutical sector at least do not have to withstand the severe processing conditions found in some bulk chemical operations. Indeed the most severe operating parameters may well be those involved in steam sterilisation or an aggressive clean-in-place solution. However there are some parts of this whole sector where corrosion may be a problem, and some processes in the fine chemical sector perfectly mimic the bulk production processes in the severity of their operating conditions.

Solids recovery

A great number of pharmaceutical products are in solid form, and the final stage of the production process is thus likely to be a filter or centrifuge followed by a dryer. One of the simplest forms of filter, the nutsche, has been developed into a versatile processing device, which is capable of carrying out a precipitation reaction, filtering the precipitate by vacuum and then washing it, finishing with drying it either by a hot jacket or a through flow of hot air. Very well attuned to the needs of batch processes, the nutsche can be inverted to dump the dried solids into a collection vessel underneath it, after which the filter can be easily cleaned and made ready for the next processing batch.

In a similar way, the imperforate or perforate basket centrifuge is used to process the final slurry in a dyestuffs manufacturing process, allowing good washing of the accumulated solids, before discharge, and preparation of the centrifuge for the next batch. The nutsche filter and the basket centrifuge are available in a wide range of sizes to match the amount of slurry to be processed in each manufacturing batch.

Where the final product is in crystalline form, following evaporation and crystallisation, the perforate basket centrifuge is very commonly used to separate the crystals, although care may be needed in selecting the type of centrifuge to ensure as little damage to the crystals as possible in the separation process.

There are also many continuous processes within this sector, and the continuous vacuum filter is often used for the final separation - either a belt filter or a rotary drum design - in either case probably fitted with string or belt discharge to minimise damage to the solids.

The products of the pharmaceutical sector (and especially biochemicals) are often very valuable and it frequently pays to fit a fine filter or even an ultrafiltration membrane on the filtrate or centrate flows, to extract another fraction of solid product.

The broths resulting from fermentation processes provide a major application for separation equipment, most often the high speed separator (disc centrifuge). If the fermentation product is released outside the cells of the yeast or other ferment, then the cells will need to be separated from the product in solution. If the product is produced inside the cells, then these latter must be disintegrated and then the cell fragments separated from the finished broth. In either case, this is becoming a very good business for the centrifuge makers - in parallel with the similar process for bioethanol production as a fuel.

Liquid filtration

In almost all of the liquid processes in this sector, intermediate solutions must be filtered to avoid disturbance of a succeeding process stage. This has commonly been done in rotary vacuum filters, but the duty is increasingly being performed by membrane filters, with their ability to separate large molecules as well as fine particles.

For much of this sector, water can be an ingredient and its required purity is always likely to be better than that provided for drinking water. This means that influent water will probably require further purification, with Ultra-Pure water now being a regular demand. Ultrafiltration with membranes can achieve this degree of purity.

Although not often regarded as a filtration process, it must be noted that chromatography finds its most varied usage in the biochemical sector, especially with its ability to separate several different components identifiably from a solution.

The final waste streams from much of this sector - dyestuff or antibiotic - can be extremely toxic, and great care must be exercised in their treatment before disposal, to minimise their potential harm, and to maximise the recovery of value from them. Here, again, membrane systems are being used more and more to achieve the required degree of separation.

These steps can be seen, for example, in the production of citric acid by the fermentation of a sugar syrup. The prepared syrup must be filtered clear of impurities (in a rotary vacuum filter), and the broth after fermentation is separated from the cell fragments by a centrifuge or another vacuum filter. The acid is precipitated as its calcium salt, with the precipitate filtered and washed on a drum filter, before the salt is resuspended and acidified to precipitate calcium sulphate. This is separated and thoroughly washed in a two stage drum filter system, and the liquor is then evaporated, crystallised, separated in a basket centrifuge, and processed again in a vacuum evaporator, before a final centrifuge and dryer.

This sort of process can be found quite often in the fine chemical sector - salicylic acid en route to aspirin, for example, or insulin manufacture, or the production of antibiotics.