Document VjVgeD0aD4Z5ZJ764DpvvmL0j

mit kaltem und warmem i, 7.. B. Serum, die Kerze?, tr. in l% iger IIC1belassen der Filter bei der mech.v m eine Prfung auf Ri. xlcr S e r r a t i a inarcesauf Keimfieiheit. Diese* (mm Hg) eimittelt unc \Vas>er ber-chichtetei Einzelheiten s. K noll,II. eld-Filter gilt in vieler! ein starkes Adsorptions lehnet: P o re n -a tn n > 4.8 1 4.7--3.6 < 3.5 .konsteiilisator mglich ,^ 3 2 Prfung auf Bakfenend'chfigkeil A) Biologische Methode: s. unter 3.2 2.3., S. 40. b) Bl.i'Oiunethode: Die Filteikerze ist in Oidnung (bakteiiendicht). wenn in n<fefeuclitetem Zustand bei einem Luftdruck von 0,3 atni keine Luftblasen auftrefan (Hock, II Chem. Fabrik 3 [1930], 219). Die Entfernung pyrogener Stoffe durch Filtration Pvro^enc sind in der Hauptsache mikrobieiie Zellwandbe^tandteile, die bis zu etwa 90,, an die Zelle gebunden sind. Sie sind nur im Tierversuch nachweisbar (. S 491) Hei Temperaturen ber *2003C werden s'*e nach etwa 30 min zerstrt. Ihre Abtrennung durch Filtration setzt zunchst die Entfernung aller Bak terienzellen, auch der durch die Hitzeaterilisaticm abgetteten, voraus. Ferner pullte vorbeugend stets darauf geachtet weiden, da es in mikrobiell anflligen Injektiondu-ungen nicht zu einer Keimvermehrung und damit Pyrogenanhaufung kommt. Die strksten Pyrogenbildner sind gramnegative Bakterien, P.fedomonas-Artcn, E . c o l i usw., aber auch grampositive Keime und Viren spielen liier eine Rolle. Wahrend die ,,echten ` Pyiogene im Tierversuch bereits nach 30 min eine Tom|*'ratnreihdlning zeigen (Slandaidsuhstanz: das Lipopolvsaecharid Pyrexal der Firma ASTA, das am Kaninchen in einer Konzentration von 0,25 y Wirkstoff,' 0,5 ml Acpia dest. inneihalb 30 min eine Temperaturerhhung um 0.8--1.5CC hervorruft), hinken die Viruspvrogene nach und zeigen eist nach 1--2 Stunden ein* deutliche Fieberwirkung. Xach Sieoeut u. Mitaib (S.-B. Ges. Ford, ges N'.-tturwiss. [Marburg] 83, 1/ 2; 81, 1 [19GlfG2], 255) bestehen zwischen den Bak terien- und Viruspvrogenen eindeutige Unterschiede. Wahrend die ersteren von der Zellwand abtrennbar (lslich) sind und erst nach lngerer Zeit (30 min) U*i einem Erhitzen auf 200 C zerstrt weiden, lassen sich die letzteien nicht ton den Viruspartikeln abtrennen, werden aber durch Hitze leichter inaktiviert *ind sind durch Antikrper neutralisierbar Die Bakterienpyrogene sind nicht a^erdninpffliichtig trotzdem gehen bei der Destillation oft Stoffe mit ber, die gleichfalls eine um mehrere Stunden verzgerte Fieberreaktion hervorrulVn. Hierbei handelt es sich wahischeinhch ebenfalls um bakterielle Abbauprodukte, i* Amine und andeie stickstoffhaltige Verbindungen. Die Entfernung der an die Bakterienzelle oder deren gi obere Bruchstcke ge bundenen ILrog.'ne geschieht durch Filtration mittels Membranfilter (maximale iktn-uweite 2`iH n n ) (Schmidt. B., V. B las-. Z Hvg 112 j 1055 5G], 183, 298), ler Seitz-Kiltersclikliten (W ilkx, H., II E. Voss. Ar/.iicinuttel-For-oh. 1 K D R cd w ZU [i lkt ., I Abt. Orig IG11P `V>|, 37o) Weit m hwimger ^ i r , ta!tet m<h du* Besi Uigung der ,,freien" , teilweise gelosten Pyrogene. Diese D'HIhmi mir mit ndsorptiv unkenden Filtern, wenn notig walireml mehrerer Fdrratioii-vorg.kttgi*, entfernt werden. Am h hierbei spielt die Bela-tung-gien/.e fdi* v*i V<Uot ii uui-lhu lu* betragt it.o h Wu k i und Vos, fr 1*hhi( :ic Idiertlache [EkSJ etwa ihn 1*il t t i - luchten, die Zu-aminen-et/ung sonders der Prolcingchait) der 7,u behandelnden Lo-uug sowie deren Py- 41 rogcngdialt eine rnlM heulende Hollo. Wird diese Belastungsgrenze nl),.r. ehiitten. "o kommt es /u cmi'iii Duk lilmx li der Pyrogene In jedem sollten Yorver.suche die jeweiligen Verhltnisse Maren. im ..iigomeinen kann man sagen da sic h aus wrigen, ni< lit all/u vh !e Ihm humlekulare Stoffe haltenden Losungen al'c Pvrogene (bis zu 1 m u l) im Vollauf dei Entkeim ung tilir.mon onllm u-n lassen KuUmdr (Serum, Piolum- isw }, hoehvisknse L , 'ringen (PJa'onaev pander) miwic oImtII.k lienaklb e Stoib- (Saponine, zuge^et/Jr Kon-'i'tvierungsnutte} u^w ) hemmen den Pyrogcnndsoiptionsproze ganz ent scheidend. Mit ober tla. h.m klncn Stoffen lassen m. !i daiber hinaus sogar dr geringen Mengen der von der Fertigung her irr den Filtei>chichien enthaltenen Pvrogene ebneren. Diese geringen Pyrogenmengen knnen wegen der hohen adsorptiven Wirkung der Filtern luchten normalerw eise vernachlssigt werden Grte Sicherheit lu d et >n jedem Falle die Verwendung einer mglichst groen Filteiflache, und davon sollte, n u n, besonders hei Inlu.sionslosungen, stets Ge brauch machen. Dextranlosungen (MG ca 50000) lassen sich mit E K S hei einer Belastung von 500 l;ru2 ausreicliend enlpyrogenisieren. Schwieriger ist es bei Eiweihydiohsten Wahrend die durch Sauren gewonnenen Hydrolysate durch eine Doppelfillration mit illv S II ausreichend von Pyrogenen befreit weiden knnen, ge lingt dies bei den hhermolekularen enzymatischen Eiweispaltprodukten nicht. Hier hilft unter Umstanden eine Vorbehandlung mit Ionenaustauschern (z. B. Amberlite der Firma Rohm & Haas) weiter. In diesem Falle berlagert man die E KS-Filterschieht mit einer etwa 5 bis 10 cm dicken Austauscherschicht. Nach K uxtscheu, H., W. F ahrig lassen sich geloste Pyrogene bei einer Kon* zentiation von 10 bis 100 y 100 ml durch eine Filterschicht (Seitz-EK) von 100 cm2 und einem Durchlauf von 251 in ausreichendem Mae entfernen. Neuerdings hat sicli nach Angaben dei Scitz-W erke bei der Entpyrogenbicrung einer l % igen GanimaglobulinloMiug auch eine 5 orfiltration m it 5 Schichte 40X 4 0 A K S 4 (die etwa 5 mm dicken Schichten enthalten neben Zellstoffen und Asbestfasern als Genistaubstanzen zur Steigerung de Filtereffektes noch einen sehr hohen Anteil an feinatteiliger Aktivkohle und sind zum Schutze der Ablsung von Kohleteilchen m it kohledichtem Filtrierpapicr hinterlegt) und eine nachfolgende Entkeim ung m it 15 E K S-Sclnchten bewhrt. Die Untersuchungen von K ienholz, M. (Arzneimittel-Forsch. 14 [19G4], 1250} haben gezeigt, da 1 ui2 Seitz-E K S-Filteiflache ausreicht, um ca. 90 m3 Wa-^T (mit einem Pyrogengehalt von etwa 500 mg; zugesetztes E . coli-Lipopolysjccharid) pyrogenfrei zu filtrieren. 42 bi" i .,,-ul bl t -r <a. i i J M - .f b . 't 4 -' i, * <t : ij. f.i - . <i,- \ i }. - o ; >i* r i t*-'f Er*j . I D *fdnoiion d 1 > Hifi# * V*- i * dwfch t j U *. H. I. " *..r Vt (M., *' > <( \*t ! * 'f |,'4f * " >' '* M *<' V. rt* P -* * ` * -I s ) ' * n k'.Ul.' *1 1* -5M.1 , * * lur { bl X >i*, % *- w* rVk-`-f >*i \ - ` D - i TRANSLATION Section 3.3. Pages 41/4P from Sterilisation - Desinfektion - Konservierung -- Chemotherapie by Dr. K.H. Vfellhaeusser (Frankfurt/M. -- Hoechst) end Professor Dr. H. Schmidt ( ifebem b. Bern) ' WITHOUT OOMMITTMENT ' 3.3. The Removal of Pyrogens by Filtration. Pyrogens are, in the m i n , constituents of the cell walls of bacteria, of which something towards JOfo are bound to the cells. They can only be detected by animal experiments (see page 491). At temperatures over 200C they are destroyed in approximately 30 minutes. A pre-condition of their separation by filtration is the removal of all bacterial cells including those that have been killed by heat sterilisation. Further, steps must be taken with injection solutions that are sensitive to microbial infection to prevent bacterial reproduction and combined therewith, accumulation of pyrogens. The strongest pyrogen formers are the gram-negative bacteria, Pseudomonas types, E. coli and so on although gram-positive bacteria and viruses can also play a part. Although the "genuine" pyrogens can induce temperature increases within 3o minutes in animal experiments, the virus pyrogens lag behind somewhat and only show a significant fever effect after 1 - 2 hours. (The standard for control - Lipopolysaccharide Pyrexal prepared by "the ASTA Company causes in rabbits when used in a concentration of 0 . 2 5 effective substance in 0.5 ml of distilled water a temperature rise of 0,8 - 1.5C within 30 minutes.) According to Siegert and collaborators (S.-B. Ges. Ford. ges. Naturwiss. (Marburg) 83, 1/2; 84, 1 (1961/62), 255) there are significant differences between bacterial and virus pyrogens. Whereas the former can be separated from the cell wall (soluble ) and are only destroyed after heating for a longer time (30 minutes) at 200C, the latter cannot be separated from the virus particles, they are more readily inactivated by heating and can be neutralised by anti-bodies. The bacterial pyrogens are not volatile in steam but, nevertheless, substances are carried over on distillation which do result in a fever reaction, although only after several hours. It is probable that the products carried over are bacterial breakdown products such as amines and other nitrogenous ha.eed compounds. 1 Continued The removal of the pyrogens bound to the bacterial cells or fragments thereof can be effected by filtration through a membrane filter (maximum pore size 250 m micron) (Schmidt, B., V. Blass; Z. Ifyg. 142 (1955/56), 183, 298), or Seitz filter sheets (Wilke, H,, H,E, Voss: ArzneiraittelForsch. 4 (1954) 8; K.D, Rudat; Zbl. Bakt., I.Abt. Qrig. 164 (l955)> 370). The removal of the "free" partly solubl e pyrogens is far more difficult. These can only be eliminated by means of adsorptive action filters end, when necessary, By repeated filtration processes. The loading limit (the available adsorptive surface) is, according to pp Wilke and Vo8 for 1000 cm filter surface (EKS) some 2000m , the composition (and particularly the protein content) of the solution to be processed and the pyrogen content all play significant roles. If the loading limit is exceeded then the pyrogenB will pasB through. In any case proving experiments should be used to clarify the corresponding relationships. In general it can be said that with watery solutions which do not contain too much high molecular weight substances all pyrogens (up to 1 mg/l) will be removed in the course of the sterilising filtration. Colloids (serum, proteins etc.), high viscosity solutions (plasma substitute) as well as surface active agents substances (Saponins, preservation additives etc.) hinder quite significantly the pyrogen adsorption process. With surface active substances the small amounts of pyrogens remaining in the filter sheetB after manufacture can even be eluted out. These small amounts of pyrogens can normally be disregarded owing to the high adsorptive action of the filter sheets. The best safety measure is, in any case, to use the greatest possible filtering surface and this should always be done, especially with infusion solutions. Dextran solutions (molecular weight approximately 50,000) can be satisfactorily depyrogenised through EKS sheets at a loading of 500 litres per, square metre. Albumen hydrolysates are more difficult and whereas hydrolysates prepared by aoid hydrolysis can be adequately depyrogenised by double filtration through EKS?, this is not adequate for the'high molecular weight products obtained by the enzymatic splitting of albumen. A pretreatment with ion exchange resins (e.g. Amberlite ' of . Roehm & Haas) is of assistance. El this case the EKS filter sheet is covered with a 5/10 cm thick layer of the ion exchange resin. According to Kuntscher, H., W. Fahrig, the solublb pyrogens in concentrations ranging from 10 to 1C0j^100/ml can be adequately removed by filtration through a single sheet (Seitz--EK) of 100 cra^ surface and a volume of ?5 litres. -2 Continued wt According to a recent report from the Seitz--\brkeja 14;.. gammaglobulin solution a prfiltration through five sheets 40 x 40cm Grade AK$4 (these sheets which are some 5 nan thick contain in addition to cellulose and asbestos fibres as the basic structure a high content of very fine activated carbon to increase the filtration effect and to prevent the washing through of the activated carbon carry on the outlet side a suitable filter paper that will hold it up) and a finishing sterilisation with 15 EK3 sheets proved satisfactory. Investigations of Kienholz, M. (Arzneimittel-Forsch. 14 (1064), 1259) ~2 have shown that 1 m of Seitz EKS shdet is adequate to depyrogenise approximately 90 water with a pyrogen content of some 500 mg from added E. eoli-Lipopolysaccharide. GO/DHD 5.12.1973. 3 A BRIEF HISTORY OF THE U..X OF ASBESTOS BEARING FILTER IKDIA FOR THE CLARIFICATION AND STERILISATION OF BEVERAGES AND DRUGS INTRODUCTION The clarification and/or sterilisation of beverages and drugs by means of filtration is a process that has long been established in both industries. The main types of filter media that carry a content of asbestos and which are used for these operations are:- (a) Filter pulp. This material is prepared from cotton or wood cellulose and . normally carries up to 5$ of asbestos. This filter medium is utilised in what are classified as pulp filters. (b) Fibrous materials. Here there are two types. One is based on cellulose and asbestos, the cellulosic portion being derived from either cotton or wood pulp, with the asbestos content ranging from 0 to IOC(0 according to grade. The other is based on kieselguhr and asbestos, the maximum asbestos content being 50^. The first type is utilised in what are classified as alluvial filters and precoat or pressure leaf filters, whereas the second type only finds usage in pressure leaf or precoat filters. (c) Filter Sheets. These are based on cellulose, kieselguhr aid asbestos, the cellulosic portion being derived from either cotton or wood pulp. The asbestos content ranges from 0 to 5C5-*, according to grade. This type of filter medium is used in what are referred to as sheet filters and which are generically, flush plate or plate and frame filter presses. FILTER PULP This material, uhich may contain up to 5/ asbestos, is used in cake form. The basic pulp is supplied by the manufacturers in blocks and to form into cakes, suitable for use in the particular type of pulp filter in use, these blocks are disintegrated in water in a disintegrating/washing unit. The blocks supplied by the manufacturers are pure cellulose and it is customary to add the requisite amount of asbestos after disintegration in water. The usual addition 1 is 2-fi, the normal maximum and, for certain special applications, up to 12-j^. When the two components - cellulose and asbestos - have been thoroughly mixed in the disintegrating/washing unit, the requisite volume of suspension is drawn off into a forming press, the water drained off by gravity and pressure, thus forming a filter pulp cake some 2 inches thick and in a format to suit the specific pulp filter in which it is to be utilised. At the end of each cycle the exhausted cakes are removed from the pulp filter, broken up and washed in the disintegrating/washing unit, during which period the material is freed from the impurities that it has filtered out from the product that was filtered. Additionally there is some loss of asbestos fibres and it is standard practice at the end of each washing cycle, to add -J/l$5 of asbestos, to maintain the asbestos content at the desired level. Developed towards the end of the 19th century, with first patents being taken out in the 1890's, pulp filters rapidly achieved popularity in the brewing trade and, by the first decade of the 20th century, were referred to in text books on brewing as standard items of equipment for beer filtration. During the first two decades of the 20th century the use of filtration for bottled beers and, for the filtration of draught lager beers presented in cask, became standard practice in the brewing industry throughout the world, with the exception that certain types of bottled beer that traditionally underwent a secondary fermentation in bottle continued to be bottled without recourse to filtration and, in the United Kingdom, draught beers continued to be presented to the public in an unfiltered condition, clarification being effected by fining with isinglass. In other words, by the 1920's, for practical purposes all the beers produced and consumed, with the exception of a small percentage of bottled beer and the cask beers presented in the United Kingdom, were clarified by passage through this asbestos bearing filter pulp. In the 1930's following the introduction of pressure leaf or precoat filters and sheet filters there were new developments for the processing of beers, all based on two stage filtration, the alternatives being:- (a) First filtration through pulp filter and second filtration through sheet filter. (b) First filtration through precoat or pressure leaf filter and second filtration through sheet filter. (c) Both first and second filtration through sheet filters. In the United Kingdom there was another development which also resulted in an increase in the volume of beer filtered i.e. the introduction of metal casks to replace the older wooden casks - now generally referred to as kegs - and which were used for the presentation to the public of carbonated filtered beers. Such beers were filtered by one of the systems specified above. It is therefore reasonable to suggest that by the end of the 1930's the bulk of beers produced throughout the world were filtered through asbestos bearing filter pulp with a relatively small percentage going through precoat or pressure leaf filters and with a fair percentage receiving their second filtration through filter sheets, also an asbestos bearing filter medium. Pulp filtration also found applications in the production of spirits and more especially, Scotch whisky, where it became one of two generally accepted methods of clarification by filtration, the other being the use of alluvial filters using fibrous materials. There is still limited usage of both methods in the production of Scotch whisky today, although the bulk - as with other spirits such as brandy, eau-de-vie, vodka and so on - are now clarified with the use of filter sheets. Pulp filtration found but little use in the preparation of drugs. FIBROUS MATERIALS The fibrous materials based on a mixture of cellulose and asbestos were developed in Germany towards the end of the 19th century, and were first used in that country on a commercial scale in 1887. The alluvial filters in which they were used were readily accepted by the wine and spirit trade, fruit juice and soft drink producers as well as by drug manufacturers. By the turn of the century they were in use on an appreciable scale in all wine and spirit producing countries and this development continued at an accelerating pace. The 1920's saw a vast expansion of usage and a similar technical development to that described for pulp filters - the introduction of two stage filtration, following the development of filter sheets and sheet filters, so that coming into the 1930's, it iB reasonable to say that wines were being processed, at the filtration stage, by one or other of the following methods:- (a) Alluvial filter using fibrous material followed by sheet filter, using filter sheets. (b) Centrifuge followed by a sheet filter dressed with filter ' sheets. 3 (c) Two stage sheet filtration, using coarse and fine grade clarifying sheets or, as an alternative to the latter, sterilising sheets. There were similar developments in fruit juice, hut more detail is given in the next section. Over the past 20 years there has been a fall off in the use of alluvial filters, although two stage filtration has been maintained, the alluvial filters being replaced by precoat or pressure leaf filters. The fibrous materials based on cellulose/asbestos mixtures were also used on a considerable scale for the clarification of drug preparations, typical products processed being simple syrup, tinctures, extracts, medicaments and lotions and, although perhaps a little bit outside the drug field, cosmetic preparations such as perfume, eau de colognes, hair washes, shampoos and so on. The second type of fibrous material referred to - based on kieselguhr and asbestos - finds its application in precoat or pressure leaf filters. It has come into general usage in these filters over the past 15 years and their main application is in the brewing industry, where particularly in America, they are used on a considerable scale. They also find application for clarification of drugs. FILTER SHEETS This type of filtering medium, supplied ready made by the manufacturers, is based on cellulose, asbestos and kieselguhr. For special applications additives may be used to achieve a specific effect, typical examples being activated carbon to clean up the palate and colour of sugar syrup solutions used in the manufacture of soft drinks and nylon or polyvinylpyrrolidone powders, used where it is desired to reduce the anthocyanogen content of a beer and so improve its shelf life. The asbestos content ranges from 0 to 50ji. This class of filtering material stud the filters in which used - sheet filters - were both developed in Germany well over 50 years ago, the first major application being for the clarification and sterilisation of water for use ty armed forces in the field, the initial supplies being made in 1917* Today filter sheets are manufactured not only in Germany but also in the United 4 States of America, Great Britain, Hexico, Argentine, Australia, India, South Africa, U.S.S.fi., Poland, East Germany, Austria, Prance end Spain. The sheet filters in which they are used are made in all these countries and in a number of others as well. ' Filter sheets, the filtering effect of which can be varied by changes in composition and in the methods of working up the constituent raw materials, are available in a wide range of porosities. The coarsest, when treated with wet strength agents to give washing characteristics, are used purely and simply as support for a filter aid such as kieselguhr. Then come a whole range of clarifying filter sheets, varying from coarse to fine clarification and finally sterilising sheets which are suitable for the sterilisation by the simple process of filtration of the most varied liquids. Indeed, there is one very specialised application in the drug field which is of considerable importance - depyrogenisation by filtration. Although originally developed for the production of potable water for the German fighting forces, sheet filters and filter sheets gained rapidly in popularity for many filtration tasks in the decade following the conclusion of World War I. In the production of drugs they offered certain technical advantages and came into general use for clarification of the most varied products -- a far wider range than that given under the previous heading - and, even more important, for the sterilisation of drugs, especially those of a thermolabile character where heat sterilisation cannot be used as it causes undesirable changes in the product itself. Apart from preparations for oral or external application such as already specified, filter sheets found ready application for both clarification and sterilisation of intravenous end intra muscular injections, vaccines, antitoxines and salines. Continuing in the drug field, the standard process for the sterilisation of "synthetic" blood plasma based on dextran as well as blood plasma itself was based on the use of filter sheets and it continues to be a standard method of sterilising these products. In the years following World War II there have been further developments in this area e.g. the separation of blood protein fractions and again, the process has been based on the use of filter sheets and it continues to be a standard method of production of such preparations. Another major area in the drug field where sheet filters have been used on a major scale is in the production of antibiotics, where the use of filter sheets for both clarifying and sterilisation may almost be described as 5 "axiomatic". To summarize with regard to the use of sheet filters in drug manufacture, it is reasonable to say that filter sheets have now been in commercial use on an ever increasing scale for the sterile filtration of intravenous and intra muscular injection preparations for something over 50 years and that blood plasmas and antibiotics, which have cone into general use in the past 25 years are, for the most part, passed through sheet filters for the essential operation of sterile filtration. In the production of wines, these filter sheets, which first became available after World War I, gained rapidly in popularity for two major filtration tasks - clarifying filtration during the course of maturation and polishing and/or sterilising filtration at the bottling stage. By the late 1930's the system had become accepted as a modern method and its use was wide spread, as can be judged from the list of countries in which filter sheets are manufactured, throughout the world. Post World War II the use of filter sheets for the final filtration of wines and spirits at the bottling stage has become standard practice. Indeed, there was a time when the same comment could be made with regard to clarification of wines during their maturation but here there have been technical changes, for the necessary clarification at this stage in the development of a wine is now generally carried out on precoat or pressure leaf filters. It is no exaggeration to say that in Europe and in many other wine producing areas, that the final filtration of wines and spirits at the bottling stage is an operation that is almost universally carried out on sheet filters dressed with filter sheets, this position gradually having been attained over the past 50 years. The decade after World War I saw a major development in the methods of producing non-alcoholic fruit juices. This was the introduction of two Bystems, both hinging on the use of filters, for the clarification and then the sterilising filtration of the product. These systems, known as the "Seitz cold process" and the "Seitz--Boehi" process make use of alluvial filters using fibrous materials for the clarifying filtration and sheet filters using filter sheets for the sterilising filtration. Major installations based on these systems were made in Germany, Switzerland and South Africa, to mention but three countries where production runs into many millions of gallons annually. In other words, non-alcoholic fruit juices produced by the methods just specified and both using asbestos bearing filtering media, have been on the market on an ' ever increasing scale for some 50 years. 6- - The introduction of filter sheets some 50 years ago also resulted in changes in the methods of handling the basic raw materials used in soft drink manufacture - water, syrup and essences or extracts. During the various stages of water treatment associated with the production of many soft drinks, filtration is an important, indeed, essential operation. Clarification is in the main, through filter sheets whereas sterilisation is sometimes achieved by chemical means i.e. chlorination or alternatively, by sheet filtration. When chlorination is used it is customary to pass the processed water to a carbon filter to eliminate excess chlorine and finally through a trap filter - usually a sheet filter - to eliminate any carbon that may have become dis entrained from the carbon filter. It has long been standard practice to filter the syrups according to the particular type of soft drink and the quality of the sugar. Dependant on the nature of the requirement filtration will be through a filter paper, a clarifying filter sheet or a special type of filter sheet carrying carbon as an additive, where it is essential to remove all colour and any off flavours. It is not unknown to resort to sheet filtration for the sterilisation of the syrup if it is produced by the "hot" system. The essences and extracts, where clarification is required, are normally processed through filter sheets. All these filtration tasks in the soft drinks industry have been practiced and continue to be practiced on an ever increasing scale over the past 25 years, with some of them - such as the clarification and sterilisation of water and the clarification of syrups, being used on quite an appreciable scale since the 1920's. In the brewing trade the availability of filter sheets after World War I revolutionised the methods of beer filtration. The pulp filters that had previously been used were either replaced by two stage sheet filtration or augmented by single stage sheet filtration, so that by the late 1930's, a high proportion of the beers produced in Europe, to mention but one major beer producing area, were passing through filter sheets. Post World War II the use of sheet filtration for the final polishing of beer, be it for presentation in bottle, in cask or in keg, became standard practice, the exception to this generalisation being the United States of America where they found only limited application, mainly due to the fact that at that time there were not sheet filters available with adequate flowrates to meet the demands of the high production packaging units in use in the American brewing industry. Techniques have indeed changed over the past 25 years for pulp filters have now been more or less completely disgarded, being replaced either by sheet filters or, alternatively, precoat or pressure leaf filters. This latter 7 development has been followed on a considerable scale in the United States of America. To stun up, it can be said that with the exception of the U.S.A. where sheet filtration has never been used on a major scale, the greater portion of the filtered beer offered to the consumer has for the past 25 years and to a lesser extent for the 25 years prior to that, received its final filtration through filter sheets. Turning briefly to spirits there has in the post World War II period, been a major change, as for practical purposes, pulp filters and alluvial filters have been completely replaced by sheet filters, with a relatively small usage of precoat or pressure leaf filters. ASBESTOS TYPE It is well worth recording that, as far as is known, all manufacturers of the various asbestos bearing filter media to which reference has now been made do not make use of the crocidolite type which has been specifically referred to in technical publications as a possible cause of gut cancers such as mesothelomias. Only the chrysotile type is used which has relatively low resistance to acid media and which, in contact with gastric juices, is subject to leaching out of its megnesium resulting in the degradation of the fibre itself into something approaching a hydrated silica gel. PARTICLE MIGRATION It is acknowledged that with all the filter media described there can and will be some migration of particulate matter from the medium itself into the filtered product. For this reason it has become standard practice to use some form of trap filter after the main filter, to ameliorate the position. Such trap filters range from simple equipment making use of fine silk as the straining medium, through ceramic candles to sintered glass or sintered stainless steel cartridges and they certainly eliminate visible particulate matter. Indeed, in some countries, the use of such trap filters is incorporated in the codes covering production of drugs and pharmaceutics. Also, for the past 15/20 years, leading sheet manufacturers have been applying a bonding agent to the outlet side of such filter sheets which effectively stop migration of visible particulate matter. 8 STATISTICS. In view of -the long history of asbestos bearing filter media in the production of beverages and drugs, the follovfing tables set out statistics covering on a world and country basis, the production figures under various headings - wines, spirits, fruit juices, soft drinks and beer - for consideration in relation to the incidence of cancers and the consumption of beverages. STATISTICS TO FOLLOW WHEN AVAILABLE GO/DMD 4-1.1973 B E B R - ANNUAL PRODUCTION WORLD WIDE Year 1953 1963 1971 Total (1,000 hectolitres) 308,800 450,700 657,669 . U. S. A. 1953 1963 1971 106,111 114,943 149,462 United Kingdom 1953 1963 1971 40,888 46,315 56,694 German Federal Republic 1953 1963 1971 26,677 59,156 90,029 W I N E - ANNUAL PRODUCTION WORLD WIDE N Year Total (1,000 hectolitres) Average Average Average 1934/1938 1949/1951 1959/1961 1970 202,600 193,413 236,573 289,227 F R U IT JUICES WORLD WIDE Year Average 1956/1960 1965 1970 - ANNUAL PRODUCTION Total I k 000 hectolitres) 21,415 27,859 35,400 / S O F T D R I N K S - ANNUAL PRODUCTION UNITED KINGDOM YEAH 1958 1959 i960 196I 1962 1963 1964 1965 1966 1967 1968 1969 1970 1971 Concentrated Soft Drinks Unconcentrated Soft Drinks Ready to Drink Equivalent i U l 0 u s a n d G a l l 0 n s1 27,599 38,786 40,103 43,400 39,800 42,600 51,400 50,700 54,700 61,500 60,400 66,400 72,100 69,800 193,831 227,382 215,136 230,100 209,100 210,300 237,800 236,300 244,100 249,000 253,000 262,200 267,800 274,000 331,826 421,312 415,651 448,300 409,000 423,000 495,000 490,000 518,000 556,000 555,000 594,000 629,000 623,000 EUROPEAN COUNTRIES Austria Belgium Denmark Finland. France Germany Holland Italy Norway Portugal Spain Sweden Switzerland 1966 1261 1968 (Mill ion 161 176 188 435 466 447 179 187 190 107 120 119 640 697 716 1983 462 1005 102 2147 523 958 109 2244 526 1200 130 30 1544 259 203 .33 1621 257 224 57 1734 ' 280 229 1969 1970 1971 litres) 210 505 201 142 833 2540 632 1400 146 63 293 245 270 489 208 183 890 2859 694 1200 157 87 1490 294 242 298 530 220 183 960 3250 771 1260 175 100 293 281 (H xp resseJ i 'i o rig in \ 1 n ro o f rralo: ill). UNITED KINGDOM Year Total 1938/1939 29,223,556 1946/1^9 1059/1960 30,872,270 74,208,667 1969/1970 152,273,000 P O T A B L E S P I R I T - CONSUIT':i'IOII (Expressed in original proof frallons) UNITED KINGDOM " Year 1938/1939 1948/1949 1959/1960 I969/1970 Total 17,394,079 14,508,756 33,432,180 76,895,752 go/dkd 9.1.1973