This article shows potential and practical imple-mentation of UV-oxidation for destruction of pol-lutants and micropollutants, like endocrine orantibiotic compounds in strong chemical andpharmaceutical wastewater. An overview of typicaltechnologies used for treatment of industrialwastewater with assets and drawbacks is given.Compounds that need to be oxidized in the des-cribed applications are 1,4-dioxane, EDTA, pyroli-dones, aromatics (phenols, toluene, …), VOCs, EE2,various Active Pharmaceutical Ingredients (API),surfactants and FOG (= Fat, Oil and Grease). Theexamples presented of UV-oxidation are located atBASF, Enva, Haupt Pharma, GSK, Merck andPharma Action. Besides photos of the installedUV-plants, flow rates, concentrations and oper-ating costs are listed as well. Understanding pos-sible reaction pathways and mechanisms de-scribed enabled Enviolet to develop optimizedprocesses and produce plants designed on base ofa single lab investigation.
Zusammenfassung
Dieser Artikel zeigt die Möglichkeiten und den prak-tischen Einsatz der UV-Oxidation zur Zerstörungvon Microverunreinigungen und Schadstoffen, wieendokrin oder antibiotisch wirksame Substanzen inkonzentriertem chemischem oder pharmazeuti-schem Abwasser. Ein Überblick zeigt die Vor-undNachteile typischer Verfahren für die Behandlungvon industriellem Abwasser auf. Die in den darge-stellten Anwendungsbeispielen abzubauendenInhaltstoffe sind 1,4-Dioxan, EDTA, Pyrolidon, Aro-maten (Phenole, Toluol, …), VOCs, EE2, verschiedeneWirkstoffe, Tenside und FOG (= fat, oil, grease). Dieaufgeführten Beispiele befinden sich bei BASF, Enva,Haupt Pharma, GSK, Merck und Pharma Action.Neben Bildern der installierten Anlagen werdenDurchfluss, Konzentrationen und Betriebskostengenannt. Reaktionswege und Mechanismen werdenbeschrieben, deren Verständnis es Enviolet ermög-licht auf Basis einer Laboruntersuchung optimierteProzesse zu entwickeln und anhand einer einzigenLabor Analyse Anlagen zu realisieren.
Introduction
This article presents a modern ap-proach for treating concentratedwastewater from chemical produc-tion, pharmaceutical productionand formulation directly at the placeof processing to avoid contaminatedsewage.
Micropollutants are getting moreand more into focus of public discus-
sion, especially those being endocrineor showing other problematic side ef-fects i. e. the development of resistanceand antibiotic resistant genes [1, 2].
These micropollutants are highlydiluted (anthropogenic) xenobioticsubstances from many different in-dustries and applications. Due totheir persistence, bioaccumulationpotential, and toxicity, it is necessaryto minimize their input into the sew-
age system and water bodies. Addi-tionally lipophilic xenobiotics mightbe adsorbed in sediments where theyinflict damage to sediment dwellingorganisms [3].
Potential emissions of micro pol-lutants into the environment may oc-cur by:. domestic wastewater polluted bythe patient
. hospitals wastewater
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. animal husbandry and veterinarymedicine
. industrial production of pharma-ceuticals
Usually domestic wastewater andwastewater from hospitals aretreated in sewage treatment plants(STP). Additionally in doctors’ sur-geries used drugs, especially contrastmedia are excreted by patients andlead to significant concentrations inSTPs. As these have no barrier formicropollutants, they are directlypassing into the water body or indi-rectly via sewage sludge used as fer-tilizer [4].
Veterinary drugs and their metab-olites can be found in the manure ofanimals and are washed into the soiland ground water or entering surfacewaters directly.
Due to GMP (Good Manufactur-ing Praxis) at least in Europe andNorthern America pharmaceuticaland chemical production sites havereduced their emissions of activesubstances dramatically in contrastto countries like e. g. India [5].
Considerable efforts are under-taken by companies following GMPregulations to meet requirementsand avoid any pollution and so besttechnologies are still required.
The growing concern about aclass of substances, which are sus-pected to interfere with the endo-crine system, has led to the first con-sequences on legal base. The com-mission of the European Union hasreceived an increasing number ofparliamentary questions since 1997on the following topics on pharma-ceuticals:. use and regulation of a range ofsuspected endocrine disruptingsubstances [6]
. investigation and prevention ofhormones and hormonal effectacting chemicals in the environ-ment
. antibiotics in aquatic environment[7]
Pharmaceutical wastewater treat-ment means that in general no recy-cling has to be taken into account, asthis would violate GMP rules for the
manufacturing of medicinal prod-ucts. An exception might be recover-ing and reuse of solvents, nitrates,etc. [8, 9]. Therefore, manufacturersneed to know how to deal with phar-maceutical wastewater and be awareof regulatory requirements.
A good example for the possibilityof recycle/reuse of residuals is fromproduction of x-ray Contract Media(CM) containing organic bound io-dine where iodide can be extractedfrom the solutions after incinerationor UV-oxidation [10] by gas scrub-bing. The recovered iodine can besold on the world marked [11].
There are (local) rules of dischargefor various parameters, that are de-fined by EPA (Environmental Protec-tion Agency, e. g.: USA, UK, Ireland …),EEA (European EnvironmentalAgency in Europe), SEPA (State Envi-ronmental Protection Agency, China)and by various institutions in manyother countries.
In the EU there are actually nobinding legal limits for APIs, but de-fining them is under process and ac-tually many manufacturers of APIsare tending to apply the PNEC (Pre-dicted No Effect Concentrations),where available, as future legal valueswill not be lower than those andWater Frame Work Directive is theactual common base [11, 12, 13].
Signif icance of micropol lutants and possibi l i t ies toprevent their emission into
the environment
Considering the consumption ofhuman pharmaceutics per year (e. g.2009) in Germany the followingclasses are the most important: Anal-gesics: 2 647 to, anti-diabetic med-ication 1310 to, antibiotics 571 to,x-ray contrast media 395 to.
In veterinary medication, anti-in-flammatories and antibiotics domi-nate the quantitative consumption,however due to their ecotoxicologi-cal or environmental significanceprescribed hormones deserve specialattention.
On base of ecotoxicological data,impact analyses have been carriedout to evaluate relevance of varioussubstances. Important parametersare PNEC and MEC (Measured Envi-ronmental Concentration). The ratiofrom MEC and PNEC characterizesthe risk for the environment. In caseof resulting ratios above 1, measuresto avoid and minimize risks are re-quired. Figure 1 shows these valuesof various APIs analyzed in Germansurface waters on base of worst-caseestimations [14].
Obviously, estrogens and antibiot-ics constitute so far the most chal-lenging classes of pharmaceuticalsdue to their properties and their ef-fect to the environment.
Synthetic 17α-ethinylestradiol(EE2) is probably the most effectiveestrogen-active substance to fish as itleads already at concentrations of0.32 ng/L to reduced egg fertilizationsuccess and sexual ratio skewed to-wards females in fathead minnows’populations [15]. The estrogenic ac-tivity of sewage is the reason for thereduced fertility of fish, despite a re-duction of about 80 to 90 % by con-ventional purification with activatedsludge process [16].
This demonstrates the need toavoid any possible emissions fromindustrial production or plants byappropriate technology. A good ex-ample for destruction of ethinylestra-diol and other APIs in wastewaterfrom production of contraceptives,thyroid hormones and narcotics isHaupt Pharma in Münster, Germany,using UV-oxidation for this task (cf.below) [17].
Design requirements for munici-pal STPs are to eliminate mainly or-ganics from sanitary wastewater andindustrial wastewater being non-toxic and showing a good bio-de-gradability. The volume rate of STPsis high and the level of contamina-tion is relatively low (Table 1).
The task of STPs is to reduce theload of substrate and nutrients be-fore the treated wastewater is re-jected into our aquatic environmentat lowest possible costs. Nearly all
STPs have no barrier for anthropo-genic substances as they show differ-ent chemical behavior on biologicaldegradation, which in STPs is themain cleaning-tool flanked by simplemechanical separation.
Most xenobiotic substances showno or a poor bio-availability and deg-radation of some APIs could be im-proved by extended retention times,which is in practice difficult consid-ering the typical flow rates. Depend-ing on the APIs’ structure a seeminglyelimination of APIs is often a result ofadsorption on sewage sludge [18].The best way to treat xenobiotics,thus also of APIs, is directly by spe-cial designed wastewater treatmentinstallations integrated on site whereAPIs are synthesized or formulated.
Table 2 gives an overview of typi-cal techniques used for treatment ofindustrial wastewater. All these tech-niques have their advantage, but asin pharmaceutical applications spe-cial requirements are defined,Table 2 extracts these under aspectsimportant for pharmaceutical waste-water treatment.
Table 2 shows clearly that onlytechniques based on oxidation cansolve the problem of API sustainably,xenobiotics, or recalcitrant organics,as operating costs are low and noconcentrate has to be disposed of.
In practice, there is often not onlyone technique as tool for state-of-the-art wastewater treatment. BASF(Ludwigshafen) for example operatesas final treatment a big biological
wastewater treatment plant withvery sophisticated sludge removalby flocculation filtration. For a suc-cessful operation, within the factorymany different techniques of pre-treatment are used to support thebiological wastewater treatment.UV-oxidation for example is used toeliminate 1,4-dioxane, EDTA, pyrrol-idones, aromatics, and other sub-stances which cannot be removedin a biological process. This success-ful concept it copied in many biggerchemical plants.
Examples in chemical andpharmaceutical industry
BASF (Ludwigshafen)Wastewater from synthesis of chelat-ing agents for detergents andcleaners, pulp and paper and agricul-ture contain mostly EDTA.
The effluent of the EDTA-manu-facturing line at BASF in Ludwigs-hafen shows a completely bio-avail-able wastewater, with the exceptionof EDTA remaining after an extrac-tion step. Therefore, BASF [19] wasfocusing on a highly selective treat-ment for elimination of this singlesubstance only. The reason was that
Fig. 1: MEC/PNEC ratio of pharmaceuticals with very good to sufficient ecotoxicological database (Source: [14]).
Table 1
Typical range of flow and concentration of STPs.
Parameter Untreated WW Treated WW
Flow in m³/d 1 000–1 000 000
COD in mg/L 50–100 Ca. 30
P in mg/L < 16 (1–5) 2 (0.5–1)
N in mg/L 30–100 5–10
Micropolutants in mg/L n.n.–0.01 No significant change
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the existing biological wastewatertreatment plant at BASF is one ofthe most developed wastewatertreatment plants at a chemical man-ufacturing site. However, as knownEDTA cannot be removed by any bio-logical treatment. Therefore, a highlyselective UV-treatment, reducing theconcentration of EDTA without anydetectable change of the matrix wasselected as pretreatment (see Fig. 2).This process keeps operational costsat a minimum (see Table 3). This typeof treatment is applied as well forselective removal of API from indus-trial wastewater at many pharma-ceutical manufacturing sites of lead-ing pharmaceutical companies.
In Fig. 3 the degradation curve ofEDTA is displayed. Striking is the rel-atively small reduction of NTA, thatis well bio available whereas EDTA iseliminated [20].
Enva IrelandEnva provides technical solutions forthe treatment of waste and waste-water to clients across all types ofindustry in Ireland and UK. This in-cludes being service providers tomany of the world’s leading pharma-ceutical companies. Enva providesservices at its own licensed wastetreatment facilities, and also pro-vides services and technology at itscustomer sites. In 2012 Enva installed2 UV based AOP (Advanced Oxida-tion Process) systems at their speci-alised chemical waste treatment fa-cility in Shannon, Ireland (see Fig. 4).These units were designed to be
Good sorptionproperties are re-quired.Genera-tion of waste
Low High
Advancedoxidation
ChemicalOxidation
YES Different elimi-nation levels canbe achieved
Low-medium
Medium
Biologicaltreatment
BiologicalOxidation
Only in rarecases
Evaporation Concentra-tion
Concentration Distillate oftenpolluted as manyingredients arepurgeable orsteam-purgeable
High High, alsodue to con-centratedisposal
Flocculation/Filtration
Mechanical NO, bad effi-ciency on re-moval of organ-ics
No relevance inpharmaceuticalindustry
Low Low
HighpressureOxidation
ChemicalOxidation
YES VeryHigh
Low
External In-cineration
ThermalOxidation
YES Low, asstorageonly
Very High
Incinerationon site
ThermalOxidation
YES High Very High
Membrane Mechanicalseparation
Concentrationof API withlower flow rate
Membranes aresensible for foul-ing, Concentratehas to be dis-posed externally
Medium High, alsodue to con-centratedisposal
Fig. 2: UV-oxidation unit for selective de-struction of EDTA at BASF in a flow be-tween 10–12 m3/h with adjustment oftreatment intensity regarding degradationand flow rate (Source: Fig. 2–4, 6, 8–12,14–20 Enviolet).
Fig. 3: Selective destruction of EDTA at BASF Ludwigshafen, Germany.
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multi-functional, so that Enva canreceive a wide variety of aqueouswastes for treatment and can operatedifferent campaigns depending onthe customer’s requirements. Theseunits are used for the treatment ofa variety of organics-contaminatedwastes, e. g. API removal, toxicity re-duction, COD (Chemical Oxygen De-mand) reduction & VOC (Volatile Or-ganic Compound) reduction. Due togood and efficient treatment at Envatwo Irish pharmaceutical companieshave installed own installations attheir production site for treatingthe full factory wastewater with spe-cific technology.
Haupt PharmaHaupt Pharma [17] in Münster asjob-shop manufacturer is operatingthe biggest site for formulation ofhigh potential sexual hormones inEurope. In 8 formulation lines alltypes of sexual hormones like EE2are formulated and packed for finalapplication. The wastewater fromCleaning in Place (CIP) is treated byAOP (see Fig. 5) to remove all hor-mones in a proper way to release
clear and clean water into the mu-nicipal sewer (see Table 5 and Fig. 6).
GSK (Singapore)Amoxicillin manufacturing site ofGSK in Singapore is one of the big-gest sites for production of antibiot-ics worldwide. It is well known thatbiological treatment plants are notvery capable treating the strongwastewater from antibiotic manufac-turing lines, due to the effect of itsingredients, which resulted at GSKSingapore in incinerating the waste-water. GSK-manufacturing site wassearching for a more suitable processto be applied for removal of severalsubstances from the strong waste-
water. A treatment system has beeninstalled (see Fig. 7 and 8) where thecapacity of strong wastewater wasincreased from 54 m3/d stepwise to100 m3/d.
The specific UV-process is remov-ing toxicity and phenol-based activestructures and is increasing the bio-availability of the strong wastewaterresulting GSK stopping incinerationof this wastewater (see Fig. 9 and 10,Table 6). Due to pre-treatment byphoto-oxidation, the existing biolog-ical system at GSK is also able tohandle this wastewater. For all envi-ronmental activities of GSK includ-ing the installation of the photo-oxi-dation GSK (together with other sus-tainability projects) was labeled with
COD 1 000–50 000 mg/L Depending on treatment fo-cus
API Various types and concen-tration
target depending on API
Bioavailability Mostly low Usually > 60 %
OPEX Varying with application
Table 5
Data of treatment at Haupt Pharma Münster.
Parameter Data Result
Flow rate 12 m³/d No change
COD 2 000–4 000 mg/L Ca. 20 % reduction rate
Sexual hormones like EE2 ≈ 10–100 mg/L < 0.01 mg/L
Bioavailability ≈ 65 % ≈ 90 %
OPEX ≈ 1–3 €/m³
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a Singapore Environment Achieve-ment Award.
BASF (Ireland)Wastewater from synthesis of Phe-nol-based functional chemicals witha background of surfactants is re-leased with flow rates between 250and 700 m3/d, depending on the ac-tual wastewater composition.
The effluent of the plant was dis-charged to a biological plant on site,but presence of not biodegradablesurfactants and several non-biode-gradable organics prevented a con-
stant and acceptable operation forBASF. Therefore a UV-based AOPwas installed on site (see Fig. 11and 12) and wastewater treated bythis process is discharged to the mu-nicipal wastewater treatment plant.The UV-based AOP effectively de-stroys all aromatic structures byopening the aromatic ring and gen-eration of small organic acids withgood bioavailability. FOG (= Fat, Oiland Grease) also being part of thiseffluent are separated before AOPand also in the first step of oxidation,as by destruction of surfactants FOGcan be easily floated and removed, as
surfactants are destroyed in the firststep of UV-oxidation.
MerckThe pharmaceutical manufacturingsite of Merck KGaA in Altdorf Swit-zerland is producing an antihyper-tensive containing a phenolic struc-ture. This production is generatingsome wastewater. This stream ofwastewater originally was collectedand sent to incineration for signifi-cant costs. A process treating thiswastewater successfully by elimina-tion of all aromatic structures, all sol-vents and huge increase of bioavail-ability of remaining organics hasbeen developed (see Fig. 13 and 14).Toxicity was removed completely.For best oxidation at highest effi-ciency, also a recuperation systemwas integrated into the UV-plant.As control, system is fully integratedinto Merck’s factory management the
Fig. 6: Selective destruction of EE2 and concentrations of COD and TOC at Haupt PharmaMünster.
Fig. 7: Treatment installation at GSK Sin-gapore (Source: GSK).
Fig. 8: Photo-oxidation installation placedat GSK for elimination of residual Amox-icillin and non bio-available organics instrong process wastewater.
Fig. 9: Parameters TOC, COD and BOD5 during the treatment at GSK Singapore.
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unit is operated with minimum per-sonal effort. Taking this unit into op-eration was significant environmen-
tal improvement for Merckcombined with huge costsaving (see Table 8).
Pharma ActionThe new GMP compliantheparin processing plantof Pharma Action(Toennies Group) hasachieved a supply chain,
in which the entire process: from an-imal slaughter via extraction of
prime raw material to refinementinto API occurs within one singlecompany. Putting a focus on sustain-ability, process solution is treatedwith UV-Oxidation to break down or-ganic substance like amino acids andeliminate organic background (seeFig. 15). With this method, treated
Fig. 11: UV-plant for treatment of aromatic processwastewater.
Fig. 10: Parameters Phenols and Bioavailability during the treatment at GSK Singapore.
Fig. 12: Treatment tanks for AOP.
Table 7
Data of treatment at BASF Ireland.
Parameter Data Result
Flow rate 360–700 m³/d
COD 10 000–17 000 mg/L ≈ 30 %
VOC ≈ 1 000 mg/L < 1 mg/L
Bioavailability 5 % ≈ 60 %
OPEX ≈ 4–5 €/m³
Fig. 13: Containerized UV-installation atMerck for treatment of strong wastewaterfrom pharmaceutical manufacturing(Source: Merck).
Fig. 15: Unit at Pharma Action for thepurification of process solution and re-covery of extraction salt (Source: PharmaAction).
Fig. 14: Photos of samples during variousstages during UV-treatment at Merck (leftto right: untreated to treated).
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solution can be recovered and reusedin the same process, resulting in sav-ings of 1 000 MT/a of salt.
Multiple API ProductionA production site for Pantoprazoleand others of a leading Japanesepharmaceutical company has beenusing UV-oxidation for years fortreating their effluent (see Fig. 16).Different API (e. g. Pantoprazole seeFig. 17 and Tab. 9) need to be de-graded below the detection limit.The special challenge for developingthis application was handling polym-erization of degradation products inthe wastewater matrix. Due to thespecific reactor design, there are nolayers or deposits on the UV-lamps,however to avoid deposits in thetanks precautions had to be takenand successfully implemented by ap-propriate treatment parameters.
API-manufacturerA leading American pharmaceuticalcompany operates a production sitethat produces wastewater with highCOD amounts containing variousAPI and solvents. The aim of treat-ment is elimination of API and re-
duction of the COD load by at least60 % to lowest possible operatingcosts and unstaffed operation. Toachieve this an online TOC-analyzersystem was implemented for moni-toring degradation and piloting pro-cess by adjustment of process pa-rameters like number of UV-reactors,dosage of oxidant and operation con-ditions (see Fig. 18 and Table 10).
Chemical Background [21]
For the major part of UV-oxidationtreatments, we find curves likeshown in Fig. 19 as an example:
The degradation process starts byoxidizing the carbon of organic mol-ecules, whereby oxygen-containingfunctional groups are formed. How-ever, no carbon dioxide is formed atfirst, which is why TOC reduction israther insignificant at the beginning.But, since C-atoms of the moleculesalready have obtained a higher oxi-dation number, less oxygen is neededfor a complete oxidation to carbondioxide and, therefore, COD concen-tration is reduced faster. With CODoxidation (=feeding molecules withoxygen) the bio-availability is typi-cally improving which is noticeable
Data of treatment at a production site Pantoprazole and other APIs.
Parameter Data Result
Flow rate 36 m³/d
COD ≈ 20 000 mg/L ≈ 5 000 mg/L
Pantoprazole ≈ 1 000 mg/L < 0.01 mg/L
Bioavailability 5 % ≈ 95 %
OPEX ≈ 8 €/m³
Fig. 16: UV-installation for Pantoprazoledestruction.
Fig. 17: Degradation of Pantoprazole (logarithmic scale).
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by an increasing BOD. The changesof COD and BOD can be described asbio-availability in % (= ratio BOD/COD x 100 %). A bio-availability of60 % can be considered “good” andbetween 40–60 % it is typically suffi-cient for the water to be dischargedto a sewage treatment plant.
An example for UV-oxidation of acomplex mixture of toxic organiccompounds in a real wastewater (finechemicals industry) containingphthalic acid derivates is illustratedin the following diagrams (Fig. 20and 21). This example is presentedbecause detailed analyses of degra-dation products and bio availabilityexist. Concentrations of carboxylic
acids are rising during the treatmentby UV-oxidation and, after reaching amaximum their concentration, isdropping as well. At this stage com-plete bio availability is alreadyachieved. This was shown by meas-urement of BOD5 (Biological OxygenDemand after 5 days) and comparingit with the COD. An adapted acti-vated sludge would lead to an evena higher bio availability.
The above given measurable re-sults are based on following reactionchains:
Light of proper wavelength splitshydrogen peroxide (H2O2) into highlyreactive hydroxyl radicals by photo-lysis (UV/H2O2-process), which re-
acts quickly with organic and inor-ganic water compounds:
Such hydroxyl radicals (OH-radi-cals) are not only generated withthe least amount of chemicals [22]but also with the most economicalenergy input by the UV/H2O2-pro-cess [23]. For this reason AOP is alsoat high target-concentrations verywell suited for effective treatmentof pollutants in aqueous solutionssuch as, highly contaminated waste-water, electroplating baths and evenultrapure process water.
The degradation of organic com-pounds via OH-radicals is initiatedby hydrogen abstraction
or electrophilic addition of OH-radicals takes place:
These initiated reactions followvarious reaction possibilities of thegenerated radicals. In presence ofoxygen an organic peroxyl-radical isformed:
Fig. 18: UV-oxidation system with inte-grated online analytics for automatic op-eration.
Fig. 19: Typical degradation of TOC, COD, BOD and resulting increase of bio-availabilityversus irradiation time.
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Furthermore, various competitivereactions can occur:
In general, polymerization is not afavored reaction because polymer-ized products may lead to precipita-tion issues on the UV lamp surface.For this reason it is important toavoid such polymerization by properprocess control design and UV reac-tor construction. Also the peroxyl-radical (RHO2
.) may for instance con-tinue its reaction as follows:
Resulting aldehydes respectively ke-tones are oxidized into carboxylic acids
by the subsequent reaction processes,which are subject to either a thermic orphoto-chemical decarboxylation.
Besides initiating reactions via OH-radicals (generated from H2O2) directphotolysis of water ingredients by UVirradiation plays a major role. How-ever, sufficient absorption of thesesubstances is required, which can beselectively destroyed under properprocess conditions. Especially the pos-sibility of a selective oxidation of toxicingredients is a big advantage in re-gard to efficiency and economics.
Another possibility of the UV-in-duced degradation processes is theuse of metal ions as catalysts, which,depending on the treatment objec-tive and wastewater ingredients,may lead to a better process effi-ciency. The best-known process isthe Photo-Fenton-Process, in whichiron-containing solutions are used ascatalyst. Based on various photo re-actions hydroxyl-radicals are gener-ated via photo reduction of metalions and initiate the above describeddegradation process. In addition,many other reactions play a roleand also resulting to the degradation
Fig. 20: Destruction of toxic compounds, COD, BOD5 and TOC during UV-treatment of realwastewater.
Fig. 21: Generation of bio available degradation products.
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of organic water ingredients (seeFig. 22).
A common prejudice against UV-based oxidation is that wastewaterhas to be very transparent for lightand should not contain any particles.That applies only to UV-disinfectionbut has no meaning for UV-oxida-tion. In contrast, often a strong colorindicates already good absorption oflight, which can be used by enhanc-ing the above mentioned direct pho-tolysis as initial reaction.
Above described possible reactionpathways lead consequently to theneed of developing process parame-ters best suited for each task. There-fore, as a general rule, lab tests arecarried out in the beginning of eachindustrial application.
The way from lab tests toindustrial applications
Typically, wastewater projects starton a laboratory scale for establish-ment of the best available technology
for a selected problem. Afeasibility study starts witha classification test usingseveral μL, which resultswith a degradation class.Then in the scale of 0.5–1L a next step is done toverify the results from clas-sification in a next scale. Ifagain good results areachieved a complete proc-ess simulation is run withca. 5–50 L also supplying asignificant volume of (in-termediate) samples forfurther testing on by-prod-ucts and or biodegradabil-ity as well as analytics on single pa-rameters like API, etc.
Based on this, customers can de-cide to go directly into a commercialproject or run further test-work onsite, up to 6 to per test, or rent acommercial scaled pilot installation.
During efficient and realistic test-ing procedures, reliable data forcommercial installations are eval-uated resulting in an appropriate
treatment process including CAPEXand OPEX.
By that method reliable data canbe supplied for:1. establishing a strategy to treat
pharmaceutical wastewater effec-tively
2. identifying the need for and ad-vantages of the treatment ofpharmaceutical wastewater atpoint of source
Fig. 22: Reaction of complex metal ions in oxygensaturated aqueous solution reduced by light-inducedtransfer of electrons (Source: [20]).
Table 11
Origins and properties of typical pharmaceutical wastewater.
API-manufacturing Formulation
Dry (Pills) Liquid (Vials)
Origin of waste-water
Chemical synthesis of API and intermediates CIP-cleaning of equip-ment
Residuals and CIP-clean-ing of equipment
Note Wide range of chemical mixture, due to reactions made API at low concentrationStarch (filling material)Wax (surface)Water
API at low concentrationorganic solvents, oftenrecoveredWater
Typical existing sol-ution
Incineration, Evaporation / Incineration
Aim of treatment Detoxification, increase of Bio-availability and direct discharge at low costs
Treatment proposed UV-Oxidation, UV-AOPoften a special treatment, mostly with high flexibility for varyingcomposition of effluent
UV-Oxidation able tohandle suspended solids
UV-Oxidation able tohandle some solvents
Following treatment Often Biological treatment none non
COD in mg/L(range)
10 000–100 000 1 000–5 000 1 000–50 000
COD in mg/L (90 %percentil)
As above 2 000–3 000 5 000–10 000(with good solvent re-covery)
TSS in g/L Up to 250 2–4 2–4
Flow rate 5–500 m³/d 5–20 m³/d 5–20 m³/d
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3. reducing investment, mainte-nance, and operating costs by se-lecting simple and effectivewastewater treatment processes
4. relation between APIs and aneasy-to-measure indicative pa-rameter, like absorbance at a cer-tain wavelength, TOC or COD…)easy to be operated by the cus-tomer, in the ideal case and athigher flow rates also by online-techniques
5. PLC controlled process, adjustingparameters based on instrumen-tation
Conclusion
In many cases, the integration of anAOP is supplied into existing struc-tures for best CAPEX. Often good re-sults are achieved by combination ofbiological and advanced oxidation invarious ways, always depending onchemical character and already exist-ing structures. Additional aspects arealso future expansions or integrationof other side streams into a new ormodified treatment system based onUV-processes. By this approach morethan 600 AOP-plants have been real-ized for these applications between1997 and 2015.
Of course manufactures use allpossibilities of wastewater savings(wastewater reductions) by opti-mized CIP rinsing processes by vali-dating minimum rinsing time andnumber of rinsing steps needed. Aswell, reuse of wastewater for coolingprocesses in non-GMP areas or plantirrigation purposes, etc. are takeninto account.
Typical Pharma applications canbe roughly assigned to followingorigins and properties of wastewateras summarized in Table 11.
L ITERATURE
[1] Bouki C, Venieri D, Diamadopoulos E.Detection and fate of antibiotic resistantbacteria in wastewater treatment plants:
a review. EUR 21201 EN Bericht derEuropean Commission (2004).
[2] A Daverio E, Ghiani M, Bernasconi C.Antibiotics and antibiotic-resistant bac-teria into aquatic environment: a review.Ecotoxicol Environ Saf. 2013 May; 91:1–9.doi: 10.1016/j.ecoenv.2013.01.016. Epub2013 Feb 13 (2013).
[3] Nentwig G, OetkenM, Oehlmann J. Effectsof Pharmaceuticals on Aquatic Inverte-brates – The Example of Carbamazepineand Clofibric Acid. In Kümmerer K. (ed.)(2004): Pharmaceuticals in the Environ-ment. Sources, Fate, Effects and Risks.2nd Edition, Springer-Verlag, Berlin, Hei-delberg.
[4] Petrovic M, de Alda MJ, Diaz-Cruz S,Postigo C, Radjenovic J, Gros M, BarceloD. Fate and removal of pharmaceuticalsand illicit drugs in conventional andmembrane bioreactor wastewater treat-ment plants and by riverbank filtration.Philos Trans A Math Phys Eng Sci. 2009Oct 13;367(1904):3979–4003. doi: 10.1098/rsta.2009.0105.
[5] Fick, Söderström, Lindberg, Phan, Tysk-lind, Larsson. Contamination of surface,ground, and drinking water from phar-maceutical production. Environ ToxicolChem. 2009 Dec;28(12):2522–7. doi:10.1897/09-073.1. Epub 2009 May 18.
[6] 50388 Federal Register/VoI. 63, No. l82/Monday, September 21,1998/Rules andRegulations Part III Environmental Pro-tection Agency 40 CFR Part 439, Phar-maceutical Manufacturing Category Ef-fluent Limitations Guidelines, Pretreat-ment Standards, and New Source Per-formance Standards, Final Rule.
[7] Community Strategy for Endocrine Dis-ruptors. A Range of Substances Suspectedof Interfering with the Hormone Systemsof Humans and Wildlife, Brussels,17.12.1999 COM (1999) 706 final.
[8] EudraLex: The Rules GoverningMedicinalProducts in the European Union, Volume4 – Good Manufacturing Practice; Me-dicinal Products for Human and Veteri-nary Use Part II: Basic Requirements forActive Substances Used as Starting Ma-terials. Brussels, 03 February 2010, ENTR/F/2/AM/an D(20lo) 3374.
[9] Teunter RH, Inderfurth K, Minner S,Kleber R. Reverse Logistics in a Pharma-ceutical Company: A Case Study, No El2003-30, Econometric Institute Reportfrom Erasmus University Rotterdam,Econometric Institute.
[10] Dr. Martin Sörensen, Prof. Dr. DietrichMaier. Entwicklung eines Verfahrens zurZerstörung von Röntgenkontrastmittelnund Antibiotika in Abwässern durch UV-Oxidation, Abschlussbericht zum DBU-Projekt AZ-22469 (2007).
[11] European Commission: Integrated Pollu-tion Prevention and Control ReferenceDocument on Best Available Techniquesin Common Wastewater and Waste GasTreatment/Management Systems in theChemical Sector, February 2003.
[12] Directive 2010/75/EU of the EuropeanParliament and of the Council of 24 No-vember 2010 on Industrial Emissions
[13] Directive 2000/6o/EC of the EuropeanParliament and of the Council of 23 Oc-tober 2000, Establishing a Framework forCommunity Action in the Field of WaterPolicy Official Journal L.327, 22/12/2000,P. 0001–0073.
[14] Bergmann A, Fohrmann R, Dr. Weber F-A.Zusammenstellung von Monitoringdatenzu Umweltkonzentrationen von Arznei-mitteln. Texte, 66/2011, Umweltbunde-samt. (http://www.uba.de/uba-info-medien/4188.html, 03.02.2015).
[15] Parrott JL, Blunt BR. Life-cycle Exposureof Fathead Minnows to an Ethinylestra-diol Concentration below 1 ng/L ReducesEgg Fertilization Success and De-Mascu-linizes Males, Environmental Toxicology,2005, Vol. 20, ISS 2, pp. 131–42.
[16] Laenge R, Hutchinson TH, Croudace CP,Siegmund F, Schweinfurth H, Panter GH,Sumpter JP. Effect of the Synthetic Es-trogen i7Alpha-Ethinylestradiol on theLifecycle of the Fathead Minnow, EnvironToxicol Chem, 2001 Jun; 20 (6): 1216–27.
[17] Eckert V1, Bensmann H1, Zegenhagen F2,Weckenmann J2, Sörensen M2 . HauptPharma Münster GmbH1, Münster (Ger-many) und a.c.k. aqua concept GmbH2,Karlsruhe (Germany) Elimination ofHormones in Pharmaceutical Waste-water, pharm. ind. 2012 Nr. 03, Seite 487(2012).
[18] Püttman W, Keil F, Oehlmann J, Schulte-Oehlmann U. Wassertechnische Strate-gien zur Reduzierung der Trinkwasser-belastung durch Arzneimittelwirkstoffe.doi 10.1007/s12302-008-0010-8, Umwelt-wiss Schadst Forsch (2008) 20:209–226.
[19] Dr. Friederich Wirsing, Dr. MartinSörensen: Beispiel der BASF AG, Elimi-nation von EDTA aus Industrieabwasserdurch UV-Oxidation; wwt Wasserwirt-schaft Wassertechnik, 11-12-2004, p. 54–55.
[20] Sörensen, Martin: Photochemischer Ab-bau hydrophiler Syntheseprodukte imHinblick auf die Wasseraufbereitung,Photochemical Degradation of hydro-philic xenobiotics with regard to watertreatment. Dissertation, UniversitätKarlsruhe (TH) (1996).
