## 2 Pharmaceuticals and Personal Care Products (PPCPs) in the Ecosystems
### Combined Chemical Engineering-Biological Methods  
#### 2.3.1 Bioreactors  
Conventional municipal WWTPs, in general, have a very low efficiency for the elimination of PPCPs from polluted waters, as mentioned above These WWTPs could be improved with physical-chemical and biological process. Among the biological processes capable of transforming the original organic compounds into other simpler and less toxic molecules, ideally carbon dioxide, those using controlled bioreactors can be performed at large scale with high PPCPs removal efficiency (Figure 3A-C). * Conventional activated sludge  
Although the secondary biological treatment in WWTPs is not specifically designed to remove organic compounds at very low concentrations or trace levels, conventional activated sludge (CAS) processes can be optimized to improve the PPCPs removal efficiency. CAS effectiveness depends on the synergistic effect of the consortium, or microorganism mixture, to remove the PPCPs [283], which is constituted by complex communities that are formed by fungi, bacteria and algae [284]. However, both to lab and full-scale, little evidence of this type of synergistic relationship has been described so far and what is the ecology that steers the degradation processes is [187; 285]. Conventional municipal WWTPs achieved removal efficiencies of >80% for fragrances, such as galaxolide and tonalide, after the secondary stage, while the uptakes for IBU, NPX, 17 \(\beta\)-estradiol and SMX were within the range 50-65% and the X-ray contrast iopromide was not significantly degraded [286]. However, other studies reached 93% depletion of IBU and 71% of SMX in different sewage treatment plants in Italy, showing important seasonal variations in the removal efficiency of 19 different PPCPs [287]. These variations comprised two main types of factors that, in turn, variate along the year: on one hand, the physical factors that are associated to the environmental conditions and, on the other, the chemical composition of the wastewater influents. Among the physical factors, temperature has the largest impact on the microbial activity, increasing degrading efficiency as temperature increased from winter to summer. With respect to the chemical composition of wastewaters, the load of some PPCPs, especially antibiotics, was lower in summer than in winter because these pharmaceuticals are less used in summer [287]. The removal efficiency of beta-blockers in CAS systems is usually low, ranging from 10% to 81% [287; 288] for different waters, seasons and geographical locations, although it has been hypothesized that the removal rate of these drugs also depend on the solid retention time (SRT) of the activated sludge process too [289]. IBU and NPX are compounds showing the desired behavior in CAS treatments since they usually reach very high removal rates (typically 90-99%). On the other hand, CBZ usually shows poor removal values (<25%) in most CAS systems developed [289]. Bioaugmentation might be one strategy for improving the effectiveness of active sludge. For example, adding _Spingomonas_ sp. or _Nitrosomonas europea_ to activate sludge increases the degradation of TCS [112; 135]. In relation to the elimination of PPCPs, the composition of the bacterial community (i.e., the identity of the taxa) could be more relevant than the bacterial diversity (i.e., number of different taxa) [290]. The increase in hydraulic retention time and the use of CAS augmented with acclimatized sludge substantially improves the elimination of CBZ and DCF, among others [291]. * Membrane bioreactors  
Membrane bioreactors (MBR) combine the conventional activated sludge technology with the use of a filtration (micro- or ultra-) membrane system. The activated sludge is suspended inside the membrane and drives the biodegradation of organic matter. Meanwhile, membrane retains microorganisms and particles and allows for the permeation of the treated water, avoiding the need to use a settler [292].