Blázquez et al. Porcine Health Management (2020) 6:16 https://doi.org/10.1186/s40813-020-00155-1 REVIEW Open Access Biosafety steps in the manufacturing process of spray-dried plasma: a review with emphasis on the use of ultraviolet irradiation as a redundant biosafety procedure Elena Blázquez1,2,3 , Carmen Rodríguez1, Jesús Ródenas1, Joaquim Segalés3,4,5, Joan Pujols2,3 and Javier Polo1,6* Abstract Spray dried plasma (SDP) is a functional protein source obtained from blood of healthy animals, approved by the veterinary authorities from animals declared to be fit for slaughter for human consumption. Blood of these animals is collected at the slaughterhouse, treated with an anticoagulant, chilled and transported to industrial facilities in which blood is centrifuged to separate the red blood cells from the plasma fraction. Plasma is then concentrated, and spray dried at high temperatures (80 °C throughout its substance) to convert it in a powder. Such method preserves the biological activity of its proteins, mainly albumins and globulins. SDP is mainly used in pig feed diets to significantly improve daily gain, feed intake, production efficiency, and to reduce post-weaning lag caused by the appearance of post-weaning diarrhea. Although SDP is considered a safe product and its manufacturing process consists of several biosafety steps, the security of the SDP is often questioned due to its nature as raw blood by-product, especially when emergent or re-emergent pathogens appear. This review provides an evaluation and validation of the different safety steps present in the manufacturing process of SDP, with special focus on a new redundant pathogen inactivation step, the UV-C irradiation, that may be implemented in the manufacturing process of the SDP. Overall results showed that the manufacturing process of SDP is safe and the UV-C radiation was effective in inactivating a wide range of bacteria and viruses spiked and naturally present in commercially collected liquid animal plasma and it can be implemented as a redundant biosafety step in the manufacturing process of the SDP. Background slaughterhouse, treated with an anticoagulant, chilled Spray-dried plasma (SDP) is a functional protein source and transported to industrial facilities where the blood is obtained from blood of healthy animals approved to be centrifuged to separate the red blood cells (RBC) from sacrificed for human consumption after veterinary in- the plasma fraction. Alternatively, the blood may be cen- spection. Blood of these animals is collected at the trifuged in the abattoir and then the chilled plasma transported to the manufacturing plant. Plasma is subse- quently concentrated either by membrane filtration or * Correspondence: Javier.polo@apc-europe.com 1 vacuum evaporation and spray-dried at high tempera- APC EUROPE, S.L., Avda, Sant Julià 246-258, Pol. Ind. El Congost, E-08403 Granollers, Spain tures (80 °C throughout its substance) to convert it to 6 APC LLC, 2425 SE Oak Tree Court, Ankeny, IA 50021, USA powder. This process preserves the biological activity of Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Blázquez et al. Porcine Health Management (2020) 6:16 Page 2 of 9 the proteins, mainly albumin and globulins, with im- standards to produce a safe high-quality product. SDP is munoglobulin G (IgG) as the predominant antibody type produced from fresh animal blood as a raw material that [1]. The SDP is produced from porcine (SDPP) or bo- requires several safety steps in its production process to vine (SDBP) blood and is commonly used in human food eliminate risks for potential biohazards. There are nu- and animal feed [1, 2]. merous safety features in the industrial manufacturing SDP has been used as a protein source in piglet feed process of SDP that effectively and collectively reduce since the late 1980s [2, 3] and is typically used at an inclu- biohazard risks to produce a safe final product (Fig. 1). sion level between 4 and 8% in the feed [4–6]. The use of The manufacturing process of SDP has several stages as SDP in feed for weaned pigs significantly improves daily discussed below. gain, feed intake, production efficiency, and piglet survival [4–6] compared to other specialty protein sources. SDP in Blood collection at the abattoir feed reduces diarrhea and the post-weaning growth lag as- The first biosafety step in the production process of sociated with weaning stress [7–9]. SDP starts with the collection of the raw material. Although the well documented benefits of SDP on animal Blood from healthy animals, passed as fit for slaugh- health and performance have long been established, its ter for human consumption, is collected at abattoirs safety may be questioned particularly in scenarios of emer- under inspection by competent authorities. Blood is ging or re-emerging diseases in animal populations because collected in a stainless-steel pan with anticoagulants it is produced from the abattoir collected animal blood. added to prevent blood clotting. Sodium citrate [10] Thus, the objective of the present manuscript is to review or sodium tripolyphosphate [11] are anticoagulants the different biosafety steps present in the manufacturing typically used for SDP production. The collection and process of SDP with special focus on the development and mixture of the blood from multiple animals contain adaptation of UV-C irradiation of liquid plasma as an add- inherent neutralizing antibodies against numerous ha- itional biosecurity step that has recently been incorporated bitual pathogens. These inherent neutralizing anti- in the manufacturing process at some facilities. This review bodies may reduce infectivity potential even before provides detailed information to the stakeholders of the further processing steps are done and contribute to swine industry about the biosafety features and standards the biosafety of the final product [12–14]. used by manufacturers of spray-dried plasma that assure To produce SDP, blood is only collected while the the overall safety of SDP in feed for swine. carcass is entire, thus minimizing exposure to other tis- sues. In addition, the blood collection system is separate Industrial production of spray-dried plasma and from the rest of the carcass processing chain. The entire its biosafety steps manufacturing process from the time that the blood is Commercial production of SDP is done following good collected to the final packaged product is done using a manufacturing practices (GMP) using high-quality closed system and avoids the possibility of cross Fig. 1 Manufacturing process of spray-dried plasma and its biosafety steps Blázquez et al. Porcine Health Management (2020) 6:16 Page 3 of 9 contamination with other tissues or from the external During the drying process, droplets interact with the environment. In North America, the collection system at hot air in the spraying chamber. As moisture is removed some abattoirs delivers the blood to an industrial centri- the temperature of the dried particle increases to a value fuge to separate RBC and plasma. After separation, the similar to the outlet air temperature [18, 19]. Inlet and plasma is concentrated or not concentrated and refriger- outlet temperatures have a major influence on the in- ated at 4 °C and transported to the processing plant. In activation of microorganisms, but the outlet temperature Europe, Latin America and other North American abat- has the highest impact and is the primary critical control toirs the collection system delivers the whole blood to point for the spray-drying process to inactivate microor- stainless steel containers that are kept refrigerated until ganisms [20]. The European Animal Protein Association subsequent transport to the processing plants. (EAPA) and the North American Spray Dried Blood and Once the daily blood collection is completed, the en- Plasma Producers (NASDBPP) have established ≥80 °C tire collection circuit is subjected to a clean in place for the outlet temperature as a good manufacturing (CIP) process using food grade approved sanitizing process standard for microbial inactivation during the agents. The CIP process ensures proper sanitization of SDP manufacturing process (www.eapa.biz). the circuit. Relatively high drying temperatures, rapid changes in temperature, and rapid dehydration are the phenomena in- Transport to the processing plants volved in microbial inactivation. Dehydration causes dam- Blood or plasma collected at the slaughterhouse is stored ages in the cells, mainly in the cytoplasmic membrane [21, in refrigerated containers and transported in isothermal 22] and also produces damage to DNA, RNA and proteins trucks that are sealed after filling. Each daily production [23] inactivating many microorganisms [20, 22–27]. lot is identified, and full traceability is retained. Many experiments of deliberated inoculation of After the transport truck arrives at the processing pathogens in plasma have demonstrated that spray- plant, a subjective inspection of the freshness of the drying is a very effective technology to inactivate im- product is done and temperature of the liquid is mea- portant pathogens of interest in the swine industry. sured to determine if the product is suitable for Pathogen inactivation results from studies using spray processing. drying of plasma inoculated with Salmonella enterica When the truck is emptied, a CIP process is done to [28, 29], E.coli enterotoxigenic strains [30], Porcine re- assure the cleaning and sanitation of the tank before the productive and respiratory syndrome virus (PRRSV) next collection is done. [31], Pseudorabies virus (PRV) [31], Swine vesicular disease virus (SVDV) [32], Porcine epidemic diarrhea Processing and spray-drying virus (PEDV) [33, 34] or African swine fever virus At manufacturing plants that receive whole blood, the (ASFV) [35] are summarized in Table 1. Furthermore, blood is delivered to a storage tank and passed through in Table 2 results from other studies are summarized a closed system to an industrial centrifuge to separate demonstrating the lack of pathogen transmission in the plasma from the RBC fraction. The RBC are stored pigs provided feed with SDP containing virus genome. for subsequent production of other products. Before There was no transmission of Porcine circovirus 2 spray drying, the plasma is concentrated with mem- (PCV-2), when naïve pigs were fed diets with SDPP branes using either nanofiltration or reverse osmosis. Al- containing genome copies of PCV-2 [36–38, 43]. ternatively, concentration by a vacuum evaporator may PCV-2 is known to be one of the most thermal re- be used at some plants. After concentration, the plasma sistant viruses of swine [44, 45]. Also, SDPP contain- is pumped into an industrial spray-dryer, which rapidly ing genome of PEDV has been reported to not be dries the concentrated liquid plasma into powder. infective when fed to millions of naïve pigs [40, 41]. Spray-drying involves the atomization of a liquid feed A retrospective study of different SDPP samples and material into a stream of heated air resulting in rapid sera from pigs provided feed with SDPP collected desiccation. The spray-drying process involves four over time, showed that SDPP containing RNA and stages of operation that affect microbial survival and the antibodies of Hepatitis E virus (HEV) did not trans- characteristics of the resulting product: 1) atomization of mit HEV to pigs [39]. These results demonstrate that the liquid source to form droplets into a hot chamber; 2) detection of virus genome in spray-dried blood prod- contact between the spray and the drying medium con- ucts should not be interpreted as an infectious mater- sisting of very hot air, at a high gas mass to liquid mass ial, only that the virus genome segments are flow volume ratio; 3) rapid moisture evaporation result- detectable and present in the material [46]. Virus iso- ing in particle formation; and 4) separation of dried par- lation or bioassay techniques are necessary to distin- ticles from the air stream [15–17] following a residence guish if virus genome segments detected in SDP can time between 20 and 90 s. cause infection. Blázquez et al. Porcine Health Management (2020) 6:16 Page 4 of 9 Table 1 Reduction factors obtained for different viruses subjected to the spray-drying treatment Virus Nucleic acid Envelope Virus size (nm) Virus inactivation expressed as Log 10 TCID50 Reference PRRSV ssRNA Yes 50–65 4.0 log [31] PEDV ssRNA Yes 90–190 > 5.2 log [34] PEDV ssRNA Yes 90–190 > 3.6 log [33] PRV ssDNA Yes 150–180 5.3 log [31] ASFV dsDNA Yes 80–200 ~ 4.0 log [35] SVDV ssRNA No 22–30 6.0 log [32] Packaging, storage, traceability and quality control been widely used in the food industry for the treatment As SDP is being produced, the powder is blended and of complex opaque liquids or other substances including stored in a small silo, then directly bagged in new pack- juices [49–53], tea [54], milk [55–57], cheese [58], wine aging materials ensuring no cross contamination after [51], egg [59], dried seafood [60] and sliced fruits and SDP production. All manufactured lots are submitted to vegetables [61–64]. UV-C irradiation technology has also standard physicochemical and microbiological analysis been used for the inactivation of several viruses in hu- that confirm all commercial lots meet specifications. man plasma products [65–71]. Post drying heat treatment and storage time The low moisture (< 9%) and very low water activity UV irradiation effect on bacteria survival in SDP (aw < 0.6) of SDP significantly reduce pathogen survival, The effectiveness of different doses of UV-C irradi- especially for bacteria and enveloped viruses during pro- ation of liquid porcine or bovine plasma on survival longed periods of storage [47]. of several bacteria of interest in farm animals includ- As an additional safety feature, most manufacturers ing Salmonella typhimurium (S. typhimurium), Sal- package and store porcine SDP (SDPP) at room monella choleraesuis (S. choleraesuis), Enterococcus temperature (> 20 °C) for at least 14 days before release faecium (E. faecium), and Escherichia coli (E. coli K88 for sale. These storage conditions of SDPP demonstrated and K99) has been evaluated [30, 72]. to be effective in inactivating certain pathogens suscep- For all bacteria tested, the 4D reduction value (UV tible to dry environments and mild temperatures, such irradiation dose at which a specific microorganism re- as PRRSV, PEDV and coronaviruses in general [34, 47]. duces its viability by 4 Log10) was achieved around 3000 J/L, which is the dose typically applied under Ultraviolet light irradiation commercial manufacturing conditions. All bacteria Ultraviolet exposure at a wavelength of 254 nm showed non-linear inactivation kinetics, having special (UV-C) is a nonthermal process that has a germi- importance for S. typhimurium and E. coli K88 and cidal effect by causing thymine-thymine and K99, in which tails appeared in their inactivation kin- thymine-cytosine dimers in DNA and thymine-uracil etics curves. The appearance of non-linear kinetic tail dimers in RNA, which disrupts microbial inactivation of S. typhimurium excludes the potential reproduction [48]. use of E. faecium as its surrogate. Tails appeared in Technological advancements have resulted in the de- inactivation kinetics when, despite increasing the dose velopment of UV-C irradiation devices that create a tur- of UV-C, the reduction in the population slows down bulent flow which allows for effective irradiation of and is not proportional to the increase in UV-C ir- opaque fluids of high viscosity. These UV devices have radiation [73]. Table 2 Studies that demonstrated lack of transmission of different swine viruses when PCR genome copies were present in SDP Virus PCR genome copies SDP inclusion level in feed Feeding duration Results Reference PCV-2 2.47 × 105.0 8% 45 days Not infective [36] 6.7 PCV-2 10 4% 42 days Not infective [37] PCV-2 7.56 × 105.0 8% 32 days Not infective [38] HEV Positive 8% 28 days Not infective [39] PEDV Positive (Ct: 30.1) 5% 14 days Not infective [40] PEDV Positive 3–8% 7 to 14 days Not infective [41] PRRSV Positive 3–8% 7 to 21 days Not infective [42] Blázquez et al. Porcine Health Management (2020) 6:16 Page 5 of 9 UV irradiation inactivation of enveloped and non- indicating that viruses belonging to the same genus enveloped viruses in SDP could be used as a surrogate organism. The effect of UV-C on different viruses of interest in the Regarding non-enveloped viruses, PPV and SVA had swine industry was also determined [74]. Viruses se- 4D reduction values very close to 3000 J/L and SVDV lected for testing was based on their different physico- had a slightly higher 4D value. In the case of PCV-2, the chemical characteristics, types of genome (DNA or 4D value could not be calculated because less than 4 RNA), genome lengths (long and short genomes), pres- log10 TCID50/mL was measured in the inoculated ence or absence of envelope and resistance to other in- plasma before UV-C treatment. Even so, PCV-2 had activation processes. Also, viruses belonging to the same higher resistance to UV-C treatment because inactiva- family and genus were selected to determine if they tion was only 2 and 3 log10 TCID50/mL at 3000 and would have similar behaviors under UV-C irradiation. 9000 J/L, respectively. These results are in agreement As outlined by the WHO (2004) guidelines [46], it is al- with the available literature, confirming the well-known ways prudent to test the inactivation process with the high resistance of PCV-2 to inactivation treatments [76]. virus of interest, choosing the strain with the greatest The overall results of the use of UV-C irradiation on known resistance. However, it is also important to test viruses demonstrated that it is a useful technology to viruses with different physicochemical characteristics to significantly reduce the viral and bacterial load in obtain information about the robustness of the inactiva- plasma. Considering that UV-C can be included as a bio- tion process [46]. safety step before the spray-drying process, the reduction Enveloped viruses selected for the studies included factor achieved by UV-C would be additive to that ob- PRV, PRRSV, PEDV, Bovine viral diarrhea virus tained by spray-drying, which has been demonstrated for (BVDV), Swine influenza virus (SIV) and Classical swine some of these viruses as previously discussed (Table 4). fever virus (CSFV) and Porcine parvovirus (PPV), SVDV, Validation of the UV irradiation effect in an animal PCV-2 and Senecavirus A (SVA) were chosen as non- model. enveloped viruses. All viruses were inoculated in liquid To validate the effectiveness of the plasma UV-C ir- plasma and subjected to different UV-C doses. The in- radiation measured by means of the viral load reduction activation curve for each virus was constructed by titra- in cell culture, a bioassay was done with different groups tion of the samples in their respective target cell at each of pigs injected intraperitoneally with UV-C irradiated UV-C dose. In general, results showed that enveloped vi- commercial liquid plasma at 0 J/L (untreated plasma), ruses have a higher sensitivity to UV-C than non- 3000 J/L, and at 9000 J/L [77]. The results of the bioassay enveloped ones, because the 4D reduction value was less showed that none of the pigs in the groups that received than 2000 J/L for all enveloped viruses (Table 3). Fur- liquid plasma irradiated by UV-C at either dose became thermore, UV-C irradiation of ASFV (strain Badajoz 71 infected or seroconverted against the different virus ge- adapted to Vero cells) inoculated plasma at 3000 J/L was nomes that were detected in the initial plasma (PCV-2, apparently able to reduce infectivity around 4 log10 PRRSV (European strains), SIV, PPV, HEV, Rotavirus A TCID50/mL [75]. (RVA); thus, confirming the efficacy of UV-C demon- Within the group of enveloped viruses, pestiviruses strated in vitro in a previous study [74]. Detection of a (CSFV and BVDV) had similar UV-C inactivation viral genome in the untreated liquid plasma does not imply infectivity by a given virus. The swine bioassay Table 3 Log reduction of viral titers expressed as Log 10 TCID50 was a very sensitive test to ascertain the infectiousness at UV-C doses of 3000 J/L in liquid plasma (references [74, 75]) of the detected genome of these viruses in the plasma Virus Log 10 TCID50 reduction at 3000 J/L used in these experiments. PRV 4.5 PRRSV > 4.0 Discussion PEDV > 4.1 The manufacturing process of SDP involves several BVDV† > 4.2 safety features including veterinary inspection at the ab- attoir, neutralizing antibodies present in pooled plasma, SIV > 5.1 the spray-drying process and post-processing storage. CSFV > 4.1 Veterinary inspection is crucial to ensure that blood ASFV ~ 4.0 from only healthy animals slaughtered for human con- SVDV 2.6 sumption is the exclusive source of raw material to be PCV-2 1.8 used for the manufacturing of blood products. There- PPV > 4.0 fore, it is vital to understand inherent safety features, such as the actions of neutralizing antibodies on patho- SVA 3.7 gen load, and to validate the biosafety steps that are part Blázquez et al. Porcine Health Management (2020) 6:16 Page 6 of 9 Table 4 Combined inactivation steps in the manufacturing process of SDP. Inactivation expressed as colony-forming unit (cfu) per g in case of bacteria and Log10 TCID50 for viruses Bacteria /Virus (enveloped or non-enveloped) Spray-Drying Reference UV-C Reference Storage at 20 °C Reference Combined Theoretical for 14 d Inactivation E. coli K88 7.3 [30] 4.3 [30] 11.6 E. coli K99 7.7 [30] 4 [30] 11.7 Salmonella typhimurium 5.4 [29] 3.6 [72] > 4.2 [29] > 13.2 Salmonella choleraesuis 5.3 [29] 5.6 [72] > 4.8 [29] > 15.7 PRV (enveloped) > 5.3 [31] 4.5 [74] > 9.8 PRRSV (enveloped) > 4.0 [31] > 4.0 [74] > 4.0 [47] > 12.0 PEDV (enveloped) > 5.2 [34] > 4.1 [74] > 3.5 [34] > 12.8 ASFV (enveloped) ~ 4.0 [35] ~ 4.0 [75] ~ 8.0 SVDV (non-enveloped) > 6.0 [32] 2.6 [74] > 8.6 Blank cell means that the inactivation associated with that step has not been determined of the manufacturing process of SDP which are directly by PCR techniques. However, PCR techniques are not implemented to inactivate and/or eliminate pathogens. able to differentiate between infective and non-infective The action of neutralizing antibodies to endemic path- viral particles [46]. In vivo bioassays or feeding studies ogens in the population has been demonstrated in vari- are still considered the most accurate method of distin- ous studies [12–14] to be an inherent safety step that guishing if viral particles in SDP are infective or not, and may contribute to the safety of blood products. The as previously discussed SDP has shown to be non- spray-drying conditions used during the manufacturing infective in feeding studies, even though viral genome of SDP represent the most critical step that contributes was present in SDP. to the inactivation of different pathogens [28, 31–34]. The UV-C treatment for the tested pathogenic bacteria Also, certain storage conditions (such as room and viruses showed Log10 reduction values very close or temperature > 20 °C for 14 days) have been demonstrated superior to the 4D value using industrial manufacturing as a safety treatment for some enveloped viruses and conditions (3000 J/L). Recommendations of WHO bacteria [34, 47]. All of these biosafety steps contribute (2004), which were developed for the evaluation of in- to the global safety of SDP, as demonstrated in several activation/removal of viruses in human plasma deriva- in vivo studies [36–39, 43, 45, 78]. tives, indicates that the use of two different inactivation Since SDP is produced from plasma with high protein methods with different mechanisms of action represent concentration and biological activity, it is important that redundant biosafety steps. Therefore, the combination of these proteins be preserved during processing. UV-C ir- UV-C irradiation of the liquid followed by spray-drying radiation was profiled as a good candidate to be imple- at 80 °C throughout its substance must be considered re- mented in the manufacturing process as a new dundant biosafety steps for production of SDP. The redundant biosafety step because of its limited impact Log10 reduction factors of each of the steps should be on biologically active proteins that benefit animal health. considered cumulative within the manufacturing Technological advancements have resulted in the devel- process, thus increasing the overall inactivation capacity opment of UV-C irradiation devices based on turbulent of the system (Table 4). flow, which enables the irradiation of opaque fluids with high viscosity efficiently. In addition, these UV devices Conclusion have been widely used in the food industry for the treat- The manufacturing process involves several safety fea- ment of other complex opaque liquids like milk or fruit tures that mitigate any biological risk for SDP use as an juices. ingredient in feed for pigs. The collection of blood from Despite that the implementation of UV-C and spray- healthy animals and the spray-drying process are two of drying as inactivation processes has shown its effective- the safety steps that have been proven to inactivate nu- ness in reducing bacterial and viral loads in plasma, the merous pathogens of interest for the swine industry. presence of some of these pathogen genomes (especially Furthermore, the presence of neutralizing antibodies viruses) detected in SDP by real time PCR (qRT-PCR) may be considered as an additional inherent safety step generates doubts about its potential infectivity. The bio- for pathogens that are able to produce neutralizing anti- safety steps to produce SDP inactivate several pathogens, bodies. Also the post-processing storage of SDP at 20 °C but the pathogen genome is not eliminated from the for 14 days has proven effective for certain enveloped vi- final product and the genetic material can be detected ruses like coronaviruses and PRRSV, while prolonged Blázquez et al. Porcine Health Management (2020) 6:16 Page 7 of 9 storage before release for sale provides more time for Competing interests authorities to react to an outbreak of a foreign animal The authors have read the journal’s policy and the authors of this manuscript have the following competing interests: Javier Polo (JPolo), Elena Blázquez disease in the manufacturing region. (EB), Carmen Rodríguez (CR) and Jesús Ródenas (JR) are employed by APC Overall results obtained with UV-C irradiation were Europe, S.A., Granollers, Spain. APC Europe, S.L.U. manufactures and sells effective for inactivating a diversity of bacteria and vi- spray dried plasma. Joan Pujols, and Joaquim Segalés declare no conflict of interest. APC EUROPE S.L.U. provided support in the form of salaries for ruses spiked and naturally present in commercially col- authors EB, CR, JR and JPolo, but did not have any additional role in the lected liquid animal plasma. Since the UV-C mechanism study design, data collection and analysis, decision to publish, or preparation of inactivation targets nucleic acids and is different than of the manuscript. the thermal inactivation of the spray-drying process, Author details UV-C can be considered an independent biosafety step 1 APC EUROPE, S.L., Avda, Sant Julià 246-258, Pol. Ind. El Congost, E-08403 in the manufacturing process of SDP. UV-C as a safety Granollers, Spain. 2IRTA, Centre de Recerca en Sanitat Animal (CReSA, IRTA-UAB), Campus de la Universitat Autònoma de Barcelona, 08193 step complies with the WHO recommendations for the Bellaterra, Barcelona, Spain. 3OIE Collaborating Centre for the Research and design of redundant biosecurity steps in the manufactur- Control of Emerging and Re-emerging Swine Diseases in Europe ing process of human blood products for medical use. (IRTA-CReSA), Bellaterra, Barcelona, Spain. 4Departament de Sanitat i Anatomia Animals, Universitat Autònoma de Barcelona (UAB), 08193 Furthermore, UV-C technology can be incorporated into Bellaterra, Barcelona, Spain. 5UAB, Centre de Recerca en Sanitat Animal the manufacturing process, and in fact it is already used (CReSA, IRTA-UAB), Campus de la Universitat Autònoma de Barcelona, 08193 in some spray-drying industrial plants. In conclusion, Bellaterra, Barcelona, Spain. 6APC LLC, 2425 SE Oak Tree Court, Ankeny, IA 50021, USA. UV-C irradiation of liquid plasma is a suitable additional inactivation step for the industrial production process of Received: 26 March 2020 Accepted: 22 May 2020 SDP that further supports the biosafety of SDP use in animal feed. References Abbreviations 1. Howell NK, Lawrie RA. Functional aspects of blood plasma proteins. I. ASFV: African swine fever virus; CIP: Clean in place; DNA: Deoxyribonucleic Separation and characterization. Int J food Sci Technol [internet]. Blackwell acid; EAPA: European animal protein association; GMP: Good manufacturing Publishing Ltd; 1983;18:747–762. Available from: http://doi.wiley.com/https:// practices; HEV: Hepatitis E virus; NASDBPP: North American spray dried blood doi.org/10.1111/j.1365-2621.1987.tb00469.x. and plasma producers.; PCV2: Porcine circovirus type 2; PEDV: Porcine 2. Gatnau R, Paul PS, Zimmerman DR. 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