Biosafety of spray dried plasma of porcine origin
Spray dried plasma of porcine origin (SDPP) is a feed ingredient derived from the blood of pigs, and is a product whose biosafety is often under scrutiny, particularly during periods of emergence or re-emergence of swine diseases in different regions of the world. In response to these concerns, a significant amount of literature has become available to evaluate the safety of commercial SDPP about a variety of bacteria and viruses affecting the swine industry. These publications indicated several aspects in the manufacturing process of commercial SDPP that contribute to the bio-safety of this functional protein ingredient, starting with the fact that only blood from healthy pigs determined as fit for slaughter for human consumption is collected for commercially produced SDPP. This is the first critical control point in the manufacturing process of SDPP. Avoidance of collecting plasma from clinically affected pigs decreases the risk of potential pathogen transmission; however, in case of asymptomatic diseases, the safety features of the whole manufacturing process should assure inactivation of such pathogens that cannot be detected at inspection. The general procedures involve collection of pooled blood at inspected abattoirs, transport to remote processing plants, drying, and packaging of the dried product. Liquid pooled plasma used in commercial production of SDPP inherently contains antibodies with neutralizing capacity against a variety of pathogens, which contributes to the biosafety of the finished product and this is an additional critical control point in the process of manufacturing SDPP .
The spray-drying process has demonstrated its efficacy as a pasteurization-like process to eliminate bacteria and viruses . During spray drying, it is ensured that plasma is exposed to temperatures over 80 °C throughout its substance and this is one of the most important critical control point in the manufacturing process of SDPP (Fig. 1).
Research, in which plasma has been inoculated with different viruses prior to drying, has shown that spray drying is an effective method to inactivate Pseudorabies virus, Porcine Reproductive and Respiratory Syndrome virus (PRRSV) , and Swine Vesicular Disease virus . Animal studies have also failed to show any evidence of transmission of Porcine Circovirus type 2 (PCV2) [59, 62–64] when diets supplemented with commercial SDPP containing the genome of this virus were fed to pigs, even though these particular virus is considered to be amongst the most heat stable swine viruses known today . However, other authors  reported PCV2 transmission in naïve pigs given an oral gavage of experimentally produced SDPP. The experimental SDPP used in this study was produced using a laboratory scale spray-dryer from the blood of a single infected pig showing PCV2 viremia without PCV2 neutralizing antibodies and clinical evidence of post-weaning multisystemic wasting syndrome. Several variables influenced these results, including high virus load (the plasma was obtained from a single pig at peak viremia), the use of low inlet (166 °C) and outlet temperatures (67-71 °C), small particle size (10 ?m), and less than 1 sec residence time which is lower than those typical for industrial dryers (inlet temperature, 170-310 °C; outlet temperature, 80-90 °C; particle size, 45–150 ?m; residence time, 20–90 sec). Moreover, as stated before, commercial SDPP is always obtained from healthy pigs determined as fit for slaughter for human consumption. The differences in source material and manufacturing processes may explain the contradicting results obtained between the study conducted by Patterson et al.  and other studies [37, 59, 62–64] that used commercially produced SDPP, even though PCV2 DNA was present in the tested commercial SDPP.
In addition, it also has been demonstrated throughout retrospective feeding studies that the manufacturing process of SDPP inactivated Hepatitis E virus , another virus of concern in the swine industry.
With the emergence of Porcine Epidemic Diarrhea virus (PEDV) in North America, feed containing SDPP was suspected to play a role in the spread of PEDV . However, there is evidence indicating that the spray drying process, even at lower temperatures than those used to produce commercial SDPP, inactivate PEDV [69, 70]. In addition, it has also been reported that PEDV inoculated in SDPP survived for less than 7 days when stored at room temperature (20-22 °C) . Similarly, other research has shown that PEDV does not survive in swine feces for more than 7 days when stored at room temperature . In a recent publication , PEDV was inoculated in several ingredients commonly used in swine diets and stored outdoors under winter time ambient conditions of Minnesota. Samples were tested for viable PEDV using virus isolation or swine bioassay at different storage days post-inoculation (DPI). Results showed that PEDV inoculated on soybean meal remained infectious for 180 DPI, while PEDV inoculated on SDPP was not infective by swine bioassay just after 1 DPI. This study demonstrated that PEDV viability in feed appears to be influenced by ingredient type, with extended survival reported in soybean meal, and therefore pointed out a potential way of PEDV introduction in North America. Furthermore, the results confirmed that SDPP was not an ingredient where PEDV can survive for a long period of time. In addition, two studies demonstrated that feeding diets containing SDPP with the PEDV genome did not cause transmission of the disease to PEDV-naïve pigs even when fed at 5 % of the diet for either 14  or 28 days . Moreover, additional swine bioassays conducted with different lots of SDPP PCR positive for PEDV genome demonstrated lack of infectivity . Even more, an epidemiological investigation of porcine origin feed ingredients and the occurrence of PEDV at Midwestern USA swine farms concluded that SDPP and porcine-origin feed ingredients in general, had negligible to very low association with PEDV in pigs consuming that feed . Finally, it has been reported that millions of pigs in PEDV free regions remained free of PEDV even though these pig populations had been fed PEDV PCR positive SDPP .
The fact that only one published study  had associated the first cases of PEDV infection in Ontario Canada with feed containing SDPP that was PCR positive for PEDV is controversial because the origin of the infectious PEDV in that study was not clear . In that paper, a bioassay reported that the SDPP used in the feed was infectious; however, the feed containing the SDPP was not infectious. Also the SDPP used in that study was manufactured more than two months earlier than the initial PEDV cases were reported . As indicated in previous studies, PEDV was unable to survive spray-drying conditions typical for commercial SDPP and PEDV did not survive in SDPP samples kept in refrigerated storage for more than 2 to 3 weeks. These data suggest that the first PEDV cases reported in Canada were a consequence of cross-contamination of the SDPP product with other infective sources.
Collectively the results of these studies provide solid evidence to support the fact that commercial SDPP is a safe product for pigs, even though the genome of various swine pathogens may be present in SDPP.
Furthermore, SDPP is a dry product with low moisture (9 %) and very low water activity (Aw 0.6). Some pathogens, especially enveloped viruses such as PRRSV, transmissible gastroenteritis virus or PEDV are not able to survive for a prolonged period in dry materials like SDPP. Therefore, as an additional safety feature, the members of the North American Spray Dried Blood Plasma Producers Association (NASDBPP) and the European Animal Protein Association (EAPA), which represent approximately 65-70 % of the spray-dried blood products produced worldwide, voluntarily stores SDP products of porcine origin at room temperature (20 °C) for two weeks after packaging as additional safety feature to assure customers inactivation of any potential post-processing contamination of pathogens on packaged product.
In addition, a worldwide leader spray dried plasma producer has recently introduced a new technology based on ultraviolet (UV) irradiation of liquid plasma before concentration and spray-drying that will be considered as a redundant safety step. UV irradiation of liquid plasma has demonstrated to no affect functionality of SDPP when supplemented in post-weaning diets and UV irradiation is a recognized technology able to inactivate a variety of pathogen including a diversity of bacteria and viruses, including porcine parvovirus, a model virus of very high heat and chemical resistant virus .