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The ingredients of SDA BIO vaccine adjuvants are “GRAS”, which is an acronym for the phrase Generally Recognized As Safe. The substances are reported on SCOGS Report Numbers: 9, 10, 35, 43, 65, 86, 88; or 21CFR. 178.3570 list. Various combinations of ingredients may reach the same immunogenicity and safety, only the listed components are selected.
No ingredient is animal origin.
Reaction tanks, components, dispensing and package systems are sterilized or irradiated.
Extreme Emulsion Stability by SDA BIO Adjuvants
Stability is the most important characteristics of vaccine formulations developed from SDA BIO adjuvants. Typical emulsion AS110, AS40, SDA1010, SDA7749, SDA701, both mineral oil and squalene formulations are as extremely stable as long time as > 1 year under as high temperature as 42°C, > 3 years under 4°C. SDA BIO adjuvanted vaccines are the only vaccines resistant to ambient temperature shipment and storage. Maximizing the stability with the most optimized particle size for antigen presentation is far more than HLB technology.
During the stability studies on the vaccine products, appropriate qualitative and / or quantitative tests, preferably in-vitro tests at 4°C, 25°C, 37°C, 42°C are performed to support the integrity of the adjuvant and its components throughout the shelf life of the vaccine. For example, tests for phase separation during storage are important for vaccines containing emulsion adjuvants.
To maximize the effectiveness of vaccines, especially those containing poorly antigenic components or highly purified antigens, it is standard procedure to add adjuvants to the vaccine. Adjuvants trigger innate immune responses that serve to enhance the adaptive response to vaccines and/or balance or shift the nature of these immune response in the direction of either type 1 or type 2 responses. They can reduce the dose of antigen to be injected or the number of doses administered, and they may prolong immunologic memory. Adjuvants work through the following four major mechanisms:
- Depot adjuvants protect antigens from degradation and prolong immune responses as a result of the sustained release of antigen over a period of time. Examples of depot-forming adjuvants include oil in water emulsions.
- Another form of adjuvants consists of particles that effectively deliver antigen to antigen-presenting dendritic cells and so enhance antigen presentation. The immune system traps and processes particles such as bacteria or other microorganisms much more efficiently than soluble antigens. As a result, particulate antigens are much more effective than soluble ones. Examples of such adjuvants include emulsions, microparticles, immune-stimulating complexes, and liposomes.
- Some antigens trigger innate immune responses by simply causing tissue damage and inflammation. Aluminum-based adjuvants cause release of inflammatory molecules and cytokines and simply trigger innate immunity. Saponin-based adjuvants and water in oil emulsions also act by causing tissue damage. Saponins (triterpene glycosides) are detergent-like molecules derived from the bark of the soapbark tree (Quillaja saponaria). Saponin-based adjuvants may selectively stimulate TH1 activity.
- The final form of adjuvant contains microbial products that often represent pathogen-associated molecular patterns that trigger innate immunity. As a result, they activate dendritic cells and macrophages through toll-like receptors and stimulate the secretion of critical cytokines such as IL-1 and IL-12. Depending on the specific microbial product used, they may enhance either TH1 or TH2 responses. Commonly used microbial immunostimulants include lipopolysaccharides (or their detoxified derivatives), killed anaerobic corynebacteria (especially Propionibacterium acnes), and killed Mycobacteria.
Many commercially available and proprietary adjuvants are combinations. For example, very effective adjuvants can be constructed by combining particulate or depot adjuvants with an immunostimulatory agent.
Selection of SDA BIO Adjuvants
Selecting the correct adjuvant is a critical step for vaccine success. Adjuvant must have a balance of safety and efficacy. Different vaccine types such as live attenuated, inactivated, recombinant, vectored, synthetic peptides, or nucleotide vaccines; different animal species, different pathogens such as virus, mycoplasma, bacteria, or parasites; different immune response duration such as short or long term; different antigen purity such as cell culture or egg crude extracts, cinematographic purified; different response profile such as humoral or cellular; different immunizing routes such as injection or mucosal. Some vaccines require emulsion and others require transparent aqueous appearance. In order to enhance immune response, VSP qualijia saponin is often used to serve as immunoenhancer.
Large Scale Preparation of Vaccine
Combination of Merckinade SDA adjuvant and antigen is a self-emulsifying procedure, and does not require high gear homogenization ! For large scale preparation, only a stirring process of moderate speed of 60-120 rpm for ~30 minutes is needed, ideally at under 25-30° C, under sterile condition. Only multi-phase
Normally add slowly the smaller quantity component to the larger quantity components, either adjuvant to antigen or antigen to adjuvant.
Self-Emulsifying/Assemblying Delivery Adjuvants for Biologics (SDA BIO)
What is the function of an adjuvant?
Adjuvants can be magic sauce of modern vaccines, they are the ingredients used in some vaccines that help create a stronger immune response in human or animal individuals receiving the vaccines. In other words, adjuvants help vaccines work better. SDA BIO vaccine adjuvants are the compositions that increase the intensity of the humoral immune response and various cell-mediated responses to the particular antigens once the adjuvents are administrated with these antigens. Adjuvants function to reduce the viscosity of the vaccines and therefore enhance the syringebility and injectability. Adjuvants mask the toxin residue in the antigen, which in turn makes vaccine more tolerated for not causing local or systemic reaction, and increase the vaccine safety. Adjuvants are useful for enabling vaccines to minimize side effects related to the immune response, such as stress and fever. Adjuvants fundementally reduce the vaccine dose and number of injections as antigen-sparing. SDA BIO adjuvants are extremely thermo stable which increases the vaccine’s stability. SDA BIO has general match with various types of antigens. SDA BIO products offer a selection of emulsion-based adjuvants oil-in-water, water-in-oil, water-in-oil-in-water, polymer-latex adjuvants that have transparent appearance. The key skill of SDA BIO “aquous adjuvants” is polymerization of water soluble ethylenic, acrylamide and hydrophilic monomers, and dispersion of an extremely high HLB oily phase emulsifier system to develop “latex”. Upon combination of this latex with high volume antigens, the system turns to oil-in-polymer nanoparticle with high capacity of retaining, slow releasing, and lymphocyte presenting the antigen. SDA BIO vaccine adjuvants of all types 1) oil-in-water formulation, 2) polymeric latex transparent formulation, 3) sub-nano-emulsion transparent complex, 4) cationic nanoemulsion for nucleic antigens, 5) multi-phase emulsion, which are standardized to be 10 times concentrates and are ready to mix/disperse with antigens.
What is the mechanism related to SDA BIO adjuvants?
Adjuvants may act by a combination of various mechanisms including formation of depot, induction of cytokines and chemokines, recruitment of immune cells, enhancement of antigen uptake and presentation, and promoting antigen transport to draining lymph nodes. Depots are produced by adjuvants for retaining antigens at the administration site so as to attract antigen presenting cells that stimulates immune system. The adjuvant allows the progressive diffusion of the antigen to ensure an effective and prolonged stimulation of the immune system. SDA BIO adjuvants retain antigen not only in the injection site but by carrying antigen through a mobile deposit in the circulation and through microfiddusion by droplet to lymph node cells. By binding to antigens, SDA BIO adjuvants provide a slow release and continuous stimulation of the immune system over long period. SDA BIO adjuvants are optimized to provide balance between the depot effect and reduce local and systemic body reactivity.
SDA BIO adjuvants stabilizes epitope conformation. Adjuvants will increasingly be seen not as separate add-on items but as wholly integrated elements of a complete vaccine delivery package. Nanofeatures to adjuvant function together with advanced nanomanufacturing techniques that allow very precise control of particle size, shape, texture, and surface chemistry. All of SDA BIO adjuvant products have demonstrated the capability to stabilize antigen epitopes in inactivated, recombinant, peptide and vectored vaccines.
Certain adjuvants play role in immunomodulation of the cytokine network. Adjuvants are actually classified as immunomodulatory molecules to up-regulate certain cytokines and down-regulate other cytokines. Adjuvants thus involve in the induction of major histocompatibility complex (MHC) Class I or MHC Class II responses. Adjuvants in combination with antigens are capable of directing antigen presentation by the major histocompatibility complexes (MHC) by means of fusion or disruption of cell membranes. Adjuvants may act by a combination of various mechanisms including formation of depot, induction of cytokines and chemokines, recruitment of immune cells, enhancement of antigen uptake and presentation, and promoting antigen transport to draining lymph nodes. Adjuvants activate innate immune responses to create a local immuno-competent environment at the injection site. Depending on the type of innate responses activated, adjuvants can alter the quality and quantity of adaptive immune responses.
Antigen sparing effect: SDA BIO adjuvants amplify the pathogen danger signal triggered by the administration of the antigen for certain pathogens, motivate granulocytes and monocytes, and thus stimulate initiation of innate immunity. Slowing releasing and enhanced immune response obviously reduces antigen amount per effective dose, give an equal to or greater response than high levels of antigen which generation is the most expensive step in vaccine manufacturing.
SDA BIO “Self-emulsification”, “automatic assembly”, “instant use” vaccine adjuvants is a simple combining and mixing of SDA BIO oily phase adjuvant with aquous phase antigen, the desired emulsion is automatically formed. No special equipment, no temperature control, no batch size limit. The oily adjuvants are not sensitive to temperature and are not degenerated or contaminated in the long term ambient temperature transportation and storage. The stability, homogeneity and particle size of the resulted emulsion can be easily tested by centrifugation, microscopy, laser particle size or dynamic light scattering methods. These methods are used in the vaccine quality control for fast verification of solubilization or dispersion of antigen components within the formulation. They can also be used to confirm the ability of SDA BIO vaccine adjuvants to stabilize antigenic media over the long term. we at SDA BIO have done all the fine synthesis of surfactants and polymers, as well as vaccine clinical applications for inactivated whole virus, mycoplasma, bacteria, recombinant and splitted subunit vaccines. Vaccine manufacturers simply combine and mix our adjuvant with your antigen by certain ratio of volume or weight. No specialized equipment or temperature control is required. Vaccine manufacturers do not need to repeat the effort in rheology, texturometry and tribology but to simply check the spin stability at 3000 rpm. Emulsions can be of different types: oil in water, water in oil, or multiple water in oil in water, oil-in-polymer. These different types have different safety and efficacy profiles and are adapted, in animal health, to different animal species and different types of antigens. Hydrophile-lipophile balance (HLB), which measures relative strength of the hydrophilic and hydrophobic activities of repeated macromolecules of nonionic surface active agents, is one of the key technologies. According to the HLB value of the surfactant, different kind of emulsions can be achieved. Those having a low HLB value have a high affinity for oily phases and render W/O emulsions. Those with a high HLB value have a high affinity for the aqueous phase and render O/W emulsions. when the HLB value is intermediate, i.e. around 10, W/O/W emulsions can be achieved. The fatty phase consists of C16-C18 mineral oil Drakeol 6VR or Marcol 52, unless otherwise indicated. Polymers are sodium polyacrylate type Carbomer 940 NF and co-polymers are triblock copolymer Pluronic® L121 unless otherwise indicated.
Quality of Emulsions derived from SDA BIO Adjuvants: 1) Emulsion Thermo Stability: 37°C > 2 months for O/W oil-in-water type. 4°C > 2 years for all the types. The emulsion stability at high temperature represents the potential of vaccine in resisting disconnection of cold chain during vaccine distribution. 2) Emulsion Viscosity: < 20 mPa s. for all types. In modern animal factories, veterinarians no longer fix individual animals for vaccine injection. Instead, they do continuous injections when animals are runing around. Such a low viscosity of emulsion vaccine make it possible to accomplish instant push of 2 mL in 0.1 second, or “flying needle” as farmers call it. 3) Particle Size: < 200 nm, most optimized particle size for antigen presenting. Surfactant structure and HLB value determine conductivity, viscosity, particle size, and stability, which are actually the direct indicators efficacy and the safety of adjuvants. HLB required to obtain certain emulsion type and quality can be very different when using different oils. HLB is such accurately designed for SDA BIO, any significant surfactant activities from antigen molecules or impurities which have polar and non polar groups may lead to fine tune requirement of HLB. 4) Long protection: one vaccination for most of the anmals. Applicable to both prophylactics for population and therapeutic for individual animals. 5) Various administration routes: injection, eye spray and mucosa adhesion nasal spray (around 70 percent of immune cells reside near the mucosal surface where initial infection occurs), aquous fluid oral gel.
SDA Bio Inc. located in the Triangle Research Park of North Carolina, is vaccine adjuvant manufacturing facility. We deliver water–in–oil (W/O), water–in–oil–in–water (W/O/W), oil–in–water (O/W) and polymer based adjuvants to Latin and North America countries. Our manufacturing site in China deliver thousand tons of oil phase adjuvants for generating various vaccine emulsions. Our HLB technology has also been extended to other areas of agriculture and human health.
SDA0701 Gel Vaccine
(with Purified or Crude Antigen)
USDA Licensure of Vaccine Adjuvants
USDA Vaccine Adjuvants Approval & License #1: Adjuvants and Excipients
USDA Vaccine Adjuvants Approval & License #2: VETERINARY SERVICES MEMORANDUM NO. 800.51
- Efficacy studies (Veterinary Services Memorandum 800.202) Download Below
- Safety studies (Veterinary Services Memorandum 800.204) Download Below
According to USDA Document Number: CVB-SOP-0078 <Adjuvants and Excipients>, Section/Area: CVB-SOP-PEL-REV, The Food Safety and Inspection Service (FSIS) transferred the official responsibility to evaluate adjuvants and excipients used in Veterinary Biologies back to the Animal and Plant Health Inspection Service (APHIS) in 2006. Center for Veterinary Biologies (CVB) Notice 06-13 provides details regarding this transfer. FSIS had been providing chemical, toxicological, and pathologic evaluations of new adjuvants/excipients, but APHIS now has the scientific resources necessary to conduct these evaluations. Resuming adjuvant reviews eliminates a step in the approval process that industry must follow and requires contact only with APHIS.
All new product licensing packages should include a thorough description and the composition of any adjuvants. Veterinary Services Memorandum 800.5] provides guidance regarding appropriate data that should be submitted for adjuvants. In general, all new product license applications should contain the following information:
- Generic name of adjuvant (and Trade Name if applicable)
- Chemical composition of adjuvant (list all ingredients and proportions)
- Amount of completed/total adjuvant per dose of product
- Dose volume of product
- Animal species in which the product is to be used
- Route of administration (and specific anatomical site, if designated)
- Information regarding source, grade, quality of tests performed (if any) on each lot
- Slaughter withdrawal period proposed [at least 21 days is required as per title 9, Code of Federal Regulations (9 CFR), section 112.2(a)(8)]
- Other products for which the adjuvant/excipient has been approved (if applicable)
Reviewers should compare the additive description and composition with historic data regarding adjuvants and excipients on file at the CVB. A spreadsheet containing ^proved adjuvants is available to facilitate review of historic data (see adjuvant spreadsheet). The spreadsheet contains information regarding adjuvants and miscellaneous additives that have been approved for use by the CVB. Please note that not all of the products that these approved additives are to be used in are currently licensed. Some products are in the pre-license stage. Some products listed have been licensed but may not be currently manufactured. The adjuvant spreadsheet may not contain all of the adjuvants approved by the CVB. It is simply meant to be used as a tool for reviewers to use when reviewing adjuvant submissions. Reviewers are encouraged to contact the Adjuvant Coordinated Review Team (CRT) chair if revisions or updates to this spreadsheet are identified. Additional data regarding previously approved adjuvants are filed in the adjuvant folder for each firm, located in the file
Additional data and evaluation may be required fbr previously approved adjuvants that are to be included in products in unique ways. The reviewer should consist with the Adjuvant CRT if any questions arise regarding adjuvants. The purpose of the Adjuvant CRT is to generate useful and timely information for the reviewer in order to facilitate scientific review of adjuvants. In order to achieve this purpose, goals of the Adjuvant CRT include:
1. The CRT will strive to provide a response to adjuvant-related questions within 4 weeks of initial consultation.
2. Pathologist on the adjuvant CRT is also available for the specific questions related to pathology at any time.
The reviewer should consult the Adjuvant CRT prior to approval of new adjuvants, or to approval of previously approved adjuvants to be used at increased levels, in different routes of administration, or with different withdrawal periods. Results of an injection site study in the host animal may be required to complete evaluation of the adjuvant.
3. Considerations for an Injection Site Study
The following guidelines should be considered when reviewing an injection site study:
3.1 A protocol should be submitted by the firm prior to conducting the study to ensure the study design is adequate. The proposed dates of conducting the study should be included to allow observation by CVB personnel if deemed necessary.
3.2 At least 10 animals of the minimum age should be included fbr adjuvants used in food-producing species other than fish and poultry:
- The firm should compare the injection site of the new adjuvant to a product matched placebo by injecting the new product on one side of the animal, and the placebo on the other side of the animal. In certain instances, a placebo other than a product-matched placebo may be considered. Justification for using other types of placebos should be included in the protocol submitted fbr review.
- The injection sites should be examined grossly by a veterinarian or board certified veterinary pathologist. The veterinarian or veterinary pathologist should also collect the tissues to be analyzed histologically. The results of gross pathologic examination should be included in the report. High resolution pictures of any gross pathology should be included.
- Histopathology of tissue samples taken from all injection sites should be analyzed by a board certified veterinary pathologist who has no knowledge regarding the products used in the study, and photographs of the histopathologic sections of the injection site should be included in the final report. The same pathologist should evaluate all the slides. The slides should be submitted to the CVB fbr Adjuvant CRT evaluation if requested.