| HS Code | 833392 |
| Product Name | Swine Pasteurella multocida Vaccine, Inactivated Veterinary Grade API for Tablets / Injections / Capsules / Powders / Granules / Premix / Solutions |
| Vaccine Type | Inactivated bacterial vaccine |
| Target Pathogen | Pasteurella multocida |
| Target Species | Swine |
| Veterinary Grade | Yes |
| Api Status | Active Pharmaceutical Ingredient |
| Dosage Forms | Tablets, Injections, Capsules, Powders, Granules, Premix, Solutions |
| Route Of Administration | Parenteral or oral depending on final dosage form |
| Immunogenicity | Induces active immunity against Pasteurella multocida |
| Inactivation Method | Chemical inactivation using agents such as formaldehyde |
| Adjuvant | May contain aluminum hydroxide or oil adjuvant to enhance immune response |
| Preservatives | May contain preservatives like thimerosal |
| Storage Condition | Store refrigerated at 2-8°C, protected from light |
| Shelf Life | Typically 12 to 24 months depending on formulation |
| Withdrawal Period | As per veterinary regulatory approval |
As an accredited Swine Pasteurella multocida Vaccine,Inactivated Veterinary Grade API for Tablets / Injections / Capsules / Powders / Granules / Premix / Solutions factory, we enforce strict quality protocols—every batch undergoes rigorous testing to ensure consistent efficacy and safety standards.
| Packing | Packaged in sterile, airtight veterinary-grade containers, sealed to maintain stability. Available quantity: 100 g per container. |
| Container Loading (20′ FCL) | 20′ FCL: temperature-controlled, palletized vaccine API in sealed, refrigerated container; staged, secured loading prevents damage and maintains cold chain integrity. |
| Shipping | Ship under strict temperature-controlled conditions to preserve potency. Package in validated insulated containers with coolants or dry ice, depending on required storage range. Use tamper-evident, leak-proof seals and compliant biological hazard labeling. Include complete documentation, MSDS, and COA. Arrange expedited air freight with temperature monitoring to ensure safe, regulatory-compliant delivery. |
| Storage | Store at 2–8°C in a refrigerator; do not freeze. Keep in the original, tightly closed container, protected from light and moisture. Ensure secure, well-ventilated storage away from feed, food, and children. Avoid excessive heat and temperature fluctuations. Once opened, use immediately or as directed. Discard unused or expired material properly. |
| Shelf Life | Shelf life: 24 months when stored at 2–8°C, protected from light, in unopened original container. |
An aqueous aluminum hydroxide-adsorbed injectable suspension is prepared by mixing the inactivated Pasteurella multocida antigen concentrate with sterile 2.0% w/v aluminum hydroxide gel, using a final Al3+ concentration of 1.0–1.8 mg/mL. The antigenic mass is adjusted to 1.0×109–5.0×109 CFU equivalent/mL against the approved reference preparation, with phosphate-buffered saline at pH 7.2±0.2 and 0.01% w/v thiomersal as preservative. Adsorption is carried out at 4°C for 18–24 h under paddle agitation at 50–80 rpm; rotor-stator dispersion above 2,000 rpm reduces gel pseudoplasticity and releases free antigen into the supernatant, which is detectable by antigen ELISA and correlates with reduced potency in pig challenge models. The terminal product is filled into 50 mL or 100 mL Type II glass vials under laminar flow using piston pumps with peristaltic recirculation. Sterility is evaluated according to 9 CFR 113.26, safety according to 9 CFR 113.100, and potency by active immunization challenge in pigs or by an approved ELISA validated against the challenge model.
Formulation of a water-in-oil bacterin requires balancing antigenic mass against oil-phase droplet size and injection-site reactivity. The aqueous antigen phase, adjusted to 2.0×109–5.0×109 CFU equivalent/mL and pH 7.0–7.4, is emulsified into light mineral oil containing 2–5% w/w mannide monooleate. A 50:50 w/w oil-to-water ratio yields a high-viscosity depot; a 30:70 w/w water-in-oil-in-water ratio reduces viscosity but requires a secondary aqueous phase containing 0.5% w/v polysorbate 80. Rotor-stator emulsification at 5,000–8,000 rpm for 5–10 min produces a D50 of 1–3 μm; high-pressure homogenization at 800–1,000 bar for three passes narrows the droplet distribution but may expose surface antigens to shear denaturation. Viscosity at 20 s⁻¹ ranges from 150–350 mPa·s for water-in-oil and 80–120 mPa·s for water-in-oil-in-water. Terminal product is filled into 20 mL or 50 mL Type I glass vials and injected intramuscularly into sows at 5 and 2 weeks pre-farrowing. Safety is evaluated under 9 CFR 113.100, stability under VICH GL44, and post-injection granuloma scoring uses a 0–3 scale.
| Parameter | Aluminum hydroxide suspension | Water-in-oil emulsion | Water-in-oil-in-water emulsion |
|---|---|---|---|
| Antigen phase proportion | 1.0–5.0 × 10⁹ CFU equiv/mL | 50% w/w aqueous phase | 30% w/w internal aqueous phase |
| Adjuvant concentration | 1.0–1.8 mg Al³⁺/mL | 50% w/w oil phase | 30% w/w oil phase |
| Mixing condition | 50–80 rpm paddle | 5,000–8,000 rpm rotor-stator | 5,000–8,000 rpm rotor-stator |
| Droplet size D50 | not applicable | 1–3 μm | 2–4 μm |
| Viscosity at 20 s⁻¹ | 15–25 mPa·s | 150–350 mPa·s | 80–120 mPa·s |
Freeze-dried antigen cakes are produced when the inactivated API is formulated with a cryoprotectant matrix before lyophilization. A representative matrix contains 2.5% w/v sucrose, 2.5% w/v trehalose, 1.0% w/v mannitol, and 0.5% w/v glycine in 10 mM Tris-HCl pH 7.4. The fill volume is 2.0 mL per 10-dose vial, and the cake is frozen to −45°C at 0.5°C/min with annealing at −20°C for 2 h to permit mannitol crystallization. Primary drying is performed at −20°C and 0.1 mbar for 36–48 h; secondary drying at 25°C for 6–10 h reduces residual moisture to ≤2.5% w/w by Karl Fischer titration per USP<921> Method Ia. Cake collapse occurs if the product temperature exceeds the glass transition temperature of the maximally freeze-concentrated amorphous phase, Tg′ −32°C. Reconstitution with sterile water for injection to 2.0 mL yields a slightly opalescent suspension with pH 7.2±0.3 and aluminum hydroxide particle flocculation that requires gentle inversion for 30 s. The terminal powder is packed under nitrogen in Type I glass vials with bromobutyl stoppers and stored at 2–8°C; stability follows VICH GL44, with moisture and sterility as critical markers.
Combination swine respiratory vaccines require selective adsorption sequencing to avoid competition for aluminum hydroxide binding sites. The Pasteurella multocida antigen is added first to the aluminum hydroxide gel at 1.5–2.0 mg Al³⁺/mL and allowed to adsorb for 12 h at 4°C; Bordetella bronchiseptica is then added at 1.0×10¹⁰ CFU equivalent/mL and Erysipelothrix rhusiopathiae at 1.0×10⁹ CFU equivalent/mL after a further 6 h interval. Reversing the order reduces Pasteurella binding by 15–30% as measured by supernatant antigen ELISA and produces lower geometric mean anti-Pasteurella titres in piglet vaccination. The final product is buffered to pH 7.0–7.5 with 10 mM phosphate and preserved with 0.01% w/v thiomersal. Terminal presentation is 100 mL multidose vials for intramuscular injection at 2.0 mL per piglet, with a booster after 2–3 weeks. Potency of each component is tested according to 9 CFR 113.100 and, where required, challenge protection in appropriate host species. Stability studies follow VICH GL44 and include pH, adjuvanted sedimentation rate, and potency retention for 24 months at 2–8°C.
| Test | Method/standard | Release limit |
|---|---|---|
| Sterility | 9 CFR 113.26 / USP<71> | No growth |
| Safety | 9 CFR 113.100 | No systemic adverse reactions |
| Potency | USDA challenge or validated ELISA | Not less than reference |
| Residual moisture, lyophilized | USP<921> Method Ia | ≤2.5% w/w |
| Aluminum content | ICP-OES | 1.0–1.8 mg Al³⁺/mL |
| pH | USP<791> | 7.0–7.5 |
An oral granule presentation is prepared by dispersing the inactivated API in 2.0% w/v sodium alginate solution at a ratio of 1.0×10⁹ CFU equivalent/g dry solids. The dispersion is extruded through a 0.8 mm nozzle into 0.5 M calcium chloride at 4°C; curing proceeds for 30 min, after which the beads are washed with sterile water and dried in a fluid-bed system with inlet air at 30°C for 45–60 min. The dried granules are filled into 500 g aluminum-laminated pouches under nitrogen and stored at 2–8°C. Terminal use is as a feed topdress for oral priming or booster dosing in pigs. This configuration is not a licensed commercial presentation for Pasteurella multocida inactivated vaccines in the United States under 9 CFR 113.100; published data for this specific configuration is limited. Tablets and capsules are similarly unvalidated: direct compression at 10–20 kN would subject the antigen to shear and localized temperature rise, and no published stability data exist for oral dosage forms containing this antigen.
In autogenous bacterin preparation, the API is diluted 1:10 in sterile phosphate-buffered saline and adsorbed to aluminum hydroxide at 1.5 mg Al³⁺/mL in a closed aseptic system. The batch size is typically 20–500 L and is mixed at 30–50 rpm for 4–6 h before filling into 100 mL or 250 mL high-density polyethylene bottles. Each batch is derived from a confirmed herd isolate and is restricted to the originating premises under state veterinary autogenous biologic provisions; all sterility and inactivation tests must be documented. Terminal product is injected intramuscularly at 2.0 mL per pig with a booster at 14–21 days. Documentation includes antigen identity by slide agglutination, pH 7.0–7.5, aluminum content, and sterility according to 9 CFR 113.26. The final product is not released without a completed safety test in 3–5 pigs and a written veterinary prescription.
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The product designated Swine Pasteurella multocida Vaccine, Inactivated Veterinary Grade API for Tablets / Injections / Capsules / Powders / Granules / Premix / Solutions is an inactivated whole-cell antigen concentrate prepared from swine isolates of Pasteurella multocida. It is not a finished immunological veterinary medicinal product; it is an active pharmaceutical ingredient intended for downstream formulation into injectable suspensions, oral tablets, capsules, powders, granules, premixes, and liquid solutions. The active fraction includes inactivated bacterial cells, outer membrane vesicles, capsular polysaccharide, and lipopolysaccharide-associated somatic antigens. Because P. multocida is a Gram-negative bacterium, the API inherently carries bacterial endotoxin; downstream formulators must therefore implement a finished-product endotoxin control strategy based on route, target species, and dose volume. Two physical presentations are commonly available: a refrigerated liquid antigen concentrate and a lyophilized antigen cake. The product model designation is manufacturer-specific and typically encodes the physical state, antigen concentration, and inactivation method; batch-specific documentation should be consulted rather than relying on a generic label code. The material is produced under veterinary good manufacturing practice and is controlled for identity, sterility, inactivation efficacy, residual formaldehyde, pH, total antigen mass, and, for lyophilized material, residual moisture. The seed lot is selected for capsular type A or toxigenic type D characteristics relevant to swine respiratory disease and atrophic rhinitis. The product is intended for formulation by licensed veterinary pharmaceutical manufacturers and is not supplied with administration instructions for end users.
In a live-attenuated Pasteurella preparation, the organism is maintained in a viable state and can replicate after administration. That property supports mucosal immune stimulation at a lower antigen payload, but it creates cold-chain constraints and excludes most tablet, capsule, and terminal heat processes. The inactivated API cannot replicate; efficacy is therefore dependent on antigen mass, particle presentation, and, in injectable formulations, adjuvant adsorption. This difference is operationally significant: sterile filtration cannot be used, because the whole bacterial cells exceed 0.20 µm, and terminal moist heat cannot be applied without destroying the antigen. A subunit vaccine based on selected outer membrane proteins or recombinant toxoid is easier to characterise and has a lower endotoxin load, but it provides a narrower antigenic repertoire. The whole-cell inactivated API retains capsular, somatic, and outer membrane determinants in a single process stream, which can be useful where field isolates are not fully typed. The trade-off is that the API carries lipopolysaccharide and requires stricter endotoxin, aggregation, and safety controls.
At production scale, the seed culture is expanded through a series of bioreactors with working volumes commonly between 10 L and 1,000 L. The growth medium is held at 36°C to 38°C, with dissolved oxygen maintained above 30% saturation and pH controlled at 7.0 to 7.8. Harvest begins with chilling to 2°C to 8°C to arrest metabolic acid production before formaldehyde addition; if chilling is delayed, continued acid production can reduce pH by 0.3 to 0.8 units and alter antigen integrity. The biomass is concentrated by disc-stack centrifugation and washed in phosphate-buffered saline. Inactivation is performed with formaldehyde at a final concentration of 0.3% to 0.5% v/v for a time-temperature combination validated to reduce viable count to below the detection limit of the sterility method. Mixing during inactivation must be sufficient to prevent bacterial clumping, because clumps can produce tailing of the kill curve. After inactivation, tangential-flow filtration with polyethersulfone cassettes is used to remove low-molecular-weight residuals and concentrate the antigen; membrane molecular weight cutoffs in the 100 kDa to 500 kDa range are common, but the selection must balance lipopolysaccharide retention against flux decay. Transmembrane pressure should not exceed 1.0 bar during whole-cell processing, as excessive pressure can compact the gel layer and lyse bacteria, releasing endotoxin-rich intracellular material into the retentate. Batch-to-batch aggregate content should be tracked by dynamic light scattering after the final concentration step.
Release testing for this API requires biological methods that are not typically found in a small-molecule active substance monograph. Identity is confirmed by reactivity with monospecific antiserum in immunodiffusion or by quantitative ELISA against the seed lot. Sterility is tested according to Ph. Eur. 2.6.1; because the inactivated whole-cell suspension may be turbid, direct inoculation of a validated volume into culture media is often used instead of membrane filtration. Inactivation efficacy is confirmed by culture in appropriate growth media and, where required, by a second passage to detect slow-growing survivors. Endotoxin is controlled by Ph. Eur. 2.6.14; the numerical acceptance limit is assigned in the marketing authorisation because the tolerated endotoxin load differs between a parenteral injection and an oral premix. Residual formaldehyde is determined by a validated method such as Ph. Eur. 2.4.18; the limit must be justified by target-species safety data and final dosage form exposure. Total antigen mass is expressed as total protein or antigen units per millilitre and is linked to the batch potency assay. For lyophilized API, Karl Fischer titration is used to confirm residual moisture not more than 3.0% w/w unless stability data support a higher limit. pH, appearance, and identity by antigen mass are also controlled, because pH drift during storage can indicate degradation or residual metabolic activity.
| Parameter | Acceptance criterion | Reference method |
|---|---|---|
| Sterility | No microbial growth | Ph. Eur. 2.6.1 / 9 CFR sterility test |
| Inactivation | No viable Pasteurella multocida recovered | Culture amplification / 9 CFR 113.26 |
| Bacterial endotoxin | As authorised for target species and route | Ph. Eur. 2.6.14 |
| Residual formaldehyde | As authorised; species-specific safety margin required | Ph. Eur. 2.4.18 |
| Residual moisture, lyophilized | Not more than 3.0% w/w unless otherwise justified | Karl Fischer titration |
| Identity | Reactive with specific antiserum or ELISA-positive | Immunodiffusion / ELISA |
| pH of liquid concentrate | 6.5 to 7.5 | Potentiometric method |
| Total antigen mass | Batch-specific; linked to potency | Total protein / antigen units |
The potency assay for inactivated Pasteurella antigens is usually a parallel-line bioassay in laboratory animals, comparing the test API against a qualified reference preparation. The release limit is expressed as relative potency; when the specification requires a lower confidence limit not less than 1.0, the batch must demonstrate antigen mass conservation through downstream processing. If no animal test is authorised, an antigen quantification ELISA may be used as a surrogate, provided the manufacturer has demonstrated correlation with protection. Published data for this specific API in non-injectable oral forms is limited; therefore each formulator must establish its own process and stability history.
For lyophilized API, the cycle design has a direct effect on reconstitution and downstream tableting. The shelf temperature during primary drying is held below the collapse temperature of the cake; for many bacterial antigen concentrates, the collapse temperature falls between -25°C and -35°C. Secondary drying is terminated when residual moisture is ≤3.0% w/w. If the primary drying temperature is set too high, microcollapse can produce a dense cake that is difficult to mill and slow to reconstitute. If the freezing step is too rapid, amorphous phases can entrap salts and create localised high-ionic-strength domains that destabilise membrane proteins. Storage after lyophilization should be at 2°C to 8°C unless real-time data support room-temperature distribution; reconstituted liquid should not be refrozen except after a freeze-thaw validation, because repeated freezing can break bacterial aggregates and alter potency test results.
For oral solid dosage forms, the lyophilized antigen must be dried to a low residual moisture before blending. In a hard gelatin capsule, moisture sorption from the capsule shell or from room air can plasticize the antigen cake and accelerate aggregation; encapsulation suites should therefore maintain relative humidity below 40% RH, and fill weight control should be verified at regular intervals. Tablet compression of biological antigens is not established as a routine commercial process for this material. If direct compression is attempted, a rotary tablet press with precompression should be used, and main compression force should be kept at the minimum required to produce a tablet hardness in the 20 N to 50 N range; published data for this specific configuration is limited. Enteric coating with a pH-sensitive acrylic polymer may be applied after confirming that the pan inlet temperature does not exceed 40°C, because higher temperatures can denature surface-exposed outer membrane proteins. For premix or granule presentations, low-shear blending with a V-blender or bin blender at 10 rpm to 25 rpm is preferable to high-shear granulation. If a granulation step is unavoidable, the impeller tip speed should be limited and the product temperature monitored, since shear-induced unfolding of membrane proteins can create insoluble aggregates that are not redispersed after reconstitution. Blend uniformity should meet an acceptance value of not more than 15.0 as defined in Ph. Eur. 2.9.40 for solid dosage forms, unless the authorised specification justifies a different limit. Oral solutions and liquid oral presentations should be formulated at physiologically compatible pH; high-pH buffers above 8.0 should be avoided because they can hydrolyse lipopolysaccharide acyl chains and reduce antigen integrity.
For parenteral presentations, the API is typically combined with aluminium hydroxide gel at an aluminium content of 2.0 mg to 3.0 mg Al³⁺ per dose or with a non-mineral oil adjuvant. The adsorption step should be controlled by measuring free antigen in the supernatant; incomplete adsorption can shift the safety profile and reduce potency. The whole-cell antigen cannot be sterile-filtered because the bacterial particles exceed 0.20 µm, so aseptic processing is mandatory, and final product sterility is confirmed by Ph. Eur. 2.6.1. Subvisible particle counts for the finished parenteral product are monitored by light obscuration according to Ph. Eur. 2.9.19; appropriate limits are assigned in the marketing authorisation. The formulation pH should remain between 6.5 and 7.5. Buffers containing phosphate above 10 mM should be evaluated for their effect on aluminium hydroxide adsorption, because phosphate anions can compete with antigen phosphoryl groups for ligand exchange sites on the adjuvant surface. Oil-in-water adjuvants require high-shear emulsification; shear rates above 10,000 s⁻¹ can denature or aggregate outer membrane proteins and should be avoided in the presence of antigen. Final aqueous suspensions often exhibit a viscosity of 10 mPa·s to 100 mPa·s at 20°C; oil-based formulations may exceed this range, and syringeability should be assessed with the intended needle gauge. Container-closure compatibility should be confirmed with the final formulation, because adsorption of antigen to glass or polymer surfaces can reduce delivered dose at low protein concentrations.
Regulatory classification creates additional differences from other product categories. In the United States, a finished inactivated Pasteurella multocida bacterin may be regulated under 9 CFR 113.70, while the API supplied to a formulator is governed by the approved outline of production and current good manufacturing practice requirements. In the European Union, the finished immunological veterinary medicinal product must comply with Regulation (EU) 2019/6 and relevant Ph. Eur. general chapters. Importing jurisdictions may require batch-specific potency data generated in the target species or in a recognized laboratory animal model. Compared with live-attenuated Pasteurella products, this inactivated API has no reversion risk and no post-vaccination shedding, but it generally requires a higher antigen payload and an adjuvant. Compared with toxoid-only or subunit products, it retains a broader range of somatic and capsular antigens, but carries more endotoxin. The material should not be combined with amine-based additives in aqueous solution because residual formaldehyde can react with primary amines to form Schiff-base adducts and reduce antigen integrity. If lyophilized, it should be reconstituted with a vehicle of defined ionic strength and used immediately; prolonged holding after reconstitution at ambient temperature is not recommended unless formulation-specific stability data support such use.
