| HS Code | 657101 |
| Product Name | Genlian Jiedu Powder Veterinary Grade API |
| Grade | Veterinary Grade |
| Type | Active Pharmaceutical Ingredient (API) |
| Physical Form | Powder |
| Appearance | Yellowish-brown to brown free-flowing powder |
| Odor | Characteristic herbal odor |
| Taste | Slightly bitter |
| Solubility | Partially soluble in water, forming a suspension |
| Particle Size | At least 95% passes through 80 mesh |
| Microbial Limits | Complies with veterinary microbial purity requirements |
| Applicable Dosage Forms | Tablets, Injections, Capsules, Powders, Granules, Premix, Solutions |
| Storage Conditions | Sealed, cool, dry, protected from light |
| Shelf Life | 24 months |
As an accredited Genlian Jiedu Powder 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 | 25kg net in sealed double polyethylene-lined fiber drums, labeled for veterinary grade API use. Store dry, cool, protected from light. |
| Container Loading (20′ FCL) | 20′ FCL container loading: Genlian Jiedu Powder veterinary grade API packed in sealed, palletized drums, moisture-protected, safely stowed for transport. |
| Shipping | Genlian Jiedu Powder veterinary-grade API is shipped in sealed, moisture-proof containers with tamper-evident packaging to preserve potency. Transport uses temperature-controlled, secure logistics to avoid contamination and degradation. Full documentation, including certificate of analysis and safety data sheet, accompanies each shipment, ensuring regulatory compliance and product integrity upon delivery. |
| Storage | Store Genlian Jiedu Powder veterinary-grade API in a tightly sealed container, protected from light and moisture. Keep in a cool, dry, well-ventilated area below 25°C. Avoid exposure to high temperature or humidity. Ensure container is properly labeled and securely stored, out of reach of children and animals. |
| Shelf Life | Shelf Life: 24 months in original sealed container, stored in a cool, dry place, protected from light. |
In high-throughput poultry drinking-water systems, the acceptance of a botanical API powder is decided less by chemical assay alone than by sieve retention, wetting speed, and the absence of insoluble particles capable of lodging in nipple drinker seals or proportioner diaphragms. A soluble-farm-pack line is typically built around a carrier pre-blend containing 40–60 wt% Genlian Jiedu Powder Veterinary Grade API dispersed in 200-mesh anhydrous glucose monohydrate or spray-dried lactose. The pre-blend is passed through a vibratory sifter fitted with a 160 μm stainless steel woven-wire screen conforming to ASTM E11-22; the retained fraction is resubmitted to a pin mill operated at 3,000–6,000 rpm until ≥90% passes a 150 μm test sieve under Ph. Eur. 2.9.12. Final drinking-water concentration is set at 0.25–1.00 g/L for oral administration, but the working range is adjusted against total dissolved solids in source water because carbonate hardness above 250 ppm CaCO₃ equivalent accelerates sedimentation of botanical cell-wall fragments. Moisture content is controlled to ≤5.0% w/w by ISO 6496:1999 loss-on-drying determination before filling. Compliance for the finished medicated powder requires a veterinary medicinal product marketing authorization under Regulation (EU) 2019/6; if the formulation is supplied as a top-dress or water-miscible feed additive rather than a therapeutic premix, conformity with Regulation (EC) No 1831/2003 must be separately demonstrated. Terminal product types include 100 g and 500 g heat-sealed polyethylene-aluminium sachets for farm packs, 5 kg barrier pouches for central water medication tanks, and proportioner-ready canisters labelled with dose rates per 1,000 L of drinking water. Production-scale bottling lines are operated with dried-air purging to prevent hygroscopic bridging at rotary auger filling heads.
In grower-finisher feed mills, direct addition of fine botanical API powder to a horizontal paddle mixer is the most frequent cause of failed homogeneity audits, because the API fraction segregates along the mixer shaft when its bulk density differs from the corn-soybean meal carrier by more than 0.15 g/cm³. To prevent segregation, the powder is first extended into a working premix at 20–50 kg/tonne using ground rice hulls or calcium carbonate of matched particle size; this intermediate is then metered into complete feed at 2–5 kg/tonne. Mixing is performed in a 2,000 kg twin-shaft paddle mixer for 8–12 min after final ingredient addition, with discharge sampled at ten points according to ISO 6498:2012. A coefficient of variation exceeding 5.0% for the tracer or marker compound indicates either dead-space accumulation at the mixer end-plates, electrostatics from low-humidity air below 30% RH, or overworn ribbon blades. Pellet conditioning must avoid steam temperatures above 65°C because the botanical matrix contains heat-labile phenylpropanoid and iridoid marker compounds; extended retention beyond 30 s at 70°C produces batch-to-batch marker loss that is difficult to distinguish from raw material variability. Compliance under Regulation (EU) 2019/6 requires that the premix not be placed on the market as a feed additive without a veterinary medicinal product authorization when therapeutic claims are attached. Undesirable substances are screened against Directive 2002/32/EC; heavy-metal, pesticide, and botanical foreign-matter limits are confirmed on each incoming API lot. Finished products include 5 kg and 20 kg multi-wall paper bags with inner polyethylene liners for medicated premix, 25 kg complete meal feeds, and short-time pelleted feeds for farm delivery. Feed mills with vacuum coating lines may apply a post-pelleting liquid suspension of the powder in 0.5–1.0% soybean oil to reduce fines, but this step demands line cleaning after each batch to prevent cross-contamination with ionophore coccidiostats.
| Dosage route | Monitored parameter | Control range | Reference method |
|---|---|---|---|
| Drinking-water powder | Retention on 150 μm test sieve | ≤10% | Ph. Eur. 2.9.12 |
| Swine premix | Mixer coefficient of variation at discharge | ≤5.0% | ISO 6498:2012 |
| Injection solution | Pre-filtration turbidity | ≤3 NTU | Ph. Eur. 2.2.1 |
| Tablet core | Crushing strength | 60–100 N | Ph. Eur. 2.9.8 |
| Hard capsule | Uniformity of mass | ±5% deviation from mean | Ph. Eur. 2.9.5 |
Aqueous extraction for injectable dosage forms is not a simple dilution step; it is a purification sequence in which tannins, protein-polysaccharide complexes, mineral ash, and fibre-derived colloidal matter must be reduced before terminal sterilisation. The powdered API is extracted in purified water at a 1:8 to 1:12 weight-to-volume ratio, held at 60–80°C for 90–120 min in a jacketed stainless steel extraction vessel with continuous low-shear agitation. The resulting decoction is clarified in a decanter centrifuge operating at 6,000–10,000 × g, followed by depth filtration through 5–10 μm cellulose-polyester sheets and a sequence of 0.45 μm and 0.22 μm polyethersulfone membrane filters. The clarified liquid may be concentrated under vacuum at 40–50°C until total solids reach 0.1–0.2 g/mL; this concentration range prevents the excessive viscosity that destabilises steam-sterilised solutions and causes filter blinding on automated filling lines. Sterility assurance is governed by Ph. Eur. 5.1.1, bacterial endotoxin control by Ph. Eur. 2.6.14, and particulate clarity by Ph. Eur. 2.2.3. Residual solvent and impurity evaluation follows VICH GL18(R), especially when extraction aids or organic cosolvents are used in upstream processing. The main operational boundary is that aqueous botanical matrices can precipitate at pH below 3.0 or above 8.5; therefore pH adjustment is performed with dilute hydrochloric acid or sodium hydroxide only after pilot-scale stability screening. Published data for this specific polyherbal powder configuration is limited, and each extraction campaign must be qualified for yield, clarity, and heat stability before scale-up. Terminal finish forms include 10 mL, 50 mL, and 100 mL Type I glass vials for large-animal injection, sealed with bromobutyl closures and aluminium caps. A lyophilized presentation in 20 mL vials is manufactured when the aqueous solution shows unacceptable colour change during shelf-life studies; the cake is reconstituted in water for injection at the point of use. Filling lines for these products require an isolator or restricted access barrier system meeting EU GMP Annex 1 requirements for aseptic processing.
Direct compression of Genlian Jiedu Powder Veterinary Grade API is rarely feasible without granulation because botanical powders exhibit poor flow, low bulk density, and variable compressibility. A dry granulation route is preferred for water-sensitive marker compounds. The API is blended at 30–65 wt% with microcrystalline cellulose, croscarmellose sodium at 3–6 wt%, and colloidal silicon dioxide at 0.5–1.0 wt%; magnesium stearate is limited to 0.5–1.0 wt% because excessive lubricant reduces tablet hardness and extends disintegration. The blend is compacted in a roller compactor at roll pressure 6–10 kN/cm, and the ribbons are milled through a 1.0–1.25 mm screen to produce granules with a friable but flowable structure. Compression is performed on a rotary tablet press at 25–45 rpm with pre-compression force 4–8 kN and main compression force 12–18 kN. Tablet cores are specified at 500–1,500 mg total weight with crushing strength between 60 N and 100 N under Ph. Eur. 2.9.8, because lower hardness produces edge chipping during blister-packing and higher hardness slows disintegration beyond 30 min under Ph. Eur. 2.9.1. Dissolution testing uses Ph. Eur. 2.9.3 with a rotating paddle apparatus at 50 rpm in 900 mL of dilute hydrochloric acid at 37°C; however, botanical marker dissolution can exhibit large inter-tablet variability if the granule size distribution is not held within 20–40% retained on 250 μm. In-process sampling and control follows 21 CFR 211.110 for weight variation, hardness, and moisture. The critical boundary in humid climates is the moisture override: the granules absorb atmospheric moisture rapidly above 60% RH, causing sticking at the press feed frame and capping. Dehumidified compression rooms maintaining 35–45% RH and 20–25°C are standard practice. Finished tablet types include 200 mg, 400 mg, and 800 mg API-strength tablets in polyvinyl chloride-aluminium blisters or high-density polyethylene bottles with silica gel desiccant. Aqueous film coating with hydroxypropyl methylcellulose is applied only when clinical palatability requires taste masking; the coating pan exhaust temperature is held below 50°C to avoid marker degradation and tablet core expansion.
For pelleted or granulated feed applications in calf and ruminant grower programmes, the powder is introduced at the conditioner inlet only after steam pressure has been reduced to 0.8–1.2 bar. The addition rate in complete pelleted feed is 1.0–3.0 kg/tonne, with lignosulfonate binder added at 0.5–1.5 wt% of the meal to improve pellet durability without masking the botanical powder in the fines fraction. Short-time conditioning is limited to 60–65°C for 20–30 s; the pellet die is selected with a compression ratio between 1:8 and 1:10 to avoid excessive shear heating. Post-pellet cooling must return pellet temperature to no more than 5°C above ambient before bagging, and final moisture is held at ≤12%. Regulatory compliance for feed hygiene rests on Regulation (EC) No 183/2005, sampling protocols on ISO 6498:2012, and undesirable-substance limits on Directive 2002/32/EC. Terminal products include 25 kg woven polypropylene bags of calf grower pellets, 500 g granular top-dress packs for on-farm mixing, and granulated mineral-premix blends for feed mills. The primary production bottleneck is dust generation at the die outlet, which can carry fine API-containing particles into the cooler and create cross-contamination risk; cyclone extraction with baghouse filtration is therefore maintained at negative pressure of −50 Pa relative to the pelleting floor.
Hard hydroxypropyl methylcellulose capsules are used when dose flexibility and palatability require a dust-free, pre-metered form that avoids the compression forces applied in tableting. The API is filled at 40–70 wt% of the total fill weight into size 0 or 00 capsules, with total fill weight between 400 mg and 800 mg. Because botanical powders often have poor flow, the blend is evaluated by Carr index and Hausner ratio before filling; if Carr index exceeds 25%, fumed silica is added at 0.5 wt% in a low-shear tumble mixer operating at 15–20 rpm for 15–20 min. Filling is performed on a dosator or tamping-pin capsule machine at 2,000–5,000 capsules/h for pilot-scale batches; automatic machines with 100,000 capsules/h throughput require a mechanically pre-compacted slug of the powder to stabilise fill weight. Uniformity of mass is tested under Ph. Eur. 2.9.5 with ≥90% of individual capsule weights within ±5% of the mean. Dissolution is conducted under Ph. Eur. 2.9.3 conditions adapted to the target species; the capsule shell hydrates and releases the powder as a suspension in the gastrointestinal lumen, so wetting speed of the powder rather than disintegration time is the controlling release parameter. The main incompatibility is with hygroscopic excipients such as sorbitol and anhydrous citric acid, which increase moisture uptake and cause the capsule shell to soften or embrittle at 45% RH or above. Packaging therefore uses aluminium foil blister strips of 10 capsules or high-density polyethylene bottles of 60 capsules with desiccant, and labelled storage is controlled at 15–25°C with ≤60% RH. Terminal formats include 250 mg, 500 mg, and 750 mg capsule strengths for equine oral administration, supplied to veterinary compounding pharmacies and licensed manufacturers rather than as direct-to-farm consumer packs in markets where the product has not been registered as a veterinary medicinal product under Regulation (EU) 2019/6.
Competitive Genlian Jiedu Powder Veterinary Grade API for Tablets / Injections / Capsules / Powders / Granules / Premix / Solutions prices that fit your budget—flexible terms and customized quotes for every order.
For samples, pricing, or more information, please contact us at +8615365186327 or mail to admin@ascent-chem.com.
We will respond to you as soon as possible.
Tel: +8615365186327
Email: admin@ascent-chem.com
Flexible payment, competitive price, premium service - Inquire now!
`Genlian Jiedu Powder Veterinary Grade API` is supplied as a multi-constituent botanical extract powder intended for incorporation into seven veterinary dosage forms: tablets, injections, capsules, powders, granules, premix, and solutions. The product designation itself functions as the model identifier in supply-chain and stability records; where a manufacturer-specific material code is assigned, that code is shown on the certificate of analysis and in the site master file but does not replace the product designation. Published monographs specific to this product are limited. Consequently, release and stability decisions rely on authenticated botanical reference materials, supplier batch data, and standard pharmacopoeial methods. The API is not a chemically defined single molecule; therefore its specification is necessarily broader than that of a synthetic parenteral API. The control strategy includes identity by high-performance thin-layer chromatography or high-performance liquid chromatography fingerprint, particle size by laser diffraction, loss on drying, total ash, heavy metals, residual solvents, and microbial limits appropriate to the intended route.
Typical release values observed for the veterinary-grade material include a yellowish-brown to brown fine powder appearance, a laser-diffraction particle-size target of D90 ≤ 180 µm for solid oral and premix use, loss on drying ≤ 5.0% by USP <731>, total ash ≤ 8.0% by USP <561>, and heavy metals ≤ 10 ppm by USP <233>. Microbial limits for non-sterile oral applications are typically total aerobic microbial count ≤ 10³ CFU/g and total combined yeast and mold count ≤ 10² CFU/g with absence of Escherichia coli when tested under USP <2021>/<2022>. For injectable dosage development, the same powder should not be considered sterile solely on the basis of botanical extraction; sterile filtration or terminal sterilization must follow, and bacterial endotoxin limits must be calculated from the maximum intended dose under USP <85> or Ph. Eur. 2.6.14.
Transfer from one dosage form to another changes the critical material attributes that dominate batch performance. For solid dosage forms, particle-size distribution and moisture are most important. A powder with D90 ≤ 180 µm is usually acceptable for wet granulation, but direct compression requires independent confirmation. Using USP <1174>, a powder intended for direct compression should show an angle of repose ≤ 40°, a compressibility index ≤ 25, and a Hausner ratio ≤ 1.34. If these values are not met, wet granulation in a high-shear granulator or fluid-bed granulator is used. The granulation endpoint is not fixed; it is determined by impeller power consumption, chopper current, and subsequent sieve analysis. In capsules, the product is often blended with a direct-fill excipient such as lactose monohydrate or microcrystalline cellulose. Capsule filling equipment should be set for a fill-weight variation appropriate to the capsule size, with final dosage-unit uniformity verified by USP <905>. If the blend bulk density varies more than ±10% batch-to-batch, volumetric filling machines may produce weight variation outside the target range, so dosing-disc or gravimetric adjustment is required.
| Quality attribute | Test method | Solid oral / premix target | Injectable / solution target |
|---|---|---|---|
| Appearance | Visual comparison against sealed reference | Yellowish-brown to brown fine powder | Solution clarity evaluated after reconstitution |
| Identification | HPTLC / HPLC fingerprint | Matches authenticated botanical reference | Matches authenticated botanical reference |
| Particle size | ISO 13320 | D90 ≤ 180 µm | Reconstituted solution passes 0.45 µm prefilter |
| Loss on drying | USP <731> | ≤ 5.0% | ≤ 3.0% for dry injectable powder |
| Total ash | USP <561> | ≤ 8.0% | ≤ 8.0% |
| Heavy metals | USP <233> | ≤ 10 ppm | ≤ 10 ppm |
| Microbial limits | USP <2021>/<2022> | TAMC ≤ 10³ CFU/g, TYMC ≤ 10² CFU/g | Final product tested sterile by USP <71> |
| Bacterial endotoxin | USP <85> / Ph. Eur. 2.6.14 | Not specified unless dose-based risk exists | Dose-based limit calculated from maximum exposure |
On a rotary tablet press, precompression and main compression forces depend on tooling diameter, fill depth, and required tablet hardness. No single published compression profile is available for this exact botanical API; however, a press equipped with 8 mm round tooling generally operates with precompression force around 2–5 kN and main compression force sufficient to achieve 8–12 kp tablet hardness for conventional immediate-release formulations. The product should be pre-screened through a 0.6 mm or 0.8 mm stainless-steel mesh before blending, because residual botanical agglomerates may survive low-shear blending and cause content-uniformity deviations. Hardness is not a release specification by itself; disintegration time should be tested using USP <701> and dissolution using USP <711>. A discriminating dissolution method should quantify a marker compound rather than total soluble solids, because the product is multi-constituent.
For oral powders and granules, the product is usually dry-blended with a palatable carrier and a flow aid such as colloidal silicon dioxide at 0.5–1.0 wt%. Overwetting during granulation can reduce marker stability and increase drying time in a fluid-bed dryer; a target granule moisture of ≤ 3.0% after drying reduces caking and microbial stability risk. In a V-blender or intermediate bulk container blender, fill volume should remain between 40% and 60% of total capacity for optimal mixing. If the API concentration in a premix is below 1%, a geometric dilution step is used to prevent segregation. The final premix is tested for blend uniformity by collecting 10 representative samples; a relative standard deviation of ≤ 5.0% for marker assay is a common acceptance criterion.
In premix applications, particle size and bulk density interact with carrier particle size to control segregation. If the carrier has a volume median diameter far above the API, the API can migrate through interstitial spaces and accumulate at the bottom of the container. Sieve analysis under ISO 2591-1 or laser diffraction under ISO 13320 should be performed on both API and carrier. A practical approach is to select a carrier whose volume median diameter is within 3 to 5 times the API D50, although published data for this exact product are limited. Moisture uptake in open atmospheres above 60% RH can increase sticking on tablet tooling and caking in premix bags; therefore the product should be stored in sealed, moisture-resistant packaging and pre-drying may be required before use. Loss on drying remains a meaningful control point: if material exceeds 5.0%, flowability and microbial risk are usually higher. A fluid-bed dryer or vacuum dryer may be used to reduce moisture to ≤ 3.0% before dry milling; the drying temperature should be evaluated for marker stability, and heated air above 60 °C is often avoided for botanical extracts unless stability data support it.
Unlike synthetic small-molecule APIs, botanical powders do not have a defined melting point or crystalline polymorphism; therefore traditional polymorph screening by differential scanning calorimetry is less informative. Instead, batch comparability is assessed through chromatographic fingerprint and particle-size overlap. This represents a difference from other products: standardized synthetic APIs frequently use polymorph identification as a release criterion, while the botanical grade requires a broader identification panel and stricter control of residual non-active plant components.
For liquid solutions, the powder is dissolved or dispersed in water or a co-solvent system. Solubility is generally matrix-dependent and should be measured in the intended vehicle at the target concentration. If the product is intended for oral solution, filtration through a 0.45 µm membrane before packaging reduces visible particulate contamination. If the product is intended for injection, the solution must be sterile, pyrogen-controlled, and compatible with the container-closure system. Because botanical extracts often contain high-molecular-weight polysaccharides, proteins, and tannins, direct passage through a 0.22 µm sterilizing filter may be difficult if the solution is not sufficiently purified. A staged filtration train of 1.0 µm, 0.45 µm, then 0.22 µm is used; filter capacity is checked by incremental throughput, and the bubble point or pressure-decay test is performed before and after filtration. Published data for this specific product in injectable form are limited; therefore filtration compatibility and extractables must be studied on the actual solution.
Injectable dosage development imposes requirements that do not exist for oral powders and premixes. The acceptance limit for bacterial endotoxins is dose-dependent and is calculated as K/M, where K is the threshold pyrogenic dose per kg and M is the maximum dose per kg per hour; for veterinary parenterals this calculation follows the principles of USP <85> and Ph. Eur. 2.6.14. If a dose limit is not specified by a regional monograph, the developer must justify the limit from target species and route. The API is non-sterile, so aseptic filling cannot begin before bioburden reduction or terminal sterilization. Heat sterilization of a botanical solution may degrade marker compounds; therefore sterilizing filtration is often evaluated first. The filter membrane must be compatible with the co-solvent or pH-adjusted vehicle; nylon, polyethersulfone, and polyvinylidene fluoride membranes are not equally compatible with all extract fractions. Prefiltration through depth filter media may be necessary to reduce colloid load. The final filled solution is tested for sterility under USP <71>, and visible particulate matter is assessed under USP <790> or Ph. Eur. 2.9.20. Where the product is marketed as a dry powder for reconstitution, the reconstituted solution must meet the same particulate and sterility expectations as a ready-to-use injection.
Products marketed only as oral premix powders often do not include endotoxin control, bioburden reduction, or particulate testing; an injectable-grade product requires these additional controls. The distinction is not simply labeling. It is a change in manufacturing environmental control, final release testing, and stability protocols.
Moisture control has an outsized effect on solid oral operations. At residual moisture above 5.0%, botanical powders can form firm agglomerates that pass through a mill but re-agglomerate in hoppers, resulting in flow blockages on rotary tablet presses and erratic capsule filling. In a twin-shell blender, caked material can adhere to the shell walls and leave the blend undermixed; in a ribbon blender, dead zones can develop near the discharge valve if the powder is cohesive. If open handling occurs at relative humidity above 60%, moisture gain can be rapid; pre-drying or humidity-controlled rooms are required. In capsules, powder bridging in the hopper can produce weight variation exceeding ±10%, and the defect is often intermittent rather than gradual. Tablet manufacturing may show picking and sticking on punches when moisture is high; punch-coating solutions may reduce the symptom but do not correct a moisture-related failure. Therefore batch release should include loss on drying and, where justified, water activity measurement. A water activity ≥ 0.60 increases the probability of microbial proliferation in non-sterile botanical powders; for this reason, bulk packaging with desiccants and sealed polyethylene-aluminium liners is recommended.
| Attribute | `Genlian Jiedu Powder Veterinary Grade API` | Unrefined botanical powder | Single-marker standardized extract |
|---|---|---|---|
| Identification | Multiple marker HPTLC/HPLC fingerprint against authenticated reference | Often limited to botanical microscopy | Single marker content only |
| Particle size | D90 ≤ 180 µm by ISO 13320 | Variable, no defined target | Often D90 ≤ 250 µm but not lot-controlled |
| Moisture | ≤ 5.0% by USP <731> | Variable | ≤ 6.0% sometimes claimed |
| Heavy metals | ≤ 10 ppm by USP <233> | Often absent from CoA | ≤ 10 ppm if specified |
| Microbial control | USP <2021>/<2022> limits | Not routinely controlled | Generally controlled for oral use |
| Endotoxin control | USP <85> possible for injectable development | Not evaluated | Not evaluated for injection |
| Use in tablets, capsules, granules, premix, solutions, and injections | Yes, after dosage-form-specific process adjustment | No, mainly feed premix or extemporaneous powder | Usually limited to oral capsules or granules |
The product should not be combined with strong acids, strong alkalis, or oxidizing agents unless compatibility has been demonstrated in the finished formulation. If organic extraction solvents are used, residual solvent levels should be controlled under USP <467>. Botanical extracts may contain naturally occurring minerals; total ash and acid-insoluble ash are controlled by USP <561>. If the API is stored in humid tropical conditions, the manufacturer should verify that desiccant quantity is sufficient for the expected moisture load. Batch records should include the supplier's sieve fraction or laser-diffraction data because final blend behavior often correlates with the fraction below 45 µm rather than the mean particle size alone. The powder is not intended for human use; veterinary target species, withdrawal periods, and residue control remain the responsibility of the marketing authorization holder.
