玻璃体液随年龄增长而出现皱缩，进而导致黄斑牵拉，后者可引起视力降低和成像变性，并且是黄斑裂孔形成的危险因素之一。目前唯一可选的VMT有效疗法为移除玻璃体液的玻璃体切割术。然而，玻璃体切割术后患者将有4至6周无法正常工作和生活，并且需在1至2周内采用极为不便的俯卧位。
近日，欧洲药品管理局（EMA）人用药品委员会（CHMP）推荐批准用于治疗玻璃体黄斑牵引综合征（VMT）的首个药物Jetrea上市。
Jetrea含有新型活性物质重组人蛋白奥克纤溶酶（ocriplasmin）。Ocriplasmin对玻璃体液和视网膜交界面的蛋白具有酶活性。通过降解上述蛋白，Ocriplasmin可松解玻璃体液与黄斑之间的粘连，进而消除黄斑牵引。CHMP推荐批准Jetrea用于治疗VMT，其中包括直径≤400μm的相关性黄斑裂孔。推荐剂量为患目单剂量125mg玻璃体内注射。CHMP同时要求生产商向计划应用Jetrea的医务人员提供相关信息。
美国食品与药物管理局（FDA）也于2012年10月批准了Jetrea用于治疗症状性玻璃体黄斑黏连（VWA）。

JETREA 0.5 mg/0.2 ml concentrate for solution for injection 1. Name of the medicinal product
JETREA 0.5 mg/0.2 ml concentrate for solution for injection
2. Qualitative and quantitative composition
Each vial contains 0.5 mg of ocriplasmin* in 0.2 ml solution.
After dilution with 0.2 ml of sodium chloride 9 mg/ml (0.9%) solution for injection, 0.1 ml of the diluted solution contains 0.125 mg ocriplasmin.
*Ocriplasmin is a truncated form of human plasmin produced by recombinant DNA technology in a Pichia pastoris expression system.
For the full list of excipients, see section 6.1.
3. Pharmaceutical form
Concentrate for solution for injection (sterile concentrate).
Clear and colourless solution.
4. Clinical particulars
4.1 Therapeutic indications
JETREA is indicated in adults for the treatment of vitreomacular traction (VMT), including when associated with macular hole of diameter less than or equal to 400 microns (see section 5.1).
4.2 Posology and method of administration
JETREA must be prepared and administered by a qualified ophthalmologist experienced in intravitreal injections. The diagnosis of vitreomacular traction (VMT) should comprise of a complete clinical picture including patient history, clinical examination and investigation using currently accepted diagnostic tools, such as optical coherence tomography (OCT).
Posology
The recommended dose is 0.125 mg (0.1 ml of the diluted solution) administered by intravitreal injection to the affected eye once as a single dose. Each vial should only be used once and for the treatment of a single eye. Treatment with JETREA in the other eye is not recommended concurrently or within 7 days of the initial injection in order to monitor the post-injection course including the potential for decreased vision in the injected eye. Repeated administration in the same eye is not recommended (see section 4.4).
See section 4.4 for instructions on post-injection monitoring.
Special populations
Renal impairment
No formal studies have been conducted with JETREA in patients with renal impairment. No dose adjustment or special considerations are anticipated for patients with renal impairment (see section 5.2).
Hepatic impairment
No formal studies have been conducted with JETREA in patients with hepatic impairment. No dose adjustment or special considerations are anticipated for patients with hepatic impairment (see section 5.2).
Elderly
The elderly population has been studied in clinical studies. No dose adjustment is required.
Paediatric population
There is no relevant use of JETREA in children aged under 18 years in vitreomacular traction (VMT), including when associated with macular hole of diameter less than or equal to 400 microns. Currently available data on paediatric use are described in section 5.1.
Ethnicity
Experience is limited in groups other than Caucasians.
Method of administration
Single use vial for intravitreal use only.
Preoperative antibiotic drops may be administered at the discretion of the treating ophthalmologist.
Precautions to be taken before handling or administering the medicinal product
The intravitreal injection procedure should be carried out under controlled aseptic conditions, which include the use of surgical hand disinfection, sterile gloves, a sterile drape, a sterile eyelid speculum (or equivalent) and the availability of sterile paracentesis (if required). The periocular skin, eyelid and ocular surface should be disinfected and adequate anaesthesia and a broad spectrum topical microbiocide should be administered prior to the injection according to standard medical practice.
For instructions on dilution of the medicinal product before administration, see section 6.6.
The injection needle should be inserted 3.5-4.0 mm posterior to the limbus aiming towards the centre of the vitreous cavity avoiding the horizontal meridian. The injection volume of 0.1 ml is then delivered into the mid-vitreous.
4.3 Contraindications
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
Active or suspected ocular or periocular infections.
4.4 Special warnings and precautions for use
Post-injection monitoring
JETREA is administered by intravitreal injection only. Intravitreal injections have been associated with intraocular inflammation/infection, intraocular haemorrhage and increased intraocular pressure (IOP). Proper aseptic injection techniques must always be used. Following the intravitreal injection, patients should be monitored for any side effects such as (but not limited to) intraocular inflammation/infection and elevation in IOP. Transient increases in IOP including transient blindness and non-perfusion of the optic nerve have been seen within 60 minutes of injection of JETREA. Monitoring for increases in IOP may consist of a check for perfusion of the optic nerve head immediately after the injection and tonometry within 30 minutes following the injection. Intraocular inflammation/infection may be assessed using biomicroscopy between 2 and 7 days following the injection. Patients should be instructed to report symptoms suggestive of intraocular inflammation/infection or any other visual or ocular symptoms without delay. If any of the above events occur the patient should be treated according to standard medical practice.
Other warnings and precautions
The safety and efficacy of JETREA administered to both eyes concurrently has not been studied. Therefore administration to both eyes concurrently is not recommended.
Repeated administration of JETREA in the same eye has not been adequately studied and is therefore not recommended.
There are no clinical data on concomitant use of ocriplasmin with VEGF-inhibitors.
JETREA has not been studied in patients with large diameter macular holes (> 400 microns), high myopia (> 8 dioptre spherical correction or axial length > 28 mm), aphakia, history of rhegmatogenous retinal detachment, lens zonule instability, recent ocular surgery or intraocular injection (including laser therapy), proliferative diabetic retinopathy, ischaemic retinopathies, retinal vein occlusions, exudative age-related macular degeneration (AMD) and vitreous haemorrhage. Treatment is not recommended in such patients.
The potential for lens subluxation or phacodonesis cannot be ruled out (see section 4.8 and 5.3).
There is limited experience in patients with non-proliferative diabetic retinopathy or history of uveitis (including active severe inflammation) or significant eye trauma. Caution should be exercised when treating such patients.
The effect of ocriplasmin (particularly in inducing resolution of vitreomacular adhesion or causing total posterior vitreous detachment [PVD]) is reduced in subjects with an epiretinal membrane (ERM) or a diameter of VMA > 1500 microns (see section 5.1).
Due to a potential increase in tractional forces, there is a risk of occurrence of new or enlarged macular holes (see section 4.8).
There is a risk for a significant, but transient loss of visual acuity during the first week after the injection. Patients should be monitored appropriately (see section 4.8).
4.5 Interaction with other medicinal products and other forms of interaction
No formal interaction studies have been performed.
Ocriplasmin is a proteolytic enzyme with serine protease activity which could be present in the eye for several days after intravitreal injection (see section 5.2). Administration in close temporal association with other medicinal products in the same eye may affect the activity of both medicinal products and is therefore not recommended.
No systemic interactions are anticipated.
4.6 Fertility, pregnancy and lactation
 Pregnancy
There are no data for the use of JETREA in pregnant women. No reproductive toxicology studies have been performed. The systemic exposure of JETREA is expected to be very low after intravitreal injection. JETREA should be used during pregnancy only if the clinical benefit outweighs the potential risks.
Breast-feeding
It is unknown whether JETREA is excreted in human milk. JETREA should be used during breast-feeding only if the clinical benefit outweighs the potential risks.
Fertility
There are no data on the effect of JETREA on fertility.
4.7 Effects on ability to drive and use machines
The intravitreal injection of JETREA may be followed by temporary visual disturbances (see section 4.8). In these cases, patients should not drive or use machines until the visual disturbances have resolved.
4.8 Undesirable effects
 Summary of the safety profile
Over 800 patients have been treated with an intravitreal injection of JETREA, with over 570 patients treated with the recommended dose of 0.125 mg.
All adverse reactions were ocular. The most commonly reported were vitreous floaters, eye pain and photopsia, as well as conjunctival haemorrhage resulting from the injection procedure. Most of the adverse reactions occurred within the first week after the injection. The majority of these reactions were non-serious, mild in intensity and resolved within 2 to 3 weeks.
The incidence of serious adverse reactions that occurred in all clinical studies was 2.2% in JETREA treated patients and 2.4% in control patients.
Tabulated list of adverse reactions
The following table summarises the adverse reactions that occurredin clinical studies with a reasonable possibility of causality to the injection procedure or JETREA.
The adverse reactions are listed by MedDRA system organ class and frequency using the following convention: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to < 1/1,000); very rare (< 1/10,000) and not known (cannot be estimated from the available data). Within each frequency grouping, adverse reactions are presented in the order of decreasing clinical importance.

Eye disorders

Very common Vitreous floaters, eye pain, conjunctival haemorrhage Common Visual acuity reduced*, visual impairment, vision blurred, retinal haemorrhage, vitreous haemorrhage, retinal tear*, retinal detachment*, intraocular pressure increased, macular hole*, macular degeneration, retinal degeneration, macular oedema, retinal oedema, retinal pigment epitheliopathy, metamorphopsia, vitreous adhesions*, conjunctival oedema, eyelid oedema, vitritis, anterior chamber cell, anterior chamber flare, iritis, photopsia, conjunctival hyperaemia, ocular hyperaemia, vitreous detachment, retinogram abnormal*, eye irritation, dry eye, foreign body sensation in eyes, eye pruritus, ocular discomfort, photophobia, chromatopsia* Uncommon Transient blindness, lens subluxation*, scotoma, visual field defect, diplopia, hyphaema, miosis, pupils unequal, corneal abrasion, anterior chamber inflammation, eye inflammation, conjunctival irritation

* see section 'Description of selected adverse reactions'
Description of selected adverse reactions
Visual acuity reduced
In the placebo-controlled pivotal phase III studies, 7.7% of JETREA patients and 1.6% of placebo patients had acute transient ≥ 2-line (≥ 10 ETDRS letters) loss in best corrected visual acuity (BCVA) during the first week after injection with no alternative explanation for the change. Visual acuity decreases were generally reversible within 2 weeks without intervention. See section 4.4 for monitoring recommendations.
Chromatopsia
Dyschromatopsia (generally described as yellowish vision) has been reported as a common adverse reaction in patients injected with JETREA. The majority of events were non-serious, mild and generally resolved spontaneously. The median time to resolution was 3 months.
Retinogram abnormal
Electroretinographic (ERG) changes (a- and b-wave amplitude decrease) have been reported as a common adverse reaction in patients injected with JETREA; in the majority of cases dyschromatopsia was also reported. In approximately half of the cases, the ERG changes had resolved at the time of the last follow-up. The median time to resolution was 6 months. ERG changes were not predictive of negative outcomes in terms of visual acuity.
Retinal breaks (tears and detachment)
In the placebo-controlled pivotal phase III studies, retinal breaks (tears and detachment) were reported in 1.9% of patients injected with JETREA vs. 4.3% injected with placebo. Most of these events occurred during or after vitrectomy in both groups. The incidence of retinal detachment that occurred pre-vitrectomy was 0.4% in the JETREA group and none in the placebo group, while the incidence of retinal tears (without detachment) that occurred pre-vitrectomy was 0.2% in the JETREA group and 0.5% in the placebo group.
Macular hole
In the placebo-controlled pivotal phase III studies, cases of new onset or worsening of macular hole were reported for 6.7% of all patients injected with JETREA vs. 9.6% injected with placebo. Although in placebo-controlled pivotal phase III studies, JETREA has shown benefit in inducing closure of macular holes associated with vitreomacular traction, in some instances increased traction with subsequent progression or development of new macular hole has been observed. Development of these events is part of natural disease progression; however, a contribution of ocriplasmin in some cases appears plausible based upon its mechanism of action.
Vitreous adhesions
In the placebo-controlled pivotal phase III studies, cases of worsening of vitreomacular adhesion/vitreomacular traction were reported for 1.5% of all patients injected with JETREA vs. 1.1% injected with placebo. Development of these events is part of natural disease progression; however, a contribution of ocriplasmin in some cases appears plausible based upon its mechanism of action.
Lens subluxation/phacodonesis
One case of lens subluxation/phacodonesis was reported in clinical studies in adults and appears to have been possibly related to treatment with JETREA. In a paediatric study evaluating JETREA as an adjunct to vitrectomy, one case of subluxation was reported in a premature infant who received a single intravitreal injection of JETREA 0.175 mg. Lens subluxation was observed in 3 animal species at ocriplasmin concentrations above the intended clinical concentration (see section 5.3).
Based on the proteolytic activity of ocriplasmin, preclinical and clinical findings, the potential for lens subluxation or phacodonesis cannot be ruled out. If this event occurs, it should be treated according to standard medical practice.
See section 4.4 for monitoring recommendations. Routine observation is recommended in all above situations.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system:
United Kingdom
Yellow Card Scheme
Website: www.mhra.gov.uk/yellowcard
Ireland
Pharmacovigilance Section
Irish Medicines Board
Kevin O'Malley House
Earlsfort Centre
Earlsfort Terrace
IRL - Dublin 2
Tel: +353 1 6764971
Fax: +353 1 6762517
Website: www.imb.ie
e-mail: imbpharmacovigilance@imb.ie
Malta
ADR Reporting
The Medicines Authority
Post-Licensing Directorate
203 Level 3, Rue D'Argens
GŻR-1368 Gżira
Website: www.medicinesauthority.gov.mt
e-mail: postlicensing.medicinesauthority@gov.mt
4.9 Overdose
The clinical data on the effects of JETREA overdose are limited. One case of accidental overdose of 0.250 mg ocriplasmin (twice the recommended dose) has been reported. The patient had a decrease in BCVA of 21 ETDRS letters from baseline that returned to within 9 letters of baseline at the end of the study. The patient also developed mild conjunctival hyperaemia, eye inflammation and miosis which resolved with corticosteroid eye drops.
If an overdose occurs, close monitoring is recommended. If an adverse reaction occurs, it should be treated according to standard medical practice.
5. Pharmacological properties
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Ophthalmologicals, Other ophthalmologicals, ATC code: S01XA22
Mechanism of action
Ocriplasmin has a proteolytic activity against protein components of the vitreous body and the vitreoretinal interface (VRI) (e.g. laminin, fibronectin and collagen) and aims to dissolve the protein matrix responsible for the abnormal vitreomacular adhesion (VMA). The tight binding of the protein components within the macular area of the VRI contribute to vitreomacular traction (VMT), leading to visual impairment and/or macular holes.
Clinical efficacy and safety
The efficacy of JETREA was demonstrated in 2 multicentre, randomised, double-masked, placebo-controlled, 6-month studies in patients with VMT. A total of 652 patients (JETREA 464, placebo 188) were randomised in these 2 studies (TG-MV-006 and TG-MV-007).
In both pivotal studies, the proportion of patients who achieved VMA resolution at Day 28 (primary endpoint) was significantly (p≤0.003) higher in the JETREA group compared with the placebo group. The difference continued to be statistically significant through Month 6 in each study (p≤0.024). In the integrated data, 26.5% in the JETREA group compared with 10.1% in the placebo group achieved VMA resolution at Day 28 (p<0.001). The difference was maintained from Day 7 through Month 6 (Figure 1).
Figure 1: Proportion of patients with VMA resolution up to Day 180 (Month 6) (TG-MV-006, TG-MV-007 and integrated data)

Patients with no ERM at baseline were more likely to achieve VMA resolution at Day 28 compared with those who had ERM at baseline. In the integrated data, the VMA resolution rate at Day 28 was higher in patients treated with JETREA compared to placebo in both the subgroup without ERM (37.4% vs. 14.3%, p<0.001) and with ERM (8.7% vs. 1.5%, p=0.046).
Patients with a smaller VMA diameter at baseline (≤ 1500 microns) were more likely to achieve VMA resolution at Day 28 compared with those who had a diameter > 1500 microns. In the integrated data, the VMA resolution rate at Day 28 was higher in patients treated with JETREA compared to placebo in both the subgroup with VMA ≤ 1500 microns at baseline (34.7% vs. 14.6%, p<0.001) and with VMA > 1500 microns at baseline (5.9% vs. 0%, p=0.113).
In the integrated data, 106 (22.8%) and 47 (25%) in the JETREA and placebo groups respectively had full thickness macular hole (FTMH) at baseline. Of these, the proportion of patients who achieved FTMH closure without vitrectomy at Day 28 was higher in the JETREA group than the placebo group (40.6% vs. 10.6%, respectively; p<0.001). A difference was maintained through the end of the studies (Month 6).
A significantly higher percentage of JETREA treated patients experienced total PVD at Day 28 compared to placebo treated patients (integrated data: 13.4% vs. 3.7%, respectively; p<0.001).
During the studies, vitrectomy could be performed at the discretion of the Investigator. JETREA treated patients were less likely to have had a vitrectomy by the end of the study (Month 6) compared with placebo treated patients (integrated data: 17.7% vs. 26.6%, respectively; p=0.016).
A higher proportion of JETREA treated patients gained ≥ 2 or ≥ 3 lines in BCVA (irrespective of vitrectomy) at Month 6 (28.0% and 12.3%, respectively) compared with patients treated with placebo (17.1% and 6.4%) (p=0.003 and p=0.024, respectively). Also the proportion of patients gaining ≥ 2 or ≥ 3 lines in BCVA without vitrectomy favoured JETREA at Month 6 (23.7% vs. 11.2%, p<0.001 for a gain ≥ 2 lines and 9.7% vs. 3.7%, p=0.008 for a gain ≥ 3 lines).
In the integrated analysis of the National Eye Institute Visual Function Questionnaire-25 (VFQ-25), a numerical favour of JETREA over placebo was shown in each sub-scale score, as well as the composite score. The difference for improvement in the general vision sub-scale score was statistically significant (6.1 JETREA vs. 2.1 placebo, p=0.024).
Paediatric population
The European Medicines Agency has waived the obligation to submit the results of studies with JETREA in all subsets of the paediatric population in the treatment of vitreomacular traction (VMT), including when associated with macular hole of diameter less than or equal to 400 microns (see section 4.2 for information on paediatric use).
The safety and efficacy of ocriplasmin in paediatric subjects scheduled for vitrectomy was investigated in study TG-MV-009. A single intravitreal injection of 0.175 mg (above the recommended dose), or placebo, was injected in the mid-vitreous of 24 eyes of children aged 0 to 16 years, 30 to 60 minutes prior to the planned start of vitrectomy. The main reasons for vitrectomy were retinal detachment and retinopathy of prematurity. Treatment with ocriplasmin did not demonstrate an effect on posterior vitreous detachment rate, vitreous liquefaction grade, immediate postoperative retinal reattachment rate, development of proliferative vitreoretinopathy, or stage of retinopathy of prematurity. The safety findings observed in study TG-MV-009 were consistent with the known safety profile for JETREA. Based on the results of this study, the use of JETREA as an adjunct to vitrectomy in children, to facilitate vitreous separation and removal, is not recommended.
5.2 Pharmacokinetic properties
Ocriplasmin levels in the vitreous decrease rapidly after intravitreal administration. In a clinical study in patients scheduled for vitrectomy receiving 0.125 mg JETREA (corresponding to a theoretical start concentration of 29 µg/ml vitreous), mean ocriplasmin activity was 9% of theoretical start concentration 2-4 hours after injection and below the lower level of quantification at 7 days.
Because of the small dose administered (0.125 mg), detectable levels of ocriplasmin in systemic circulation are not expected after intravitreal injection.
When administered intravenously, ocriplasmin enters the endogenous protein catabolism pathway through which it is rapidly inactivated via its interactions with protease inhibitor α2-antiplasmin or α2-macroglobulin. The inactive ocriplasmin/α2-antiplasmin complex is cleared from the circulation with a half-life (t1/2) of several hours.
Renal impairment
No studies have been conducted to examine the pharmacokinetics of ocriplasmin in patients with renal impairment since the systemic exposure is expected to be very low after intravitreal administration.
Hepatic impairment
No studies have been conducted to examine the pharmacokinetics of ocriplasmin in patients with hepatic impairment since the systemic exposure is expected to be very low after intravitreal administration.
5.3 Preclinical safety data
The intravitreal toxicity of ocriplasmin has been evaluated in rabbits, monkeys and minipigs. Ocriplasmin induced an inflammatory response and transient ERG changes in rabbits and monkeys, while no inflammation or ERG changes were observed in minipigs. In rabbits and monkeys, the incidence of vitreous cell infiltrates tended to resolve over time. In monkeys, after administration of 125 µg/eye (68 µg/ml vitreous) the ERG was fully recovered by Day 55. Lens subluxation was observed in the 3 species at ocriplasmin concentrations at or above 41 µg/ml vitreous, a concentration above the intended clinical concentration of 29 µg/ml. This effect appeared to be dose-related and was observed in all animals administered intravitreal ocriplasmin more than once. Pathological changes related to intraocular haemorrhage were observed in rabbits and monkeys. It remains unclear if this haemorrhage is related to the injection procedure itself or administration of ocriplasmin. No systemic toxicity was observed after intravitreal administration of ocriplasmin.
The systemic toxicity of ocriplasmin has been evaluated in both rat and dog. Intravenous administration of 10 mg/kg was generally well tolerated in both rat and dog whether administered as single dose or as repeated dose.
No carcinogenicity, mutagenicity or reproductive and developmental toxicity data are available.
6. Pharmaceutical particulars
6.1 List of excipients
Mannitol
Citric acid
Sodium hydroxide (pH adjustment)
Water for injections
6.2 Incompatibilities
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products, other than sterile, preservative-free, non-buffered diluent sodium chloride 9 mg/ml (0.9%) solution for injection.
6.3 Shelf life
18 months
After thawing
The medicinal product should be diluted and used immediately. However, chemical and physical in-use stability of unopened product in the original carton protected from light has been demonstrated for up to 8 hours when stored below 25°C. Do not refreeze a vial once it has been thawed.
After opening/dilution
From a microbiological point of view, the medicinal product must be used immediately after opening/dilution. The vial and any unused portion of the diluted solution should be discarded after single use.
6.4 Special precautions for storage
Store in a freezer (-20°C ±5°C).
For storage conditions after thawing and opening/dilution of the medicinal product, see section 6.3.
6.5 Nature and contents of container
0.2 ml solution in a vial (type I glass) closed with a latex-free chlorobutyl rubber stopper. Pack containing 1 vial.
6.6 Special precautions for disposal and other handling
Vials are for single use only.
To prepare JETREA for intravitreal injection, adhere to the following instructions:
1. Remove the vial from the freezer and allow to thaw at room temperature (takes about 2 minutes).
2. Once completely thawed, remove the protective polypropylene flip-off cap from the vial.
3. Disinfect the top of the vial with an alcohol wipe.
4. Using aseptic technique, dilute by adding 0.2 ml of sodium chloride 9 mg/ml (0.9%) solution for injection (sterile, preservative-free, non-buffered) into the JETREA vial and gently swirl the vial until the solutions are mixed. The diluent should be withdrawn from an unopened container which should be used only once. The remaining sodium chloride 9 mg/ml (0.9%) solution for injection should be discarded. The diluted solution should be used immediately as it contains no preservatives.
5. Visually inspect the vial for particulate matter. Only a clear, colourless solution without visible particles should be used.
6. Using aseptic technique, withdraw all of the diluted solution using an appropriate sterile needle (slightly incline the vial to ease withdrawal) and discard the needle after withdrawal of the vial contents. Do not use this needle for the intravitreal injection.
7. Replace the needle with an appropriate sterile needle, carefully expel the air from the syringe and adjust the dose to the 0.1 ml mark on the syringe (corresponding to 0.125 mg ocriplasmin).
8. Inject 0.1 ml of the diluted solution immediately into the mid-vitreous as it contains no preservatives.
9. Discard the vial and any unused portion of the diluted solution after single use.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
7. Marketing authorisation holder
ThromboGenics NV
Gaston Geenslaan 1
B-3001 Leuven
Belgium
8. Marketing authorisation number(s)
EU/1/13/819/001
9. Date of first authorisation/renewal of the authorisation
Date of first authorisation: 13 March 2013
10. Date of revision of the text
20 March 2014
Detailed information on this medicinal product is available on the website of the European Medicines Agency http://www.ema.europa.eu.
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产地国家: 欧洲共同体
原产地英文商品名:
JETREA 0.5MG/0.2ML SINGLE USE VIAL
原产地英文药品名:
OCRIPLASMIN
中文参考商品译名:
JETREA玻璃体注射剂 0.5毫克 0.2毫升
中文参考药品译名:
OCRIPLASMIN
生产厂家中文参考译名:
THROMBOGENICS, INC
生产厂家英文名:
THROMBOGENICS, INC