Respreeza

1 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 
  



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1. NAME OF THE MEDICINAL PRODUCT 
 
Respreeza 1,000 mg powder and solvent for solution for infusion. 
Respreeza 4,000 mg powder and solvent for solution for infusion. 
Respreeza 5,000 mg powder and solvent for solution for infusion. 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Respreeza 1,000 mg powder and solvent for solution for infusion 
One vial contains approximately 1,000 mg of human alpha1-proteinase inhibitor*, as determined by its 
capacity to neutralize human neutrophil elastase. 
After reconstitution with 20 ml solvent, the solution contains approximately 50 mg/ml of human 
alpha1-proteinase inhibitor. 
The total protein content is approximately 1,100 mg per vial. 
 
Respreeza 4,000 mg powder and solvent for solution for infusion 
One vial contains approximately 4,000 mg of human alpha1-proteinase inhibitor*, as determined by its 
capacity to neutralize human neutrophil elastase. 
After reconstitution with 76 ml solvent, the solution contains approximately 50 mg/ml of human 
alpha1-proteinase inhibitor. 
The total protein content is approximately 4,400 mg per vial. 
 
Respreeza 5,000 mg powder and solvent for solution for infusion 
One vial contains approximately 5,000 mg of human alpha1-proteinase inhibitor*, as determined by its 
capacity to neutralize human neutrophil elastase. 
After reconstitution with 95 ml solvent, the solution contains approximately 50 mg/ml of human 
alpha1-proteinase inhibitor. 
The total protein content is approximately 5,500 mg per vial. 
 
*Produced from the plasma of human donors. 
 
Excipients with known effect 
Respreeza contains approximately 1.9 mg sodium per ml of reconstituted solution (81 mmol/l). 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Powder and solvent for solution for infusion. 
 
The powder is white to off-white. The solvent is a clear and colourless solution. 
The reconstituted solution has an approximate osmolality of 279 mOsmol / kg and a pH of 7.0. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Respreeza is indicated for maintenance treatment, to slow the progression of emphysema in adults 
with documented severe alpha1-proteinase inhibitor deficiency (e.g. genotypes PiZZ, PiZ(null), 
Pi(null,null), PiSZ). Patients are to be under optimal pharmacologic and non-pharmacologic treatment 
and show evidence of progressive lung disease (e.g. lower forced expiratory volume per second 



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(FEV1) predicted, impaired walking capacity or increased number of exacerbations) as evaluated by a 
healthcare professional experienced in the treatment of alpha1-proteinase inhibitor deficiency. 
 
4.2 Posology and method of administration 
 
First infusions should be administered under the supervision of a healthcare professional experienced 
in the treatment of alpha1-proteinase inhibitor deficiency. Subsequent infusions can be administered by 
a caregiver or by the patient (see section 4.4). 
 
Posology 
The recommended dose of Respreeza is 60 mg / kg body weight (bw) administered once weekly. 
 
Elderly population 
The safety and efficacy of Respreeza in elderly patients (65 years of age or older) have not been 
established in specific clinical trials. 
 
Patients with renal or hepatic impairment 
No special investigations have been performed. No alternative dose regimen can be recommended in 
those patients. 
 
Paediatric population 
The safety and efficacy of Respreeza in the paediatric population (below 18 years) have not been 
established. No data are available. 
 
Method of administration  
Respreeza should only be administered intravenously by infusion after reconstitution. 
The powder must be reconstituted with water for injections (see instructions on reconstitution in 
section 6.6) and administered using an intravenous administration set (supplied with the 4,000 and 
5,000 package). 
 
The reconstituted solution should be infused intravenously at an infusion rate of about 0.08 ml / kg bw 
/ min. This infusion rate may be adjusted, based upon patient tolerability. The recommended dose of 
60 mg / kg bw will take approximately 15 minutes to infuse. 
One vial of Respreeza is for single use only. 
 
For detailed information regarding the administration of the reconstituted solution, see the instructions 
at the end of section 6.6. 
 
4.3 Contraindications 
 
• Hypersensitivity to the active substance or to any of the excipients listed in section 6.1 (see also 

section 4.4). 
• IgA deficient patients with known antibodies against IgA, due to the risk of severe 

hypersensitivity and anaphylactic reactions. 
 
4.4 Special warnings and precautions for use 
 
Traceability 
In order to improve the traceability of biological medicinal products, the name and the batch number 
of the administered product should be clearly recorded. 
 
The recommended infusion rate given under section 4.2 should be adhered to. During the first 
infusions, patient’s clinical state, including vital signs, should be closely monitored throughout the 
infusion period. If any reaction takes place that might be related to the administration of Respreeza, 
the rate of infusion should be decreased or the administration should be stopped, as required by the 
clinical condition of the patient. If symptoms subside promptly after stopping, the infusion may be 
resumed at a lower rate that is comfortable for the patient. 



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Hypersensitivity 
Hypersensitivity reactions may occur, including in patients who have tolerated previous treatment with 
human alpha1-proteinase inhibitor. 
 
Respreeza may contain trace amounts of IgA. Patients with selective or severe IgA deficiency can 
develop antibodies to IgA and, therefore, have a greater risk of developing potentially severe 
hypersensitivity and anaphylactic reactions. 
 
Suspected allergic or anaphylactic type reactions may require immediate discontinuation of the 
infusion, depending on the nature and severity of the reaction. In case of shock, emergency medical 
treatment should be administered. 
 
Home-treatment / self-administration 
There are limited data regarding the use of this medicinal product in home-treatment / self-
administration. 
Potential risks associated with home-treatment / self-administration are related to the handling and 
administration of the medicinal product as well as to the handling of adverse reactions, particularly 
hypersensitivity. Patients should be informed of signs of hypersensitivity reactions. 
 
The decision of whether a patient is suitable for home-treatment / self-administration is made by the 
treating doctor, who should ensure appropriate training is provided (e.g. regarding reconstitution, use 
of Mix2Vial® set, assembly of intravenous tubing, infusion techniques, maintenance of a treatment 
diary, identification of adverse reactions and measures to be taken in case such reactions occur) and 
the use is reviewed at regular intervals. 
 
Transmissible agents 
Standard measures to prevent infections resulting from the use of medicinal products prepared from 
human blood or plasma include selection of donors, screening of individual donations and plasma 
pools for specific markers of infection and the inclusion of effective manufacturing steps for the 
inactivation / removal of viruses. Despite this, when medicinal products prepared from human blood 
or plasma are administered, the possibility of transmitting infective agents cannot be totally excluded. 
This also applies to unknown or emerging viruses and other pathogens. 
 
The measures taken are considered effective for enveloped viruses such as human immunodeficiency 
virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV) and for the non-enveloped hepatitis 
A (HAV) and parvovirus B19 virus. 
 
Appropriate vaccination (hepatitis A and B) should be considered for patients in regular/repeated 
receipt of human plasma-derived proteinase inhibitors. 
 
Smoking 
Tobacco smoke is an important risk factor for the development and progression of emphysema. 
Therefore, cessation of smoking and the avoidance of environmental tobacco smoke are strongly 
recommended. 
 
Sodium content 
Respreeza 1,000 mg powder and solvent for solution for infusion 
This medicine contains approximately 37 mg (1.6 mmol) sodium per 1,000 mg Respreeza vial. This is 
equivalent to 1.9% of the recommended maximum daily dietary intake of sodium for an adult. 
 
Respreeza 4,000 mg powder and solvent for solution for infusion 
This medicine contains approximately 149 mg (6.5 mmol) sodium per 4,000 mg Respreeza vial. This 
is equivalent to 7.4% of the recommended maximum daily dietary intake of sodium for an adult. 
 
Respreeza 5,000 mg powder and solvent for solution for infusion 



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This medicine contains approximately 186 mg (8.1 mmol) sodium per 5,000 mg Respreeza vial. This 
is equivalent to 9.3% of the recommended maximum daily dietary intake of sodium for an adult. 
 
That should be taken into consideration for patients on a controlled sodium diet. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
No interaction studies have been performed. 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
No animal reproduction studies have been conducted with Respreeza and its safety for use in human 
pregnancy has not been established in controlled clinical trials. Since alpha1-proteinase inhibitor is an 
endogenous human protein, it is considered unlikely that Respreeza will cause harm to the foetus when 
given at recommended doses. However, Respreeza should be given with caution to pregnant women. 
 
Breast-feeding 
It is unknown whether Respreeza / metabolites are excreted in human milk. The excretion of human 
alpha1-proteinase inhibitor in milk has not been studied in animals. A decision on whether to 
continue/discontinue breast-feeding or to continue/discontinue therapy with Respreeza should be 
made, taking into account the benefit of breast-feeding to the child and the benefit of human alpha1-
proteinase inhibitor therapy to the woman. 
 
Fertility 
No animal fertility studies have been conducted with Respreeza and its effect on human fertility has 
not been established in controlled clinical trials. Since human alpha1-proteinase inhibitor is an 
endogenous human protein, no adverse effects on fertility are expected when given at recommended 
doses. 
 
4.7 Effects on ability to drive and use machines 
 
Dizziness may occur following the administration of Respreeza (see section 4.8). Therefore, 
Respreeza may have a minor influence on the ability to drive and use machines. 
 
4.8 Undesirable effects 
 
Summary of the safety profile 
Hypersensitivity or allergic reactions have been observed during the treatment. In the most serious 
cases, allergic reactions may progress to severe anaphylactic reactions even when the patient has 
shown no hypersensitivity to previous administrations (see section 4.4). 
 
For safety information with respect to transmissible agents, see section 4.4. 
 
Tabulated list of adverse reactions 
The adverse reactions (ARs) collected from six clinical studies in 221 patients and post-marketing 
experience are presented in the table below according to the MedDRA system organ classification 
(SOC and Preferred Term (PT) Level). Frequency per patient (based on six months of exposure during 
clinical trials) has been evaluated according to the following convention: common (≥1/100 to <1/10), 
uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000) and very rare (<1/10,000). The 
frequency of ARs during post marketing only is considered as “not known (cannot be estimated from 
the available data)”. 
 
Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. 
  



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Frequency of adverse reactions (ARs) in clinical studies and post-marketing experience with 
Respreeza  
 

System organ class 
(SOC) Frequency of ARs 

 Common 
(≥1/100 to 

<1/10) 

Uncommon 
(≥1/1,000 to 

<1/100) 

Very rare 
(<1/10,000) Not known 

Blood and lymphatic system 
disorders 

   Lymph node 
pain 

Immune system disorders  Hypersensitivity 
reactions 
(including 
tachycardia, 
hypotension, 
confusion, 
syncope, oxygen 
consumption 
decreased and 
pharyngeal 
oedema) 

Anaphylactic 
reactions 

 

Nervous system disorders Dizziness, 
headache  

Paraesthesia Hypoaesthesia   

Eye disorders    Eye swelling 
Vascular disorders  Flushing   
Respiratory, thoracic and 
mediastinal disorders 

Dyspnoea    

Gastrointestinal disorders Nausea   Lip swelling 
Skin and subcutaneous tissue 
disorders 

 Urticaria, rash 
(including 
exfoliative and 
generalized) 

Hyperhidrosis, 
pruritus 

Face 
swelling 

General disorders and 
administration site conditions 

 Asthenia, 
infusion-site 
reactions 
(including 
infusion site 
hematoma) 

Chest pain, 
chills, pyrexia 

 

 
Paediatric Population 
Safety and effectiveness in the paediatric population have not been established. No data are available. 
 
Geriatric population 
The safety and efficacy of Respreeza in elderly patients (65 years of age or older) have not been 
established in clinical trials. 
 
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 
listed in Appendix V. 
 
4.9 Overdose 
 
Consequences of overdose are unknown. 



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In the event of overdose, the patient should be observed closely for the occurrence of adverse reactions 
and supportive measures should be available as necessary. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Antihemorrhagics, proteinase inhibitor, ATC code: B02AB02 
 
Human alpha1-proteinase inhibitor is a normal constituent of human blood. Human alpha1-proteinase 
inhibitor has a molecular weight of 51 kDa and belongs to the family of serine protease inhibitors. 
 
Mechanism of action 
Human alpha1-proteinase inhibitor is understood to be the primary anti-protease in the lower 
respiratory tract, where it inhibits neutrophil elastase (NE). Normal healthy individuals produce 
sufficient alpha1-proteinase inhibitor to control the NE produced by activated neutrophils and are thus 
able to prevent inappropriate proteolysis of lung tissue by NE. Conditions that increase neutrophil 
accumulation and activation in the lung, such as respiratory infection and smoking, will in turn 
increase levels of NE. However, individuals deficient in endogenous alpha1-proteinase inhibitor are 
unable to maintain appropriate antiprotease defence and experience more rapid proteolysis of the 
alveolar walls starting prior to the development of clinically evident chronic obstructive lung disease 
in the third or fourth decade. 
 
Pharmacodynamic effects 
The administration of Respreeza increases and maintains serum levels and lung epithelial lining fluid 
(ELF) levels of alpha1-proteinase inhibitor leading to a slowdown of the progression of emphysema. 
 
Clinical efficacy and safety 
 
RAPID studies 
The safety and efficacy of Respreeza was evaluated in a randomized, double-blind, placebo-
controlled, multi-center study (RAPID) followed by a 2-year open-label extension study (RAPID 
extension study). A total of 180 subjects with alpha1-proteinase inhibitor deficiency characterized by a 
serum alpha1-proteinase inhibitor level < 11 μM (i.e. < 50 mg/dL as determined by nephelometry) and 
clinical evidence of emphysema, were randomized to receive a weekly 60 mg / kg bw intravenous 
dose of either Respreeza (93 subjects) or placebo (87 subjects) for up to 24 months. The subjects 
ranged in age from 31 to 67 years (median age 54 years) with average baseline alpha1-proteinase 
inhibitor levels of approximately 6.15 µM, and average volume-adjusted CT lung density of 47 g/L 
/50 g/L for Respreeza and placebo subjects, respectively. 
One-hundred forty subjects (76 Respreeza-treated subjects and 64 subjects treated with placebo in the 
RAPID Study) continued into the RAPID extension study and were treated with a weekly 60 mg / kg 
bw intravenous dose of Respreeza for up to 24 months. 
 
The studies investigated the effect of Respreeza on the progression of emphysema, assessed by the 
decline of lung density, measured by computer tomography (CT). 
Respreeza-treated subjects demonstrated a consistent pattern of slower lung density decline than those 
receiving placebo (see Figure 1). The annual rate of lung density decline, as measured by CT scan at 
total lung capacity (TLC) over 2 years was lower with Respreeza (-1.45 g/L) as compared with 
placebo (-2.19 g/L), reflecting a 34% reduction (p = 0.017, 1-sided). 
 
The RAPID extension study demonstrated that the reduced rate in lung density decline was maintained 
for subjects continuously treated with Respreeza for 4 years (see Figure 1). 

  



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Figure 1: Changes in Lung Density (TLC) from baseline in the RAPID and RAPID Extension 
studies 

 

 
 
Single doses of 120 mg / kg bw have been administered to 137 subjects treated with Respreeza. 
 
Pediatric population 
The European Medicines Agency has waived the obligation to submit the results of studies with 
Respreeza in all subsets of the pediatric population in chronic obstructive pulmonary disease (COPD) 
due to alpha1-proteinase inhibitor deficiency (see section 4.2 for information on pediatric use). 
 
5.2 Pharmacokinetic properties 
 
Four clinical studies were conducted with Respreeza in 89 subjects (59 males and 30 females) to 
evaluate the effect of Respreeza on serum levels of alpha1-proteinase inhibitor. The subjects ranged in 
age from 29 to 68 years (median age 49 years). At screening, serum alpha1-proteinase inhibitor levels 
were between 3.2 and 10.1 µM (mean of 5.6 µM). 
 
A double-blind, randomized, active-controlled, crossover pharmacokinetic study was conducted in 
13 males and 5 females with alpha1-proteinase inhibitor deficiency, ranging in age from 36 to 
66 years. Nine subjects received a single 60 mg / kg bw dose of Respreeza followed by a comparator 
product, and 9 subjects received comparator product followed by a single 60 mg / kg bw dose of 
Respreeza, with a wash-out period of 35 days between doses. A total of 13 post-infusion serum 
samples were taken at various time points up to Day 21. Table 1 shows the mean results for the 
Respreeza pharmacokinetic parameters. 
 

Table 1: Pharmacokinetic parameters for alpha1-proteinase inhibitor following a single 
60 mg / kg bw dose of Respreeza 

Pharmacokinetic Parameter Mean (standard deviation)* 
Area under the curve (AUC0-∞) 144 (±27) µM x day 
Maximum concentration (Cmax) 44.1 (±10.8) µM 
Terminal half-life (t1/2ß) 5.1 (±2.4) days 
Total clearance 603 (±129) mL/day 
Volume of distribution at steady state 3.8 (±1.3) L 

* n=18 subjects. 
 
A population pharmacokinetic analysis was conducted using data from 90 Respreeza-treated subjects 
from the RAPID trial. The population estimate of mean half-life was 6.8 days. The model predicted 
mean steady-state concentration was 21.8 µM after a 60 mg /kg bw / week dose. The population 



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pharmacokinetic analysis did not indicate that there were any significant effects of age, gender, 
weight, or baseline serum antigenic alpha1-proteinase inhibitor concentrations on the clearance of 
Respreeza. 
 
Pharmacokinetic/pharmacodynamic relationship 
In a double-blind, controlled clinical study to evaluate the safety and biochemical efficacy of 
Respreeza 44 subjects were randomized to receive 60 mg / kg bw intravenous dose of Respreeza once 
weekly for 24 weeks. The mean trough serum alpha1-proteinase inhibitor levels at steady state (weeks 
7-11) were maintained above 11 µM. The mean (standard deviation) of the steady state trough serum 
alpha1-proteinase inhibitor level for Respreeza-treated subjects was 17.7 µM (2.5). 
In a subgroup of subjects enrolled in this study (10 Respreeza-treated subjects) broncho-alveolar 
lavage was performed. Epithelial lining fluid measurements (ELF) of alpha1-proteinase inhibitor levels 
showed a consistent increase following treatment. ELF levels of antigenic alpha1-proteinase inhibitor 
and alpha1-proteinase inhibitor: NE complexes increased from baseline. Free elastase was 
immeasurably low in all samples. 
Following the completion of the RAPID study, an analysis of achieved median alpha1-proteinase 
inhibitor levels and lung density decline was conducted. This analysis revealed an inverse linear 
relationship between trough serum alpha1-proteinase inhibitor levels and the annual decline in lung 
density as measured by volume adjusted CT scans for subjects receiving 60 mg / kg bw intravenous 
dose of Respreeza. 
 
5.3 Preclinical safety data 
 
The safety of Respreeza has been assessed in several preclinical studies. Non-clinical data reveal no 
special risk for humans based on safety pharmacology and short-term toxicity studies. Repeat dose 
toxicity studies longer than 5 days, reproductive toxicity studies and carcinogenicity studies, have not 
been performed. Such studies are not considered meaningful due to the production of antibodies 
against the heterologous human protein in animals. Since human alpha1-proteinase inhibitor is a 
protein and a physiological constituent of human blood, it is not expected to present carcinogenic, 
genotoxic, or teratogenic effects. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Powder: 
Sodium chloride 
Sodium dihydrogen phosphate monohydrate 
Mannitol 
 
Solvent: 
Water for injections 
 
6.2 Incompatibilities 
 
This medicinal product must not be mixed with other medicinal products, except those mentioned in 
section 6.6. 
 
6.3 Shelf life 
 
Respreeza 1,000 mg powder and solvent for solution for infusion 
3 years 
 
Respreeza 4,000 mg powder and solvent for solution for infusion 
2 years 
 



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Respreeza 5,000 mg powder and solvent for solution for infusion 
2 years 
 
From a microbiological point of view, the product should be used immediately after reconstitution. 
However chemical and physical in-use stability has been demonstrated for 3 h at room temperature (up 
to 25 °C). Do not freeze the reconstituted solution. 
 
6.4 Special precautions for storage 
 
Do not store above 25 °C. Do not freeze. 
For storage conditions after reconstitution of the medicinal product, see section 6.3. 
 
6.5 Nature and contents of container and special equipment for administration 
 
Respreeza 1,000 mg powder and solvent for solution for infusion 
Respreeza 1,000 mg of powder in a glass vial (type I), closed with a rubber (bromobutyl or 
chlorobutyl) stopper and an aluminium seal with a plastic flip-off cap.  
20 ml of water for injections in a glass vial (type I), closed with a rubber (chlorobutyl) stopper and an 
aluminium seal with a plastic flip-off cap. 
 
Respreeza 4,000 mg powder and solvent for solution for infusion 
Respreeza 4,000 mg of powder in a glass vial (type I), closed with a rubber (bromobutyl or 
chlorobutyl) stopper and an aluminium seal with a plastic flip-off cap.  
76 ml of water for injections in a glass vial (type I), closed with a rubber (chlorobutyl) stopper and an 
aluminium seal with a plastic flip-off cap. 
 
Respreeza 5,000 mg powder and solvent for solution for infusion 
Respreeza 5,000 mg of powder in a glass vial (type I), closed with a rubber (bromobutyl or 
chlorobutyl) stopper and an aluminium seal with a plastic flip-off cap.  
95 ml of water for injections in a glass vial (type I), closed with a rubber (chlorobutyl) stopper and an 
aluminium seal with a plastic flip-off cap. 
 
 
Presentations 
Each pack contains: 
 
Respreeza 1,000 mg powder and solvent for solution for infusion: 
One single-use powder vial 
One solvent vial of 20 ml water for injections 
One transfer set 20/20 (Mix2Vial set) for reconstitution 
 
Respreeza 4,000 mg powder and solvent for solution for infusion: 
One single-use powder vial 
One solvent vial of 76 ml water for injections 
One transfer set 20/20 (Mix2Vial set) for reconstitution 
Administration set (inner box): 
One IV infusion set 
One butterfly set 
Three alcohol swabs 
 
Respreeza 5,000 mg powder and solvent for solution for infusion: 
One single-use powder vial 
One solvent vial of 95 ml water for injections 
One transfer set 20/20 (Mix2Vial set) for reconstitution 
Administration set (inner box): 
One IV infusion set 
One butterfly set 



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Three alcohol swabs 
 
Not all pack sizes may be marketed. 
 
 
6.6 Special precautions for disposal and other handling 
 
General instructions 
• The reconstitution should be performed according to the instructions provided below. 
• The product must be reconstituted, administered and handled with caution using aseptic technique 

to maintain product sterility. 
• Do not use provided sterile ancillaries for reconstitution and administration if their package is 

opened or if they are damaged. 
• The powder must be reconstituted with solvent (water for injections). 
• Total reconstitution of the powder should be obtained within 5 minutes (1,000 mg presentation) 

or 10 minutes (4,000 mg and 5,000 mg presentation). 
• Inspect the reconstituted solution for particulate matter and discoloration prior to administration. 
• The reconstituted solution should be clear, colorless to slightly yellow, and free from visible 

particles. 
 
Follow the steps provided below for the preparation and reconstitution of Respreeza: 
 
1. Ensure that the Respreeza vial and water for injections vial are at room temperature (up to 25°C). 
2. Remove the plastic flip-off cap from the water for injections vial. 
3. Wipe the rubber stopper of the water for injections vial with an antiseptic like an alcohol swab and 
allow it to dry. 

4. Open the Mix2Vial set by peeling off the lid (Figure 1).  
Do not remove the Mix2Vial set from the blister package. 

 

 
Figure 1 

5. Place the water for injections vial on an even, clean surface and hold the 
vial tight. Take the Mix2Vial set together with the blister package and 
vertically pierce the water for injections vial with the blue tip of the 
Mix2Vial set (Figure 2). 

 

 
Figure 2 

6. Carefully remove the blister package from the Mix2Vial set by holding at 
the rim and pulling vertically upwards. Make sure that you only pull away 
the blister package and not the Mix2Vial set (Figure 3). 

 

 
Figure 3 

7. Remove the plastic flip-off cap from the Respreeza vial. 
8. Wipe the rubber stopper of the Respreeza vial with an antiseptic like an alcohol swab and allow it to 
dry. 



 12 

9. Place the Respreeza vial on an even and firm surface. Invert the water for 
injections vial with the Mix2Vial set attached and vertically pierce the 
Respreeza vial with the clear tip of the Mix2Vial set (Figure 4). The water 
for injections will automatically flow into the Respreeza vial. 
 
NOTE: Ensure all water has transferred into the Respreeza vial. 

 

 
Figure 4 

10. Follow steps below to remove entire Mix2Vial set from Respreeza vial: 
 

• With one hand tightly grasp the Respreeza vial as shown in Figure 5. 
• With the other hand tightly grasp the water for injections vial and the 

blue part of the Mix2Vial set. 
• Bend the entire Mix2Vial set to the side until it disconnects from 

the Respreeza vial (Figure 5). 
 
Discard the water for injections vial with the entire Mix2Vial set. 

 

 
Figure 5 

11. Gently swirl the Respreeza vial until the powder is completely dissolved 
(Figure 6). DO NOT SHAKE. Take care not to touch the rubber vial stopper. 

 

 
Figure 6 

12. Inspect visually the reconstituted solution. The solution should be clear, colourless to slightly 
yellow, and free from visible particles. Do not use solutions that are discoloured, cloudy or have 
particles. 
13. If more than 1 vial of Respreeza is needed to achieve the required dose, repeat instructions 1 to 12 
above using an additional package containing an unused Mix2Vial set. 
 
Use a separate, unused Mix2Vial set, and a water for injections vial for each Respreeza vial. 
14. Use aseptic technique to transfer the reconstituted solutions into the administration container (e.g., 
empty intravenous bag or glass bottle; (not supplied) via a commercially available intravenous fluid 
tubing transfer set (not supplied)). 
 
Administration 
 
The reconstituted solution must be administered using an IV infusion set.  
 

1. Make sure that the air vent cap and the roller clamp of the IV infusion set are closed. 
VERTICALLY pierce the Respreeza vial with the IV infusion set spike while twisting the IV 
infusion set spike gently or connect it to an infusion container. 

2. Elevate the Respreeza vial/infusion container or hang on an infusion stand. 
3. Prime the drip chamber by squeezing it until the Respreeza solution has filled the chamber 

roughly half-way. 
4. Open the air vent cap of the IV infusion set. 



 13 

5. Slowly open the roller clamp of the IV infusion set and let the Respreeza solution flow until it 
reaches the end of the tubing with no air bubbles.  

6. Close the roller clamp. 
7. Disinfect the injection site with an antiseptic like an alcohol swab before carefully inserting the 

needle into the vein. Make sure that there is no more air in the butterfly tube left. 
8. Connect the end of the IV infusion set to the butterfly set and open the roller clamp again. 
9. Infuse the reconstituted solution into the vein. The solution should be infused at an infusion rate 

of about 0.08 ml per kg body weight each min, as determined by your response and your 
comfort. The recommended dose of 60 mg per kg of body weight will take approximately 15 
minutes to infuse. 

 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
CSL Behring GmbH 
Emil-von-Behring-Strasse 76 
D-35041 Marburg 
Germany 
 
 
8. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/15/1006/001 
EU/1/15/1006/002 
EU/1/15/1006/003 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 20 August 2015 
Date of latest renewal: 23 April 2020 
 
10. DATE OF REVISION OF THE TEXT 
 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu. 



 14 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX II 
 
A. MANUFACTURER(S) OF THE BIOLOGICAL ACTIVE 

SUBSTANCE(S) AND MANUFACTURER(S) 
RESPONSIBLE FOR BATCH RELEASE 

 
B. CONDITIONS OR RESTRICTIONS REGARDING 

SUPPLY AND USE 
 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE 

MARKETING AUTHORISATION 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO 

THE SAFE AND EFFECTIVE USE OF THE MEDICINAL 
PRODUCT 



 15 

A. MANUFACTURER(S) OF THE BIOLOGICAL ACTIVE SUBSTANCE(S) AND 
MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE 

Name and address of the manufacturer of the biological active substance  

CSL Behring LLC 
Route 50 North 1201 N. Kinzie 
Bradley, IL 60915 
United States 
 
Name and address of the manufacturer responsible for batch release 

CSL Behring GmbH 
Emil-von-Behring-Strasse 76 
35041 Marburg 
Germany 
 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 

Medicinal product subject to restricted medical prescription (see Annex I: Summary of Product 
Characteristics, section 4.2). 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 
AUTHORISATION  

 

• Periodic safety update reports (PSURs) 
 

The requirements for submission of PSURs for this medicinal product are set out in the list of 
Union reference dates (EURD list) provided for under Article 107c(7) of Directive 2001/83/EC and 
any subsequent updates published on the European medicines web-portal. 

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 
EFFECTIVE USE OF THE MEDICINAL PRODUCT 

 

• Risk management plan (RMP) 
 

The marketing authorisation holder (MAH) shall perform the required pharmacovigilance activities 
and interventions detailed in the agreed RMP presented in Module 1.8.2 of the marketing 
authorisation and any agreed subsequent updates of the RMP. 

An updated RMP should be submitted: 

• At the request of the European Medicines Agency; 

• Whenever the risk management system is modified, especially as the result of new 
information being received that may lead to a significant change to the benefit/risk profile or 
as the result of an important (pharmacovigilance or risk minimisation) milestone being 
reached.  

 
• Obligation to conduct post-authorisation measures  
 



 16 

The MAH shall complete, within the stated timeframe, the below measures: 

Description Due date 
Post authorisation efficacy study (PAES): A randomized, long-term 
PAES has been agreed to study the dose-relationship if the higher API 
levels achieved in the blood might influence the rate of lung density 
decline and whether that would support an increased dose of 120mg/kg 
the MAH should conduct and submit the results of a randomized, long 
term, efficacy study conducted according to an agreed protocol. 

Submission of final 
clinical study report by 
31 March 2025 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 



 17 

 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 
  



 18 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 



 19 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER BOX 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Respreeza 1,000 mg powder and solvent for solution for infusion 
Human alpha1-proteinase inhibitor 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Human alpha1-proteinase inhibitor 1,000 mg 
After reconstitution with 20 ml solvent, the solution contains approximately 50 mg/ml of human 
alpha1-proteinase inhibitor. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: sodium chloride, sodium dihydrogen phosphate monohydrate, mannitol. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Powder and solvent for solution for infusion  
 
1 single-use powder vial 
1 solvent vial of 20 ml water for injections 
1 transfer set 20/20 (Mix2Vial set) for reconstitution 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
 
For intravenous use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 



 20 

9. SPECIAL STORAGE CONDITIONS 
 
Do not store above 25 °C. Do not freeze. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
CSL Behring GmbH, 35041 Marburg, Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/15/1006/001 
 
13. BATCH NUMBER 
 
Lot 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Respreeza 1,000 mg 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 
  



 21 

PARTICULARS TO APPEAR ON THE IMMEDIATE PACKAGING 
 
POWDER VIAL 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Respreeza 1,000 mg powder for solution for infusion 
Human alpha1-proteinase inhibitor 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Human alpha1-proteinase inhibitor 1,000 mg 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients : Sodium chloride, sodium dihydrogen phosphate monohydrate, mannitol. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Powder for solution for infusion 
 
1,000 mg 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
 
For intravenous use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Do not store above 25 °C. Do not freeze. 
 
 



 22 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
CSL Behring  
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/15/1006/001 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
  



 23 

PARTICULARS TO APPEAR ON THE IMMEDIATE PACKAGING 
 
SOLVENT VIAL 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Solvent for Respreeza  
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Water for injections 
 
 
3. LIST OF EXCIPIENTS 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
20 ml 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
CSL Behring  
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/15/1006/001 



 24 

13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
 



 25 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER BOX 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Respreeza 4,000 mg powder and solvent for solution for infusion 
Human alpha1-proteinase inhibitor 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Human alpha1-proteinase inhibitor 4,000 mg 
After reconstitution with 76 ml solvent, the solution contains approximately 50 mg/ml of human 
alpha1-proteinase inhibitor. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: sodium chloride, sodium dihydrogen phosphate monohydrate, mannitol. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Powder and solvent for solution for infusion  
 
1 single-use powder vial 
1 solvent vial of 76 ml water for injections 
1 transfer set 20/20 (Mix2Vial set) for reconstitution 
Administration set (inner box): 
1 IV infusion set 
1 butterfly set 
3 alcohol swabs 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
 
For intravenous use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 



 26 

9. SPECIAL STORAGE CONDITIONS 
 
Do not store above 25 °C. Do not freeze. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
CSL Behring GmbH, 35041 Marburg, Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/15/1006/002 
 
13. BATCH NUMBER 
 
Lot 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Respreeza 4,000 mg 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 
  



 27 

PARTICULARS TO APPEAR ON THE IMMEDIATE PACKAGING 
 
POWDER VIAL 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Respreeza 4,000 mg powder for solution for infusion 
Human alpha1-proteinase inhibitor 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Human alpha1-proteinase inhibitor 4,000 mg 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients : Sodium chloride, sodium dihydrogen phosphate monohydrate, mannitol. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Powder for solution for infusion 
 
4,000 mg 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
 
For intravenous use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Do not store above 25 °C. Do not freeze. 
 
 



 28 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
CSL Behring  
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/15/1006/002 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
  



 29 

PARTICULARS TO APPEAR ON THE IMMEDIATE PACKAGING 
 
SOLVENT VIAL 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Solvent for Respreeza  
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Water for injections 
 
 
3. LIST OF EXCIPIENTS 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
76 ml 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
CSL Behring  
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/15/1006/002 



 30 

13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
 
 



 31 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER BOX 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Respreeza 5,000 mg powder and solvent for solution for infusion 
Human alpha1-proteinase inhibitor 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Human alpha1-proteinase inhibitor 5,000 mg 
After reconstitution with 95 ml solvent, the solution contains approximately 50 mg/ml of human 
alpha1-proteinase inhibitor. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: sodium chloride, sodium dihydrogen phosphate monohydrate, mannitol. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Powder and solvent for solution for infusion  
 
1 single-use powder vial 
1 solvent vial of 95 ml water for injections 
1 transfer set 20/20 (Mix2Vial set) for reconstitution 
Administration set (inner box): 
1 IV infusion set 
1 butterfly set 
3 alcohol swabs 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
 
For intravenous use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 



 32 

9. SPECIAL STORAGE CONDITIONS 
 
Do not store above 25 °C. Do not freeze. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
CSL Behring GmbH, 35041 Marburg, Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/15/1006/003 
 
13. BATCH NUMBER 
 
Lot 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Respreeza 5,000 mg 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 
 
 



 33 

PARTICULARS TO APPEAR ON THE IMMEDIATE PACKAGING 
 
POWDER VIAL 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Respreeza 5,000 mg powder for solution for infusion 
Human alpha1-proteinase inhibitor 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Human alpha1-proteinase inhibitor 5,000 mg 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients : Sodium chloride, sodium dihydrogen phosphate monohydrate, mannitol. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Powder for solution for infusion 
 
5,000 mg 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
 
For intravenous use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Do not store above 25 °C. Do not freeze. 
 
 



 34 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
CSL Behring  
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/15/1006/003 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 



 35 

PARTICULARS TO APPEAR ON THE IMMEDIATE PACKAGING 
 
SOLVENT VIAL 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Solvent for Respreeza  
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Water for injections 
 
 
3. LIST OF EXCIPIENTS 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
95 ml 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
CSL Behring  
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/15/1006/003 



 36 

13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
  



 37 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
Carton administration set (inner box) 

 
1. NAME OF THE MEDICINAL PRODUCT 

 
Administration set 
 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
-not applicable- 
 

3. LIST OF EXCIPIENTS 
 
-not applicable- 
 

4. PHARMACEUTICAL FORM AND CONTENTS 
 
-not applicable- 
 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
-not applicable- 
 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE REACH AND SIGHT OF CHILDREN 

 
-not applicable- 
 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
-not applicable- 
 

8. EXPIRY DATE 
 
Exp. date 
 

9. SPECIAL STORAGE CONDITIONS 
 
-not applicable- 
 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR 
WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
-not applicable- 
 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
CSL Behring 
 

12. MARKETING AUTHORISATION NUMBER(S) 
 
-not applicable- 
 

13. BATCH NUMBER 
 



 38 

Lot No. 
 

14. GENERAL CLASSIFICATION FOR SUPPLY 
 
-not applicable- 
 

15. INSTRUCTIONS ON USE 
 
-not applicable- 
 

16. INFORMATION IN BRAILLE 
 
-not applicable- 
 



 39 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 



 40 

Package leaflet: Information for the user 
 

Respreeza 1,000 mg powder and solvent for solution for infusion 
Respreeza 4,000 mg powder and solvent for solution for infusion 
Respreeza 5,000 mg powder and solvent for solution for infusion 

 
Human alpha1-proteinase inhibitor 

 
 
Read all of this leaflet carefully before you start using this medicine because it contains 
important information for you. 
- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor or healthcare professional. 
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours. 
- If you get any side effects, talk to your doctor or healthcare professional. This includes any 

possible side effects not listed in this leaflet. See section 4. 
 
What is in this leaflet: 
1. What Respreeza is and what it is used for 
2. What you need to know before you use Respreeza 
3. How to use Respreeza 
4. Possible side effects 
5. How to store Respreeza 
6. Contents of the pack and other information 
 
 
1. What Respreeza is and what it is used for 
 
What Respreeza is 
 
This medicine contains the active substance human alpha1-proteinase inhibitor, which is a normal 
component of the blood and is found in the lung. There, its main function is to protect the lung tissue 
by limiting the action of a certain enzyme, called neutrophil elastase. Neutrophil elastase can cause 
damage if its action is not controlled (for example, in case you have an alpha1-proteinase inhibitor 
deficiency). 
 
 
What Respreeza is used for 
 
This medicine is used in adults with known severe alpha1-proteinase inhibitor deficiency (an inherited 
condition also called alpha1 antitrypsin deficiency) who have developed a lung condition called 
emphysema. 
 
Emphysema develops when the lack of alpha1-proteinase inhibitor results in a condition in which 
neutrophil elastase is not being properly controlled, damaging the tiny air sacs in the lungs through 
which oxygen passes into the body. Because of this damage, the lungs do not work properly. 
 
Using this medicine regularly increases the blood and lung levels of alpha1-proteinase inhibitor, thus 
slowing the progression of emphysema. 
 
 
2. What you need to know before you use Respreeza 
 
Do NOT take Respreeza 
• if you are allergic to human alpha1-proteinase inhibitor or any of the other ingredients of this 

medicine (listed in section 6). 



 41 

• if you have been found to have a deficiency of certain blood proteins called immunoglobulin 
type A (IgA) and have developed antibodies against them. 

 
Warnings and precautions 
 
 Talk to your doctor or healthcare professional before using Respreeza. 
 
Information on allergic reactions: when slowing or stopping the infusion may be required? 
You may be allergic to human alpha1-proteinase inhibitor even if you have previously received human 
alpha1-proteinase inhibitors and had tolerated them well. In some cases, severe allergic reactions may 
occur. Your doctor will inform you about signs of allergic reactions (for example chills, flushing, 
faster heartbeat, fall in blood pressure, light-headedness, rash, hives, itching, difficulty in breathing or 
swallowing as well as swelling of your hands, face, or mouth) (see also section 4). 
 Tell your doctor or healthcare professional immediately if you notice such reactions during the 

infusion of this medicine. Depending on the nature and severity of the reaction, your doctor may 
decide whether to slow or stop the infusion completely and start the appropriate treatment. 

 In case of self-administration / home-treatment, stop the infusion immediately and contact your 
doctor or healthcare professional. 

 
Information on safety with respect to infections 
Respreeza is made from human blood plasma (this is the liquid part of the blood with the blood cells 
removed). 
Because blood can carry infections, when medicines are made from human blood or plasma certain 
measures are put in place to prevent these from being present in the medicine and passed on to 
patients. These include: 
• careful selection of blood and plasma donors to make sure those at risk of carrying infections 

are excluded, 
• the testing of samples of donated blood and plasma to try to avoid use of material with signs of 

virus/infections, 
• the inclusion of steps in the processing of the blood or plasma that can inactivate or remove 

viruses. 
 
The measures taken are considered effective for viruses such as human immunodeficiency virus 
(HIV), hepatitis A virus, hepatitis B virus, hepatitis C virus, and parvovirus B19 virus. 
 
However, despite these measures, when medicines prepared from human blood or plasma are 
administered, the possibility of passing on infection cannot be totally excluded. This also applies to 
any unknown or emerging viruses or other types of infections. 
 
Your doctor may recommend that you consider vaccination against hepatitis A and B if you 
regularly/repeatedly receive human plasma-derived proteinase inhibitors. 
 
 It is strongly recommended that every time you receive a dose of Respreeza the name and batch 

number of the product are recorded in order to maintain a record of the batches used. 
 
Smoking 
Since tobacco smoke is an important risk factor for the development and progression of emphysema, 
you are strongly advised to stop smoking and avoid passive smoking. 
 
Children and adolescents 
 
This medicine is not for use in children or adolescents below 18 years of age. 
 
Other medicines and Respreeza 
 
 Tell your doctor or healthcare professional if you are taking, have recently taken or might take 

any other medicines. 



 42 

 
Pregnancy, breast-feeding and fertility 
 
 If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, 

ask your doctor or healthcare professional for advice before taking this medicine. 
 
Since alpha1-proteinase inhibitor is a normal component of human blood, recommended dose of this 
medicine is not expected to cause harm to the developing foetus. However, as there is no information 
available regarding the safety of Respreeza use during pregnancy, if you are pregnant, this medicine 
should only be given to you with caution. 
It is unknown whether Respreeza passes into human milk. If you are breast-feeding, your doctor will 
discuss with you the risks and benefits of taking this medicine. 
There are no data concerning the effect on fertility but as alpha1-proteinase inhibitor is a normal 
component of human blood, no adverse effects on fertility are expected if you use Respreeza at the 
recommended dose. 
 
Driving and using machines 
 
Dizziness may occur after the administration of this medicine. If you experience dizziness, you should 
not drive or use machines until the dizziness has passed (see section 4). 
 
Respreeza contains sodium 
 
This medicinal product contains approximately 37 mg sodium per 1,000 mg Respreeza vial, 149 mg 
sodium per 4,000 mg Respreeza vial and 186 mg sodium per 5,000 mg Respreeza vial, equivalent to 
1.9%, 7.4% and 9.3% respectively, of the WHO recommended maximum daily intake of 2 g sodium 
for an adult. Your doctor or healthcare professional will take that into consideration if you are on a 
controlled sodium diet. 
 
 
 
3. How to use Respreeza 
 
After reconstitution, Respreeza is given by infusion into a vein. A healthcare professional experienced 
in the treatment of alpha1-proteinase inhibitor deficiency will supervise the first infusions. 
 
Home treatment / Self-administration 
After the first infusions, you or your caregiver might also administer Respreeza, but only after 
receiving adequate training. If your doctor decides that you are suitable for such home-treatment / self-
administration, he or she will instruct you in: 
• how to prepare and give this medicine (see the illustrated instructions at the end of this leaflet in 

“Information for health-care professionals and for patients suitable for home-treatment / self-
administration”), 

• how to keep the product sterile (aseptic infusion techniques), 
• how to keep a treatment diary, 
• how to identify side effects, including signs of allergic reactions, and measures to be taken in 

case such effects occur (see also section 2 and section 4). 
Your doctor or your healthcare professional will regularly review your / your caregiver’s infusion 
technique to ensure continued appropriate handling. 
 
Dose 
The amount of Respreeza you are given is based on your body weight. The recommended dose is 
60 mg per kg of body weight and should be administered once per week. The infusion solution is 
normally given over about 15 minutes (about 0.08 ml of solution per kg body weight each min). Your 
doctor will determine the appropriate infusion rate for you by taking into account your weight and 
your tolerability to infusion. 
 



 43 

If you use more Respreeza than you should 
Consequences of an overdose are unknown. 
 Tell your doctor or healthcare professional if you think you have used more Respreeza as you 

should. He or she will take the appropriate measures. 
 
If you forget to use Respreeza 
 Proceed with your next dose immediately and continue at regular intervals as advised by your 

doctor or healthcare professional. 
 Do not take a double dose to make up for a forgotten dose. 
 
If you stop using Respreeza 
 Do no stop using this medicine without consulting your doctor or healthcare professional. If 

treatment with Respreeza is stopped, your condition may worsen. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. Such side 
effects may occur even if you previously received human alpha1-proteinase inhibitors and had 
tolerated them well. 
 
Some side effects may be serious: 
Uncommonly (may affect up to 1 in 100 people), allergic reactions have been observed. They may 
progress in some very rare cases (may affect up to 1 in 10,000 people) to severe allergic reactions even 
when you have shown no signs of allergy on previous infusions. 
 Tell your doctor or healthcare professional immediately if you notice any sign of allergic 

reactions (for example chills, flushing, faster heartbeat, fall in blood pressure, light-headedness, 
rash, hives, itching, difficulty in breathing or swallowing as well as swelling of your hands, 
face, or mouth) during the administration of Respreeza. Depending on the nature and severity of 
the reaction, your doctor or healthcare professional may decide whether to slow or stop the 
administration completely and give appropriate treatment for the reaction. 

 In case of self-administration / home-treatment, stop the infusion immediately and contact your 
doctor or healthcare professional. 

 
The other side effects may include: 
 
Commonly (may affect up to 1 in 10 people) 
Dizziness, headache, shortness of breath (dyspnoea), nausea.  
 
Uncommonly (may affect up to 1 in 100 people) 
Altered sense of touch like burning, tingling or feeling of numbness in your hands, arms, legs, or feet 
(paraesthesia), flushing, hives (urticaria), scaly rash and rash all over the body, physical weakness 
(asthenia), infusion-site reactions (such as burning, stinging, pain, swelling or redness at the infusion 
site (haematoma)). 
 
Very rarely (may affect up to 1 in 10,000 people) 
Decreased sense of touch like burning, tingling or feeling of numbness in your hands, arms, legs, or 
feet (hypoaesthesia), excessive sweating (hyperhidrosis), itching, chest pain, chills, fever (pyrexia). 
 
Frequency not known (frequency cannot be estimated from the available data) 
Pain to the lymph glands (oval-shaped masses of tissue that are distributed throughout the body and 
which may be palpable for example in the armpit, groin or neck), swollen face, swollen eyes and lips. 
 
 
Reporting of side effects 
 If you get any side effects, talk to your doctor or healthcare professional. This includes any 

possible side effects not listed in this leaflet. You can also report side effects directly via the 



 44 

national reporting system listed in Appendix V. By reporting side effects you can help provide 
more information on the safety of this medicine.  

 
5. How to store Respreeza 
 
Keep this medicine out of the sight and reach of children. 
Do not use this medicine after the expiry date which is stated on the outer carton and the vial labels 
after EXP. The expiry date refers to the last day of that month. 
Do not store above 25 °C. Do not freeze. 
After reconstitution, the solution should be used immediately. If this is not possible, solutions can be 
stored up to 3 hours at room temperature (up to 25 °C). Do not freeze the reconstituted solution. 
 
 
6. Contents of the pack and other information 
 
What Respreeza contains 
 
The active substance is human alpha1-proteinase inhibitor. One vial contains approximately 1,000 
mg, 4,000 mg or 5,000 mg of human alpha1-proteinase inhibitor. 
The other ingredients are sodium chloride, sodium dihydrogen phosphate monohydrate and mannitol 
(see section 2). 
Solvent: Water for injections. 
 
What Respreeza looks like and contents of the pack 
 
This medicine is a white to off-white powder. 
After it has been reconstituted with water for injections, the solution should be clear, colourless to 
slightly yellow and free from visible particles. 
 
Presentations 
 
One pack contains: 
 
Respreeza 1,000 mg powder and solvent for solution for infusion: 
• 1 single-use powder vial 
• 1 solvent vial of 20 ml water for injections 
• 1 transfer set 20/20 (Mix2Vial set) for reconstitution 
 
Respreeza 4,000 mg powder and solvent for solution for infusion: 
• 1 single-use powder vial 
• 1 solvent vial of 76 ml water for injections 
• 1 transfer set 20/20 (Mix2Vial set) for reconstitution 

 Administration set (inner box): 
• 1 IV infusion set 
• 1 butterfly set 
• 3 alcohol swabs 
 
Respreeza 5,000 mg powder and solvent for solution for infusion: 
• 1 single-use powder vial 
• 1 solvent vial of 95 ml water for injections 
• 1 transfer set 20/20 (Mix2Vial set) for reconstitution 

 Administration set (inner box): 
• 1 IV infusion set 
• 1 butterfly set 
• 3 alcohol swabs 
 



 45 

Not all pack sizes may be marketed. 
 
 
Marketing Authorisation Holder and Manufacturer 
 
CSL Behring GmbH 
Emil-von-Behring-Strasse 76 
D-35041 Marburg 
Germany 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
CSL Behring NV 
Tél/Tel: +32 15 28 89 20 
 

Lietuva 
CentralPharma Communications UABTel: +370 5 
243 0444 
 
 

България 
МагнаФарм България 
Тел: +359 2 810 3949 
 

Luxembourg/Luxemburg 
CSL Behring NV 
Tél/Tel: +32 15 28 89 20 

Česká republika 
CSL Behring s.r.o. 
Tel: +420 702 137 233 
 

Magyarország 
CSL Behring Kft. 
Tel.: +36 1 213 4290 

Danmark 
CSL Behring AB 
Tel: +46 8 544 966 70 
 

Malta 
AM Mangion Ltd. 
Tel: +356 2397 6333 

Deutschland 
CSL Behring GmbH 
Tel: +49 69 30584437 
 

Nederland 
CSL Behring BV 
Tel: +31 85 111 96 00 

Eesti 
CentralPharma Communications OÜ 
Tel: +3726015540 
 

Norge 
CSL Behring AB 
Tlf: +46 8 544 966 70 

Ελλάδα 
CSL Behring ΕΠΕ 
Τηλ: +30 210 7255 660 
 

Österreich 
CSL Behring GmbH 
Tel: +43 1 80101 2463 

España 
CSL Behring S.A. 
Tel: +34 933 67 1870 
 

Polska 
CSL Behring Sp. z.o.o. 
Tel.: +48 22 213 22 65 

France 
CSL Behring SA 
Tél: +33 1 53 58 54 00 
 

Portugal 
CSL Behring Lda 
Tel: +351 21 782 62 30 

Hrvatska 
Marti Farm d.o.o. 
Tel: +385 1 5588297 
 

România 
Prisum International Trading S.R.L. 
Tel: +40 21 322 01 71 
 

Ireland 
CSL Behring GmbH 
Tel: +49 69 30517254 

Slovenija 
MediSanus d.o.o. 
Tel: +386 1 25 71 496 



 46 

  
Ísland 
CSL Behring AB 
Sími: +46 8 544 966 70 
 

Slovenská republika 
CSL Behring s.r.o. 
Tel: +421 911 653 862 

Italia 
CSL Behring S.p.A. 
Tel: +39 02 34964 200 

Suomi/Finland 
CSL Behring AB 
Puh/Tel: +46 8 544 966 70 
 

Κύπρος 
CSL Behring ΕΠΕ 
Τηλ: +30 210 7255 660 
 

Sverige 
CSL Behring AB 
Tel: +46 8 544 966 70 

Latvija 
CentralPharma Communications SIA 
Tel: +371 6 7450497 

United Kingdom 
CSL Behring UK Ltd. 
Tel: +44 1444 447405 

 
This leaflet was last revised in MM/YYYY. 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu/. 
 
----------------------------------------------------------------------------------------------------------------------- 
 
The following information is intended for health-care professionals and for patients suitable for 
home-treatment / self-administration 
 
General instructions 
• The reconstitution should be performed according to the instructions provided below. 
• The product must be reconstituted, administered and handled with caution using aseptic technique 

to maintain product sterility. 
• Do not use provided sterile ancillaries for reconstitution and administration if their package is 

opened or if they are damaged. 
• The powder must be reconstituted with solvent (water for injections). 
• Total reconstitution of the powder should be obtained within 5 minutes (1,000 mg presentation) 

or 10 minutes (4,000 mg and 5,000 mg presentation). 
• Inspect the reconstituted solution for particulate matter and discoloration prior to administration. 
• The reconstituted solution should be clear, colorless to slightly yellow, and free from visible 

particles. 
 
Follow the steps provided below for the preparation and reconstitution of Respreeza: 
 
1. Ensure that the Respreeza vial and water for injections vial are at room temperature (up to 25°C). 
2. Remove the plastic flip-off cap from the water for injections vial. 
3. Wipe the rubber stopper of the water for injections vial with an antiseptic like an alcohol swab and 
allow it to dry. 

4. Open the Mix2Vial® set by peeling off the lid (Figure 1). 
Do not remove the Mix2Vial set from the blister package. 

 

 
Figure 1 

5. Place the water for injections vial on an even, clean surface and hold the 
vial tight. Take the Mix2Vial set together with the blister package and 
vertically pierce the water for injections vial with the blue tip of the 
Mix2Vial set (Figure 2). 

 



 47 

 
Figure 2 

6. Carefully remove the blister package from the Mix2Vial set by holding at 
the rim and pulling vertically upwards. Make sure that you only pull away 
the blister package and not the Mix2Vial set (Figure 3). 

 

 
Figure 3 

7. Remove the plastic flip-off cap from the Respreeza vial. 
8. Wipe the rubber stopper of the Respreeza vial with an antiseptic like an alcohol swab and allow it to 
dry. 

9. Place the Respreeza vial on an even and firm surface. Invert the water for 
injections vial with the Mix2Vial set attached and vertically pierce the 
Respreeza vial with the clear tip of the Mix2Vial set (Figure 4). The water 
for injections will automatically flow into the Respreeza vial. 
 
NOTE: Ensure all water has transferred into the Respreeza vial. 

 

 
Figure 4 

10. Follow steps below to remove entire Mix2Vial set from Respreeza vial: 
 

• With one hand tightly grasp the Respreeza vial as shown in Figure 5. 
• With the other hand tightly grasp the water for injections vial and the 

blue part of the Mix2Vial set. 
• Bend the entire Mix2Vial set to the side until it disconnects from 

the Respreeza vial (Figure 5). 
 
Discard the water for injections vial with the entire Mix2Vial set. 

 

 
Figure 5 

11. Gently swirl the Respreeza vial until the powder is completely dissolved 
(Figure 6). DO NOT SHAKE. Take care not to touch the rubber vial stopper. 

 

 
Figure 6 



 48 

12. Inspect visually the reconstituted solution. The solution should be clear, colourless to slightly 
yellow, and free from visible particles. Do not use solutions that are discoloured, cloudy or have 
particles. 
13. If more than 1 vial of Respreeza is needed to achieve the required dose, repeat instructions 1 to 12 
above using an additional package containing an unused Mix2Vial set. 
 
Use a separate, unused Mix2Vial set, and a water for injections vial for each Respreeza vial. 
14. Use aseptic technique to transfer the reconstituted solutions into the administration container (e.g., 
empty intravenous bag or glass bottle; (not supplied) via a commercially available intravenous fluid 
tubing transfer set (not supplied)). 
 
Administration 
 
The reconstituted solution must be administered using an IV infusion set (supplied with the 4,000 and 
5,000 package). 
 

1. Make sure that the air vent cap and the roller clamp of the IV infusion set are closed. 
VERTICALLY pierce the Respreeza vial with the IV infusion set spike while twisting the IV 
infusion set spike gently or connect it to an infusion container. 
2. Elevate the Respreeza vial/infusion container or hang on an infusion stand. 
3. Prime the drip chamber by squeezing it until the Respreeza solution has filled the chamber 
roughly half-way. 
4. Open the air vent cap of the IV infusion set. 
5. Slowly open the roller clamp of the IV infusion set and let the Respreeza solution flow until it 
reaches the end of the tubing with no air bubbles.  
6. Close the roller clamp. 
7. Disinfect the injection site with an antiseptic like an alcohol swab before carefully inserting the 
needle into the vein. Make sure that there is no air in the butterfly tube left. 
8. Connect the end of the IV infusion set to the butterfly set and open the roller clamp again. 
9. Infuse the reconstituted solution into the vein. The solution should be infused at an infusion rate 
of about 0.08 ml per kg body weight each min, as determined by your response and your comfort. 
The recommended dose of 60 mg per kg of body weight will take approximately 15 minutes to 
infuse. 

 
One vial of Respreeza is for single use only. 
 
Any unused medicinal product or waste material should be disposed as instructed by your doctor or 
healthcare professional. 
 


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER(S) OF THE BIOLOGICAL ACTIVE SUBSTANCE(S) AND MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET