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0.1% W/W POLYSORBATE 80 IN WATER FOR INJECTION
PL 10673/0026

UKPAR

TABLE OF CONTENTS
Lay Summary

Page 2

Scientific discussion

Page 3

Steps taken for assessment

Page 10

Steps taken after authorisation – summary

Page 11

Summary of Product Characteristics

Page 12

Product Information Leaflet

Page 27

Labelling

Page 29

MHRA PAR – 0.1% w/w Polysorbate 80 in Water for Injection (PL 10673/0026)

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0.1% W/W POLYSORBATE 80 IN WATER FOR INJECTION
PL 10673/0026

LAY SUMMARY
The MHRA granted Octapharm Limited a Marketing Authorisation (licence) for the
product 0.1% w/w Polysorbate 80 in Water for Injection on 21st September 2007. This
product, to be available by prescription only (POM), contains polysorbate 80 and water for
injections, and is intended as a diluent for the reconstitution of freeze-dried human plasma
preparation Wilate. There are no specific active ingredients in this product.
No new or unexpected safety concerns arose from this application and it was, therefore,
judged that the benefits of using 0.1% w/w Polysorbate 80 in Water for Injection
outweighed the risks, hence a Marketing Authorisation has been granted.

MHRA PAR – 0.1% w/w Polysorbate 80 in Water for Injection (PL 10673/0026)

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0.1% W/W POLYSORBATE 80 IN WATER FOR INJECTION
PL 10673/0026

SCIENTIFIC DISCUSSION

TABLE OF CONTENTS
Introduction

Page 4

Pharmaceutical assessment

Page 5

Preclinical assessment

Page 8

Clinical assessment

Page 9

Overall conclusions and risk benefit assessment

Page 10

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INTRODUCTION
Based on the review of the data on quality, safety and efficacy, the UK granted a marketing
authorisation for the products 0.1% w/w Polysorbate 80 in Water for Injection on 21st
September 2007. The product is a prescription-only product.
This was submitted as an abridged application according to Article 10a of Directive
2001/83/EC, a bibliographic application.
The product contains no active ingredient and is to be used as a solvent for reconstitution of
the freeze-dried human plasma preparation Wilate (Factor VIII/von Willebrand factor
concentrate).
WILATE is supplied as a powder for reconstitution and intravenous injection. Originally,
WILATE was reconstituted with water for injection. However, the high von Willebrand
factor content of WILATE impaired the solubility of the lyophilisate and the appearance of
the solution was not optimal.
To provide a convenient reconstitution of the product, 0.1 % (weight to weight)
Polysorbate 80 in water for injection is used as solvent.
Unfavourable creation of foam is prevented by the reduced surface tension because of
Polysorbate 80 presence. The concentration of Polysorbate 80 is balanced between
physiological tolerability and effectiveness. 0.1% (w/w) Polysorbate 80 is as low as
possible to display sufficient solubility. Reconstitution time is significantly reduced due to
the improved way of moistening the lyophilised product even in the presence of high VWF
concentrations. The reconstituted product shows excellent short-time stability in solution.
Polysorbate 80 is a well-known substance with a very short half-live of about 15 minutes
only. Haemodynamic effects have been observed in dogs after doses of about 5 to 10mg
per kg body weight, but such high amounts are unlikely to be given.
After reconstitution with the supplied solvent, WILATE may be administered
intravenously.

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PHARMACEUTICAL ASSESSMENT
DRUG SUBSTANCE
Not applicable
DRUG PRODUCT
Other ingredients
Other ingredients consist of water for injections and polysorbate 80. Both are controlled to
their respective Ph Eur monograph. Satisfactory certificates of analysis have been provided
for each ingredient.
None of the excipients used contain material of animal or human origin.
Pharmaceutical development
A suitable pharmaceutical development section has been provided.
Manufacture
A description and flow-chart of the manufacturing method has been provided. A
satisfactory batch formula has been provided for the manufacture of the maximum batch
size.
In-process controls are satisfactory based on process validation data and controls on the
finished product. Process validation has been carried out on batches of each strength. The
results appear satisfactory.
Finished product specification
The proposed product complies with the general requirements of the Ph Eur monograph.
Batch data have been provided and show compliance with the release specification.
Container Closure System
The finished product is stored in a glass vial, with a bromobutyl rubber stopper and an
aluminium closure, in pack sizes of 2.5, 5 and 10ml. Specifications and Certificates of
Analysis for all packaging types used have been provided. These are satisfactory. The
packaging materials have been shown to comply with current guidelines concerning contact
with products for parenteral use. The manufacturer tests batches of packaging material on
receipt.
Stability
Finished product stability studies have been conducted in accordance with current
guidelines. Based on the results, a shelf-life of 5 years has been set, which is satisfactory.
Storage conditions “Protect from light”, “Store in refrigerator (2-8°C)” and “Avoid
freezing” have been included. The product can be kept at room temperature (up to 25°C)
for up to a month after taking out of refrigeration.
Conclusion
It is recommended that a Marketing Authorisation is granted for this application.

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PRECLINICAL ASSESSMENT
As this is a bibliographic application, no new preclinical data have been provided and none
are required. A suitable preclinical expert report has been provided, which was written by
an appropriately qualified person.

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CLINICAL ASSESSMENT
CLINICAL PHARMACOLOGY
No pharmacological properties have been submitted for the SPC. Instead the reader is
referred to the SPC of the product to be reconstituted. This is satisfactory for a product of
this nature.
BIOEQUIVALENCE
No bioequivalence data have been provided and none are required for an application of this
type.
CLINICAL EFFICACY
No clinical efficacy data have been provided for this application and none are required.
CLINICAL SAFETY
No clinical safety data have been provided for this application and none are required.
EXPERT REPORTS
Since the solvent (Water for Injections with 0.1% Polysorbate 80) is exclusively produced as
diluent for the freeze-dried Factor VIII/von Willebrand factor concentrate Wilate, non-clinical and
clinical assessment is available only in conjunction with the non-clinical and clinical assessment of
the concentrate Wilate. For information, the non-clinical and clinical overviews of Wilate have
been included in the dossier.

PRODUCT LITERATURE
The Summary of Product Characteristics (SPC), Patient Information Leaflet (PIL) and
packaging are satisfactory for this type of product and in compliance with current
regulations.
OVERALL CONCLUSION
The grant of a marketing authorisation is recommended.

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OVERALL CONCLUSION AND RISK BENEFIT ASSESSMENT
QUALITY
The important quality characteristics of 0.1% w/w Polysorbate 80 in Water for Injection are
well-defined and controlled. The specifications and batch analytical results indicate
consistency from batch to batch. There are no outstanding quality issues that would have a
negative impact on the benefit/risk balance.
PRECLINICAL
No new preclinical data were submitted and none are required for an application of this
type.
EFFICACY
No new or unexpected safety concerns arise from this application.
The SPC, PIL and labelling are satisfactory.
RISK BENEFIT ASSESSMENT
The quality of the product is acceptable and no new preclinical or clinical safety concerns
have been identified. The risk benefit is, therefore, considered to be positive.

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0.1% W/W POLYSORBATE 80 IN WATER FOR INJECTION
PL 10673/0026

STEPS TAKEN FOR ASSESMENT
1

The MHRA received the marketing authorisation application on 27th October
2005

2

Following standard checks and communication with the applicant the MHRA
considered the applications valid on 10th November 2005

3

Following assessment of the applications the MHRA requested further
information relating to the quality dossiers on 21st February 2006, 7th August
2006 and 24th July 2007. No further information was requested relating to the
clinical dossier.

4

The applicant responded to the MHRA’s requests, providing further information
on 21st July 2006, 2nd November 2006 and 20th September 2007 for the quality
sections.

5

The applications were determined on 21st September 2007

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0.1% W/W POLYSORBATE 80 IN WATER FOR INJECTION
PL 10673/0026

STEPS TAKEN AFTER AUTHORISATION - SUMMARY
Date
Application
submitted type

Scope

Outcome

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Summary of Product Characteristics (SPC)
1

NAME OF THE MEDICINAL PRODUCT
0.1% w/w polysorbate 80 in Water for Injection

2

QUALITATIVE AND QUANTITATIVE COMPOSITION
Water for Injections with 0.1% Polysorbate 80; 2.5 ml, 5 ml, 10 ml
For a full list of excipients, see section 6.1.

3

PHARMACEUTICAL FORM
Solvent for parental use

4
4.1

CLINICAL PARTICULARS
Therapeutic indications
Used for reconstitution of the freeze-dried human plasma preparation Wilate.

4.2

Posology and method of administration
For intravenous use.
As for the product to be reconstituted.

4.3

Contraindications
As for the product to be reconstituted.

4.4

Special warnings and precautions for use
The product should not be used if the solution is not clear or if the container is damaged.
As for the product to be reconstituted.

4.5

Interaction with other medicinal products and other forms of interaction
As for the product to be reconstituted.

4.6

Pregnancy and lactation
As for the product to be reconstituted.

4.7

Effects on ability to drive and use machines
As for the product to be reconstituted.

4.8

Undesirable effects
As for the product to be reconstituted.

4.9

Overdose
As for the product to be reconstituted.

5
5.1

PHARMACOLOGICAL PROPERTIES
Pharmacodynamic properties
As for the product to be reconstituted.

5.2

Pharmacokinetic properties
As for the product to be reconstituted.

5.3

Preclinical safety data
As for the product to be reconstituted.

6
6.1

PHARMACEUTICAL PARTICULARS
List of excipients
Water for Injections
Polysorbate 80

6.2

Incompatibilities
As for the product to be reconstituted.

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6.3

Shelf life
60 months
The product can be stored at room temperature (max. +25°C) for 1 month. In this case the shelf-life
expires 1 month after the product has been taken out of the refrigerator for the first time. The new
shelf-life has to be noted on the outer carton by the patient.

6.4

Special precautions for storage
Store in refrigerator (2°C to 8°C) protected from light. Do not freeze

6.5

Nature and contents of container
0.1% w/w polysorbate 80 in Water for Injection is supplied in colourless Type I glass vials 20 ml,
closed with bromobutyl rubber stoppers and covered with flip off cap.
The carton contains:
1 vial with 0.1% w/w polysorbate 80 in Water for Injection
1 equipment pack with the administration devices (1 disposable syringe, 1 transfer set [1 doubleended needle and 1 filter needle], 1 infusion set)
2 alcohol swabs
and the package leaflet
0.1% w/w polysorbate 80 in Water for Injection is supplied in three pack sizes with the following
filling volumes: 2.5 ml, 5 ml and 10 ml.

6.6

Special precautions for disposal
Any unused product or waste material should be disposed of in accordance with local requirements.

7

MARKETING AUTHORISATION HOLDER
Octapharma Ltd.
6, Elm Court, Copse Drive
Coventry, CV5 9RG
United Kingdom

8

MARKETING AUTHORISATION NUMBER(S)
PL 10673/0026

9

DATE OF FIRST AUTHORISATION/RENEWAL OF THE
21/09/2007

10

DATE OF REVISION OF THE TEXT
21/09/2007

AUTHORISATION

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PACKAGE LEAFLET: INFORMATION FOR THE USER
0.1% w/w polysorbate 80 in Water for Injection – 2.5 ml, 5ml, 10 ml
Solvent for parental use
Read all of this leaflet carefully before you start using this medicine.
Keep this leaflet. You may need to read it again.
If you have any further questions, ask your doctor or pharmacist.
This medicine has been prescribed for you. Do not pass it on to others. It may harm
them, even if their symptoms are the same as yours.
If any of the side effects gets serious, or if you notice any side effects not listed in
this leaflet, please tell your doctor or pharmacist.

In this leaflet:
1.
What 0.1% w/w polysorbate 80 in Water for Injection is and what it is used for
2.
Before you use 0.1% w/w polysorbate 80 in Water for Injection
3.
How to use 0.1% w/w polysorbate 80 in Water for Injection
4.
Possible side effects
5.
How to store 0.1% w/w polysorbate 80 in Water for Injection
6.
Further information

1.

WHAT 0.1% w/w polysorbate 80 in Water for Injection IS AND WHAT IT IS
USED FOR
Water for Injections with 0.1% Polysorbate 80
Used for reconstitution of the freeze-dried human plasma preparation Wilate.

2.

BEFORE YOU USE 0.1% w/w polysorbate 80 in Water for Injection

Do not use 0.1% w/w polysorbate 80 in Water for Injection
The product should not be used if the solution is not clear or if the container is
damaged.
As for the product to be reconstituted.
Take special care with 0.1% w/w polysorbate 80 in Water for Injection
As for the product to be reconstituted.
Taking other medicines
As for the product to be reconstituted.
Using 0.1% w/w polysorbate 80 in Water for Injection with food and drink
As for the product to be reconstituted.

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Pregnancy and breast-feeding
As for the product to be reconstituted.
Driving and using machines
As for the product to be reconstituted.
Important information about some of the ingredients of 0.1% w/w polysorbate 80 in
Water for Injection
As for the product to be reconstituted.

3.

HOW TO USE 0.1% w/w polysorbate 80 in Water for Injection
For intravenous use.
As for the product to be reconstituted.

If you use more 0.1% w/w polysorbate 80 in Water for Injection than you should
As for the product to be reconstituted.
If you forget to use 0.1% w/w polysorbate 80 in Water for Injection
As for the product to be reconstituted.
If you stop using 0.1% w/w polysorbate 80 in Water for Injection
As for the product to be reconstituted.

4.

POSSIBLE SIDE EFFECTS
As for the product to be reconstituted.

5.

HOW TO STORE 0.1% w/w polysorbate 80 in Water for Injection
Store in refrigerator (2°C to 8°C) protected from light. Do not freeze
Shelf-life: 60 months
The product can be stored at room temperature (max. +25°C) for 1 month. In this case
the shelf-life expires 1 month after the product has been taken out of the refrigerator for
the first time. The new shelf-life has to be noted on the outer carton by the patient.

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6.

FURTHER INFORMATION

What 0.1% w/w polysorbate 80 in Water for Injection contains
Water for Injections with 0.1% Polysorbate 80; 2.5 ml, 5 ml, 10 ml
What 0.1% w/w polysorbate 80 in Water for Injection looks like and contents of the
pack
0.1% w/w polysorbate 80 in Water for Injection is supplied in colourless Type I
glass vials 20 ml, closed with bromobutyl rubber stoppers and covered with flip off
cap.
The carton contains:
1 vial with 0.1% w/w polysorbate 80 in Water for Injection
1 equipment pack with the administration devices (1 disposable syringe, 1 transfer
set [1 double-ended needle and 1 filter needle], 1 infusion set)
2 alcohol swabs
and the package leaflet
0.1% w/w polysorbate 80 in Water for Injection is supplied in three pack sizes with
the following filling volumes: 2.5 ml, 5 ml and 10 ml.
Marketing Authorisation Holder and Manufacturer
Octapharma Ltd.
6, Elm Court, Copse Drive
Coventry, CV5 9RG
United Kingdom
This leaflet was last approved in 06/2007.
PL 10673/0026

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Expand Transcript

Source: Medicines and Healthcare Products Regulatory Agency

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.

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