MRPAR Sodium Chloride 0.9% w/v Injection BP
UK/H/0859/001/MR
Public Assessment Report
Mutual Recognition Procedure
Sodium Chloride 0.9% w/v Injection BP
MRP no: UK/H/0859/001/MR
UK licence no: PL 24598/0002
Applicant: Noridem Enterprises Limited
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MRPAR Sodium Chloride 0.9% w/v Injection BP
UK/H/0859/001/MR
Sodium Chloride 0.9% w/v Injection BP
PL 24598/0002; UK/H/0859/001/MR
LAY SUMMARY
On 11th November 2007, Austria, Belgium, Denmark, Germany, Greece, Ireland, The
Netherlands, Norway, Portugal, Spain and Sweden approved Noridem Enterprises Limited
Marketing Authorisations (licences) for the medicinal product Sodium Chloride 0.9% w/v
Injection BP (PL 24598/0002). This application was by mutual recognition procedure with the
UK as Reference Member State (RMS). A national licence had previously been granted in the
UK on 26th August 2004. This is a prescription-only medicine (POM) to be used to dissolve
or dilute some medicines so that they can be given as an injection or infusion (a drip) into
veins, muscles or other tissues in the body. It can also be used in the preparation of a number
of surgical and medical procedures, as follows:
• To clean out catheters (small devices put in your veins to inject your medicine)
• As a priming solution to fill intravenous lines (long tubes connected to your veins). This
is to make sure that there is no air being injected, in procedures such as haemodialysis
(a procedure to clean the blood when you have kidney disease)
• As a priming solution at the beginning and end of blood transfusions without causing
damage to the blood cells.
Sodium Chloride 0.9% w/v Injection BP is a type of medicine called an electrolyte. It is a
sterile salt liquid that can be used for a number of different reasons as it is very similar to your
bodily fluids.
No new or unexpected safety concerns arose from this application and it was, therefore,
judged that the benefits of using Sodium Chloride 0.9% w/v Injection BP outweighed the
risks, hence a Marketing Authorisation has been granted.
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MRPAR Sodium Chloride 0.9% w/v Injection BP
UK/H/0859/001/MR
TABLE OF CONTENTS
Module 1: Information about initial procedure
Page 4
Module 2: Summary of Product Characteristics
Page 5
Module 3: Product Information Leaflet
Page 12
Module 4: Labelling
Page 17
Module 5: Scientific Discussion
Page 21
1 Introduction
2 Quality aspects
3 Non-clinical aspects
4 Clinical aspects
5 Overall conclusions
Module 6
Steps take after initial procedure
Not applicable
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MRPAR Sodium Chloride 0.9% w/v Injection BP
UK/H/0859/001/MR
Module 1
Product Name
Sodium Chloride 0.9% w/v Injection BP
Type of Application
Known Active Substance
Initial application
Bibliographic (Article 10a)
Chemical substance
Prescription only
Sodium chloride
Solvent for parenteral use, 0.9% w/v
Noridem Enterprises Ltd, Evagorou & Makariou, Mitsi Building
3, Suite 115, 1065 Nicosia, Cyprus
United Kingdom
Austria, Belgium, Denmark, Germany, Greece, Ireland, The
Netherlands, Norway, Portugal, Spain, Sweden
UK/H/0859/001/MR
Day 90: 11/11/2007
Active Substance
Form
MA Holder
RMS
CMS
Procedure Number
Timetable
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MRPAR Sodium Chloride 0.9% w/v Injection BP
UK/H/0859/001/MR
Module 2
SUMMARY OF PRODUCT CHARACTERISTICS
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NAME OF THE MEDICINAL PRODUCT
UK: Sodium Chloride 0.9% w/v Injection BP.
BE: Sodium Chloride Noridem 0.8% w/v Injection BP
DK: Natriumklorid Noridem
ES: Sodium Chloride Noridem 9mg/ml (0.9%), solution for injection
SE: Natriumklorid Noridem 9mg/ml, solution for injection
NO: Natriumklorid Noridem
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QUALITATIVE AND QUANTITATIVE COMPOSITION
Sodium Chloride 9mg/ml or 0.9%w/v (Ph. Eur.)
For full list of excipients, see section 6.1.
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PHARMACEUTICAL FORM
Solution for injection and solvent for parenteral use.
A clear colourless liquid.
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4.1
CLINICAL PARTICULARS
Therapeutic indications
Sodium chloride injection is indicated as a pharmaceutical aid and diluent for the infusion of compatible
drug additives and for diluting or dissolving drugs for parenteral administration.
Other indications for sodium chloride injection include flushing of IV catheters, as a priming solution in
haemodialysis procedures and to initiate and terminate blood transfusions without haemolysing red
blood cells. Sodium chloride injection may be added to compatible carbohydrate solutions such as
dextrose in water to produce electrolytes.
4.2
Posology and method of administration
Dosage:
The volume given and administration rate are dependent upon the additive.
Administration:
For parenteral use.
The directions for use of the additive will dictate the administration route.
4.3.
Contraindications
Hypernatremia, hyperchloremia and those contraindications related to the additive.
4.4.
Special warnings and precautions for use
Newborn babies, both premature and at term, may exhibit excessively high sodium levels due to
immaturity if renal function. As a result, in newborn babies, both premature and at term, repeated
injections of sodium chloride may only be given after determining blood serum levels.
Sodium Chloride must be used with caution in patients with hypertension, heart failure, pulmonary or
peripheral oedema, impaired renal function, pre-eclampsia, hypreraldosteronism, and other diseases and
treatments (e.g. corticosteroids) associated with sodium retention.
4.5
Interaction with other medicinal products and other forms of interaction
None known when used as a diluent or priming solution.
4.6
Pregnancy and lactation
This solution does not present any hazard to pregnant women, to the foetus or to the breast-fed child.
4.7
Effects on ability to drive and use machines
None stated.
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MRPAR Sodium Chloride 0.9% w/v Injection BP
UK/H/0859/001/MR
4.8.
Undesirable effects
Unwanted reactions may be associated with the administration technique and consist of fever, infection
at the injection site, local pain or reaction, venous irritation, venous thrombosis or ohlebitis spreading
from the injection site, extravasation
4.9
Overdose
Administration of quantities which may have adverse effects is very unlikely as vials contain a
maximum of 20 ml.
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5.1
PHARMACOLOGICAL PROPERTIES
Pharmacodynamic properties
Pharmacotherapeutic group: B05X A03
Sodium chloride is the principal salt involved in the maintenance of plasma and other tissues tonicity.
Solutions of sodium chloride closely approximate the composition of the extracellular fluid of the body;
more than 90% of the cation of the extracellular fluid is sodium and more than 60% of the anion is
chloride. Furthermore, a 0.9% solution of sodium chloride is approximately isotonic with body fluids.
Thus, an injection of 0.9% sodium chloride will not appreciably affect the osmotic pressure of the body
or the chemical composition of the extracellular fluid. A 0.9% solution of sodium chloride is therefore
the choice of solvent for many drugs which have to be administered parenterally. The solution has the
added advantage of being non-irritating to tissue.
5.2
Pharmacokinetic properties
Not appropriate.
5.3
Preclinical safety data
There are no preclinical data of relevance to the prescriber which are not included in other sections of
the SPC.
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6.1
PHARMACEUTICAL PARTICULARS
List of Excipients
Water for Injection Ph. Eur.
6.2
Major incompatibilities
Compatibility should be checked when sodium chloride injection is used as a diluent or solvent.
6.3
Shelf life
2 years.
Discard after single use, discard any unused portion.
6.4
Special precautions for storage
Store below 25°C.
6.5
Nature and contents of container
Polypropylene ampoules, of 5 or 10 ml, packed into cartons of 50 ampoules, or of 20 ml, packed into
cartons of 20 ampoules.
Not all pack sizes may be marketed
6.6
Special precautions for disposal
Use only if the solution is clear without visible particles.
Discard after single use.
Discard any unused portion.
7.
MARKETING AUTHORISATION HOLDER
Noridem Enterprises Ltd., (trading as Fannin)
Evagorou & Makariou,
Mitsi Building 3, Suit.115,
1065 Nicosia, Cyprus.
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MRPAR Sodium Chloride 0.9% w/v Injection BP
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MARKETING AUTHORISATION NUMBER
24598/0002
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DATE OF THE FIRST AUTHORISATION OR RENEWAL
7 September 2005
10
DATE OF REVISION OF THE TEXT
17/07/2008
UK/H/0859/001/MR
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MRPAR Sodium Chloride 0.9% w/v Injection BP
UK/H/0859/001/MR
Module 3
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MRPAR Sodium Chloride 0.9% w/v Injection BP
UK/H/0859/001/MR
Module 4
Labelling
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MRPAR Sodium Chloride 0.9% w/v Injection BP
UK/H/0859/001/MR
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MRPAR Sodium Chloride 0.9% w/v Injection BP
UK/H/0859/001/MR
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MRPAR Sodium Chloride 0.9% w/v Injection BP
UK/H/0859/001/MR
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MRPAR Sodium Chloride 0.9% w/v Injection BP
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Module 5
Scientific discussion during initial procedure
1.
INTRODUCTION
Background
This application was submitted by Noridem Enterprises Limited for Sodium Chloride
0.9% w/v Injection BP, via the Mutual Recognition Procedure. The UK acted as
Reference Member State for the procedure, which was granted a UK licence on 26th
August 2004.
Sodium Chloride 0.9%w/v Injection is indicated as a pharmaceutical aid and diluent for
the infusion of compatible drug additives and for diluting or dissolving drugs for
parenteral administration.
Other indications for sodium chloride injection include flushing of IV catheters, as a
priming solution in haemodialysis procedures and to initiate and terminate blood
transfusions (without haemolysing red blood cells). Sodium chloride injection may be
added to compatible carbohydrate solutions, such as dextrose in water, to produce
electrolytes.
Based on the review of the data on quality, safety and efficacy, the RMS considered that
the application for Sodium Chloride 0.9% w/v Injection BP could be approved for the
indications stated above.
Day 90 for the procedure was 11th November 2007, subsequent to which Marketing
Authorisations were approved in Austria, Belgium, Denmark, Germany, Greece, Ireland,
The Netherlands, Norway, Portugal, Spain and Sweden.
Overall Benefit/Risk Assessment
Sodium Chloride 0.9% w/v Injection BP is a well-known and widely used solvent. It is
compatible with an extensive number of substances and can be used as a vehicle/diluent
for the parenteral administration of other medicinal products.
No preclinical studies were conducted, and none are required as the product is
well-established for medicinal use.
No clinical studies were conducted, and none are required as the product is
well-established for medicinal use.
The RMS has been assured that acceptable standards of GMP are in place at all sites
responsible for the manufacture and assembly of this product prior to granting its national
authorisation.
For manufacturing sites within the community, the RMS has accepted copies of current
manufacturer authorisations issued by inspection services of the competent authorities as
certification that acceptable standards of GMP are in place at this site.
2.
QUALITY ASPECTS
S. Active Substance
Synthesis of the drug substance from the designated starting materials has been
adequately described, and appropriate in-process controls and intermediate specifications
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MRPAR Sodium Chloride 0.9% w/v Injection BP
UK/H/0859/001/MR
are applied. Satisfactory specification tests are in place for all starting materials and
reagents, and these are supported by relevant certificates of analysis.
An appropriate specification is provided for the active substance sodium chloride, with
suitable test methods and limits. Batch analysis data are provided and comply with the
proposed specification.
The active sodium chloride is packaged in multiple layer paper bags. Suitable
specifications have been provided for all packaging materials and the primary packaging
has been shown to comply with current guidelines concerning contact with foodstuff.
Appropriate shelf-lives have been set for active sodium chloride, based on the available
stability data provided by the active substance manufacturers. No formal stability data
has been provided by the applicant, which is acceptable given that the active is known to
be very stable and the European Pharmacopoeia monograph contains no degradation
products.
P. Medicinal Product
Other Ingredients
The only excipient used in this product is water for injections. Satisfactory certificates of
analysis have been provided to show that it complies with the current European
Pharmacopoeia monograph.
No excipients of human or animal origin are used in this product. No genetically
modified organisms are used in this product.
Pharmaceutical Development
The objective of the development programme was to produce a solution for injection
containing 0.9% w/v sodium chloride that complied with the current British
Pharmacopoeia monograph.
Manufacturing Process
An appropriate account of the manufacturing process has been provided. The
manufacturing process has been validated and has shown satisfactory results.
Finished Product Specification
The finished product specification is satisfactory and in-line with the current British
Pharmacopoeia monograph. Test methods have been described and have been adequately
validated, as appropriate. Batch data have been provided and comply with the release
specification. Certificates of analysis have been provided for any working standards used.
Container-Closure System
The product is packed into polypropylene 5 or 10ml ampoules packed into cartons of 50
or 20ml ampoules packed into cartons of 20.
Satisfactory specifications and certificates of analysis have been provided for all
packaging components. All primary packaging complies with the relevant regulations
regarding materials for parenteral use.
Product Stability
Stability studies were performed in the packaging proposed for marketing and in
accordance with current guidelines. All results from stability studies were within
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MRPAR Sodium Chloride 0.9% w/v Injection BP
UK/H/0859/001/MR
specified limits. These data support a shelf-life of 2 years with the storage condition
‘Store below 25°C’.
Bioequivalence/Bioavailability
No bioequivalence studies have been submitted for this application and none were
required.
Summary of Product Characteristics (SPC), Patient Information Leaflet (PIL),
Labels
The SPC, PIL and Labels are pharmaceutically acceptable.
A package leaflet has been submitted to the MHRA along with results of consultations
with target patient groups ("user testing"), in accordance with Article 59 of Council
Directive 2001/83/EC, as amended. The results indicate that the package leaflet is wellstructured and organised, easy to understand and written in a comprehensive manner. The
test shows that the patients/users are able to act upon the information that it contains.
MAA Forms
The MAA forms are pharmaceutically satisfactory.
Expert Report
The pharmaceutical expert report has been written by an appropriately qualified person
and is a suitable summary of the pharmaceutical dossier.
Conclusion
The grant of a marketing authorisation is recommended.
3. PRE-CLINICAL ASPECTS
No new preclinical data have been supplied with this application and none are required
for an application of this type.
4. CLINICAL ASPECTS
Clinical Pharmacology
No new data were submitted and none are required for this type of application.
Efficacy
No new data were submitted and none are required for this type of application.
Safety
No new data were submitted and none are required for this type of application.
Summary of Product Characteristics (SPC), Patient Information Leaflet (PIL),
Labels
The SPC, PIL and labels are medically acceptable. The SPC is consistent with that for
other similar products.
Conclusion
The grant of a marketing authorisation is recommended.
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MRPAR Sodium Chloride 0.9% w/v Injection BP
5.
UK/H/0859/001/MR
OVERALL CONCLUSION
QUALITY
The important quality characteristics of Sodium Chloride 0.9% w/v Injection BP 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.
NON-CLINICAL
No new preclinical data were submitted and none were required for an application of this
type.
EFFICACY
No significant new or unexpected safety concerns were found during the clinical
development.
The SPC, PIL and labelling are appropriate for a product of this type.
BENEFIT-RISK ASSESSMENT
The quality of the product is acceptable and no new preclinical or clinical safety concerns
have been identified. Extensive clinical experience with Sodium Chloride 0.9% w/v
Injection BP is considered to have demonstrated the therapeutic value of the compound.
The benefit-risk is considered to be positive.
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