Aguettant launches in Europe the first Sulfite Free EPINEPHRINE plastic Pre-Filled syringe Sterile field ready - Luer Lock - individually blisterized

1. PRESS
RELEASE
AGUETTANT’S
RANGE OF EMERGENCY
INJECTABLE MEDICINE
IN READY-TO-ADMINISTER
SYRINGES IS GOING GLOBAL

2. OVERVIEW
1/ Sulfite-free adrenaline,
a new product available
as a ready-to-administer, pre-filled syringe............4
2/ The pre-filled syringe,
a range of READY-TO-ADMINISTER
emergency medicine................................................8
3/ Aguettant, a key player in emergency
medicines both in France and worldwide............14
4/ History of the pre-filled syringe,
from R&D to marketing.........................................16
5/ Laboratoire Aguettant Profile..........................18

3. SULFITE–FREE
ADRENALINE,
NOW AVAILABLE
IN A PRE-FILLED SYRINGE
Less than two months after inaugurating their new premises in Gerland, Lyon
(40 million investment), Laboratoire Aguettant, a global player in injectable
essential medicine, once again demonstrate their dynamism with the launch
of a new sulfite-free adrenaline pre-filled syringe. This new product has been
distributed in Germany and the Netherlands since June 2016, in the UK and
Ireland since August 2016 and since September 2016 in France, Portugal,
Belgium and Austria. This new syringe greatly enhances Laboratoire Aguettant’s
existing range of pre–filled syringes which already includes ephedrine, atropine
and phenylephrine.
This ready-to-administer presentation indicated in cardiopulmonary resuscitation and adult acute
anaphylaxis, helps eliminate harm to both healthcare professionals and patients. Developed by
Laboratoire Aguettant, this new pre-filled syringe does not contain sulfites which are allergenic
preservatives with known effects.
Sulfites (e.g. metabisulfite) are used as antioxidants and preservatives in the industry and can
trigger bronchoconstriction and life-threatening anaphylactic shock, especially in the asthmatic
population. The asthma prevalence levels in the UK and Ireland are amongst the highest in Europe
(1 in 10 people in the UK* and 1 in 11 people in Ireland **) and within this population between 3%
to 10% individuals are sulfite sensitive***.
THE FIRST READY-TO-ADMINISTER,
sulfite-free adrenaline pre-filled syringe
1/
P.4 P.5
* Asthma UK, Asthma facts and statistics [Internet]. Cited on 01/10/2016. https://www.asthma.org.uk/about/media/facts-and-statistics/
**AsthmaSocietyofIreland,Facts&figuresonasthma[Internet].Citedon01/10/2016.https://www.asthma.org.uk/about/media/facts-and-statistics/
*** Vally H, Misso NLA. Adverse reactions to the sulphite additives. Gastroenterol Hepatol Bed Bench 2012; 5(1):16-23).

4. It took Aguettant’s teams several years to develop, register, and industrialise this new product.
Adrenaline is a molecule which is particularly sensitive to oxidation. Therefore, manufacturing
and packaging procedures of this sulfite-free product have been designed to protect the active
ingredient - adrenaline - from degradation, by using an oxygen absorber and a foil pouch which
act as a barrier to light and gases.
KEY
FIGURES
R&D
INVESTIMENT
€1MILLION
DISTRIBUTION
WORLDWIDE
DESIGN
and manufacturing features
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5. I L Y O N - G E R L A N D , V I S I T E G U I D É E I
P.8
AGUETTANT
PRE–FILLED
SYRINGESA RANGE OF
READY–TO–ADMINISTER
EMERGENCY MEDICINES
A PATENTED SYSTEM
of administration
Innovation no.1:
Opening system
The syringe’s opening mechanism is patented. The syringe is air
and water tight thanks to a frangible tip cap allowing the luer–lock
connector to be fully protected and remain sterile until the time of use.
Innovation no.2:
Terminal vapour sterilisation of the
plunger and stopper
The sterilisation between the seal lips is carried out in moist heat,
(the patented design allows the vapour to penetrate the inter–lip area)
at 121°C. These two innovations allow an optimised manufacturing
process that guarantees the sterility of the syringe, including critical
spaces, as well as ensuring the solution’s stability.
10UPCOMING
PRODUCTS
25MILLION
UNITS PRODUCED IN
5 YEARS
€120MILLION TURNOVER
WITHIN
5 YEARS
KEY
FIGURES
SALES DISTRIBUTION
IN UNITS:
70%WORLDWIDE
30%FRANCE
TOTAL R&D
INVESTMENT
SINCE THE FIRST
PRE–FILLED SYRINGE:
€15MILLION
2/
P.8 P.9

6. EPHEDRINE
Indications :
• Treatment of hypotension during spinal or epidural anaesthesia.
• Preventive treatment of hypotension during spinal anaesthesia (in France only).
• Strength available: 30 mg/10 ml.
• Available since 2009.
ATROPINE
Indications :
• Treatment of decreases in heart rate (sinus bradycardia and AVB): cardio–
pulmonary resuscitation.
• Pre-operative treatment: prevention of vagal reactions.
• Strengths available: 0.5 mg/5 ml – 1 mg/5 ml – 3 mg/10 ml.
• Available since 2013.
Indications :
• Cardiopulmonary resuscitation in adults and children, and anaphylactic
shock in adults.
• Strength available: 1 mg/10 ml.
• Available since 2016.
PHENYL-
EPHRINE Indications :
• Treatment of hypotension during spinal, epidural or general
anaesthesia.
• Preventive treatment of hypotension during spinal anaesthesia (in
France only).
• Strength available: 500 micrograms/10 ml.
• Available since 2015.
ADRE-
NALINE
LABELLING
During a national survey on the labelling of
anaesthetic syringes in France, 91% of people
interviewed stated that the identification of syringes
using pre-printed colour labels would decrease the
risk of syringe swaps*.
Using coloured labels in accordance with the
NF ISO 26825 standard and the recommendations of
scientific societies such as the SFAR (French Society
for Anaesthesia and Resuscitation) and The Royal
College of Anaesthetists** helps decrease the risk
of medication errors. Aguettant’s labels meet these
colour coded recommendations and have double
graduation scale for easy identification and clear
reading.
* Q. Levrat, A. Troitzky, V. Levrat, B. Debaene. Enquête nationale sur le marquage des seringues
d’anesthésie en France. AFAR 2008 ; 27 :384 -389.
** Société Française d’Anesthésie et de Réanimation
BENEFITS
of pre-filled syringes
For patients:
• reduction in the risk of medication errors;
• reduction in the risk of hospital–acquired
infections;
• reduction in the risk of glass particle
contamination.
For healthcare
professionals:
• reduction in the risk of needle stick injuries
and cuts;
• time savings: decrease the number of
preparation steps allowing more time for
direct patient care. (references page 20 – 21)
For healthcare
organisations:
• reduction in the risk of medical errors;
• reduction in drug wastage;
• reduction in staff injuries;
• reduction in patient infections;
• decrease in costs;
• standardisation of practices.
4 EMERGENCY MEDICINES
for a quicker response to patient needs
The ready-to-administer device decreases the number of preparation steps and thus helps decrease the
associated risks.
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7. THE RISKS
W O R L D W I D E
MEDICATION ERRORS
• In anaesthesia, 1 in 20 perioperative medication administrations included a ME and/or
ADE (1).
• 1 error per 200 anaesthetics bolus injections (2).
• The incidence of medication errors in anaesthesia is estimated 1 in 211 anaesthetics (3).
• 61% of medication errors are administration errors, such as: wrong drug, wrong route
of administration, wrong time of administration, wrong dose (too much or too little drug
given), wrong form, wrong technique of administration, wrong flow for IV drugs (4).
• Medication errors often lead to adverse events: 0.9% of death or serious or irreversible
damage (5).
• Around half of adverse events are preventable (6).
• Using pre-filled syringes instead of drawing up from glass ampoules removes the risk of
medication errors due to drug preparation process (7).
RISKS OF GLASS PARTICLES
AND MICROBIAL CONTAMINATION
• Pre-filled syringe reduces syringe-preparation time by at least by 50% (8).
• Less preparation steps prior to administration = less risk of microbial contamination (9).
• No risk of glass particles contamination compared to a self drawn syringe from a glass
ampoule (10).
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8. P.14
I L Y O N - G E R L A N D , V I S I T E G U I D É E I
P.14
AGUETTANT,
A KEY
PLAYERIN EMERGENCY MEDICINE
WORLDWIDE
Laboratoire Aguettant has a strong business structure in Europe and worldwide. Aguettant
products are sold in 60 countries through subsidiaries or partners.
Aguettant Subsidiaries: Spain, Italy, Belgium, United Kingdom, Germany and Vietnam.
Aguettant Partners: Finland, Denmark, Sweden, Norway, Switzerland, Portugal, Greece,
Romania, United Arab Emirates, Kuwait, Canada and Poland.
AGUETTANT
PRE–FILLED SYRINGES
around the world
AVAILABLE
COMING SOON
3/
P.14 P.15

9. P.16
I L Y O N - G E R L A N D , V I S I T E G U I D É E I
P.16
HISTORY
OF THE
PRE–FILLED
SYRINGE,
FROM R&D TO DISTRIBUTION
AN INNOVATIVE
CONCEPT
In 2005, the laboratory
designed an innovative
plastic syringe protected by
two international patents
and demonstrating several
benefits.
NEW
PRODUCTS
COMPLEX
DEVELOPMENTBetween 2006
and 2009,
several parallel
development processes were conducted, both
internally and with the support of external
partners. The laboratory focused on developing
the administration system, the manufacturing
process, and the first syringe’s molecule
(ephedrine).
Since 2009, Laboratoire
Aguettant has
continuously innovated and
developed new molecules
in ready-to-administer
pre-filled syringes.
Before the launch of
each new product, the
research and development
department works on
the compatibility of the
molecule with its container
- the polypropylene
pre-filled syringe - and
the product’s resistance
to export conditions,
whilst ensuring that it
meets the regulations of
the destination country.
The range of pre-filled
syringes which now
includes 4 different
molecules ( ephedrine,
atropine, phenylephrine,
and adrenaline ) is
expanding. Laboratoire
Aguettant is currently
working on new projects,
with the development
of new products and
improvements in the
administration system.
S U B M I S S I O N
OF MARKETING
A U T H O R I S AT I O N
DOSSIERS AND
INDUSTRIALISATION
In July 2009, Laboratoire
AGUETTANT obtained its MA*
for the ephedrine pre–filled
syringe, meeting stringent
regulatory, and healthcare authority requirements
for a new administration system. The industrial line
was operational in July 2009. Production of the 10 ml
presentation became operational in September of the
same year and was followed by the 5 ml presentation in
May 2010.
*Marketing authorization
4/
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10. LABORATOIRE
AGUETTANT
PROFILE
PRESENCE IN
60COUNTRIES
KEY
FIGURES
€107MILLION
TURNOVER IN
2015
+26%TURNOVER IN
4 YEARS
540EMPLOYEES
6SUBSIDIARIES
AGUETTANT is a pharmaceutical laboratory dedicated to the
development, production, and marketing of medicines which
are essential to hospitals. Their expertise in the development of
innovative, injectable medicines makes AGUETTANT a renowned
player in intensive care, anaesthesia, micronutrients and neurology.
AGUETTANT is an independent laboratory which, for over a century,
has been committed to working with healthcare specialists and
hospitals to provide better patient care through:
expertise: to develop and produce essential injectable
medicines;
a mission: to provide patients and healthcare professionals
with essential medicines to be administered in a reliable and safe way.
5/
P.19P.18

11. 1– Nanji, Anesthesiology 2016.
This prospective observational study found
that approximately 1 in 20 perioperative
medication administrations, and every
second operation, resulted in a medication
error and/or an adverse drug event. More
than one third of these errors led to observed
patient harm, and the remaining two thirds
had the potential for patient harm.
2– Webster C. S. et al. A prospective,
randomised clinical evaluation of a
new safety-orientated injectable drug
administration system in comparison with
conventional methods, Anaesthesia, 2004.
3– Cooper L. et al, Medication Errors
in Anesthesia: A Review, International
Anesthesiology Clinics, Volume 51, Number
1, 1-12, 2013.
4- Rivière A, Piriou V, Durand D, Arnoux
A, Castot-Villepelet A. Medication errors in
anaesthesia: a review of reports from the
French Health Products Agency. Ann Fr
Anesth Reanim. 2012 Jan;31(1):6-14.
5 - Valentin A, Capuzzo M, Guidet B,
Moreno R, Metnitz B, Bauer P, Metnitz P;
Research Group on Quality Improvement
of the European Society of Intensive
Care Medicine (ESICM); Sentinel Events
Evaluation (SEE) Study Investigators. Errors
in administration of parenteral drugs in
intensive care units: multinational prospective
study. BMJ. 2009 Mar 12;338:b814.
6- Abeysekera A. et al, Drug error in
anaesthetic practice : a review of 896 reports
from the Australian Incident Monitoring Study
database, Anaesthesia, 2005, 60, 220-227.
REFERENCES
7- Adapa R. M. et al, Errors during the
preparation of drug infusions:
a randomized controlled trial, HYPERLINK
«http://bja.oxfordjournals.org/»
http://bja.oxfordjournals.org; 1-6, July 2012.
8- Weinger M. B. et al, Drug wastage
contributes significantly to the cost of
routine anesthesia care, Journal of Clinical
Anesthesia 13: 491-497, 2001
Apfelbaum J. F. et al, Outsourcing Anesthesia
Preparations, Part II: Balancing costs,
Efficiency and Quality Care, Anesthesiology
news Special Report 2010.
9 - Cousins D. H. et al. Medication
errors in intravenous drug preparation and
administration : a multicentre audit in the
UK, Germany and France, Qual Saf Health
Care 2005; 14: 190-195.
10-7-LyeS.T.etal.Correspondence,
Glass particle contamination : is it here to
stay? Anaesthesia, 2003, 58 pages 84-105
Carraretto A. R. et al, Glass ampoules: Risks
and Benefits, Rev Bras Anestesiol 2011; 61:
4: 513-521.
P.21P.20

12. ORGANISATIONS
In Europe and worldwide, many organisations recommend the use of pre-filled syringes:
In Europe:
SFAR ( Société Française d’Anesthésie Réanimation )
- G. Aulagner et coll. Prévention des erreurs médicamenteuses en anesthésie, novembre 2006.
HAS ( Haute Autorité de Santé )
Outils de sécurisation et d’auto-évaluation de l’administration des médicaments, juillet 2011.
EBA ( European Board of Anaesthesiology - UEMS Anaesthesiology Section and Board )
EBA recommendation for Safe Medication Practice:
Drug syringe preparation and labelling
All medications prepared for routine use in anaesthesia, intensive care, emergency
medicine and pain medicine should be clearly labelled.
The EBA recommends that pre-filled syringes should be used wherever possible. Hospital
pharmacies and manufacturers should be encouraged to supply them particularly in the first
instance for high risk medicines and ones administered as infusions that are prone to dilution errors.
EMA (European Medicines Agency)
14 avril 2015 - EMA / 606103 / 2014
Pharmacovigilance Risk Assessment Committee (PRAC)
1307 : General considerations
1308 -1309 : Medicines for acute use in emergency situations should be presented in a
ready-to-use format without the need for measuring of doses or solutions.
In the US:
APSF ( Anesthesia Patient Safety Foundation )
The APSF is advocating different features that could lead to predictable and prompt improvements in
medication safety in the operating room. Among those features, the use of prefilled syringes whenever
possible is recommended..
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13. Contacts medias
Elsa Esteves - ee@monet-rp.com
Tél: 04 78 37 34 64 - www.monet-rp.com
LABORATOIRE AGUETTANT
Coralie Mannino - coralie.mannino@aguettant.fr
Tél : 04 78 61 47 69 - www.aguettant.fr
This document is for the exclusive use of journalists from medical and economical press.
AGUETTANT LTD
N°1 Farleigh House, Old Weston Road,
Flax Bourton, Bristol, BS48 1UR, UK
Tél : +44 (0)1275 463691