PRESSRELEASE

AGUETTANT’SRANGE OF EMERGENCY

INJECTABLE MEDICINEIN READY-TO-ADMINISTER

SYRINGES IS GOING GLOBAL

OVERVIEW1/ 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

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,sulfi te-free adrenaline pre-fi l led syringe

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* Asthma UK, Asthma facts and statistics [Internet]. Cited on 01/10/2016. https://www.asthma.org.uk/about/media/facts-and-statistics/** Asthma Socie ty of Ireland, Facts & figures on asthma [Internet]. Cited on 01/10/2016. 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).

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.

KEYFIGURES

R&DINVESTIMENT

€1 MILLION

DISTRIBUTION

WORLDWIDE

DESIGNand manufacturing features

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AGUETTANTPRE–FILLED SYRINGESA RANGE OF READY–TO–ADMINISTER EMERGENCY MEDICINES

A PATENTED SYSTEMof 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.

10 UPCOMING

PRODUCTS

25MILLIONUNITS PRODUCED IN

5 YEARS

€120MILLION TURNOVER

WITHIN5 YEARS

KEYFIGURES

SALES DISTRIBUTION

IN UNITS:70% WORLDWIDE

30% FRANCE

TOTAL R&DINVESTMENTSINCE THE FIRST PRE–FILLED SYRINGE:

€15

MILLION

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EPHEDRINEIndications :• 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.

ATROPINEIndications :• 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

LABELLINGDuring 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 seringuesd’anesthésie en France. AFAR 2008 ; 27 :384 -389.** Société Française d’Anesthésie et de Réanimation

BENEFITSof pre-fi l led 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 MEDICINESfor 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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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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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

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HISTORYOF THEPRE–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.

NEWPRODUCTS

COMPLEXDEVELOPMENT

Between 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

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LABORATOIREAGUETTANT

PROFILEPRESENCE IN

60

COUNTRIES

KEY FIGURES

€107 MILLION

TURNOVER IN

2015

+26%

TURNOVER IN4 YEARS

540 EMPLOYEES

6

SUBSIDIARIES

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.

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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, 2001Apfelbaum 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- Lye S. T. et al. Correspondence, Glass particle contamination : is it here to stay? Anaesthesia, 2003, 58 pages 84-105Carraretto A. R. et al, Glass ampoules: Risks and Benefits, Rev Bras Anestesiol 2011; 61: 4: 513-521.

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ORGANISATIONSIn 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 / 2014Pharmacovigilance Risk Assessment Committee (PRAC)1307 : General considerations1308 -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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Co n taC t s m e d i a s

Elsa Esteves - ee@monet-rp.comTél: 04 78 37 34 64 - www.monet-rp.com

LABORATOIRE AGUETTANTCoralie Mannino - coralie.mannino@aguettant.frTél : 04 78 61 47 69 - www.aguettant.fr

This document is for the exclusive use of journalists from medical and economical press.

AGUETTANT LTDN°1 Farleigh House, Old Weston Road,Flax Bourton, Bristol, BS48 1UR, UKTél : +44 (0)1275 463691