Neurotoxins countermeasures: the French Military Health Service auto-injector Lt Col BARDOT Sébastien, Pharmacist Dr GHSI meeting, Washington, Oct 4-5, 2009
Contents INEUROPE overview: the current product already available Production capacities at «Pharmacie Centrale des Armées» Future prospects for Ineurope
INEUROPE: a neurotoxin s antidote Therapeutic approach: An anticholinergic drug: 2mg atropine An anticonvulsivant: 20 mg avizafone A reactivator of cholinesterase: 350 mg pralidoxime French strategy: pyridostigmine + two INEUROPE per soldier
INEUROPE: medical device + Drug Water for injection drugs Internal bypass
INEUROPE: medical device + drug Ineurope before use Reconstitution 1. Remove the red security collar 2. Screw the cap for reconstitution Ineurope after reconstitution Injection 1. Remove the upper red security 2. Push the auto-injector on to the leg 3. Injection is automatic Ineurope after injection
INEUROPE: important datas Approved product in France (since march 2008) Active Pharmaceutical Ingredients: GMP Stability: Shelf life is 4 years (between +2 C and +8 C) After reconstitution: shelf life is 6 months (in ambiant temperature) Another stability data: at 25 C, shelf life is 1 year Security tests and clinical trial have been conducted succesfully: Toxicity and security tests: rodent and cytomolgus monkey (avizafon and association), mutagenicity Clinical trial and tolerability : 40 healthly volunteers (avizafon and pralidoxime alone, and association) for pharmacologic and pharmacokinetics data
INEUROPE: important datas Medicine for french soldiers since 2004 Indication registrated: first injection since primary intoxication symptoms appear, and if necessary a new administration within 15 min Applications for french people in development since registration (city of Paris firefighters, civilian rescue) Tests managed for military and emergency use : exposition to warm or cold conditions, to dust, to shocks and vibration, validation of all security device for reconstitution medical device (CE marking) by manufacturer Sedat Tokyo 1995 Operational tests in french army forces (STAT) Neurotoxin resistant packaging 5500 intoxicated 12 death 700 hospitalized
INEUROPE: important datas Ineurope : registrated european mark IN : Intoxication/ NEUR : Neurotoxiques/ OP : Organophosphorés The «3 in 1» french autoinjector approved medicine A drug easy to use for emergency A finished product already available Possible contract with the french military health service Col. Nicole GROS-PELLETIER, pharmacist doctor email: nicole.gros-pelletier@sante.defense.gouv.fr Production at «Pharmacie Centrale des Armées»
Production capacities The «Pharmacie Centrale des Armées» (PCA) PCA: military pharmaceutical manufacturer for military and public health needs Inside the french department of Defense A historical manufacturer for french military supply since 1792 The french Ministry of Defense opened the new PCA in september 2003 A GMP production plant in Orleans A high quality production managment in a new building since 2003 french agency authorization in 2002 Ineurope is one medicine among anothers products against NRBC intoxications: tablets, capsules, vials, autoinjectors
PCA is located in Orleans 100km south of Paris Production capacities
Production capacities Pharmacie Centrale des Armées / 110 employees Logistics Quality control Production 8.000 m² Offices
Production capacities 70 000 units of Ineurope produced per year Theoretical capacities are up to 250 000 units per year, on current equipments) All manufacturing and packaging operations Aseptic process in restricted area: 15 validated operators Qualified equipments: Filling machine Freeze drying Needle positioning equipment Outsourcing and contracts for other countries are conceivable
Production capacities
Future prospects for INEUROPE For a better efficacy against organophosphorus agents Evolution concerns one active ingredient «pralidoxime» may be changed in HI6 Without other modification: combination atropine/avizafone/new oxime in the same device New combination using the same pharmaceutical technology aseptical filing and freeze drying technology Dose: 650 mg of HI6. Efficacy studies (animals) will confirm dose
Future prospects for INEUROPE HI6 DMS development API from two providers A french provider: lab scale production, kilolab for 2010 Analytical development: HPLC analysis, impurities, forced degradation (solution ph, oxydation, light and heat) Mutagenicity tests Process development Compatibility with pharmaceutical process without changing steps of process (effect of sterilizing filters, silicone tubing and rubber stopper) Freeze drying test for combination with new oxime HI6 (650 mg) First lab scale production for the finished product First stability ICH studies began in july 2009
Future prospects for INEUROPE Various combination are possible into the cartridge: liquid/liquid, liquid/solid, liquid/freeze dried Reusable, modifiable system for the medical device Evolutive device depending of the therapeutical progress: next generation oxime, new anti convulsant A working group for the new oxime project in PCA: Production to perfect manufacturing process, Quality Control for new analytical methods and stability studies, Quality Insurance for quality defects, Regulatory Affairs for clinical/security studies and authorizations
Conclusion INEUROPE Neurotoxins countermeasure auto-injector already available in the French Health Service PRODUCTION CAPACITIES outsourcing or contracts conceivable DEVELOPMENT French Health Service is already working on the new generation of auto-injector
Neurotoxins countermeasures: the French Military Health Service auto-injector Thank you for your attention Questions?