ISPE Tampa Conference February 2010 Tampa, Florida USA. Market Overview and Manufacturing Processes

Transcription

1 Prefilled Syringes: Market Overview and Manufacturing Processes Jörg Zimmermann, Vetter Pharma-Fertigung GmbH&Co. KG February 2010 Tampa Conference Overview Introduction to prefilled syringes Market overview: volumes worldwide, volumes in the US, EU and rest of the world Products in prefilled syringes Market shares bulk and pre-sterilized syringes Market shares suppliers Processes for bulk and pre-sterilized syringes Summary and conclusions 2 1

2 Introduction to Prefilled Syringes Tip-cap syringes Staked needle syringes Syringes Vetter LyoJect 3 Introduction to the Market of Prefilled Syringes 1 Prefilled syringes first introduced into the market at the end of the 1970s Market in the US still lags behind Europe in terms of conversion from vials 2008: market valued at approx. 39 Billion US$ 2008: volume in total approx. 1,5 Billion units 4 2

3 Introduction to the Market of Prefilled Syringes 2 Market for Prefilled Syringes has slowed down recently from double to single digit growth Market-growth directly correlated to the introduction of biotech-products Glas syringes still dominate the market, plastic prefills showing slow growth, ie for diluent syringes 5 Markte shares of dosage forms [%] cartridges/pens ampoules syringes 6,1% 7,0% 7,4% 7,4% 23,0% 22,5% LCD 13 bn LCD 13 bn LCD 41 bn Infusion - bags/bottles 20,7% 21,8% LCD 39 bn vials 38,7% 37,1% LCD 67 bn Source: IMS Health 6 LCD = local currency dollars Local currency sales converted to U.S. dollars using the average exchange rates for the specified time period. Note: No comparability of sales values over years 3

4 Markte shares of dosage forms [units] Total volume 4,9 5,2 5,5 5,9 6,7 6,9 7,4 6,8 % cartridges/pens syringes 0,3 0,3 0,7 0,7 0,4 0,8 0,4 0,9 0,44 1,1 0,51 1,4 0,58 1,3 0,68 1,4 vials ,2 4,4 3,9 3,9 4,0 4,8 5 5, Source: IMS Health 7 Estimated Market-shares: bulk and presterilised USA 5% 95% Presterilised Bulk Japan 50% Presterilised Bulk 50% Europe Presterilised 30% Bulk 70% 8 4

5 Products in Prefilled Syringes: Biologics Currently 28 blockbusters on the market Market value: 71 billion US$ (2009) Products in syringes marked in blue (excl. Insulins) Aranesp Avastin Avonex Betaferon Copaxone Enbrel Epogen Erbitux Erypo Gardasil Herceptin Humira Lovenox Lucentis Mabthera Neorecormon Neulasta Neupogen Pegasys Prevnar Rebif Remicade Synagis Varivax Source: IMS Health 9 Introduction to the Market of Prefilled Syringes Suppliers: Glas syringes: Becton Dickinson, Bünder Glas, MGlas, Nuova Ompi, Schott etc. Rubber components: West Pharmaceutical Services, Helvoet, Daikyo etc. 10 5

6 System and Process Advantages Differentiation of a product in the market Cost savings in active substance use due to reduced overdose with pre-filled syringes in comparison with vials Reduced material consumption, easy storage and disposal Risk reduction of microbiological contaminations during use High dosage accuracy and sterility assurance 11 Added value through minimal overfill requirements System comparison ampoule versus prefill Single-chamber syringe with V-OVS Fill volume, e.g. Overfill volume for pre-filled Vetter system Overfill for ampoule 0.8 ml ml (+ 1.8%) 0.15 ml (+ 18%) 12 6

7 Advantages for the User Improvement of the patient s acceptance Simplified medication Safe handling and high user-friendliness for the hospital personnel Reduction of needle stick injuries Prevention of mix-up through labeling of the individual system 13 Process for Bulk Syringes 1 Preparation of rubber components at the site of filling: washing, siliconisation and sterilisation Preparation of the syringes at the site of filling: washing, siliconisation and sterilisation Choice of siliconisation and sterilisation process based on the syringe type 14 7

8 Process for Bulk Syringes 2 Tip cap syringes: spray siliconisation of silicone oil emulsion followed by dry heat sterilisation Advantages: dry heat sterilisation is also depyrogenisation silicone oil is fixed to the glass surface even distribution with minimal quanities of silicone oil and good break-loose and gliding forces 15 Process for Bulk Syringes 3 Staked needle syringes: spray siliconisation with pure silicone oil followed by steam sterilisation in an autoclave Staked needle syringes cannot be sterilised by dry heat due to the glue holding the canula Washing process needs to be validated to exceed 3 log endotoxin reduction even distribution with minimal quantities of silicone oil and good break-loose and gliding forces 16 8

9 Automated Autoclave loading / Automated dry heat tunnel loading 17 Process for Pre-sterilised Syringes 1 Rubber components prepared p at the vendor: washing, siliconisation, sterilisation (usually gamma-irradiation) Glass syringes also prepared at the vendor: washing, siliconisation, sterilisation (usually ethylenoxide-gassing) Syringes are handled in plastic tubs 18 9

10 Closure Preparation (for both processes) Stoppers and Front Closures Preparation includes: Washing with final rinse WfI Siliconisation Assembly Autoclaving/Sterilisation o 3log endotoxin reduction required 19 Process for Pre-sterilised Syringes 2 Sterilisation and filling on different sites requires transport t validation and check for integrity of the packed material before use System for introduction of the components into the cleanroom needed: glove-box systems with manual decontamination, VHP-locks, e-beam tunnels 20 10

11 Tub for Pre-sterilised Syringes process video 21 Transferprocess for Pre-sterilised Syringes Removal of the bag Transport into Class A Transfer of the tubs into the air look Opening of the sealing 22 11

12 Process for Pre-sterilised Syringes 2 VHP-locks: points to consider Duration of decontamination and aeration size of the locks! Line performance might be affected Penetration of VHP 23 Process for Ready-to-Fill Syringes 2 E-beam tunnels: points to consider Radiation control Size and weight of the guns and shields Courtesy of GSK Bio 24 12

13 Syringe filling process Compounding 0.22 µm storage filtration Sterile filtration & filling Terminal sterilisation Lyophilisation Visual inspection Secondary packaging Barrel preparation & sterilisation optional Closure preparation (& autoclaving) µm Storage Filtration Class C + local LAF protection Pressure Compounding vessel Storage vessel - Sterilised connected 26 13

14 Sterile Filtration & Filling Class C+ local LAF protection Pressure Class A/B Sterile filter Dosing pump(s) Break tank Storage vessel Filling needle(s) Sterile filtration performed as in-line filtration immediately prior to filling 27 Sterile Filtration & Filling Filling: Video of the process (VLA4) Animation of filling Animation of stoppering 28 14

15 System comparison: Pre-sterilised Pro s Potentially easier regulatory change (second source) Lower initial investment in equipment Con s Reduced flexibility in using different syringe types No choice in the siliconisation process (oil/emulsion) No choice of sterilisation process Sterilisation and filling on different sites Higher unit cost 29 System comparison: Bulk Pro s Con s Flexible siliconisation i process Bigger investment t Flexible sterilisation process For large volume products significantly lower total unit cost Dry heat sterilisation = depyrogenation Less transfers of sterilised units, lower contamination risk 30 15

16 System comparison: bottom line Bulk process requires sophisticated know-how Bulk process gives maximum control on the process Sterilisation as core pharmaceutical activity is where the filling is Bulk process requires higher initial investment Transfer of production process from one site to another requires validation and stability, regardless of the process 31 Thank you for listening! Jörg Zimmermann Director of Production, Langenargen Site Vetter Pharma-Fertigung GmbH & Co.KG February 2010 Tampa Conference 16

17 Spray Siliconisation 33 Spray Siliconisation 34 17

18 Needle Siliconisation 35 Syringe Filling 36 18

19 Stopper Placement 37 19