High-speed Rotary Tablet Press Courtoy PERFORMA P with Multi-Control 4 System

Transcription

1 = = = Attachment 1 GEA Pharma Systems - Courtoy High-speed Rotary Tablet Press Courtoy PERFORMA P with Multi-Control 4 System Proposal: COUR /12 from GEA Process Engineering nv - Courtoy 31 st March 2011 GEA Process Engineering nv Bergensesteenweg 186, 1500 Halle, Belgium Tel: Fax: = courtoy@geagroup.com /

2 1.0 TABLE OF CONTENTS 1.0 TABLE OF CONTENTS CONTACTS INTRODUCTION COMMERCIAL DETAILS Price Summary PERFORMA P Tablet Press Optional Features and Equipment Documentation and Engineering Services Packing & Shipment Service Rates Commercial Terms and Conditions Payment Terms Currency and Pricing Delivery Terms Warranty Exclusions Limitation Of Liability Maximum Liability Miscellaneous Validity SCOPE OF SUPPLY PERFORMA TM P Optional Features and Equipment Documentation and Engineering Services TECHNICAL DATA ENCLOSURES General Terms and Conditions 31 COUR /12 Page 2 of 35 GEA Pharma Systems - Courtoy

3 2.0 CONTACTS Customer contact: Mr Titos Vasilopoulos Managing Director GEA Pharma Systems Contacts: Area Sales Manager: Paul De Smet Phone No: Agent: Contact: paul.desmet@geagroup.com Costas D. Mitsoras Ltd. Tassos Arniakos Phone No: / mirasco@hol.gr COUR /12 Page 3 of 35 GEA Pharma Systems - Courtoy

4 3.0 INTRODUCTION GEA Pharma Systems supplies advanced technologies for the processing of Active Pharmaceutical Ingredients (API) for the production of oral and parenteral dosage forms. GEA Pharma Systems strives for Price/Performance Leadership providing its customers with highly cost-effective, integrated systems for the pharmaceutical industry. GEA Pharma Systems is dedicated to innovation and thereby providing durable quality through its well-established brands: Aeromatic- Fielder and Collette - batch and continuous granulation, drying, pelletizing and coating; Buck - contained materials handling; Courtoy - tablet compression; and Lyophil - pharmaceutical freeze drying. GEA Pharma Systems activities include partnering with customers to develop new products and enhance clinical effectiveness; the supply of R&D-scale and stand-alone production equipment; and the installation of complete integrated production lines. Today, we are pleased to enclose our proposal for a: Courtoy high-speed rotary tablet press PERFORMA P with MC4 control system for EU or TSM D, B or BB tooling. COUR /12 Page 4 of 35 GEA Pharma Systems - Courtoy

5 4.0 COMMERCIAL DETAILS For detailed technical specification refer to Section PRICE SUMMARY PERFORMA P Tablet Press (See section 5.1) 3 PERFORMA P BASIC MACHINES One PERFORMA P rotary tablet press (See section 5.1 for detailed description), including: Modular construction machine frame Stainless steel hexagonal machine housing with 3 windows Drive module with AC 3-phase motor with frequency inverter and cooling unit Pharmaceutical compression zone, including: Exchangeable turret, featuring Exchangeable Die Disc (EDD) Complete upper cam Double rotary paddle feeder Scraper and powder recycling finger Ejection finger with pneumatic reject valve Light-weight tablet chute with two outlets Dust extraction nozzles designed for optimal dust extraction Set of pre-compression and main compression rollers Set of bottom cam tracks Top and bottom punch jamming detection Powder in-feed system Machine and punch lubrication systems PC/PLC-based control system Multi-Control 4 for fully automatic machine and production control; 21CFR part11 compliant; featuring colour graphical interface Tool kit and calibration punches Comprehensive technical documentation The price of the basic machine is the same for the D, B and BB tooling version. Compression tooling (i.e. upper and lower punches and dies) is NOT included in the above- mentioned prices, unless included as an option. COUR /12 Page 5 of 35 GEA Pharma Systems - Courtoy

6 4.1.2 Optional Features and Equipment (See section 5.2) m1 m2 m3 m5 m6 m8 m10 m11 m12 m15 m17 c1 c3 c5 c6 c20 c22 p5 3 x Additional overfill cam 3 x Powder hopper on top of the machine 3 x Constant Level system 1 x Agitator system for poor-flowing powders 3 x Upper punch guides with exchangeable bushings and keyways for shaped tooling; including keyways for lower punch guidings 3 x Tablet chute with sampling gate 3 x Price supplement for closed feeder with slide-in wear plate 1 x Additional turret including upper & lower cam tracks and EDD capability 1 x Bi-layer kit, enabling bi-layer tablet production 1 x Arm to lift turret / upper guide part from the machine 2 x Trolley to hold and transport the turret 3 x Compression force monitoring & Dual Control System 3 x Equal porosity tabletting 3 x Ejection force monitoring 3 x Ethernet connection for remote diagnosis/maintenance MC4 3 x Weight re-calibration using Combi-Test 3 x Combi-Test Kraemer (Checkmaster) 3 x PharmaTechnology deduster / metal checker COMBI 500 CE FINAL PRICE AFTER DISCOUNT : Divided into: 2 Performa P machines ( at each) Performa P machine with Bi-layer capability Discount for future spare parts: - 45% during initial 5 years COUR /12 Page 6 of 35 GEA Pharma Systems - Courtoy

7 4.1.3 Documentation and Engineering Services (See section 5.3) Documentation and Validation d1 Comprehensive technical documentation (including Operation and Maintenance manual in English) INCLUDED d3 IQ/OQ procedures & checklists for machine qualification INCLUDED on site (in English) Mechanical/Electrical IQ/OQ documentation to support validation activities is standard in English language. Translation into other languages can be quoted on demand Factory Acceptance Test The FAT is at fixed cost for a period of three times two days, as indicated below. The customer representatives expenses (hotel, travel, spending money, etc.) are not included and are to be paid by the customer. Additional days required by the customer will be charged at the rate in use at the time of acceptance test. The placebo material for the FAT trial is to be supplied by the customer. INCLUDED Engineering Services On Site On-site assistance will be provided at fixed cost for a period of ten days, as indicated below, including the GEA Pharma Systems - Courtoy engineer s travel and hotel expenses. The fixed price is based on 8-hour working days and covers weekday work only. Additional hours (i.e. over 8 hours per day) worked on weekdays will be invoiced separately at 150% of standard rates. Saturday working hours will be invoiced at 150%, Sunday working hours will be charged at 200% (see section 4.2 Service Rates). s12 s13 On-site installation supervision & IQ/OQ (12 days) On-site training and start-up assistance (12 days) Packing & Shipment s2 3 Pallet packing of machine & peripherals INCLUDED COUR /12 Page 7 of 35 GEA Pharma Systems - Courtoy

8 4.2 SERVICE RATES SERVICE RATES (2011) (Installation, Commissioning and Training) Technician (Service, Maintenance) Travel, hotel expenses and local transport are at customer s account - Normal working hours (between , max. 8 hours/day) 90,00 EUR/hour - Travel hours 80,00 EUR/hour - Overtime Each additional hour (outside ) & work on Saturdays Work on Sundays and official holidays 135,00 180,00 EUR/hour EUR/hour Engineer (Supervision of Erection & Installation / Start-Up / Validation / Calibration / Training) Travel, hotel expenses and local transport are at customer s account - Normal working hours (between , max. 8 hours/day) 110,00 EUR/hour - Travel hours 100,00 EUR/hour - Overtime Each additional hour (outside ) & work on Saturdays Work on Sundays and official holidays 165,00 220,00 EUR/hour EUR/hour Project Manager / Software Specialist Travel, hotel expenses and local transport are at customer s account - Normal working hours (between , max. 8 hours/day) 130,00 EUR/hour - Travel hours 120,00 EUR/hour - Overtime Each additional hour (outside ) & work on Saturdays Work on Sundays and official holidays 195,00 260,00 EUR/hour EUR/hour TRAVEL EXPENSES / HOTEL EXPENSES Travel expenses (car) 0,60 EUR/km Travel expenses (rental car, plane, train or boat) Invoiced at Cost Copy of vouchers will be attached to final invoice Hotel expenses / Boarding / Miscellaneous / Incidentals Invoiced at Cost Copy of vouchers will be attached to final invoice Notes: The minimum charge for Support Service is four (4) hours at the base rate, plus travel time (door to door), and reasonable living and incidental expenses in connection with the service performed. Above service rates are valid until end of December Service Rates are subject to change without notice. COUR /12 Page 8 of 35 GEA Pharma Systems - Courtoy

9 4.3 COMMERCIAL TERMS AND CONDITIONS The specific terms and conditions in this section and General Terms and Conditions of Sale form an integral part of this quotation/order confirmation. Where in conflict, the specific terms take precedence over the General Terms Payment Terms down payment will be payable upon receipt of an invoice, after Factory Acceptance Test (FAT) and before shipment will be payable upon receipt of an invoice, after Site Acceptance Test (SAT) but maximum 120 days from delivery if the delay is not due to Courtoy All invoices are payable in EUR. * If the FAT is postponed for more than four weeks upon customer s request, the invoice for payment of this instalment will be issued four weeks upon the initially agreed FAT date Currency and Pricing Prices are quoted in EUR, unless otherwise specified. All itemised prices are quoted ex-works, unless otherwise specified. All prices quoted are exclusive of Duty and Value Added Tax. Packaging and Freight are quoted separately. The price of stainless steel is increasing significantly due to the volatility in commodity prices particularly nickel, chromium and molybdenum. As a result we are unable to fix the value of the stainless steel content of the equipment specified at the time of this quotation. We therefore reserve the right to adjust the price at the time of order placement to reflect the change in the price of stainless steel between the date of this quotation and the date of order placement. For the avoidance of doubt the adjustment in the price will only be based on the direct cost of the stainless steel to be purchased to produce the equipment Delivery Terms Shipment ex-works will be determined upon final settlement of all technical and commercial details. Delivery time will be confirmed upon receipt of purchase order. For the equipment described in this quotation, the current (EXW) delivery time is 8 months. Delivery: CIF Athens as per Incoterms COUR /12 Page 9 of 35 GEA Pharma Systems - Courtoy

10 4.3.4 Warranty The parts comprising the Plant shall be free of defects in workmanship and materials for a period of 12 months from the date of initial operation or 18 months from delivery, whichever occurs first (the Warranty Period ). Seller s warranty is limited to Seller repairing or replacing (on an ex works manufacturing plant basis), in its sole discretion, the parts determined by its authorized representative of Seller to be defective in materials or workmanship at the time of delivery. Seller s warranties under the Contract do not cover, and Buyer assumes responsibility for, all defects, losses and damages arising from or relating to: wear and tear parts; use of nonoriginal spare parts; use of lubricants, consumables, utilities and/or feed that do not strictly conform to the requirements of the Contract (if the feed characteristics are not specified in the Contract, then the feed must not deviate from any samples provided by Buyer prior to contract); modifications to the Plant without Seller s express written consent; corrosive or abrasion; faulty maintenance or operation, including failure to comply with Seller s manuals or instructions; information, design, buildings, equipment or other works supplied by Buyer or on its behalf, including any failure, defect or non-conformity of upstream or downstream equipment; failure of Buyer to provide sufficient protection for the Plant against external conditions; or any conditions or circumstances not due to the fault of Seller. Seller assumes no responsibility and shall have no liability for any repairs or replacements undertaken by Buyer without Seller's prior written authorization. In case of any defective computer hardware or software that is acquired, directly or indirectly, by Seller from original manufacturers, Seller s obligation shall be limited to transferring to Buyer any warranties obtained by Seller. Buyer is responsible for all labour, equipment and charges used or incurred in the removal, transport, installation and commissioning of repaired or replaced parts. Buyer shall notify Seller in writing as soon as possible though in any event not later than ten days after detection within the Warranty Period of any alleged defect covered by Seller s warranty, giving detailed information of the alleged defect and the reason that it is considered Seller's responsibility. In addition, Buyer shall provide details to include projected direct costs and delays (number of people, rental equipment, etc.), if any, which may result from such alleged defect. Seller and Buyer will then mutually agree to a reasonable response time. Seller will have access to all relevant operating and maintenance data and to the job site to inspect and review with the installation contractor and Buyer's personnel any alleged defect when Seller believes such a visit is necessary. The warranty stated above in this Clause is the only warranty made by Seller. Seller hereby excludes and disclaims to the fullest extent permitted by applicable law all conditions, warranties, guarantees and stipulations, express (other than those expressly stated in the Contract) or implied, statutory, customary or otherwise which, but for such exclusion, would or might subsist in favour of Buyer, including without limitation any warranty of merchantability or fitness for particular purpose or any warranty as to the suitability, functionality or performance of the Plant. COUR /12 Page 10 of 35 GEA Pharma Systems - Courtoy

11 4.3.5 Exclusions Our quotation comprises delivery of the items, documentation and engineering services as stated in section 4.1 and described in section 5.0. There may be some items, utilities and services required for the equipment or for installation of the equipment which are not included in our quotation. Such supplies are to be provided by the Client on site. All costs involved are to be borne by the Client. In case of any doubts regarding items and services not included, please contact us Limitation Of Liability No consequential damages Seller shall in no case be liable for any loss of revenues or profits; loss of opportunity, production or contracts; loss of or damage to feed or other raw materials or product; plant downtime or delays; penalties; recall costs; or for any consequential, special, punitive, exemplary, indirect or incidental losses or damages howsoever caused Maximum Liability Except to the extent an exclusion or limitation of Seller's liability is prohibited by law (in which circumstances Seller's liability shall only be limited to the extent permitted by applicable law), Seller s aggregate liability to Buyer under or in connection with the Contract, including any liability arising out of or relating to the performance and/or breach and/or termination of this Contract, shall in no case exceed the payments received from Buyer under the Contract or the Contract price, whichever is less Miscellaneous If any provision of the Contract is determined to be invalid or unenforceable, this shall not affect the validity or enforceability or the remaining provisions and the parties shall agree on substitute provisions that achieve as closely as possible the same economic effect. Captions are for convenience only. The Contract sets forth the entire and sole understandings between Seller and Buyer with respect to the subject matter thereof; Seller s data in product information and price lists are binding only if expressly stated in the Contract. The Contract may not be assigned by Buyer without Seller s prior written consent. COUR /12 Page 11 of 35 GEA Pharma Systems - Courtoy

12 4.3.9 Validity This proposal is valid for 1 month. Issued Approved Paul De Smet Area Sales Manager Johan Van Evelghem Sales Director Pharma GEA Pharma Systems - Courtoy 31 st March 2011 COUR /12 Page 12 of 35 GEA Pharma Systems - Courtoy

13 5.0 SCOPE OF SUPPLY 5.1 PERFORMA TM P The Courtoy PERFORMA TM P press is a single-sided rotary tablet press, available for EU or TSM tooling standard. Its technical characteristics for each type of tooling are given in the Technical Details table in Section 6 of this quotation The Machine Frame Combination of heavy cast iron frames and high-strength steel tension rods for maximal machine rigidity and vibration absorption. The upper cast iron parts are entirely nickel coated for stainless protection. Four anti-vibration pads under the machine Provisions for crane lifting and slots for fork truck lifting Modular construction with 4 clearly separated and isolated compartments: (1) The drive module, containing main drive motor and reduction gearbox, adjustment motors, air compressor for pneumatic compensators, punch lubrication system and cooling unit. Electrical connection box at the back of the base module (2) The pharmaceutical compression zone, containing the exchangeable turret including the top cam, the compression rollers with guides, the lower cam tracks, powder feeder, tablet chute and dust extraction. The compression zone is totally separated from the remainder of the machine, while removable guards made of FDA guideline compliant plastic protect the rollers and cam tracks from the powder. (3) Electromechanical top module, containing drive motors for feeder and the optional constant level system, as well as the pre- and main compression compensators. The powder in-feed system is separated from this area and can be easily removed through a removable front panel. (4) Electrical cabinet, containing the electrical and electronic components, including the PLC and PC, placed against the backside of the machine. This way, a separate electrical cabinet and cabling to the press are avoided. If desired, the electrical cabinet can be supplied separate from the machine, at extra cost. The use of only two tensile rods allows for perfect accessibility to the compression zone once the three front doors are open The Machine Housing Hexagonal machine housing in stainless steel 304 with 3 large plexiglass windows (front, left and right) to give excellent accessibility all around the machine. The windows are supported by gas springs, to maintain the necessary pressure on the window seals. COUR /12 Page 13 of 35 GEA Pharma Systems - Courtoy

14 The housing stands on its own feet on the floor independent from the machine frame. There is only a soft packing seal between machine frame and machine housing, NO fixed connection. This construction considerably reduces vibrations and noise, even at high compression forces and high speeds. Machine housing sealed against the floor and with sealed stainless steel roof panel. All windows are interlocked The Drive Module Main motor and worm gear reduction box in bottom of the base module for maximal vibration suppression. AC 3-phase motor with frequency control for a wide speed range; can be stopped by braking and restarted at any speed. Frequency control including overload protection. Special zero-play worm wheel gearbox, to reduce noise and to provide constant speed without ripple. Drive belt between gearbox and main shaft prevents heat transfer from gearbox to die table. Vertical spindle rotating on oversized conical bearings, holding the turret. A cooling unit, based on air ventilation, in the machine base improves heat evacuation to the outside of the machine The Pharmaceutical Compression Zone Turret including one (1) Exchangeable Die Disc (EDD) of choice: an EDD for conventional dies (EDD-CD) or an EDD for the innovative Die Shells (EDD-DS) Complete upper cam, mounted on the turret Double rotary paddle feeder with independent drives and with tool-free disassembly Magnetically mounted scraper and powder recycling finger Ejection finger with pneumatic reject valve Low friction, light weighted tablet chute with two outlets (good and reject) for maximum flexibility. A sampling flap and outlet is available as an option. Well positioned dust extraction nozzles, designed for optimal dust extraction. The nozzles are connected to the principal dust extraction connection at the top of the machine. The principal connection is equipped with an underpressure monitoring device for the dust extraction system. A pressure sensor, located near the external connection point for the dust extraction, measures the underpressure in the outflow of air and dust. In the Multi- Control 4 software, an upper and lower underpressure limit can be set. Whenever the underpressure goes outside the specified band, an alarm is generated and the machine will stop production. The punch guides are equipped with specially designed double-lip seals to prevent dust migration into the guides and oil spots on the tablets. COUR /12 Page 14 of 35 GEA Pharma Systems - Courtoy

15 The turret is easily exchangeable, using a simple and removable lifting arm. The disconnection and removal of the turret is guided step by step by the Multi-Control 4 control system. The turret can be opened using the same lifting arm, enabling simple and quick manual exchange of the Exchangeable Die Disc (EDD). Minimal number of parts inside the compression zone. One set of pre-compression rollers One set of main compression rollers Bottom cam tracks High torque teeth coupling between the turret and the central spindle Top and bottom punch jamming detection Ejection cam height regulation Fill cam height regulation Powder in-feed Powder is fed into the tablet press through a tube made of FDA guideline compliant plastic, featuring a DN 80 tri-clamp connection, on top of the machine. As an option, the Constant Level system can be installed or, alternatively for poorly flowing powders the agitator system The Turret Forged steel for maximal strength (NO cast iron as this is too brittle and breaks easily when punch jamming occurs or a die is tightened too hard). Three parts: (1) lower punch guide section, (2) Exchangeable Die Disc section, and (3) upper punch guide section. Entirely nickel-plated for stainless protection. Working surface of the die table: hard chromium plated and ground, giving a flat stainless and very hard surface for an ideal action of scrapers and minimal powder loss. Spring-loaded lower punch brakes for uniform filling The Compression Cycle THE FILL OVERFILL Overfilling is done under the first paddle of the double rotary feeder = filling paddle. Standard delivered: one overfill cam of choice: 8, 10, 12, 14, 16, 18 or 19 (max in case of B & BB tooling) or 20 (max in case of D tooling). Automatic identification of the installed overfill cam and saved as product parameter. Easily removable cam for removal of lower punches. The overfill cam can be removed and installed without removing any of the lower punches. COUR /12 Page 15 of 35 GEA Pharma Systems - Courtoy

16 FINAL FILL OR DOSING Fill cam or dosing cam is adjusted in vertical position through the control system using an electro-motor with high-precision control loop for accurate tablet weight control Reduced slope and adjustable flight retainers for uniform filling even at high speeds Integrated lower punch tight detection by spring-loaded system and proximity switch Second scraper paddle of the feeder scrapes excess of powder above the die away and brings it back in the first chamber of the feeder. A re-circulation groove in the centre of the turret recovers the powder that escapes between the feeder and the die table surface. This recovered powder is scooped out of the groove and fed into the dies BEFORE they go under the feeder = PRE-FILLING. Powder scraper and die closing plate (after the feeder) and powder recuperation finger (before the feeder) is maintained in contact with the die table using magnets. This allows a very simple design, easy for cleaning and installation. THE PRECOMPRESSION 2 well-dimensioned hardened steel pre-compression rollers, diameter 160 mm Lifetime lubricated sealed bearings and guidings Top roller mounted on the unique Courtoy Air Compensator for constant precompression force under extended dwell time. Pre-compression height adjustment by electro-motor and encoder on lower roller. Closed loop position control and adjustment through control system. Maximum pre-compression force of 10 kn: The air compensator allows an extended dwell time requiring a significantly lower force than any other system. Overload protection: The pneumatic system has greater sensitivity to overload and reacts faster to an overload situation than a hydraulic or electro-mechanical protection system. THE MAIN COMPRESSION 2 well-dimensioned hardened steel main compression rollers, diameter 160 mm Lifetime lubricated sealed bearings and guidings Top roller mounted on the unique Courtoy Air Compensator; to be used for either constant thickness tabletting or constant force tabletting. (The latter is also called Equal Porosity Tabletting.) In case of constant force tabletting, the dwell time is considerably longer, often resulting in better quality tablets and/or increased machine output. Top punch penetration manually adjustable between 1 and 4 mm, by means of an excenter axis. Tablet thickness adjustment by electro-motor and encoder on lower roller. Closed loop position control and adjustment through control system. COUR /12 Page 16 of 35 GEA Pharma Systems - Courtoy

17 Overload protection: The pneumatic system has greater sensitivity to overload and reacts faster to an overload situation than a hydraulic or electro-mechanical protection system. Maximum main compression force up to 80 kn in case of constant thickness tabletting. In case of constant force tabletting (i.e. Equal Porosity Tabletting), the maximum compression force is limited to 60 kn. THE EJECTION Variable slope ejection cam for optimal ejection curve, resulting in less capping problems. Exchangeable bronze wear plate Adjustable ejection height Ejection finger with integrated pneumatic reject valve for out-of-tolerance tablets. THE TABLET CHUTE Tablet chute in PU: food approved, easy to clean and light weighted. Double channel tablet chute for good tablets and out-of-tolerance tablets. Reject flap valve in good-tablet outlet for non-controlled tablets: i.e. tablets produced in manual mode and at machine start-up. An obstruction sensor is installed on the tablet chute cover, detecting any blockage of the tablet chute in the good-tablets outlet. The sensor is a robust capacitive sensor, easy to adjust and insensitive to dust accumulation in the tablet chute. Additional flap and outlet for automatic tablet sampling available as an option. THE TOP CAM One central piece in steel with 4 exchangeable wear parts in bronze. This avoids replacing the complete cam when certain parts are worn out due to punch friction. Up-going and down-going acting cams are double-sided (= act on both sides of the punch) to minimise cam and tooling wear. The complete cam is mounted on bearings on the turret. A spring loaded lever system prevents the cam from rotating with the turret. Top punch tight detection: When the torque on the top cam surpasses a pre-set value, the spring loaded lever system will move. This is detected by a proximity switch, generating the appropriate alarm Machine Lubrication No open oil lubrication system by using the latest state of the art dry and lifetime grease lubrication systems Punch Lubrication System Sophisticated punch lubrication system based on volumetric dosage of oil quantity. COUR /12 Page 17 of 35 GEA Pharma Systems - Courtoy

18 Oil and compressed air are mixed in adjustable proportion and conducted in a tube to the point of lubrication, where they are ejected as an oil mist on the punches. Accurate control on the oil volume per stroke of the micro-pump Totally separated lubrication systems for upper and lower punches, allowing independent set-up Upper punches at 2 points: Punch body and punch head. Lower punches at 4 points: inside punch body, outside punch body, punch head and ejection cam. All lubrication points are mounted rigidly inside the cam tracks and no position adjustment is needed Other Tool kit for basic disassembling and cleaning operations Calibration punches for calibration of the different position regulation units. Electrical wiring and software control for peripheral equipment: tablet deduster, metal detector and/or automatic tablet sampling system. Connectors are nicely incorporated and hidden behind a door Multi-Control 4 The MULTI-CONTROL Version 4 is the latest generation of Courtoy control systems for rotary presses. The system s hardware and software is designed to allow for full compliancy with the 21CFR PART11 guideline. It is a fully automated monitoring, control and reporting system based on a PLC/PC hardware configuration. The PLC controls entirely the machine (i.e. machine control and production control) while the PC is used as operator interface and for data storage & reporting, allowing more functions compared to the basic ITS control system, which is based on a PLC only: Automated audit trail Detailed batch reporting, including operator activity and alarm logging, as well as the generation of distribution and trending graphs when the optional AWS or Combi-Test is used. Individual password protected user accounts Multiple user access levels (one start level, 4 operational levels and one design level) Fully automated recovery of data, even after a PLC crash. Memorisation of actual values of machine parameters for extremely fast start-up of a new batch Maintenance screens are available to check & solve electrical problems on the machine Automatic punch length compensation Easy input of sensor offset and sensitivity On-line help and troubleshooting functions including pictures COUR /12 Page 18 of 35 GEA Pharma Systems - Courtoy

19 The PC is an HP/COMPAQ desktop with Windows XP operation system, using Siemens WinCC software for visualisation and communication with the PLC. The PLC is a SIEMENS S7. The PC and PLC are both located in the electrical cabinet attached to the back of the tablet press main body and integrated in the machine housing. Optionally, the electrical cabinet can be detached from the main body as a stand-alone unit in stainless steel 304 and a set of cables between electrical cabinet and tablet press. The system proposes a menu driven 15 colour graphical interface to the operator. This userfriendly interface will lead the operator step by step through the logic sequence of the press adjustments and starting the automatic production control. An accelerated start-up procedure is available in case the machine will continue producing the same product as during the previous production run. The system allows adapting a wide number of product, machine and system settings simply by touching the correct buttons on the sensitive PC touch-panel. No separate keyboard or mouse is used, but both can be connected if required. The system automatically locks the settings and parameters that are not allowed to be modified. All press adjustments are memorised as a combined Batch-Product-Tooling-Equipment- Press definition, giving an optimal flexibility for organising the recipe database. At the beginning of a batch, the machine parameter settings for a specific product are recalled from the recipe database. The operator then does further batch depending fine-tuning of certain settings - such as feeder speeds and fill depth. Once the correct tablets characteristics are reached, the operator switches the automatic production control mode on by simply pushing a key on the screen. The automatic mode can be switched on and off by pressing this same key. The MULTI-CONTROL 4 features a complete control of all production stops with clear messages on the screen - and on print-outs - for production alarms (production out of range, defective punch identification, etc.) and equipment alarms (top or bottom punch jamming, precompression or main compression overload, motor overload, door open, tablet chute obstruction, no powder, lubrication failure, etc.). More than 100 different alarms are continuously monitored and automatically reported when activated. Only the production alarms are recorded in the logbook. The Multi-Control 4 allows easy network integration using a standard Ethernet card in the PC. Specific software for communication with customer s network is not included. Connection by OPC is possible. In order to enable full compliance with the FDA guideline 21CFR Part 11, Uninterrupted Power Supply (UPS) is a standard feature of the MC4 control system. In case of power failure, the UPS allows supplying enough power to the computer, the AWS or Combi-Test (if used), the screen, the PLC and the back-up device to shutdown gracefully, without loss of any data. As an additional back-up device, a DVD drive is included in the PC, which allows saving all batch report data on a separate medium. The Multi-Control 4 scope of supply also includes a full colour laser printer, connected to the PC via Ethernet. This printer allows the operator to print detailed and configurable end of batch COUR /12 Page 19 of 35 GEA Pharma Systems - Courtoy

20 reports. The Multi-Control 4 can be set up to print production information such as machine parameters, alarms and weighing results from the AWS or Combi-Test (if these optional peripherals are used). The Multi-Control 4 is based on the same principle for tablet weight control as the ITS and other previous Courtoy control systems: Variations in tablet thickness under CONSTANT FORCE AT PRE-COMPRESSION are monitored by the system and used to adjust the fill depth of the dies. Under the given circumstances, these variations in thickness are in LINEAR relation with the tablet weight and allow therefore for an accurate and fast correction of tablet weight. The constant force at pre-compression is exerted thanks to the unique Courtoy Air Compensator, having many other advantages such as extended dwell time for better tablet quality. The unique Courtoy Air Compensator is also used at the main compression stage, as a punch overload protection system. The air pressure in the Air Compensator is set to a value slightly higher than the desired main compression force. The pneumatic piston of the Air Compensator will automatically move when the compression force exceeds the air pressure, making the Air Compensator a very fast-acting, passive system, which does not need any actuation. COUR /12 Page 20 of 35 GEA Pharma Systems - Courtoy

21 5.2 OPTIONAL FEATURES AND EQUIPMENT M.1 Additional overfill cam The basic machine is delivered with one (1) standard overfill cam (to be chosen by the customer). This option includes for one (1) additional standard overfill cam of choice. M.2 Powder hopper on top of the machine This option covers the supply of a powder hopper supported by a ring, positioned on 4 poles on the top frame. The hopper will be designed to fit the specific installation requirement and interface with the customer s powder feeding system. The inlet of the powder hopper can be equipped with either a Mueller cap, or alternatively lay-flat tubing, for dust-free connection with the powder feeding system. M.3 Controlled powder infeed: Constant Level system The Constant Level system has the following features: A rotary dosing valve located in the top module, but separated from this and easy accessible via a front door, carries the powder column above the press. The valve is driven by an electro-motor Transparent tube connection to the feeder, with infra-red powder level detector The level sensor controls the motor in such way to have a constant powder level above the feeder, resulting in constant & reduced powder pressure inside the feeder. This is very important to reach constant tablet weight at very high tabletting speed. Totally TOOLFREE (dis)assembling The rotary valve can be used as shut-off valve The Constant Level system combined with the double rotary paddle feeder answers the feed requirements of nearly all powders and granules while at the same time being a simple construction for easy maintenance and cleaning. M.6 Upper punch guides with exchangeable bushings and keyways for shaped tooling + lower punch guides with keyways This option includes for exchangeable bushings for the upper punches. Equipping the turret with such exchangeable bushings can result in significant maintenance cost savings: when the guidings of the upper punches are worn out, only these bushings need to be replaced, eliminating the need to replace the entire turret. The bushings are much lower in cost compared to a new expensive entire turret. These exchangeable bushings for the upper punches are equipped with keyways for the upper punches. This is necessary when shaped (i.e. non-round) tablets need to be produced on the machine. COUR /12 Page 21 of 35 GEA Pharma Systems - Courtoy

22 When selecting this option, the guidings for the lower punches will also be equipped with keyways, but they will not be equipped with exchangeable bushings. Keyways in lower punch guidings are necessary in case of round tablets with emboss (or break line) on both upper and lower face, whereby both embosses must have fixed orientation relative to one another (e.g. double break line). IMPORTANT REMARK: When this option is not selected, upper and lower punches with keys cannot be used on the machine! M.8 Tablet chute with sampling gate This tablet chute has an additional sampling channel in addition to the good tablets channel and the out-of-tolerance tablets channel. An additional sampling flap directs the tablets to the sampling outlet. As the diverter flap is controlled on a time basis, a sample will contain a noncontrolled number of tablets: a sample typically contains between 20 and 30 tablets. (Singlestation sampling is available as an option.) The sampling gate can be used for manual sampling (i.e. samples are taken manually at the sampling outlet) or automatic sampling (i.e. samples are diverted to a tablet analyser for inprocess control). Just like the standard tablet chute, this tablet chute has a dust-tight plexiglass cover. M.10 Price supplement for closed feeder with slide-in wear plate This option includes for a feeder base plate with exchangeable slide-in wear plate in foodapproved "ketron" plastic material. The support plate of the feeder is adjusted in such a way that the wear plate is in contact with the rotating die table, eliminating the opening between feeder base plate and die table surface. This set-up reduces the amount of powder that re-circulates around the die table and reduces the powder losses, resulting in an increased yield of the compression process. The wear plate has however a reduced life time depending on the speed of the tablet press and the physical characteristics of the powder to be compressed, and needs to be replaced on a regular time interval. The slide-in wear plate is available with different sizes of the powder opening, depending on tablet dimensions. M.12 Bi-layer kit This option includes all the mechanical parts required for bi-layer tablet production: Two single-paddle feeders Second powder feeding and dosing system Tamping roll for first-layer compression, including force measurement sensor Special-design powder scraper fingers Bi-layer dedicated upper and lower cam tracks, including one overfill cam COUR /12 Page 22 of 35 GEA Pharma Systems - Courtoy

23 M.15 Lifting arm to remove the turret from the machine The arm can be used to either lift the entire turret out of the machine, or to swing out the upper punch guide part, clearing the way for the EDD to be lifted out manually. M.17 Trolley to hold and transport the turret Once the turret is removed from the machine, it can be deposited onto this trolley for easy transportation. C.1 Compression force monitoring & Dual Control System This option features a load cell under the lower main compression roller including the necessary signal amplification and filtering to measure the force exerted by the compression roller via the lower punch on the tablet during final compression. Compression force monitoring The MC4 measures the peak values of all individual punches and displays them in a colour bar graph on the operator interface panel together with the average, maximum, minimum and standard deviation. This bar graph can be viewed by pressing the corresponding software push button on the operator interface panel. It is possible to print all individual peak values of one complete revolution of the turret by pressing the appropriate button on the control system interface. This is very useful in case the numeric value of the peak force for each individual punch is required. Stop function The average compression force is calculated on a user-defined number of punches, varying from 1 to 99. The control system will monitor this average compression force signal during production and stop the press if the average force signal exceeds the upper or lower tolerance limit, provided such limits have been set and activated. The control system will then display an appropriate alarm message on the operator interface panel. The operator defines the upper and lower tolerance limits in the appropriate set-up screen. Dual Control The Dual Control System allows for an additional control loop to maintain the tablet hardness as constant as possible. The main compression height is adjusted continuously and automatically, with the aim to keep the average main compression force as close as possible to the set value introduced by the operator. By maintaining the compression force as constant as possible, irrespective of fluctuations in tablet weight and granule characteristics and irrespective of changes in punch length (due to thermal expansion), the resulting tablet hardness will also remain as close as possible to the target value. However, the accuracy of this control loop and the resulting hardness tolerance depend on powder characteristics. COUR /12 Page 23 of 35 GEA Pharma Systems - Courtoy

24 When the Dual Control functionality is activated, it is also possible to activate the Dual Tablet Rejection function: tablets are then also rejected when their individual main compression force value is outside the pre-set rejection limits. These rejection limits are part of the products recipe parameter settings. This Dual Tablet Rejection system offers greater security for the tablet quality as tablets can now be rejected from the good product stream for two independent reasons: 1) Tablet weight is out of specification: a tablet is rejected when its displacement on precompression is outside the reject limits. 2) Tablet hardness is out of specification: a tablet is rejected when its main compression force is outside the reject limits. Therefore, the Dual Control system offers: 1) Better process control: tablet weight and hardness are continuously - and independently from one another - monitored and controlled by 2 separate control loops 2) Better quality guarantee: tablets are only accepted if they successfully pass TWO tests: both pre-compression displacement and main compression force have to be within spec. C.3 Equal porosity tabletting This option includes for the possibility to work in "equal force compression" mode (EFC) on the main compression station, in addition to the conventional "equal thickness compression" mode (ETC). When working in ETC mode, the upper and lower compression rollers are fixed in position during the compression. All tablets are then compressed to the same (i.e. "equal") thickness, while the peak compression force will vary with the weight of the tablets: a heavier tablet will require a higher compression force; a lighter tablet will require a lower compression force. These variations in peak compression force are typically within a band of +/-20% for weight variations within the acceptable weight tolerance limits. This results in important variations in porosity and density from tablet to tablet, and consequently significant variations in tablet hardness and disintegration time. Moreover, the thickness of the tablets will not be exactly equal due to differences in punch length and slight differences in machine deformation as a result of the variations in peak compression force. When compressing tablets in EFC mode, the same (i.e. equal) peak compression force is exerted on each individual tablet, independent of the weight of the tablet and the length of the punch. As a result, the variability in tablet weight and punch length does not induce variability in tablet density & porosity, but only a limited variability in tablet thickness. As the tablet porosity is equal for all tablets, the hardness and disintegration time will show significantly less variability within a sample and between different samples of the same batch. Moreover, when working in EFC mode, the compression dwell time is longer compared to the ETC mode. This results in a better de-aeration of the powder bed and a better inter-particulate bonding. Consequently, a higher tensile strength is achieved for a given machine speed, or a higher machine speed can be achieved for a specific required tablet hardness. COUR /12 Page 24 of 35 GEA Pharma Systems - Courtoy

25 EFC is a novel compression method made possible on Courtoy tablet presses thanks to the air compensator system on the main compression station, and offers better process control and higher consistency in tablet quality aspects (hardness, disintegration time, etc.). Note: the maximum main compression force is limited to 60 kn when working in EFC mode. C.5 Ejection force monitoring This option features a load cell under one of the two supports of the ejection cam including the necessary signal amplification and filtering measuring the force exerted by the lower punches on the front end of the ejection cam. The control system (Multi-Control 4) will monitor this ejection force signal during production and stop the press when a preset limit is exceeded. The control system will then display an appropriate alarm message on the operator interface panel. This system cannot measure the individual ejection force for each tablet, as the load cell is only supporting part of the ejection cam and several punches are in contact with the ejection cam at any moment. This feature is therefore intended as a sensitive system to detect jamming of the bottom punches in their guiding and/or increasing resistance by the compressed tablets against ejection from the dies. By detecting an increase of the overall and average ejection force, this system provides an effective protection of the cam tracks and compression tooling. C.6 Ethernet connection for remote software diagnosis & maintenance This option includes for a ethernet connection installed on the machine to allow GEA Pharma Systems - Courtoy engineers to perform software trouble shooting and software maintenance remotely. The price quoted includes one year s support by GEA Pharma Systems - Courtoy software engineers, who will be available for remote software trouble-shooting and maintenance during GEA Pharma Systems - Courtoy office hours. C.20 Automatic weight correction using data feedback from Combi-Test This option includes for the software module (including validation and testing) for automatic tablet weight correction by re-calibration of the primary control loop. This re-calibration is based on the average tablet weight, fed back by the Combi-test (optional), and is done by re-adjusting the pre-compression height and the die fill depth according to the difference between actual and nominal tablet weight. IMPORTANT NOTE: As re-calibration is done by adjusting the PRE-compression height, the FINAL compression height is NEVER changed. As a result, final tablet thickness remains UNCHANGED and tablet hardness remains also CONSTANT (as long as powder/granule characteristics are unchanged). Therefore, on a Courtoy tablet press, there is NO need for feed-back and re-correction of thickness and hardness. COUR /12 Page 25 of 35 GEA Pharma Systems - Courtoy

26 C.22 Combi-Test (KRAEMER) The Combi-Test system will take samples of tablets at programmable time intervals by means of an electromagnetic sampling gate in the tablet chute. Time interval between samples is set in the tablet press control system. (In case of doublesided or double-layer machine, side A and B will be sampled one after the other.) Tablets are transported from the press to the Combi-Test by means of a vacuum transport system. This system is standard included in the scope of this option. The Combi-Test can be installed on a table or on the floor nearby the tablet press. The flexible tablet transport tube has a maximum length of 5 m. The Combi-Test will measure the individual weight, thickness and hardness values for a pre-set number of tablets and send this data back to the tablet press control system. Weight, thickness and hradness values are compared to the standard Pharmacopea limits or customer in-house tolerance limits and the press will be stopped in case too many tablets are out of T1 and/or T2 tolerance limits. Depending on the type of tablet press control system, the individual weight-thicknesshardness values, their mean value and standard deviation will be printed or logged in the batch report after each sampling cycle. In case of Multi-Control 3 control system, the data is available in graphical format, including historical trending graphs and distribution graphs. The hardware used for the COMBI-TEST is the KRAEMER CompuLab, model UTS CI: Modular tablet testing system for measuring weight, thickness, diameter and hardness For use as table top or floor model on stand Including patented KRAEMER separating feeder Standard measuring range for weight 0-2,9 g, thickness 0-10 mm, diameter 0-30 mm, hardness N Operating and display panel for all four parameters, including calibration features Configuration program for customer specific applications 2 interfaces RS232 2 network interfaces RS422/RS485 Including: 1 tester unit 2 waste bins Plexiglas 1 calibration set 1 operating manual 1 power cable 1 RS232 serial cable COUR /12 Page 26 of 35 GEA Pharma Systems - Courtoy