PHARMACEUTICAL GLASS CONTAINERS AND PARENTAL DRUGS INSPECTION

Transcription

1 PHARMACEUTICAL GLASS CONTAINERS AND PARENTAL DRUGS vision technologies Optrel Inspection Systems is a brand of SPAMI - the engineering division of Stevanato Group. With more than 25 years of experience, Optrel has developed advanced inspection technologies for pharmaceuticals products, and is focused on the inspection machine market for the pharmaceutical industry, including parenteral drugs, injectables and solid dosage inspection with automatic and semiautomatic equipment. glass machinery plants & accessories 3/

2 Cosmetic inspection Cosmetic inspection stations are used to control the integrity of container glass surfaces and the correct crimping of alu-seals by means of high resolution linescan cameras, which guarantee 360 continuous inspection. Alphanumeric codes or datamavision technologies INTRODUCTION Established in 1982, Optrel has a long tradition in the inspection machine market for the pharmaceutical industry, with automatic and semiautomatic machinery. Thanks to the merge with the Stevanato Group, Optrel has, based on the same field proven technology, developed a range of inspection machine for empty glass articles: ampoules, vials and syringes. The range of defects covered match the requirement from the PDA glass task force and also include metrological controls recorded in a SCADA-like interface for production control. The system is 21CFR11 compliant with regards to recipes and batch recording. Contaminant inspection and performance Automatic inspection machines perform particle inspection by gently spinning the product and blocking the container in front of cameras. The vision system can, by quickly acquiring a sequence of images, recognize the moving particles inside the liquid, even in presence of printing or dirt on the external glass surface. Optrel s Vision System is based on 150frames/sec CCD cameras and strobe LED light illuminators. Several illumination schemes can be programmed in order to emphasize the detection of different contaminants such as glass fragments, fibers, rubber, plastic, metal rust and carbonization. Special optical configuration is available for the detection of floating particles in meniscus liquid. over the years The pharmaceutical industry is a very strictly regulated environment, and even more so that of parenteral drug production because of the critical products it manufactures. The first subcutaneous injection using a hypodermic needle was carried out in 1855, but mass introduction of this medical practice is closely connected to the World Wars. At the same time, the medical community started to emphasize the need for high quality in the preparation of parenteral drugs. In fact, in 1915, the U.S.P. IX (US pharmacopoeia) described the need for injectables compound to be true solutions and specified the methods for preparation and sterility condition. In the 1942 the requirement for visual clarity of parenteral products was introduced in the U.S.P. XII in order to define and control the quality of injectable products purchased in support of the military during World War II. These directives were used by the FDA in its role as the Quality Control Office for all the pharmaceutical purchased by the Armed Forces. Requirements for visual inspection of parenteral drugs have been present since 1947 in the United States, Europe and Japan pharmacopeias. The regulamentary bodies specified the condition for human inspection in terms of luminous flux, liquid agitation and time duration. Nowadays, it is accepted that human inspection limit is 50µm even if a detection efficiency of 95 per cent is recognized for particles of 200µm diameter and higher. In the 1960 and 1970, this standard was applied as a final test to samples of finished products, not to 100 per cent online inspection, and the sampling was in accordance with MIL-STD-105. U.S.P. XIX (1980), Supplement 1, initiated the philosophical requirement for a zero-defect quality standard for foreign matter and particles. Thanks to the availability of optical sensors and electronic processing systems, several companies started to develop opto-electronic devices for 100 per cent inspection of parenteral drugs reaching the state of the art limit of 30µm. Optrel was founded in 1982 with the mission of developing such technology focusing on the pharmaceutical market. It began with semi-automatic systems for automatic transport of containers, thus speeding up inspection and increasing accuracy with stable illumination and spinning conditions. The company then went on to design automatic systems for inspecting ampoules, vials and cartridges based on embedded vision systems and PLC automation. In 2007, Optrel was acquired by Stevanato Group as an indirect recognition of the high quality level reached and its well established presence in the pharmaceutical market. The synergy between Optrel and Stevanato has led to a new generation of inspection machines for tubular and mould-based pharmaceutical glass containers. Glass inspection is a hot topic, most pharmaceutical manufacturers have started to carry out 100 per cent inspection of the empty containers before filling to reduce waste of product at the end of production. The classification of glass defects follows specifications from the PDA (Parenteral Glass Association) technical committee.

3 MCA200 trix printed on the alu-seal or glass surface can also be controlled by means of OCR (Optical Character Recognition) or code reading. The correct shape of ampoule tips and ring colour coding are controlled using a multiple view optical configuration. Special PAT inspections Vision techniques are complemented by special PAT (Process Analytical Technology) controls integrated in the machine configuration. Spectroscopy detectors verify the colour of liquid drugs and the moisture of solids. Turbidimeters measure the content of aluminium gel phosphate in vaccine and the aggregation of proteins. Headspace gas analyzes check the integrity of freezedried products, while high voltage spark tests detect microcracks in liquids. The machine has been designed to be inserted into all the modern pharmaceutical production lines. Several options of the infeed system have been designed in order to satisfy most client demands. The main machine turret is equipped with 24 spindles. The lower part of the spindle is rotated or stopped according to the inspection required. Each container undergoes a series of inspections along the carousel by means of monochromatic CCD digital cameras. Each inspection station consists of a camera and its dedicated LED light source available from the bottom or from the rear. An additional station for tip shape inspection with its dedicated reject device can also be supplied. All the acquired images are sent directly to the PC and processed by a dedicated vision system. The container is accepted if all inspection results are received as positive by the PLC. The system works with Siemens WinCC scada. Validation procedure can, if requested, be in compliance with CFR21 part. 11. Ampoule inspection with ongoing production inside the main turret of the MCA 200 Technological features Production speed ranges from 100 to 400 pcs/min., with machines covering all container dimensions available in pharmaceutical production: MCA ampoules and vials up to 26mm diameter and 20ml MCA150/49 ampoules, vials and cartridges from 8.75 to 49mm diameter and 50ml MCA150/66 vials up to 66mm and 250ml MCA1000 vials and bottles to 1,000ml Maintenance-free mechanics All machines have been designed and built in compliance with GAMP5 (Good Automated Manufacturing Practice). Change format is operated without the need for special tools in less than half an hour. The machines cinematic is maintenance free (without gear boxes), with electrically synchronized servomotors through a dedicated processing control unit. glass machinery plants & accessories 3/

4 vision technologies MCA150/66 The machine has been designed to be inserted into all the modern pharmaceutical production lines. MCA150/66 is specialized in particles inspection and cosmetic inspection. Particles and fill level inspection are formed by three detecting stations. Cosmetic inspection can check: alu-seal (crimping and defects), missing cap, cap defects, missing flip-off, missing stopper, scrub on the container, cracks on the container, defects on the container. The main machine turret is equipped with 24 spindles. The motion of the machine is obtained with a brushless motor. The lower part of the spindle is rotated or stopped according to the inspection to perform. The machine is equipped with View from the top of vial ainspection path on the MCA 15 three independent rotation section and an optional pre-rotation motor for suspension products is also available. Each container undergoes a series of inspections along the carousel by means of monochromatic CCD digital cameras. Each inspection station consists of a camera and its dedicated LED light source available from bottom or from the back. All the acquired images are sent directly to the PC and processed by our dedicated vision system. The container is accepted if all inspection results are received as positive by the PLC. This system works with Siemens WinCC scada. If requested validation procedure could be in compliance with CFR21 part. 11. Vials during the inspection process inside the main turrett Vision system setting and process Optrel s Vision System, designed for easy customization and security, is enabled only when the machine operates in automatic mode, thus ensuring a perfect ratio among inspection results, container position and correct spinning process. Correct container inspection will not be possible if one of these characteristics is missing. The programming interface is based on a worksheet style with functions dedicated to the imaging tasks. Functions are documented in line, the syntax is checked before running and each and every calculus error is reported and trapped. The script and the inspection parameters are saved and traced with audit trail for change log. Each vision recipe is identified as per product name, revision number and date. HMI Interface and PLC The HMI interface is built on Siemens WinCC Flexible automation software, which is 21CFR11 certified; metrological controls are recorded in a SCADA-like interface for production control. Production data are automatically backed-up in real time by a redundant disk array (RAID). Machine controls and vision parameters are recorded and secured for changes by audit trail module. Real-time control of the machine is operated by a Siemens S7-300 PLC; the vision system and the motion control unit are connected with the PLC by means of a deterministic Profibus connection. The computer system is backedup by a UPS for continuous operations under poor electrical utility. When a product is selected on the HMI interface, the information is sent automatically to the vision system that loads the appropriate product. When a new batch is start- 76 glass machinery plants & accessories 3/2011

5 MCA 400 MCA400 LIGHT DEVICE DEFECTS SEPARATION by CATEGORIES INTERFACE (HMI) DATA SAVING Particles and fill level Cosmetic Inspection (Tip detection and Colour ring) Special LED light source available in different configuration: from the bottom and from the rear, diffused and polarized. Rejected containers are collected in different trays based on the kind of defect Inspection results viewed in real time Friendly and familiar display Easy to use Simple monitoring of process, and management of all parameters. Failure and alarm handling Inspection parameters password protected Knapp test automatic mode: extremely useful for the daily verification of machine performances In the user s language Production data and preset parameters available for printing Double hard disk for data saving VALIDATION DOCUMENTS Machine in compliance with the most important standard regulations and guideline. CFR21 part Audit Trail - cgmp and GAMP5 Ampoules just loaded into the main turret to be inspected for particles and fill level glass machinery plants & accessories 3/

6 vision technologies Freeze dried vials inspected by the MCA200/66FD 78 glass machinery plants & accessories 3/2011 ed, the vision recipe is backed up with the PLC parameters in the batch historical log and traced along batch running. When the machine is delivered to the customer, a basic set of products is pre-configured and tested. Adding new products can be carried out when needed, by the customer or by Optrel technicians. The parameters of the vision system are saved as a group of files on the PC flash disk. Each file is identified with the product name to which it is dedicated, thus guaranteeing easy identification of the parameters to be used to carry out inspection. When a product is selected on the HMI interface, the information is sent automatically to the vision system that loads the appropriate product and the machine is ready to start only when the vision system communicates to the PLC that it is ready to start. The automatic inspection machine is able to perform: cosmetic inspect to control the integrity of the vials body and the correct shape of the tip; contents of containers to control the presence of particles or fibers inside the product and the filling volume; and the process control is totally automatic. Knapp Test Automatic mode A statistical method, known as Knapp Test, was developed in the 1980s to evaluate the inspection performances of the machine and comparison to he manual inspection. To simplify these operations, the inspection machine implements an automatic Knapp mode, which guides the operator in executing the tests and collecting the results with direct comparison to manual inspection performances. A basic setup of all products known at the moment of the Knapp test is set by Optrel technicians. CONCLUSIONS The continuous evolution of PC technology has driven the performance of inspection machine to new levels. Innovative tools for a better knowledge of production quality are now available for 100 per cent control in real-time at reasonable costs. Optrel is now working on the development of a real-time recording of defect images for off-line analysis and collections of statistical observations related to particles analysis. This development will enable to study particle size and morphology distribution in order to investigate the nature of contaminants during production. SPAMI Via Molinella Piombino Dese (PD) Italy Tel: Fax: [email protected] [email protected]