Highlights of Current Machine vision Activities in the Pharmaceutical Industry

This year's Interphex Show at the Javits Center in New York City had an expanded theme, and is now called the International Pharmaceutical Industry Congress. The new umbrella represents three shows in one: what had been traditionally called the Interphex Show, plus Pharma-IT Expo and Pharmaceutical Contract Services & Outsourcing Expo. On the Show floor the exhibitors were 'pigeon- holed' into 'pavilions' where neighboring exhibits were somewhat consistent by application focus: automation and control, packaging, processing, contract services and outsourcing and research and development. For the most part machine vision companies could be found in the packaging or automation and control pavilions.

It appeared that there were more booths with machine vision being exhibited this year than in the last two years. At least 17 booths were demonstrating machine vision systems. In addition, several companies known to be in the machine vision business were exhibitors, but were not exhibiting their application-specific machine vision-based products for some reason. All in all, the show reflects the embracing of machine vision by the pharmaceutical industry. As the technology has become more rigorous, machine vision is now able to fulfill the promises of yesteryear. Most of the machine vision solutions being promoted have been around for years. It has been over 20 years since the first system was introduced to perform filled ampoule inspection, for example. Today, systems can meet the sensitivity requirements and throughputs demanded by the industry. The same can be pretty much be said of the other systems being exhibited - they have been around a long time and finally can satisfy the requirements and creeping expectations of the industry.

Also driving industry acceptance has been the emergence of an infrastructure to support machine vision, so it is no longer an 'island of automation.'  Line information systems recognize that machine vision is just another data collector and seamlessly integrate the data into computer-based management information systems that optimize line performance, minimize downtimes and yield productivity and quality improvements over more manual systems. These systems are also responsive to FDA requirements for Good Manufacturing Practices, especially when it comes to packaging lines and potential concerns that might be experienced, such as mislabeled product, wrong product in wrong carton, etc.

Being promoted heavily by the machine vision exhibitors were product offerings complying with the latest FDA dictates on Electronic Records/Electronic Signatures - 21 CFR Part 11.  It would seem that this regulation, along with the FDA's January 9 issued document 'Food Security Preventative Measures,' probably obsolete most machine vision systems that have been installed. Both documents require that extra attention be paid to security measures associated with computer-based systems. This includes fortifying access control measures as well as providing an electronic trail for all transactions. The traceability requirements imposed should increase the use of bar codes, including 2D bar codes and lot and date code verifiers and readers.

Machine vision systems would fall under their definition of a 'closed system:' an environment in which access is controlled by persons who are responsible for the content of electronic records that are on the system. In this case the FDA suggests that procedures and controls shall include:

A) Validation of systems to ensure accuracy, reliability, consistent intended performance and the ability to discern invalid or altered records.
B) The ability to generate accurate and complete copies of records in both human readable and electronic form.
C) Protection of records to enable their accurate and ready retrieval throughout the records retention period.
D) Limiting system access to authorized individuals.
E) Use of secure, computer-generated, time-stamped audit trails to independently record the date and time of operator entries and actions that create, modify or delete electronic records.
F) Use of operational system checks to enforce permitted sequencing of steps and events, as appropriate.
G) Use of authority checks to ensure that only authorized individuals can use the system, electronically sign a record, access the operation or computer system input or output device, alter a record, or perform the operation at hand.
H) Use of device (e.g. terminal) checks to determine, as appropriate, the validity of the source of data input or operational instruction.
I) Determination that persons who develop, maintain, or use electronic record/electronic signature systems have the education, training and experience to perform their assigned tasks.
J) The establishment of, and adherence to, written policies that hold individuals accountable and responsible for actions initiated under their electronic signatures, in order to deter record and signature falsification.
K) Use of appropriate controls over systems documentation including:

a. Adequate controls over the distribution of, access to, and use of documentation for system operation and maintenance.
b. Revision and change control procedures to maintain an audit trail that documents time-sequenced development and modification of systems documentation.  

The document also reviews the use of electronic signatures and record linking, and it permits the use of biometrics. Those not based on biometrics shall employ at least two distinct identification components such as an identification code and password. In this case procedures have to be in place to ensure that the identification code and password are periodically checked, recalled, or revised( e.g. to cover such events as password aging). In addition attempts at unauthorized use must not only be detected but also reported in an immediate and urgent manner.

Several of the vendors suggesting compliance admitted that different pharmaceutical companies appear to be interpreting the regulation differently. So while they are purporting to offer fully compliant systems it may very well be that based on interpretation they may still have some work to do to satisfy the interpretation of any specific customer. In any event there would be an opportunity to replace older systems that can not be made to conform to the regulations as well as to upgrade those that can be made to conform with newer software.

At least one company at the show - Stelex (Bensalem, PA) - was offering a 'ComplianceBuilder' - a software package that leverages existing automation and provides a response to the requirements for fully automated audit trails, electronic signatures, security and validation. In some cases the use of this software where a machine vision system is in place could make the overall system responsive to the FDA requirements.

In addition to lots of noise among the vision exhibitors about 21 CFR Part 11, the apparent machine vision 'application du jour' was proofreading. Global Vision showcased their TVS Color Proof Reader, a system that compares the images of labels, cartons, and inserts to a stored master or digital PDF file. System detects errors such as missing or additional text and graphics, broken type, registration and color deviations, incorrect fonts and text sizes and inconsistent bar codes. System can handle different languages. Co-located in their booth was GxP Partners (Langhorne, PA), an integrator that offers a seamless integration of the TVS system, providing automatic access to improved masters and discrepancy forms, eliminating PDF downloads and hardcopy signoffs throughout the review and approval process - from pre-print production to the packaging floor. Global Vision also exhibited their Digital Page and Clinspec. Digital Page verifies spelling, detects missing text and graphics, added text and graphics, position, font/style changes and point size changes. Clinspec performs OCR on both fixed text and variable text of labels used on containers for products used in clinical trials.

Also demonstrating a proofreading system was Eisai. It was developed by Toppan Printing Company for the pharmaceutical market and is being marketed in the U.S. by Eisai.

Though not present at Interphex this year, offering products competing directly with Global Vision is a company called Complete Inspection Systems (Melbourne, FL). Their AutoProof Pro document inspection system includes OCR, ICR, barcode verification, document encryption and security features. Their Docu-Manage module is a Document Management System incorporating multi-user interaction for creation, management and retrieval.

Missing this year were companies like Rotoflex and VRP offering on-line print inspection systems for rewinders. On the other hand, SYSTECH was promoting their print quality inspection system, which they sell adapted to rewinders. It is a template matching system based on training on a 'golden' image. System can handle rewinder speeds up to 150 FPM. Cincinnati Industrial Automation was featuring a vision system with multiple cameras and with what they called 'absolute subtraction' that can essentially perform a proofreading operation on a labeled container. It can handle containers with flat panels or elliptical shapes but not round bottles where the labels wrap around the container. They suggest that it is sensitive to missing periods and the like. SYSTECH was also exhibiting a system with equivalent on-line functionality.

Other companies with a more general-purpose flavor offering on-line date and lot code verification, 2D matrix code or bar code reading included: RVSI/Acuity Imaging, Accu-Sort, Automated Visual Inspection Systems, Cognex, Optel Vision, Xyntec and SYSTECH.  RVSI introduced Visionscape I-Pak Express (priced under $15K) a two-camera system, which uses their Visionscape 1000 frame grabbers and a PC.  Banner Engineering introduced its PresencePlus Pro embedded vision processor.  Using a 640 X 480 CCD camera tethered to a box with an embedded processor, and a PLC arrangement that piggybacks on the box, this general-purpose system will sell for under $3K with optics, lighting and cabling. Tools include normalized correlation, edge finding, histogram and other gray scale tools, etc.

In the case of application-specific machine vision systems, the following companies were offering solid dosage inspection systems: AC Compacting (now handling the Proditec line from France that was formerly being handled by Mocon in North America), Eisai (handling the product developed by Shonogi, Seidenader, M.W. Technologies), Driam/Maschinpex and Daiichi Jitsugyo America (handling product developed by Kanebo).

These systems can typically be adapted to handle various types of solid dosage products (coated, film-coated, uncoated, embossed, bisectable, gelatin capsules) as well as different shapes (round, oval, oblong, etc.). They can detect shape flaws such as diameter, length, width, thickness, broken, etc. as well as visual concerns such as marks, black spots, blotches, peeling, reflectance anomalies, etc. as well as geometric flaws, such as cracks, chips, nicks, irregular edges, missing, etc.  In the case of capsules, they can generally detect additional conditions such as telescoped, split, bent, double caps, etc. Depending on product, they can handle throughputs from about 50,000 per hour to 180,000 per hour. Several of these companies have adapted this capability to inspect the print on solid dosages immediately after printing.

It was noted that AC Compacting is also handling the Covan Vision System products out of Belgium for general-purpose applications such as OCR/OCV and blister pack inspection.

The other classic application-specific machine vision system found in the pharmaceutical industry is one that performs vial and ampoule inspection.  Companies offering such products at the show included: Seidenader, Eisai and Daiichi Jitsugyo America - the Kanebo system.  Seidenader exhibited a version of their system, adapted to syringe inspection, that uses 13 cameras.  

Another classic application is blister pack inspection: looking for foreign, broken, contaminated solid dosage in the blister pack before sealing. Today most of these systems use color-based processing. Companies at the show exhibiting this capability included Automated Visual Inspection Systems, SYSTECH, Romaco, Micron Automation (who handle the Scanware system out of Germany) and AC Compacting handling the Covan Vision System out of Belgium. The latest version of the Romaco system uses a Firewire-based color camera with megapixel resolution. Several systems could also be seen on blister packaging machinery. Klockner Medipak incorporated the Scanware system. For the most part, the machine vision-based blister pack inspection systems found on the blister packaging machines themselves are generally OEM products.

What follows is a table meant to depict many of the companies seen at the recent Interphex Show as well as some that are known suppliers of the systems reflected in the table. Significantly, there are numerous system integrators and suppliers of package line material handling or blister pack machinery that also offer machine vision systems as value adders to their services. For the most part these systems use general-purpose machine vision systems as the basis of their systems or, especially in the case of blister pack applications, commercially available turnkey blister pack inspection systems. The 'other' class in the table is meant to reflect other applications found in the pharmaceutical industry. Some of these include slat counter verification, color and ring sequence detection on ampoules, container inspection (label, cap, etc.), insert counters, empty container or empty vial/ampoule inspection, etc.

It is noted that PQI refers to print quality inspection and this can be either at the label/printed material stage while being printed or on a rewinder or on-line after label application onto a container. The X-ray-based systems referred to in this table can either be those that verify the presence/completeness of filled cartons, detect contaminants or monitor the fill height of a container.

Table of Companies Offering Machine Vision-Based Solutions
for the Pharmaceutical Industry