Reducing time to market, optimizing the use of equipment and assets, maximizing yield and reducing the costly validation process are key requirements for pharmaceutical manufacturers. When new technology emerges, such as the increasing use of blow-fill-seal delivery, providers of ancillary processes such as packaging machinery vendors can also take a role in aiding the pharma companies. This article describes how packaging vendors can play their part.Blow-fill-seal (BFS) products are rapidly gaining ground as the preferred delivery method for many oral and ophthalmic treatments in the pharmaceutical industry. The adoption of BFS has, however, created new requirements for product packaging systems. This article examines these requirements and discusses how they can best be addressed.
Secondary packaging equipment will comprise a carton former, a top-loading platform, a tray closer and a case packer — all located at the end of the packaging line. To further reflect the reality of modern installations, the line will be configured to handle several BFS card formats as single or multiple packs, as well as various sizes of tray.
Clearly, for applications in the pharmaceutical industry, verification of printed data, such as lot numbers and expiry dates, is an essential requirement. Fortunately, this can readily be achieved in this packaging line using vision systems.
In many pharmaceutical manufacturing plants, cards of BFS vials are blown, formed, filled and sealed in a process that is separate from the packaging line. Typically, the cards are made up of four or five vials containing the portioned pharmaceutical infusion liquid. After manufacture, these cards are bulk stored with random orientation.
The first stage of the packaging process is, therefore, to deload the cards by placing them on a transport conveyor that moves them to a bowl feeder; automatically stopping and starting the conveyor system can readily prevent overloading.
When the BFS cards leave the bowl feeder, they must then be placed and stacked precisely ready for flow wrapping. The high throughput needed in today's installations means that a robot-based solution with picking rates of at least 100 products/min is virtually essential.
Let us not forget however, that the orientation of the BFS cards at this stage is still not uniform. A vision system is, therefore, needed to capture an image of each product and determine its orientation. With this information, the robot system can work at maximum efficiency and with the minimum risk of product damage. Conveniently, the same vision system can be used to verify key product parameters and initiate the rejection of any products that fail to meet the required specifications. A separate image is captured for each and every product, which means that the product profile can be accurately verified by comparing it with a stored reference shape.
A log of rejected profiles can also be maintained and the reject rate calculated in real-time. Should this rate exceed a preset value, arrangements will usually be in place to halt the operation of the machine so that the source of the problems can be determined and addressed.
The type of robot used for placing and stacking the BFS cards is important. Conventional multi-axes designs have limited flexibility, often combined with high inertia that limits operating speeds. An alternative design however, uses a structure based on jointed arms suspended below the operating mechanism. The arms meet at the gripper device, giving the robot an overall appearance somewhat similar to a spider with its legs joined at their tips.
This arrangement allows arms with low mass to be used, so it has inherently low inertia, which means that high operating speeds can be achieved with ease. It also provides the versatility needed to allow the system to handle multiple pack sizes and product stacking patterns.
BFS products are most frequently supplied in hermetically sealed packaging; making use of materials with low permeability for oxygen and water vapour and additional functions such as light protection.
Flow wrappers are readily available, but not all can provide an extended dwell time for the sealing cycle while maintaining the necessary high throughput. Extended dwell time is highly desirable, if not essential, in pharmaceutical applications with the highest requirements for sealing integrity and tightness.
Further features appropriate to the pharmaceutical industry that are provided by industry-orientated flow wrapping machines include water-cooled cover plates for the longitudinal sealing section to protect the product, and gas flushing to facilitate the use of modified and controlled atmosphere packaging. Cross-seal gusseting for multipacks is also useful, as is online verification of sealing parameters to control process reliability. Finally, in our example application, which involves the use of multiple packaging formats, a fully servo-driven machine will offer the benefit of fast, easy recipe changes.
Carton forming and filling
Flow-packed BFS products are invariably supplied in cartons. Typically, in the pharmaceutical industry, these are designed with a front flap closure that is tucked in, with dust flaps to each side. Carton forming is a relatively straightforward process, but 100% inspection is recommended to ensure that the cartons are glued perfectly every time. Facilities for inserting user information leaflets can also be provided at this stage.
Loading the flow-packed products into the cartons is another process where robots provide an optimum solution. In this case, robots of relatively conventional design can be used, but there are still a number of special features that aid productivity and flexibility.
For example, the ability of the loading system to stack the flow packs vertically or horizontally is invaluable, as is product-specific handling design to place the flow packs very tightly within the carton, thereby minimizing the size of carton needed for a particular product.
After being filled by the robot loading systems, the cartons require closing. An essential element of this process is precise carton control to ensure that the dust flaps are folded inside, before the top flap is closed and the front flap is tucked in. With most packs, no glue is required, and facilities for changing the pack size without having to change machine parts are highly desirable. In many cases, this is also a convenient stage to mark the cartons with final production data by laser coding, printing or labelling.
The final stage
The last operation to be performed by our integrated packaging line is the packing of the individual cartons into cases for shipping. A similar robot system to that used for carton filling can conveniently be used for this process, complemented by a case closer that folds the case flaps and seals them with tape.
Qualifying the system
In the pharmaceutical industry, there are clear demands for good manufacturing practice (GMP) and machine qualification procedures. Extensions to FDA regulations, including 21 CRF Part 11, have also placed greater emphasis on validation and product traceability. Purchasers of packaging lines can address all of these requirements by drawing up detailed specifications but, in some cases, there may be a faster, easier and more cost-effective approach.
This is to make full use of the application adjusted standard documentation supplied by the system vendor, adding to it only where necessary. This procedure is considerably simplified when, as suggested in this article, the whole of the packaging installation is sourced from a single supplier.
Naturally, relying on vendor documentation is only an option when the system purchaser can be totally confident that this is dependable and comprehensive.
The most enlightened suppliers to the pharmaceutical industry have addressed these issues by, for example, developing basic standard documents for functional design specification and design qualification, as well as installation qualification (IQ) and operational qualification (OQ) plans based on customer end-user requirement specifications (URS). In this process, adherence to the V-model commonly used in the pharmaceutical industry is an advantage.
Another development that suppliers of packaging machinery to the pharmaceutical industry have had to accept in recent years is the pressing need of their customers to bring new products to market quickly. This demand is not only addressed by shortened delivery times, but also by achieving full productivity as soon as possible after installation.
Careful design of the installation plays a significant role in this by ensuring that the system is easy to install and commission. Comprehensive pretesting and prequalification at the vendor's premises is another important element, but there is a further key factor, which is easily overlooked. This is the quality and unification of the operator interface.
A well-designed operator interface, based on modern graphical display and touchscreen technologies, greatly reduces the need for operator training and the risk of errors during the early stages of operation. Similarly, the use of a common control technology for all sections of the packaging process such as feeding, handling, flow-wrapping and secondary packaging ensures a consistent look and feel that further reduces the need for training. These are important ingredients in putting the installation to productive use in the shortest possible time.
BFS packaging creates its own special demands. Attention to detail at each stage of the packaging process, following the guidelines discussed in this article, provides a solid foundation for satisfying these demands. Overall, however, the best solution is to adopt a holistic approach to the specification, design and purchasing of the whole packaging system.
Such an approach not only guarantees that the line components will function optimally with each other, but also simplifies and speeds both commissioning and operator training. Finally, providing that a supplier is selected who is aware of and responsive to the particular needs of the pharmaceutical industry, the holistic approach can do much to reduce the cost and effort involved in meeting the industry's stringent technical requirements.
The economies in the system approach described are not only suitable for packing blockbuster products with high volumes involved, but are also realizable for smaller production by leveraging system and product flexibility in the engineering phase. Such an approach brings about time-to-market reductions, which is vital for both big pharma, small pharma and subcontract manufacturers. The use of packaging systems, rather than discrete standalone equipment, reduces the validation process since the vendor can share the responsibility for validating its system. Partnering with a large a reputable supplier also underwrites this approach because there is assurance of continuity of identical spare parts and again a responsibility for the entire system.
Andreas Graf is product manager pharma, medical and healthcare at Bosch Packaging, Germany.