Packaging Generic Drugs: An Insight to Manufacturing
I completed a 12-month Co-Op full-time at the Canadian pharmaceutical company, APOTEX Inc. With yearly sales of more than $1 billion Canadian Dollars, they are Canada's largest generic drug manufacturer. Among other areas of production, I had been working for the Packaging department.
As the Packaging Technical Coordinator, I initiated and led various continuous improvement projects for GMP (Good Manufacturing Practice) machines and equipment used in both bottling and blistering packaging lines. The majority of the projects focused on minimizing machine failure and downtime by optimizing mechanical and electrical preventive maintenance task list steps, scheduling ideal maintenance frequencies, and formulating techniques to rebuild and/or assemble machines and their components.
The goal of this page is to provide a visual representation of the packaging manufacturing lines for both bottling and blistering, as well as an explanation of how the systems within each line interact to allow the incoming generic drugs to be properly packaged and ready for shipping as finished goods. The information on the internet is highly fragmented and does not provide enough high-level insight to those interested in the pharmaceutical manufacturing process, or at least the packaging aspect of the production process, which is why I believed it was important to clearly depict it for those who may perhaps find better means to improve the manufacturing process.
Below are two different methods by which drug product is delivered to end customers: bottles & blisters. We shall analyze how the drug product is packaged in both bottling packaging lines & blistering packaging lines to form the actual product.
Drug product inside “bottles”
Drug product inside “blisters”
Bottling Packaging Line
The following flow chart process shows how the bottling packaging lines work.
Bottling Packaging Line: Visual representation of connected machine systems and their corresponding system inputs
Bottling Packaging Process Explanation:
Bottle Unscrambler: The empty bottles that will contain the generic drug product are input into the Bottle Unscrambler. The machine unscrambles the plastic bottles supplied in bulk using pneumatics, orients the bottles to their correct position with the help of an electronic sensor, and air rinses the inside of the bottles with ionized air. The correctly oriented empty bottles are consequently placed with gaps on the conveyor belt, forming a single file.
Desiccant Inserter: If desiccant packets are required to be inserted inside the bottles, then a Desiccant Inserter is placed after Bottle Unscrambler, otherwise there is no need for one. This is a machine where a long string of desiccants are inputted and it automatically cuts and inserts the number of desiccants needed inside each bottle as it detects the bottles passing underneath on the conveyor.
Bottle Filler: The generic drug products produced from the drug manufacturing lines are brought and kept on a feed hopper which goes through a Bottle Filler mechanism that measures the number of drug products needed to fill each bottle. As it detects the bottle passing underneath on the conveyor, it fills it with the correct amount of drug products.
Bottle Capper: The bottles, now filled with drug products and desiccants, are closed with the cap by the Bottle Capper. All of the bottle caps are vertically placed in several rows attached to the Bottle Capper, where a belt system allows for the caps to be correctly aligned to the mouth opening of the bottles at the right time and get capped/enclosed. To tighten the cap onto the bottle and keep it upright, two belts moving in opposite directions are always in contact on the left and right sides of the cap on the bottle, ensuring the right torque is provided. The condition of the clutch is an important factor for ensuring the right amount of torque for cap tightness; an over-tight cap would prove difficult for consumers to unscrew, whereas a loose cap can cause product leakage and spoilage.
Induction Sealer: The capped bottles go through non-contact induction sealing to create a hermetic seal. An electromagnetic field produced by the sealing head of the Induction Sealer heats the aluminum foil liner inside the cap. Since it is hot, the heated foil also melts the polymer layer on the interior seal. The heat, along with the pressure from the cap, causes the inner seal to adhere to the lip of the bottle container, creating a hermetic seal (complete and air-tight).
Bottle Cap Retorquer: After the induction sealing process, the bottle caps get slightly loosened due to which they need to be re-tightened. Thus, the Bottle Cap Retorquer is responsible for retorquing the caps onto the bottles, ensuring the right amount of torque is provided again, but now on a hermetic sealed capped bottle.
Weight Checker: The Weight Checker, as the name suggests, simply measures the mass of the bottles as it passes through on the conveyor. This may not always be necessary for the bottling packaging lines.
Bottle Labeller: The Bottle Labeller could be either of the two systems - it could either be a system where it prints on the provided blank sticker bottle labels and then sticks them onto the bottles, OR a system where pre-printed sticker labels are provided and the system just sticks them onto the bottles. Usually, it is the latter case that is most prevalent. There are rotating cylindrical rollers with a chain of labels, through which the bottles pass by, getting the right amount of sticker label stuck onto it at the desired position.
Vision System: The Vision System is responsible for correctly documenting and verifying if the information on the labeled bottles is accurate and positioned correctly and if not, it is rejected in a side bin. The system has several cameras that enable it to check if the packaged bottle so far has met quality criteria.
Bottle Shrink Wrapper: In the Bottle Shrink Wrapper, the labeled bottles containing the generic drugs are separated and stacked into groups of 4, 6, 8, or any number of bottles, based on the possible configuration. This group of bottles is then covered in the shrink wrapping film and undergoes heat treatment, whereby it comes out as a shrink-wrapped bundle of bottles. Several such bundles of bottles are made continuously.
Bundle Labeller: Every bundle passes through the Bundler Labeller, whereby it is labeled with pre-printed or to-be-printed sticker labels that help identify the bundles, which themselves contain certain labeled bottles. There could be a vision system involved here that tracks the label on the bundles themselves. All of these bundles are then kept within a huge cardboard box ready for storage and/or shipment to end customers or users.
Blistering Packaging Line
The following flow chart process shows how the blistering packaging lines work.
Blistering Packaging Line: Visual representation of connected machine systems and their corresponding system inputs
Blistering Packaging Process Explanation:
Blistering Machine: This equipment is the most complicated, but not complex. This means that there are several things going on at the same time within this machine that allows for the blisters to be created with the drug product inside. This can be divided into 4 parts as described below.
(a) Forming Film Station: The forming film is kept in a cylindrical roll that rotates in certain step sizes, allowing the forming film to move through a sealing station where it is pressed by heated plates from the top and bottom to form the hollow pockets in the film. It is in these pockets where the drug product shall be kept inside.
(b) Hopper Feeding Drug Product: This feeds the drug product from above, in the hollow pockets that have now been formed on the forming film, at the correct orientation. There is a vision system involved here that confirms correct position of drug product in the pockets.
(c) Lidding Foil with Printing: The lidding foil is also on a separate cylindrical roll that rotates in certain step sizes, allowing the lidding foil to be printed with drug product-related information via a printer. It then moves on to meet the forming film with pockets containing drug products.
(d) Blister Sealing, Perforation & Separation: This is where the lidding foil and the forming film with drug product meet and are sealed together via a sealing roller, at certain temperatures and pressures. The lidding foil completely seals onto the forming film, containing the drug product safely inside. It then passes to a perforation stage where it is cut to form 2, 3, or 4 blisters per row. The blisters are then separated with a time delay via a gating system such that all blisters that have now been formed pass in a single file as it goes onto a conveyor.
Blister Stacking Magazine: The blisters that are now travelling on a conveyor, pass a system where they are vertically or horizontally stacked in groups of 3, 4, 5, or whatever the desired number is. This number is important since it will be the number of blisters that will be fitted inside each carton when it moves to the next stage.
Cartoner: The labelled cartons and leaflets are stacked inside the Cartoner machine on separate belt systems. The labelled cartons and leaflets move through a conveyor where tucking and folding arms aid to open the cartons and allow for the required number of blisters to be intaken from the blister stacking magazine and then close the carton with glue. By this method, many several cartons containing the desired number of blisters are formed.
Weight Checker: The cartons then move past a weight checker machine, which as the name suggests, measures the weight of each carton, ensuring it is well within the range.
Carton Tracker: The carton tracker is responsible to keep track of the number of cartons that are passing by since it is timed to allow for an upcoming process where the cartons are to be stacked into groups and bundled.
Carton Bundler: The cartons are guided by linear guides to be stacked in desirable configurations, such as in groups of 4, 6, or 8. Once the group of cartons is formed, a pusher mechanism moves it to the shrinkwrapping stage where it is wrapped in the shrink-wrapping film and heated to create a shrink-wrapped carton bundle. Once each bundle comes out, a vision system is usually involved here to check if each bundle is correctly done.
Bundle Labeller: This machine is responsible for sticking the bundle label stickers onto the bundles.
Vision System: The Vision System here finalizes the bundle documentation and verifies it is fully safe and of quality. All these bundles of cartons that each contain a set of blisters are then kept within huge cardboard boxes ready for storage and/or shipment to end customers or users.
Insights & Opportunities
Generally, the blistering packaging lines face at least 4-5 times the machine system failure, breakdowns, errors, or faults compared to the bottling packaging lines. This stems from the complexities of simply manufacturing the blisters, primarily in the first stage of blistering. This sheds light on the opportunities in this manufacturing sphere: to improve the blistering machines with effective maintenance and rebuilds or by rethinking the design of the blistering machines themselves.
If you are using a machine made by some manufacturer for your pharmaceutical packaging lines, then you are constrained by the ability of the machine to do a certain desired activity. You have to operate around it. Thus, continuous improvements (replacement and rebuild analysis, maintenance frequency scheduling, preventive maintenance steps optimization) are mostly all that can be done on it. Although rare but not unusual, pharmaceutical companies may create their own designs that can be retrofitted in the manufacturer’s machines to improve the effectiveness and efficiency of the process.
If you are the manufacturer of the machines themselves, there are plenty of opportunities to think about how to best redesign the process/machine that creates blisters from scratch, so that a better solution can be presented to pharmaceutical companies. Usually, manufacturers develop tweaks in the overarching holistic system of blistering machines that currently exist, but could a new design process be thought of?
Blister packaging has a higher preference and market demand globally, but its relative supply is also 4-5 times lower than that of bottles, at least in North America. Because of this, it is crucial to concentrate on finding ways to improve blister production while maintaining bottling output.