However, timely market entry requires integrated processes, reports Markus Burkert (pictured), Product Manager, Pharma Liquid and Sustainability, at Syntegon Technology GmbH. System providers act as technological partners and offer flexible solutions for high-volume production.
Whatever their condition, patients urgently need effective control: weight loss is the main objective for obese people, whereas type 2 diabetes requires a regulated release of insulin.
Patients with type 2 diabetes can produce insulin themselves, but often not in sufficient quantities. Medicines based on incretin mimetics are proving to be an effective treatment option for both indications.
The products are experiencing increased demand as, following recent approvals, they can also be used for weight control.
Hormone-driven weight loss
Some of the high-dose, subcutaneously injectable medications only need to be administered once a week. Autoinjectors or pens enable easy self-medication: patients administer the exact dose by simply pressing a button.
However, drugs based on incretin mimetics owe their success not only to their practical handling; clinical studies have shown that the products can lead to weight reduction of more than 15% within a few months.
The recombinant active ingredients also influence the patients’ sensation of hunger: by stimulating the production of the hormone incretin in the body, patients feel satiated for a longer period.
Meanwhile, the few approved weight management products that only need to be administered once a week have sparked a veritable race for more medicines.
According to GlobalData, more than 50 drugs targeting the same mechanism were undergoing clinical trials at 40-plus companies in early 2024. Most of the products are injectables, although some are administered orally.
The liquid formulations are to be launched on the market either as prefilled syringes in autoinjectors or as cartridge-based pens. Unlike autoinjectors, pens can be used up to five times. Patients only need to change the needles before each use. Single-use autoinjectors do not require this step.
Challenging glass cylinders
Cartridges, however, which are the main component of pens, present manufacturing companies with specific challenges: unlike the ready-to-use (RTU) syringes of autoinjectors, the glass cylinders are usually not presterilised and not processed simultaneously in large quantities.
On the contrary, manufacturers must ensure sterile individual filling, which includes flexible assembly and inspection in addition to high output — as well as additional upstream processes such as cleaning, siliconisation and sterilisation.
Should manufacturers rely on large-volume cartridges, which are filled as RTUs, the same systems can be adapted to accommodate this container type, resulting in leaner processes without the upstream steps.
High-performance cleaning machines pave the way for aseptic filling: they remove product residues and other contaminants from the inside and outside of the containers so that potentially harmful substances can no longer compromise the safety of operators and patients.
Advanced systems offer pretreatment in an ultrasonic bath. Flexible configurations for cleaning stations also enable product-specific and efficient sanitisation.
State-of-the-art cleaning systems further make sure that the cartridges are siliconised. The thin silicone layer inside the containers has a major influence on the speed of the rubber stopper during administration and, hence, on the pressure of the administered medication.
If the inner walls have too much silicone, the stoppers slide too quickly and the pressure inside the patients’ tissue increases excessively.
Too little silicone, by contrast, might result in the stopper sliding too slowly and the drug not penetrating the tissue sufficiently. State-of-technology sterilisation tunnels fixate the silicone layer thanks to even heat distribution and sterilisation speed.
High-volume filling and sealing
High-performance filling and sealing machines with an output of 600 units per minute are standard equipment for manufacturers who want to meet global demand and remain competitive.
However, high quantities alone are not sufficient to meet the requirements of efficient production. The often small opening of the containers requires highly precise filling. Common equipment concepts therefore include time-pressure filling (TPF) systems with a large number of filling stations.
For perhaps obvious reasons: the sensitive GLP-1 agonists call for filling methods such as TPF that don’t expose them to thermal and mechanical stress. After the cartridge stoppers have been placed and checked with a sensor, the cartridges are filled at separate stations.
Leading technology providers rely on sensor filling for maximum precision. This helps to achieve the optimum fill level and avoid air bubbles in the liquid, thereby reducing costly rejects.
Owing to high sterility requirements, cartridges are filled in production environments that ensure the strict separation of drugs and operators.
The new version of EU GMP Annex 1 places additional emphasis on effective separation: isolator technology will establish itself as the long-term standard in filling as it guarantees automatic biodecontamination and a stable pressure difference compared with the operator environment.
Customised assembly
The filled and sealed cartridge is the centrepiece of the pen, which is ideally assembled on flexible platforms. Although the numerous pen and injector types on the market have similar components, they vary in terms of size, material and shape.
Leading machine manufacturers have developed solutions that combine standardisation and customisation in close co-operation with their customers, resulting in platforms that offer the required flexibility and capacity and can process both autoinjectors and pens.
Common pen assembly machines are designed for standard four-part disposable pens, which consist of a pen cap, a cartridge holder, the cartridge and a dispensing mechanism.
These solutions allow companies to choose between manual, semiautomated and fully automated assembly with quick, tool-free changeovers. Small manual workstations have proven to be the ideal solution for initial clinical trials.
As soon as commercial production begins, semiautomated or fully automated assembly systems come into play. Thanks to this scalable approach, process validation can be transferred from one assembly platform to another. This makes for versatile processes with minimal downtime between batches, facilitating prompt time to market.
Containers without cracks or defects
Inspection plays an important role: this process step makes sure that cartridges do not break on the way to the patient or during use. It is the linchpin for patient safety and a regulatory requirement for parenterally administered medications.
High production volumes require fully automated and highly flexible systems for comprehensive inspection: different systems for visual inspection and leak detection — preferably on a single platform — enable containers to be precisely checked for cosmetic defects, intrinsic and extrinsic contamination, and leaking closures.
In view of the increasing global demand for weight control medicines, but also because of the expected focus on cartridges, this kind of system will become ever-more important — especially when combined with flexible, safe and efficient processes throughout the entire value chain.
Sidebar: Not only widespread, type 2 diabetes and obesity are also interrelated. People suffering from obesity have an increased risk of developing type 2 diabetes. According to estimates by the International Diabetes Federation, 540 million people worldwide are currently living with diabetes, more than 90% of whom have type 2. What’s more, the World Obesity Federation estimates that approximately four billion people — half the world's current population — could be severely overweight by 2035.