At Adragos Leipzig, quality is at the heart of everything we do. We specialise in non-sterile liquids, such as cough syrups and other liquid medicines, and non-sterile semi-solids. While these products do not need to be made in aseptic conditions, maintaining quality standards is absolutely essential to ensure patient safety.
As a contract manufacturer, we make a wide variety of different products, with batch sizes from very small runs right through to 4000L. The products themselves range from simple solutions to solutions containing thickening agents such as xanthan gum, as well as suspensions and emulsions. We also manufacture and fill products that are best described as semi-solids, creams and ointments. And our portfolio extends past pharmaceuticals, and into food supplements and cosmetics, too. We also have a new filling line here that allows us to work with liquid products that have a very high alcohol content.
As we move a product from small-scale production to larger volumes, there are a number of challenges we need to overcome. Mixing is critical for liquid products, and choosing the right technology for the consistency of the liquid is important. Our smallest mixer, with a volume of 15L, is perfect for galenic-scale runs, and can also be used as a full production device for very small batches of specialist products.
Going from 15L galenical batches to 1200L and even up to our largest, 4000L, vessel, there will inevitably be wrinkles that need ironing out. Stirring your cup of coffee to dissolve sugar is quick and easy; stirring thousands of litres of coffee to dissolve many kilograms of sugar in it is a far more complex task!
Validation and Regulation
Of course, in the pharmaceutical world, validation of our processes is key to proving all is well. We make risk assessments for each process to identify the critical points, with data collected on pilot runs to support the scale-up to larger batches. Some additional data are required as the batch sizes increase for non-sterile liquids, and additional homogeneity studies will be needed for semi-solids to prove consistency throughout the batch. This is particularly important for pharmaceutical creams, gels and ointments, as it ensures the dose will be correct every time.
For pharmaceuticals, Annex 15 covers the validation process in Europe, and is vital for gaining and retaining European GMP certification. Validation extends to the computer systems to ensure data integrity, both of records and the lab equipment and other devices that collect those data. This includes both networked machines, and standalone systems.
Many of the products we make were first developed elsewhere, and then the process transferred into our facility for manufacturing. The tech transfer team here in Leipzig will work with the customer on the full tech transfer plan. This will cover aspects as diverse as raw materials and packaging. We may be able to find better prices for raw materials than their original suppliers, for example. And for excipients, if we work with our already-validated suppliers, the burden on the QC lab will be reduced, saving money.
If packages of product remain from the previous production run, these can be used to assist method transfer and analytical method validation. This can be done in parallel with the production of the galenical batches, ready for the first pilot batch, or full-scale
production. Every step will require full validation, including the final packaging, before the batch is released.
The process is a little simpler for food supplements and cosmetic products, as full validation is not required: we just have to show that the products meet the specifications. However, microbial control is important regardless. For drug products, we will typically test every batch; for cosmetics, every 10th batch will usually suffice, depending on the specification. It is not normally required to microbially test raw materials, unless they are ingredients such as liquid sugar solutions that provide a good microbial food source, or the container has been opened and it has passed the retest date.
EU GMP guidelines also mandate ongoing stability studies. For pharmaceuticals, a full ICH stability study is required, and we have stability chambers covering multiple climate zones. For cosmetics, the requirements are not so strict, but stability is important when it comes to setting expiry dates, and checking how it is likely to behave when being transported if it is exposed to extremes of temperature.
Quality means reliability at every step of our manufacturing. Careful control of the process is key, and continuous monitoring allows us to remediate any issues before they cause wider problems. It allows us – and our customers – to be sure that the product meets specifications, and will be safe for patients and consumers.
