Any manufacturing process needs to make the product correctly every time. It’s particularly important when making pharmaceuticals because of the level of regulatory oversight. Quite rightly, to ensure patient safety, there are strict rules about how products are made and how they need to be tested and analyzed to document that what leaves the factory meets all requirements. We also need to prove that the medicines will maintain this quality level until expiration.
This is why one of the core duties of the team at Adragos Athens is to develop and validate analytical methods to support activities such as process validation controls, stability tests, and dissolution profiles. The validation of the methods is essential to ensure they reliably give accurate results.
Validated methods in Good Manufacturing Practices (GMP)
Once the R&D department has defined the final formulation and developed the analytical methods, our Good Manufacturing Practice (GMP) analytical team here in Athens takes over, validating those methods for the final product. We work according to current GMP protocols, strictly following all the relevant good manufacturing practices guidelines, and always ensuring data integrity.
We constantly communicate with other departments, including R&D, regulatory affairs, and clinical. It’s extremely important to have a close collaboration between departments, transferring insights and knowledge about the final formulation, the final analytical methods, and the results concerning the investigational medicinal products (IMPs) or validation batches into our group.
We also carefully plan and are responsible for the transfer of the analytical method back to the Adragos GMP manufacturing site or the CMO where the drug is being made, allowing their own QC departments to run the methods ahead of commercial batch release. Of course, we remain in close contact with the manufacturing groups, and if there are any challenges with the implementation of the method, we are there to help.
Patient safety is at the heart of everything we do. Without a validated process, the product will not get a license. The methods need to be completely repeatable, giving accurate results every time.
Process validation controls and IMP testing
We carry out thorough process validation controls on the registration batches, ensuring that both the CMO and our regulatory team receive the results required for the product’s marketing authorization application. This process is fundamental for proving the reliability and consistency of the GMP manufacturing process, as well as for establishing the final product’s specifications, including critical quality attributes.
In the case of IMPs, we perform all necessary testing on bio batches to confirm the integrity and quality of the product intended for bioequivalence studies. Also, to meet the requirements outlined in the Guideline on the Investigation of Bioequivalence, in vitro dissolution tests are conducted as a complement to the bioequivalence studies.
These tests are critical to verify that the product in clinical trials meets the required safety, efficacy, and quality standards. By ensuring the bio batches adhere to strict good manufacturing practices guidelines, we support the regulatory submission for bioequivalence studies, which is key to demonstrating that the generic or new formulation performs similarly to the reference product in terms of pharmacokinetics and therapeutic effect.
This comprehensive approach ensures regulatory compliance, product safety, and consistent GMP manufacturing performance, paving the way for a successful market launch.
Stability studies According to GMP Guidelines
Another essential task for my group is evaluating the stability of the validation batches. Stability according to International Council for Harmonisation (ICH) protocols is closely followed to determine the shelf life of the product and define the storage conditions that will be required to maintain its integrity. Again, all of this is carried out according to GMP guidelines. All these data are passed on to the regulatory affairs department, with whom we work extremely closely to ensure a smooth process during submission to the regulatory authorities.
Stability tests are designed to assess the percentage of the active substance throughout the product’s shelf life and give an insight into any degradation that may occur within the final dosage form. If it has degraded to any extent, does it remain within the specified allowable limits? And what is the cause of any degradation – is it caused by temperature or humidity levels, for example, or has there been an interaction with any component of the container, closure, or packaging?
If the products require some form of preservative, we will assess how long it provides effective protection from microbes. We will also check whether it is consumed by any of the components of the drug formulation, either the active or any of the excipients. For solid dosage forms, whether capsules, tablets, or film-coated tablets, we carry out dissolution tests.
Any variations over time will need to be addressed. For example, are different storage conditions required? If degradation is observed at room temperature, then refrigeration may provide a simple way to prevent it. The stability tests are the key to finding out how the product is best stored and for how long.
During ICH stability testing, if required, the product’s stability is assessed in both upright and inverted positions of the container. This helps determine if the container’s closure system impacts the product’s integrity.
Additionally, for products in multidose containers, in-use stability studies are conducted at both the beginning and near the end of the shelf life to determine the exact usage period of the container.
Batch release and GMP status
Those first validation batches allow us to evaluate the GMP manufacturing process, and the impact on product shelf life and storage conditions. By proving this, you ensure it can then be used for the release of commercial batches, as long as the validated protocol is accurately followed every time.
The Greek authorities audit our labs and procedures every three years, and we also undergo frequent audits by our clients, both before they contract us to work with them and after the agreement is in place. We are also FDA-ready, having pre-emptively undergone an external assessment of our quality systems, and the small number of gaps they identified have all been completed. We welcome this oversight, as it reassures everyone that everything is being done as it should be.
