The growth in the biosimilar market since 2006 has been significant. Biosimilars have no meaningful clinical differences between the originator medicine in terms of safety and efficacy and are typically less expensive than the originator. These factors lead to the popularity of biosimilars to help bring safe and effective drugs to market at an affordable price
What are biosimilars and biological medicines?
A biosimilar medicine is a type of biological medicine that is developed to be highly similar and clinically equivalent to the existing biological medicine. A biosimilar contains a version of an active substance of an already approved biological medicine, which is referred to as the ‘reference medicine’ or ‘originator medicine’. It is similar to reference medicine in terms of quality, structure and biological activity. To understand the key features of biosimilars, you should first understand the class of medicines that they are part of – biological medicines. Biological medicines, or biologicals, contain active substances that are derived from a biological source, for example from living cells or organisms. Biologicals are used in clinical trials and crucial in the treatment of many serious conditions such as cancers, diabetes and autoimmune disease. Did you know 8 of the top 10 selling pharmaceuticals were biologicals? Many of the biologicals licensed are proteins that can vary greatly in size and structure from simple proteins such as insulin to complex antibodies. Biosimilar medicines are those that have a high degree of similarity to another biological medicine already licensed. Biosimilar companies can gain market approval for their biosimilars when market protection of the original biological has finished. The approval of the biosimilar is supported by evidence proven in clinical trials demonstrating no meaningful clinical difference between the biosimilar and the originator medicine.
What is batch variability and why does it occur?
The manufacturing of complex biologicals is significantly more intricate than chemically-derived molecules. Most of them are manufactured by sophisticated biotechnology processes such as cell systems or recombinant DNA technology. The complex nature of these molecules and the manufacturing process means there is a degree of variability called ‘microheterogeneity’. This means that there are subtle differences in the structure of the active substance within and between batches. To ensure efficacy and patient safety with this variability in mind, the microheterogeneity must be within an acceptable range. This can be achieved by adjusting manufacturing processes to guarantee consistency among batches. However, there may be a small variability within or between batches of the same biological medicine. This can occur during manufacturing if the process is modified during the commercial life of the medicine, for example when increasing the scale of production. Manufacturers apply strict measures and regulations to make sure that, despite variability, there is consistency between batches, and that any differences present in the batches do not affect the safety or efficacy of the medicine. Typically when using the same manufacturing process, variability within a batch or between batches batch-to-batch is very low.
What are the key regulatory considerations of biosimilar development?
To ensure consistency and quality of all biological medicines, including biosimilars, the EU legislation upholds strict requirements for the manufacture of all medicines:
Manufacturers in the EU must hold a manufacturer’s license and are legally obliged to comply with Good Manufacturing Practice (GMP), the agreed standards to obtain a medicine with proven quality.
National regulatory authorities in the EU regularly inspect manufacturing sites for compliance with GMP requirements.
If some manufacturing steps take place outside the EU, then non-EU manufacturers, importers and wholesale distributors are obliged to follow the same strict requirements and are also regularly inspected.
For biological medicines, some of the GMP requirements have been adapted to take into account their specific nature (e.g. use of appropriate aseptic techniques, refrigeration and other storage conditions, stability, transport etc.).
What does this mean for biosimilars in clinical trials?
Clinical trials are carried out to prove that the active substance is highly similar to the reference medicine, this is known as biosimilarity. Clinical trials aim to demonstrate high biosimilarity so that the biosimilar can rely on the efficacy and safety experience of the reference biological medicine, therefore avoiding the repetition of clinical trials. Clinical trials for biosimilars do not need to include all of the studies that are needed for the reference medicine in order to prove safety and efficacy for patients. It is important to note that biosimilars are not considered generics of biologicals. This is because of the natural variability caused by the complex manufacturing of biologicals as discussed above.
CSI has experience in sourcing biosimilars for clinical trials
CSI has extensive experience in sourcing products for biosimilar studies even in countries where strict government regulations exist. Want to find out more about sourcing biosimilars for your clinical trial? Get in touch with us to discuss your requirements.
Summary
A biosimilar medicine is a type of biological medicine that is developed to be highly similar and clinically equivalent to the existing biological medicine. A biosimilar contains a version of an active substance of an already approved biological medicine, which is referred to as the ‘reference medicine’ or ‘originator medicine’. It is similar to reference medicine in terms of quality, structure and biological activity.
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