Therapeutics
Pluripotent stem cell.
Coloured scanning electron micrograph (SEM) of a pluripotent stem cell derived from a macrophage white
blood cell. Magnification: x4000 when printed at 10 centimetres wide. Image courtesy of
Steve Gschmeissner/ Science Photo Library
meeting pipeline requirements. Physicians and patients are crucial to the future adoption of bio- logical therapies as each party is vital to the dis- cussion and global attitude. Likewise, the regula- tory approval process for biologics, biosimilars and biobetters, requires significant data support from each stage of development, including physio- chemical characteristics combined with a consid- erable functional comparison evaluation. Each biological therapy seeking approval is assessed on an individual basis, by a specific agency, which may prevent a global release if two agencies dis- agree on the approval of the biologic therapy under investigation. Several key recommendations for biologics have been identified to augment global development and co-ordination, which include: (a) comprehensive clinical trials to identi- fy any differences between biological therapies (ie biologics vs biosimilars); (b) European Medical Agency (EMA), World Health Organization (WHO) and the FDA guidance on regulatory ele- ments and approval processes guidelines to ensure the safety along the biological product therapeutic cycle; (c) continued education for healthcare pro- fessionals on basic scientific principles for the biomanufacturing processes and pharmacovigi- lance reports for biologicals that have been licensed for use. As biosimilars emerge into the market, the FDA is currently demanding Phase III clinical trials that can be extensive and costly in order to approve the therapy for use, while they
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do not require this level of additional studies for generic drugs. As a biologic, biosimilar or biobet- ter is tested for the clinical trial programme, phar- macokinetic (PK) analysis, clinical efficacy and safety, as well as immunogenicity are assessed with the aim of demonstrating its effectiveness and similarity between the biologic originator and biosimilar or biobetter. By definition, a biosimilar should behave identically and show the same pharmacological activity to that of the biologic originator. However, regulatory agencies have issued new requirements and advice, suggesting that the clinical trials should be tailored to testing whether the product can be considered a biosimi- lar and demonstrate the similarity of its activity in order to detect any sort of important clinical dif- ferences. Thus, most companies strive for the bio- logic that can overcome immunogenicity, time- sensitivity and decay, as well as prove clinical effectiveness in treatment. This reduces global risk along the value chain, from manufacturers, CROs and clinicians, all the way to patients2,3. Many of the advancements for biologics, biosim- ilars and biobetters have been due to oncology research. Fifty biosimilars are in the pipeline for the US development programme for biosimilars, and the EU has approximately 20 biosimilars approved and effective in the market for cancer therapy4,5. However, four of the main biological therapies, namely Erbitux® (cetuximab), Rituxan® (rituximab), Herceptin® (trastuzumab) and
Drug Discovery World Summer 2017
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