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FSH is a member of the pituitary/placental glycoprotein hormone family including luteinizing hormone, thyroid-stimulating hormone, and chorionic gonadotropin. These heterodimeric hormones share a common alpha-subunit and a highly homologous but distinct beta-subunit. The determinant loop of the FSH beta-subunit acts both as a specificity discriminator and as an essential receptor-binding site. The three-dimensional structure of hCG illustrates the proximity of the determinant loop to the carboxyl-terminal residues of the common alpha-subunit. Thus, site-directed mutagenesis was used to mak high-resolution substitutions at this carboxyl-terminal locus. The effects of those substitutions were studied. Twelve single mutations and one composite mutation were made of the region of hFSH alpha 74-92, each residue substituted by alanine. Side chain replacement in this region of FSH proved to be detrimental to binding. hFSH with mutations of either alpha S85A, alpha T86A, alpha K91A, or alpha S92A only retained 10% or less of the hFSH receptor-binding activity, while compared to these, mutants alpha H79A, alpha Y88A, and alpha Y89A retained slightly more binding activity. The single mutant alpha F74A and composite mutant alpha V76A/E77A binding activity was reduced to half of that of wild-type (WT) hFSH. In contrast, mutations of either alpha K75A, alpha T80A, alpha H83A, or alpha H90A did not adversely affect receptor binding, demonstrating the specificity of observed effects. The hFSH and mutant hormones were tested in an in vitro bioassay for stimulation of progesterone production. Those mutations that did not affect receptor binding (alpha K75A, alpha T80A, alpha H83A, and alpha H90A) did not affect signal transduction, measured by progesterone responses. After comparison of wild-type and mutant hFSH activities determined in radioreceptor assays (ID50) and in vitro bioassays (ED50), it became evident that signal transduction correlated with receptor binding.

Background Many publications have demonstrated that robotic automation represents a unique solution to assure absolute quality and safety of the oncologic treatment admixture process. Nevertheless, there are a small number of preparations (i.e. investigational drugs) that are currently not candidates for robotic preparation. In order to extend the total quality concept to the entire production process, we have designed and implemented an automation platform composed of: (1) a robotic system for automated admixtures (APOTECAchemo); (2) a guided preparation system to support manual admixtures (APOTECAps); (3) workflow management software that manages all pharmacy production activities for both systems (APOTECAmanager). Purpose Here we focus the attention on APOTECAps to analyse the measurable improvements in production quality it has introduced. It is important to understand the overall impact on a pharmacy activity in relation to both error reduction and workload. Material and methods A 4-month period of using APOTECAps was monitored in the University Hospital of Ancona (the first hospital with the entire platform). Regarding APOTECAps, the production time and errors intercepted were extrapolated from the system log file that records every single operation. Concerning the manual procedure, a third operator clocked the compounding time. Results The number of medicines analysed was192 with 25 active ingredients. 11 mistakes were intercepted (5.7%): 3 were associated with wrong component supplied, 4 with tolerance exceeding 10%, 3 with adjustment of amount of drug or solvent. In terms of preparation time, the mean time was 220 s and 125 s respectively for the guided and the manual preparations. The guided procedure came out 1.8 times slower than the traditional manual procedure. Conclusion The implementation of a guided preparation system increases medicines quality and patient safety. 11 potential medicines errors were intercepted at an early stage, giving us the chance to rectify them. However, a high level of control comes with an important impact on the working time required to produce the products. References and/or acknowledgements No conflict of interest.

Background In 2007, the University Hospital of Ancona started the journey in automating IV compounding. At the end of 2009, the clinical validation process and workflow reorganisation ended, the second robot was introduced to set up a fully automated IV oncology pharmacy. The laboratory is composed of two APOTECAchemo systems and a laminar airflow cabinet which work from 8 am to 4 pm. There are 3 technicians from 8 am to 2 pm and 1 technician from 10 am to 4 pm. We work in a just-in-time production (80% for outpatients and 20% inpatients) and the rush hours go from 9 am to 1 pm. Two systems are used until 2 pm and one system works for the entire day. Purpose To take stock of 7 years of experience in automated IV compounding. Material and methods The production data were analysed in terms of doses and type of preparations delivered, by means of the statistical tools of APOTECAchemo. Results Before 2010 10,400 treatments were produced automatically in a year and in 2010 this increased to 16,300 (80% of our annual production). In the following years, production increased with 19,300, 19,600 and 20,300 treatments in 2011, 2012 and 2013 respectively. In August 2014, we passed the threshold of 100,000 treatments compounded with APOTECAchemo, representing 95% of the treatments compounded. The annual production consists of 85% in bags, 10% in syringes and 5% in elastomeric pumps. 56 different active ingredients are used. Conclusion Automation ensures the highest quality standards because every step of the compounding process is controlled and traced Automation can cover more than 90% of daily preparations even in a just-in-time system. Automation allows a more intelligent and efficient management of human resources: for every 10,000 treatments automated, one FTE technician can be elevated to higher value-added tasks To take advantage of automation, the workflow should be redesigned (i.e. introduce multi-dose vials and drug days). References and/or acknowledgements No conflict of interest.

Background Antineoplastic drugs are considered ‘high-risk drugs’ due to the increased frequency of human technical errors in their preparation. It is essential for pharmacists to be responsible for setting up, centralising and managing cytotoxic drugs (CDs). To this end, the Division of Anticancer Drugs of L’Aquila (Italy) acquired on June 2012 a Robotic System, APOTECAchemo, the first worldwide system for chemotherapy compounding in a controlled atmosphere. Purpose To analyse the impact of centralising and automating CD preparation for all the Departments in the Hospital of L’Aquila, to avoid any possibility of human error and to optimise the use of the remainder of CDs. Materials and Methods Three high cost monoclonal antibodies (bevacizumab, cetuximab and trastuzumab) were chosen for analysis in this study during the period June–September 2012. The criteria for product suitability were evaluated by analysing the APOTECAchemo database in which all stages of the production process are recorded (picture of the bottle used, weight, and dose accuracy). The cost analysis was evaluated by calculating the daily amounts left over of the three drugs that were previously discarded and are now fully re-used. Results The average error was for 168 preparations of bevacizumab + 0.45% (DS = 1.85), for 67 preparations of cetuximab + 0.71% (DS = 1.13) and for 152 preparations of trastuzumab −0.57% (DS = 1.8). In the period under review, 85.9 g of bevacizumab, 37.5 g of cetuximab and 43.8 g trastuzumab were prepared using material that would previously have been discarded. This provided considerable saving for the three drugs (€29,893) which corresponds to approximately €90,000 per year. Conclusions The centralised system and the use of APOTECAchemo is successful both in terms of patient and operator safety and cost benefit for the Hospital. No conflict of interest.