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Route 521 commenced operating on 18 July 1992 as part of the Red Arrow network of bus routes aimed at commuters in Central London linking some of the capital's main railway termini.
During late 2003, early 2004, a series of onboard fires on Mercedes-Benz O530Gs led to withdrawal of the entire fleet, while Mercedes-Benz made some modifications. During this period limited services operated using a variety of different buses on route 521.
In September 2009, as part of the move to replace London's articulated buses, the O530Gs were replaced by Mercedes-Benz O530 Citaros.
Another criticism of articulated buses was the low number of seats, with only 49 per vehicle. A standard rigid Citaro has 44 seats, however the new ones for route 521 have just 21, with room supposedly for up to 76 standers, leading to criticism the new buses were "cattle trucks" and even more crowded than the buses they replaced.
In December 2013, two trial BYD electric buses were introduced. In September 2016, Alexander Dennis Enviro200EV bodied BYD electric buses began to operate the route, making it and route 507 the first battery electric bus routes in London. In September 2016, the buses on this route and on the 507 have received new digital route displays.
On 28 August 2021, the PVR was cut to 15 vehicles rather than 32.
Route withdrawal
On 23 November 2022, it was announced that route 521 would be withdrawn following a consultation, with routes 59 and 133 being rerouted to replace it either side of St Paul's. These changes were implemented on 29 April 2023.