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Essentially, the best way to do it in a company with a lot of travel is to have a dedicated internal guy dealing with travel. This works!
As the Procurement Manager in a Further Education College I am responsible for securing our travel and hotel requirements. Common sense, good geographical knowledge, reasonably extensive worldwide travel experience and a sound knowledge of airline, train and hotel online booking systems means I am rarely bettered in price when compared to the Expedias, Opodos and other booking engines.
I book individuals and groups of students and lecturers on travel throughout the UK, Europe and the US/Canada, occasionally even Japan. While it does take a bit of time to get it right, a 'sixth sense' tells you when you know you've got the right deal, and we wouldn't have it any other way. While our policies are reviewed regularly, we don't feel we could obtain any better value by using a corporate travel agent. And as a public sector organisation, every penny counts, and every penny is accountable.