AstraZeneca has replaced Skanska with Mace on its Cambridge HQ and pushed back completion of the project to 2020.
The scheme was first unveiled in 2013 with an expectation that the £330m research centre and corporate HQ would be completed by 2016.
However, since then the cost has increased to more than £500m and the programme has faced delays.
Skanska was appointed in 2015, having worked with AstraZeneca on this scheme since 2014 as well as schemes overseas.
The contractor was also picked to build the neighbouring Papworth Hospital, which has itself been hit by delays.
The pharmaceutical giant has now moved to replace Skanska and appointed Mace as project manager.
A spokesman said: “We have agreed to transition from Skanska to Mace as the construction manager for the scientific fit-out and commissioning phase of the project.
“Following a transition period, we will be able to communicate an update as to when we can commence occupation of the facility. At the moment, this points to the first half of 2020.”
Staff employed on the site are expected to transfer to Mace, with a staged handover taking place between AZ, Skanska, Mace and the supply chain until November.
An AstraZeneca spokeswoman told the Cambridge Independent there was water egress in the building’s basement as well as issues with design and roof loadings that needed to be resolved.
She said: “There are some engineering and design issues on site, not related to who the construction manager is. It is really complex. We want to get it right rather than get it fast.”
Skanska UK president and CEO Gregor Craig said: “The decision to part ways has been taken between Skanska and AstraZeneca, following constructive discussion over recent weeks. The Skanska team has made a valuable contribution to the project and achieved a great deal. Our focus now is to conclude our activities and transition the team in the most effective way possible.”
AstraZeneca and Skanska have been contacted for further comment.