Farrell (ankle) and George (knee) have withdrawn from the squad with injuries sustained in last Saturday's 32-15 win over Australia.
Gloucester's Harry Elrington and Jack Singleton have now been called up to Eddie Jones' 34-man squad.
Joe Marler will join on Friday after completing his 10-day isolation period following a positive Covid-19 test.
George, 31, was not named in the initial autumn squad but the Saracens hooker was recalled a day later following an injury to Luke Cowan-Dickie.
Saturday's game at Twickenham (15:15 GMT) will see England aim to make it three wins from three from their autumn internationals, having also beaten Tonga on 6 November.