The biggest problem on generation ships is the fact that the first generation may pass all of the tests with 100% grades. Their offspring, however, could be a mess that put the generation ship into a horrible position and when you are 30 years from Earth a problem like that could end with everyone dying.
On board bioengineering/nanotechnology. It is most likely that this won't happen until next century or more and by that time technology will have changed drastically.
Within the next century or so a generational ship may not even be required.