Separate as soon as the vulva starts to swell before discharge, and I'd say at least a week after the discharge has changed to a clear or straw color.
Spay the female so to best preven mammary cancer. After first heat increases risk of cancer drastically.
Neuter the male to prevent prostate cancer.
If you must breed, ensure that the dogs are champion line and have titles to their names. This betters the breed, as long as the genetic history is clear of common breed specific ailments and diseases. Also, find a mentor to help you. There are many reputable breeders that will be willing to teach you.
Or be a backyard breeder and go into the situation unknowing what you are really doing. Up to you.