The present invention relates to a method of producing a non-food crop Nicotiana plant that is optimized for producing plant-manufactured biologicals. These can be industrial or research enzymes or proteins, as well as pharmaceutical or therapeutic proteins such as vaccines, antigens, enzymes, antibodies, etc. that can be isolated and purified and administered to a subject. The invention also discloses sterile interspecific Nicotiana hybrids with high biomass produced by the method of the invention, and the seeds, tissue cultures, methods of selecting these plants and regenerating these plants.