IF you are referring to ISO 9001 requirements: You can make all the changes you want and issue the new quality manual, but you will have to notify your registrar. They will probably want a copy - It's their call, though.
I have been through it and typically a phone call does it unless you make significant changes in which case they will probably want a copy to review.
You say you have made "significant" changes. Call your registrar contact and have a chat. If your quality manual is the only document in your system which has changed, it probably will not be a big deal. But - If you have made changes which flow down and cause changes to lower level documents, such as procedures, the impact of the changes may be important.
Also remember - A "Quality Manual" is no longer a requirement as of ISO 9001:2015.