6. The manufacturer shall inform the holder of the relevant product licences of any material alteration in the premises or plant used in connection with the manufacture or assembly of the medicinal products to which the relevant product licences relate or in the operations for which such premises or plant are so used and of any change, since the granting of the relevant product licences in respect of any person—
(a)responsible for supervising the production operations, or
(b)responsible for quality control of the medicinal products to which the relevant product licences relate, or
(c)in charge of the animals from which are derived any substance used in the production of the medicinal products to which the relevant product licences relate, or
(d)responsible for the culture of any living tissues used in the manufacture of the medicinal products to which the relevant product licences relate.