definiens: means an application submitted to the FDA to allow a sponsor to make changes in a drug product that already has anapproved NDA, which for major changes requires FDA approval of the supplemental NDA prior to distribution of the drugproduct made using the change ( i.e., any change in the drug substance, drug product, production process, quality controls, equipment, or facilities that has a substantial potential to have an adverse effect on the identity, strength, quality, purity, orpotency of the drug product as these factors may relate to the safety or effectiveness of the drug product ) and for minorchanges requires submission of the supplemental NDA at least thirty ( 30 ) days prior to distribution of the drug product madeusing the change ( i.e., any change in the drug substance, drug product, production process, quality controls, equipment, orfacilities that has a moderate potential to have an adverse effect on the [ * ] = Certain confidential information contained in this document, marked by brackets, has been omitted and filedseparately with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended