guidelines on variations to a registered pharmaceutical product

Guidelines on Variations to a Registered Pharmaceutical ProductMarketing Authorization of a Pharmaceutical Product for Human Use and itsannexes (Document No. DAR/GDL/005), and Guidelines for registration ofVeterinary Pharmaceutical Products (August 2001).This guidance document is applicable only to APIs and excipients manufacturedby chemical synthesis or semi-synthetic processes and FPPs containing suchAPIs and excipients. APIs from fermentation, biological, biotechnological orherbal origin are treated as special cases. The applicant is requested to contactNDA regarding planned variations to such products.The notification requirements for API-related changes differ depending on themanner in which API information was submitted with the original FPP application,namely: use of a WHO prequalified API, use of a European PharmacopoeiaCertificate of Suitability (CEP), or as provided in full within the dossier.The conditions and documentation stipulated in this guideline for API-relatedvariations focus primarily on those FPPs that relied upon the provision of fullAPI information within the FPP dossier. When an FPP relies upon a CEP ora prequalified API, FPP applicants are required to notify NDA only when theassociated CEP or Confirmation of API Prequalification document has beenrevised.Whenever FPPs have been registered on the basis of approval by a stringentregulatory authority (SRA) (innovator products or generic products) or WHOprequalification, subsequent applications for variations should also be approvedby the same SRA and WHO PQP, and NDA should be notified of the approvalof the changes.When a variation leads to a revision of the summary of product characteristics(SmPC), patient information leaflet (PIL), labelling and packaging leaflet,updated product information has to be submitted as part of the application.For variations that require generation of stability data on the API or FPP, thestability studies required, including commitment batches should always becontinued to cover the currently accepted retest or shelf-life period. NDA shouldbe informed immediately if any problems with the stability appear during storage,e.g. if outside specification or potentially outside specification.Applicants should be aware that some variations may require the submissionof additional consequential variations. Therefore, for any given change theapplicant should consider if one or more variations may be required to besubmitted.Doc. No.: DAR/GDL/005 Revision Date: 8 th July 2013 Review Due Date: 16 th July 2016Revision No.: 1 Effective Date : 16 th July 2013 Page 4 of 70