From: Gunther, Barbara [barbara.gunther@spcorp.com] Sent: Wednesday, March 26, 2003 6:28 PM To: 'fdadockets@oc.fda.gov' Cc: Angiuoli, Anthony Subject: Comments/Questions regarding Estrogen and Estrogen/Progestin Draf t Guidance Dockets Management Branch (HFA-305) Food and Drug Administration 5630 Fishers Lane, Room 1061 Rockville, MD 20852 Dear Sir or Madam: Please find following comments/questions for [Docket No. 03D-0007] Draft Guidance for Industry entitled "Estrogen and Estrogen/Progestin Drug Products to Treat Vasomotor Symptoms and Vulvar and Vaginal Atrophy Symptoms - Recommendations for Clinical Evaluation." 1. The guidance is written specifically for Estrogen and Estrogen/Progestin drug products, and does not mention non-progestin products (eg, SERMs, SPRMs) that may be used in combination with Estrogens to protect the endometrium. If the guidance also applies to such non-progestin products, this should be specified in the document. 2. Section III Part C, Inclusion and Exclusion Criteria. What is the recommended washout period for women taking raloxifene? 3. Section III Part D, Monitoring. The draft guidance recommends that serum levels of the parent compounds and metabolites be measured. Please identify the metabolites that should be measured specifically for estrogens. 4. Section III, Part E, Primary Endpoints. The guidance recommends 4 co-primary endpoints. Regarding the mean change in severity of moderate to severe vasomotor symptoms, please clarify how this is to be measured, ie, would there be a scoring system to quantify the severity of hot flashes? Would mild vasomotor symptoms be included in the analysis? 5. Section III, Part E, Primary Endpoints. Is it recommended that the product achieve statistical significance for all 4 of the co-primary endpoints? 6. Section IV, Drug Products Containing Estrogen Plus Progestin. The guidance states that approval will be based on two criteria: (1) that each component contribute to the efficacy and safety as defined in the combination drug policy. Does this mean that each component be tested individually for efficacy and safety? Thank you for your help in this matter. I am out of the office until April 7th. Should you need to contact us, please email Anthony Angiuoli who is copied on this email. Sincerely, <<...OLE_Obj...>> _____________________________ Barbara Line Gunther MA, MBA Schering-Plough Research Institute Worldwide Regulatory Affairs - Oncology Tel # (908) 740-4828 Fax # (908) 740-2566 Email barbara.gunther@spcorp.com ********************************************************************* This message and any attachments are solely for the intended recipient. If you are not the intended recipient, disclosure, copying, use or distribution of the information included in this message is prohibited -- Please immediately and permanently delete.