Docket Management
Docket: 88N-0038 - Records and Reports Concerning Experience With Approved New Animal Drugs
Comment Number: EC -2

Accepted - Volume 2

Comment Record
Commentor Mrs. Becky Armfield Date/Time 2002-04-03 15:40:37
Organization Novartis Animal Health US, Inc.
Category Company

Comments for FDA General
1. General Comments 1. Are unapproved products that meet the requirements of 801 (e)(1) of the Act to be included in ADE and defect counts? 2. Where is the primary repository for foreign report records (US versus the foreign country)? 3. For US product manufactured outside the United States, what is the appropriate district office for reporting 3day alerts for manufacturing defects? 4. We believe that an examination without administration or dispensing of medications does not qualify as professional intervention, and is not appropriate as the sole means to classify an adverse event as serious. If the veterinarian has examined the animal and feels that no treatment is indicated, professional intervention in the outcome of the case has not occured. 5. Page 5060 of the FR notice does not clearly distinguish between submission requirements for OTC and Rx promotional material. This section should be clarified to indicate applicability to Rx products only, as per the existing approved regulations. 6. Will an electronic signature validated and in compliance with Part 11 suffice for an authorized signature on a 1932 form? 7. If a reporter contacting a Sponsor indicates that he or she does not believe that an event is drug related, or states that they do not wish to file an ADE report with FDA, the Sponsor should not be required to supersede the reporter's hands-on evaluation of the case. 8. 514.80(b)(4)(iv)(A) (see page 5060 of the FR) states that any manufacturing/product defects not previously reported must be included. Based on the definition of a defect in 514.3(g) and the preamble response to comment 12 (see page 5049 of the FR), we understand that the scope of what is considered to be a manufacturing/product defect has now been limited to that which is a problem associated with public health or animal safety or that which is a significant , chemical, physical, or other change or deterioration in the drug product or signficant defective packaging or labeling error. Any defects that may result in serious adverse drug events should be reported within 3 days under 514.80 (b)(1). We understand that any defects that fit the definition in 514.3(g) and are not previously reported under 514.80(b)(1), must be reported in the periodic Drug Experience Report (DER), under 514.80(b)(4)(iv). We interpret the current wording in the interim rule to mean that non-significant defects that may affect physical appearance but not public health or animal safety are not included in the definition of a manufacturing/product defect and therefore are not required to be reported to the FDA at all. Examples of non-significant defects would be a misaligned die-cut of a blister unit that does not affect the integrity of the package seal or labeling, or an empty blister well. Although these non-significant defects would not be reported in the DER, all complaints should be handled and documented as per 211.198 and reviewed annually as per 211.180(e)(2). Any trends in non-significant defects resulting in proposed or executed changes in the manufacturing process should be submitted/reported to the FDA either as a supplemental application or in the MCSR. >>> If this interpretation is correct, the final rule needs to be clarified to indicate that non-signficant defects are not required to be reported in 514.80(b)(4)(iv) but are still required to be handled by the firm as per 211.198 and reviewed as per 211.180(e)(2). 9. The table in 514.80 references 514.80(b)(2), Fifteen-day NADA/ANADA Alert Report requirements in the answer to the question What are the requirements for reporting product/manufacturing defects? However, the 15-day alert requirement applies to serious, unexpected adverse drug events. The definition of adverse drug experience in 514.3 (a),(h), and (i), is interpretted as related to medical events, not the physical attributes of the drug or package, as defined separately in 514.3(g). Therefore, how is the fifteen-day reporting requirement relevent to manufacturing/product defect reporting? If a product defect was discovered as result of information pertaining to an ADE, wouldn't the defect be required to be reported within 3 days as per 514.80(b)(1)? Any other significant defect will be reported under 514.80(b)(4)(iv). >>> For clarity and consistency, it is suggested that no 15 day alert reference appear in the table in the final rule. Reporting timelines under 514.80 (b)(1) and 514.80(b)(4)(iv) are adequate.

EC -2