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InvaGen Pharmaceutic als. Inc. InvaGen Pharmaceuticals, Inc. Te1:631-231-3233 Fax:631-231-4248 4 2 3 7 11 FEB 28 A 9 :09 Division of Dockets Management Food and Drug Administration Department of Health and Human Services 5630 Fishers Lane, Room 1061 Rockville, MD 20852 February 24, 2011 Amendment to Citizen petition Re: Amendment to Citizen Petition (Docket # FDA-2011-P-0047-0001/CP) for InvaGen's Meclizine Hydrochloride Chewable Tablets, 25 mg ANDA # 200791 Dear Sir/Madam, I have herewith enclosed the amendment for the Citizen Petition document (Docket # FDA-2011- P-0047-0001/CP) filed on 01/14/2011, in reference to the telephonic conversation with OGD on 02/23/2011, to file the amendment for the citizen petition to confirm -Pfizer's Antivertt Chewable Tablets, 25 mg (RLD) was not discontinued for safety and efficacy reasons and for further review of InvaGen's Meclizine Hydrochloride chewable tablets, 25 mg ANDA # 200791". In reference to the above, InvaGen is filing the amendment for the citizen petition document in accordance with section 505(j) (2) (C) of the Federal Food, Drug and Cosmetic Act and 21 CFR 314.93 and 21 CFR 10.30 and firm is committed to assist with any issues identified. If there are any questions or comments, please do not hesitate to contact me via telephone at (631) 231-3233 or via facsimile at (631) 231-4248. Sincerely,. Sudhakar R. Vidiyala, Ph.D F-D/H)ou-P--oo 4/7

@ InvaGen Inc Amendment to Citizen Petetion, Docket # FDA-2011-P-0047-0001/CP February 24, 2011. Division of Dockets Management Food and Drug Administration Department of Health and Human services 5630 Fishers Lane, Room 1061 Rockville, MD 20852 CITIZEN PETITION The undersigned, submits this petition under section 505(j) (2) (C) of the Federal Food, Drug and Cosmetic Act and 21 CFR 314.93 and 21 CFR 10.30 requesting the Commissioner of Food and Drugs to make a determination that the Pfizer's Antiverte chewable tablets 25 mg, containing Meclizine Hydrochloride 25 mg per tablet was not discontinued for safety and efficacy reasons and is suitable for the submission of an Abbreviated New Drug Application (ANDA). A. Action Requested InvaGen requests the Commissioner of the Food and Drug Administration to make a determination that the discontinued formulation Pfizer's Antivert Chewable Tablets 25 mg was not discontinued for safety and efficacy reasons. The petitioner believes that the Pfizer's Antivert Chewable Tablets, 25 mg was not withdrawn for the reasons of safety and efficacy. The continued presence of Antivert Tablets, 25 mg (current RLD held by Pfizer for Antivert Oral Tablets) on the market is a clear indication that the discontinued product(antivert Chewable Tablets, 25 mg) remains safe and effective since both are identical with respect to active ingredient, strength and route of administration except the dosage form. The petitioner therefore requests that its Meclizine Hydrochloride Chewable Tablets, 25 mg ANDA is eligible for approval upon completion of the review process, though the currently Pfizer's Antivert Chewable Tablets, 25 mg are having discontinued status in Orange book.

InvaGen Inc!nyeGen Inc. This petition therefore requests the Commissioner of the Food and Drug Administration to make a determination that : "The Pfizer's Antivert chewable tablets 25 mg, containing Meclizine Hydrochloride 25 mg per tablet was not discontinued for safety and efficacy Reasons". B. Statement of Grounds e The active ingredient in both Antivert Tablets 25 mg (oral ) and Antivert chewable Tablets 25 mg, i.e., Meclizine is an antihistamine which shows marked protective activity against nebulized histamine and lethal doses of intravenously injected histamine in guinea pigs. It has a marked effect in blocking the vasodepressor response to histamine, but only a slight blocking action against acetylcholine. Its activity is relatively weak in inhibiting the spasmogenic action of histamine on isolated guinea pig ileum. The Pfizer's Antivert was approved for both Oral tablets and chewable on February 14, 1957 under NDA # 010721. The InvaGen's product Meclizine Hydrochloride chewable tablets, 25 mg has been developed for chewable tablet. Petitioner submitted the ANDA # 200791 with Pfizer's Antivert Chewable Tablets, 25 mg as RLD (as was the case at the time of ANDA submission, Pfizer's Antivert Chewable Tablets,25 mg held RLD status though Antivert Chewable Tablets 25 mg were not available in the market ) is valid and approvable subject to meeting the Agency's requirements for filing an ANDA.(Please refer Attachment -1 for the copies of the relevant pages of November,09 Orange Book). Later orange book was revised the RLD status for Pfizer's Antivert Chewable Tablets 25 mg as "discontinued" (Please refer Attachment -2 for the copies of the relevant pages from current Orange Book discontinued products) and accordingly FDA requested

InvaGen Inc InvaGen to file the citizen petition to confirm The Pfizer's Antiverte chewable tablets 25 mg were not discontinued for safety and efficacy reasons and also to continue further review process of its ANDA # 200791. The petitioner particularly requests the FDA to make a determination that InvaGen's Meclizine Hydrochloride Chewable Tablets,25 mg referring to the originally approved RLD Antivert Chewable Tablets, 25 mg (now discontinued) would not render the product less safe or effective based on the following facts. B.1. Referencing discontinued RLD and Regulations : The Orange Book contains a list of all drug products approved by the Food and Drug Administration (FDA) which are eligible for submissions as ANDAs. The current date of the electronic Orange Book lists Antivert Chewable Tablets,25 mg, under the "Discontinued Drug Products section". It is known from the 21 U.S.0 Section 355 (j) (6) Code of Federal Regulations that when an ANDA makes a reference to a discontinued label of a drug, FDA may still approve the ANDA upon determination that the formulation was not withdrawn for reasons of safety or effectiveness. The petitioner is not aware of any documentation which establish that the Antivert chewable tablets 25 mg was discontinued for safety or efficacy reasons. In FDA's "Additions/Deletions for prescription and OTC Drug products list", Antivert Chewable Tablets 25 mg has been marked with symbol "@", which indicates "drugs that have been discontinued from marketing or that have has their approvals withdrawn for other than safety or efficacy reasons. (Please refer attachment-3 for FDA's "Additions/Deletions for prescription and OTC Drug products listed January-2010, 30 th edition).

InvaGen Inc In the Labeling comments dated, November 30, 2010 on InvaGen's Meclizine Hydrochloride Chewable Tablets, 25 mg ANDA #200791, OGD is recommended to omit the text related to Vertigo in dosage and administartion, though the Antivert labeling is common for both Oral and chewable tablets. It is known from the Code of Federal Regulations that when an ANDA makes reference to a discontinued label of a drug, FDA may still approve the ANDA upon determination that the formulation was not withdrawn for reasons of safety or effectiveness (21 U.S.C. Section 355 (j)(6) and 21 CFF! Ej 314.122 and 314.161). Similarly, FDA is also authorized to approve an ANDA that omits in its labeling an aspect of the listed drug. In this circumstance, omission from the NDA's labeling of inactive ingredients is allowed if the omission does not render the generic drug product less safe or effective than the listed drug. (21 CFR 314.127 (a)(7)). (Please refer attachment-4 for labeling copies of both brand Antivert labeling and InvaGen's Meclizine Hydrochloride Chewable Tablets labeling along the details of reasons for differences between brand and InvaGen's labeling) B.2. Conclusion: For all reasons stated above in this statement ground, the petitioner seeks FDA to make a determination that the discontinued formulation of Antiverte chewable tablets 25 mg was not withdrawn by Pfizer for reasons of safety or effectiveness and that the use of that labeling, product would not render the InvaGen's Meclizine Hydrochloride Chewable Tablets, 25 mg less safe or effective and would be therapeutically equivalent to the currently marketed Pfizer's Antivertt oral tablets 25 mg and discontinued Antivert Chewable Tablets, 25 mg. Accordingly, this petition seeks a determination that the InvaGen's drug product Meclizine Hydrochloride Chewable Tablets, 25 mg is suitable for submission as an Abbreviated New Drug Application (ANDA).

InvaGen Inc C. Environmental Impact: This petition is entitled to a categorical exclusion under 21 CFR 25.30 and 25.31 D. Economic Report: The petitioner agrees to provide an economic analysis if requested by the agency. E. Certification The undersigned certifies, that, to the best knowledge and belief of the undersigned, this petition includes all information and views on which the petition relies, and that it includes representative data and information known to the petitioner, which is unfavorable to the petitioner. Respectfully Submitted, Sudhakar.R. Vidiyala, Ph.D InvaGen Pharmaceuticals, Inc., Hauppauge, NY-11788. Attachments: 1. Copies of the relevant pages of November,09 Orange Book. 2. Copies of the relevant pages from current Orange Book discontinued products. 3. FDA's "Additions/Deletions for prescription and OTC Drug products listed January-2010, 30 th edition. 4. Labeling copies of both brand Antivert and InvaGen's Meclizine Hydrochloride Chewable Tablets labeling along the comparison and reasons for differences between brand and InvaGen's labeling.

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