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Margaret M Dotzel (202) 778-1998 mdotzel@zuckerman,com April 23, 2009 Division of Dockets Management Food and Drug Administration 5630 Fishers Lane, Room 1061 Rockville, MD 20852 Re: Comments to King Citizen Petition Docket No. 2009P-0040 Dear Sir or Madam: I am writing on behalf of Sun Pharmaceutical Industries Limited to respond to King Pharmaceuticals, Inc. January 29, 2009 citizen petition. Introduction In December 2007, Sun Pharmaceutical Industries Limited (hereinafter referred to as "the Applicant") filed an ANDA application for surnatriptan succinate injection referencing Glaxo Smith Kline’s (GSK’s) Imitrex STATDose® Injection. Both the drug portion (sumatriptan succinate) of the combination product and its labeling are the same. In addition, the performance of the autoinjector device in the GSK product and the autoinjector device in the Applicant’s product are similar and meet applicable FDA standards, although certain aspects of the Applicant’s device that are not related to performance are not identical to the GSK device. Importantly, the Applicant has demonstrated that its product is bioequivalent to the GSK product. As discussed below, the differences between the two products are both beneficial and in one important respect necessary to meet current ISO standards that have been recognized by FDA. On January 29, 2009, King (the maker of several autoinjector products) filed a citizen petition requesting FDA to confirm that any ANDA application for sumatriptan succinate injection containing an autoinjector is only eligible for approval if the autoinjector is identical to the reference product’s autoinjector in performance, physical characteristics, and labeled instructions. King argues that an autoinjector that is not identical will adversely affect public health because of the risk of confusion and improper use of the substituted product. King further asks FDA to clarify drug nomenclature to ensure consistent identification of dosage form, route of administration, and strength for all drug products containing sumatriptan. King’s 2009 citizen petition refers to an earlier citizen petition that King filed on Sep 26, 2007, which is pending at the Agency. In the 2007 petition, King requests that FDA 1. Decline to approve or stay the approval of any ANDA submitted under section 505(j) that references a drug product containing an autoinjector as the listed drug, unless it has been demonstrated that the proposed autoinjector is the "same" as the autoinjector in the Reference Listed Drug ("RLD"); 2. Refuse to designate any drug product containing an autoinjector approved under sections 505(b) or 505(j) as therapeutically equivalent to an RLD containing an autoinjector, unless it has been demonstrated that the autoinjector is pharmaceutically equivalent to, bioequivalent to, and has the same labeling as the autoinjector contained in the RLD; and 3. Require that sponsors of new drug products containing autoinjectors conduct appropriate clinical studies in patients under the conditions for which the autoinjector is indicated if: (i) the sponsor files a section 505(b)(2) application or an application pursuant to a suitability petition, and (ii) the autoinjector is not the "same" as the autoinjector in the RLD. The Applicant does not object to FDA clarifying drug nomenclature to ensure consistent identification of dosage forrn, route of administration, and strength for all drug products containing sumatriptan, but since such clarification is not a prerequisite to approval of a generic sumatriptan injector, any time necessary to issue such a clarification may not delay approval of Applicant’s product. More importantly, there is no legal basis for King’s claim that the Applicant’s autoinjector must be identical to the reference drug’s autoinjector, particularly since the autoinjector utilized in Applicant’s product already has been cleared by FDA and such autoinjector is in fact safer than the reference drug product’s autoinjector in that it includes additional safety features that are required by the FDA adopted consensus standards used to clear such device. In fact, King’s argument, if accepted, would mean that applicants for approval of combination drug-device products would be prohibited from meeting consensus standards recognized between approval of the reference product and submission of an abbreviated new drug application. If King were correct, then the device feature of combination products would be frozen in place at the time the reference product is approved and FDA could not encourage or even permit improvements that advance the public health. Theretbre, FDA should deny the King petition and proceed immediately to approve the Applicant’s ANDA. In addition, FDA should find that the petitioner has failed to demonstrate that delay in approval of the Applicant’s ANDA is necessary to protect the public health under Section 505(q) of the FDC Act. Background The generic injectable sumatriptan product, which is the subject of the Applicant’s ANDA, is a combination product that contains both a drug (sumatriptan succinate) and a device (the autoinjector). The reference listed drug (RLD) is GSK’s Imitrex STATDose® Injection. 2 The drug portion of the Applicant’s product is identical to the RLD. Both products contain 6.0mg/0.5 ml of sumatriptan succinate for injection. The Applicant has data demonstrating that its product is both qualitatively and quantatively similar to the reference drug and therefore qualifies fbr a waiver of traditional bioequivalence studies. The Applicant’s drug labeling is the same as the labeling of the reference drug2. The Applicant’s sumatriptan device is pre-filled with the drug. It is a needle based, spring loaded, plunger (piston) drive injector. It is disposable, self injectable, pen shaped and portable, it has a safety cover to limit needle exposure, a click at the beginning of the injection and a second click at the end. The injector has an inspection window for drug delivery confirmation. It also has safety features that prevent accidental firing of the device and needle stick injuries. The device used in the Applicant’s product has been cleared by FDA pursuant to a 510(k) notification (510(k) clearance number K050434), which was based on comparative data submitted to FDA. FDA issued an order finding the device to be substantially equivalent to Owen Mumford Autoject Mini (510(k) Clearance Number: K000482) and eligible to be marketed in United States. A 510(k) is a premarket submission made to FDA to demonstrate that the device to be marketed is at least as safe and effective as, that is, substantially equivalent to, a legally marketed device (21 C.F.R. § 807.81) that is not subject to premarket approval. Submitters are required to compare their device to one or more similar legally marketed devices and to make and to support their substantial equivalency claims. A 510(k) requires demonstration of substantial equivalence to the legally marketed device, which is referred to as the "predicate." Section 513(i) of the FDC Act provides that a device is substantially equivalent in comparison to a predicate if it¯ ¯ has the same intended use as the predicate, and has the same technological characteristics as the predicate; or ¯ has the same intended use as the predicate, and ¯ has different technological characteristics and the information submitted to FDA both; o does not raise new questions of safety and effectiveness; and 1 Nevertheless, the Applicant has performed traditional bioequivalence studies, which it will submit to FDA upon request. 2 The Applicant’s label is similar to the label of the RLD in all aspects, except that, unlike the RLD label, the Applicant’s label does not include instructions on assembly and disassembly of the device. The reason this inlbrmation is excluded is because the Applicant’s device requires no assembly. Thus, the device is actually easier to use because it has fewer instructions for the patient, as compared to the device of the RLD. The remaining steps for the Applicant’s device are similar to those in the RLD device, and hence, the Applicant’s label is in fact similar to the RLD label. demonstrates that the device is at least as safe and effective as the legally marketed device. See also 21 C.F.R. § 807.100(b). In order to demonstrate substantial equivalence, the device sponsor does not need to demonstrate that the new and predicate devices are identical. Instead substantial equivalence is established by showing that even if there are differences, the new device is as safe and effective as the predicate device and specifically that the device "[d]oes not raise different questions of safety and effectiveness than the predicate device." 21 C.F.R. § 807.100(b). The device used in the Applicant’s ANDA product was assessed using the sections and methods specified in ISO 11608:2000 "Pen injectorsJbr medical use - Part I : Pen injectors - Requirements and test methods" as they apply to injection devices with nonreplaceable prefilled cartridges. This ISO standard is an FDA-recognized consensus standard and therefore can be used to support a showing of safety and effectiveness. Activation force, needle extension, injection time, completeness of injection, functionality, and robustness were assessed; the device met all requirements and specifications provided in ISO 11608:2000. The International Standard ISO 11608:2000 relates to requirements and test methods for pen-injectors intended for human use, for evaluating drug products contained in autoinjectors. This ISO standard provides performance requirements regarding essential aspects, so that variations of design are not unnecessarily restricted. Particularly, it includes ¯ When the pen-injector is ready for injection, the cartridge holder shall allow visibility of the deliverable volume. It shall be possible to determine whether sufficient medicinal product remains in order to administer the maximum presettable dose. ¯ The pen-injector shall be designed such that it is able to deliver the labeled volume from the cartridge for which it is designed. ¯ The pen-injector shall indicate the pre-set dose. ¯ The pen-injector shall indicate, at least by visual means, that it is ready for injection. There shall be an indication of the pre-setting procedure by tactile or audible means, or both. ¯ The state of the pen-injector, when ready to deliver a dose, shall be different to its state when the dose has been delivered. The difference shall be visible. ¯ The pen-injector shall indicate, by visual, audible or tactile means or any combination of these, that the injection stroke has been completed. Design and performance features of the autoinjector device used in the ANDA product meets these standards. In addition, the device includes a safety mechanism to prevent inadvertent activation, a needle-cover that extends to cover the used needle, a cutout window on the front assembly to permit inspection of the syringe, locking tabs to prevent disassembly of the autoinjector once the two subassemblies have been connected, and 4 self-disabling after use. The autoinjector device used in the ANDA product is currently marketed in the USA under the trade name SureClickTM. SureClickTM is being used by Amgen fi~r its Aranesp® and Enbrel® products, which have been approved by FDA and for which tens of millions of doses have been delivered to U.S. patients. The Applicant’s device delivers the same amount of drug in the same arnount of time as the reference product. In addition, the Applicant’s product is delivered exactly the same as the brand - by pushing against the body and pressing a blue button. The only differences between the Applicant’s device and the brand device are that ¯ ¯ ¯ The Applicant’s product requires no preassembly of the syringe while the brand does; The Applicant’s product has safety features that prevent accidental firing and needlestick injuries; and The Applicant’s product has a window that shows that the drug has been dispensed, while the brand does not. The window also allows inspection of the injectible solution tbr presence of any particulate matter, prior to injection. The differences in the Applicant’s device make it safer than the brand in that there is less risk of needle stick injury, less risk that the patient will think drug has been dispensed when it has not, and less risk that the patient will accidentally trigger the mechanism. Analysis The Jbundation of the King petition is" that there is" a requirement in the law that the device in a generic combination product must be identical to the device in the brand combination product and that the labeling for the device must also be identical. There is, however, no such requirement in the Federal Food Drug and Cosmetic Act (FDC AcO. This is fortunate because, with respect to the Applicant’s autoinjector product, imposing such a requirement would deprive consumers of both a less expensive generic version of the product and one that is easier and safer to use. 1. The generic drug provisions of the FDC Act do not require the Applicant to use the identical autoinjector in its" combination product. King’s petition provides no statutory or regulatory authority for the proposition that the device portion of a combination product must be identical to the device portion of the reference product. Moreover, FDA has explicitly stated in guidance, that the device portion of a combination product need not be identical to the device portion of the reference listed drug. In a guidance on nasal aerosols and nasal sprays, FDA states that although assurance of bioequivalence is greatest when the generic uses the same brand and model device as the brand, if this is infeasible then FDA recommends that the designs be as close as possible to the critical dimensions of those of the reference. Guidance for Industry, Bioavailability and Bioequivalence Studies for Nasal Aerosols and Nasal Sprays for Local Action (April 2003).3 It is important to note that in the context of nasal aerosols, the design of the device is critical to assuring that the same amount of the drug is being delivered because it affects factors such as droplet size, plume geornetry, and spray pattern. As set forth below, the Applicant has demonstrated that the same amount of sumatriptan is delivered with its autoinjector and King has not even raised much less refuted that fact. King also argues that FDA should issue guidance describing the circumstances under which a drug containing an autoinjector may be approved under an ANDA. King speculates that the absence of FDA guidance on autoinjectors may reflect an internal conclusion by the Agency that the ANDA pathway is not suitable for products containing autoinjectors. There is absolutely no statutory mandate that FDA must issue a guidance before approving a particular combination product and King has no basis for claiming that the absence of a guidance suggests that the Agency has concluded that the ANDA route is not appropriate for the applicant’s product. There is nothing in FDA’s regulations or guidance to imply that this would be FDA’s position. 2. Comparative tests" have demonstrated that the Applicant’s combination product is bioequivalent and has the same perjbrmance as the Imitrex STATDose®. In the 2007 Citizen Petition, King states in Sec 2.1.1 that "an auto-injector should not be approved as pharmaceutically equivalent to another auto-injector, and should not be approved under an ANDA, unless the two auto-injectors are demonstrated to deliver identical amounts of the active ingredients in an identical dispensing time based on comparative performance testing of the auto-injectors." The Applicant performed tests to compare its device with the STATDose® device of Glaxo’s hnitrex injection product for deliverable volume and dispensing time. These tests showed that, pursuant to the standard advocated by King, the autoinjector device used in the Applicant’s product is equivalent to the autoinjector used in the reference product. The Applicant also compared the following with Imitrex STATDose® ¯ ¯ ¯ ¯ ¯ ¯ ¯ ¯ Stability Drop tests results (from 1.5m height, on various surfaces) Excessive force on device test Shield remover removal force Needle cover pre-injection force Actuator button safety force Activation force Injection time Injection depth The Applicant’s autoinjector device is similar to the reference product because 3 In fact, FDA approved a generic fluticasone propionate nasal spray that has a device that has a safety clip feature that is not included in the brand reference product device. ¯ ¯ ¯ ¯ ¯ ¯ ¯ The final delivery steps are same ("Press against the injection site and press the blue button."); The device delivers same volume of drug (0.5 ml); The depth of needle penetration is the same (4-7 mm); The delivery time is similar ( 1-2 seconds); The forces required to operate the device are similar; The colors are similar; and The safety features both products have are the same (although as discussed herein, the Applicant’s product has additional safety features). As stated above, the Applicant has also complied with FDA’s bioequivalence requirements by demonstrating that its sumatriptan succinate injection product is both qualitatively and quantitatively similar to that of the GSK product. This showing of performance equivalence of the device used in the Applicant’s product is sufficient to establish that the device is at least as safe as the device of the reference product. An ANDA pathway requires that the ANDA product meets the "sameness" criteria, and hence data establishing performance equivalence of the devices is sufficient to meet this "sameness" requirement. The Applicant has demonstrated that its device and Glaxo’s device do not differ in releasing the drug into the systemic circulation of the patient. The delivery of the drug to the patient is comparable, both in terms of volume delivered and in terms of the bioavailability of the drug, because the Applicant has demonstrated that sumatriptan injection and Imitrex STATDose® are bioequivalent. King’s own experience with an epinephrine autoinjector products supports approval of the Applicant’s ANDA. Prior to the time it was available in an autoinjector product, epinephrine was available in ampuls. King obtained approval for the Epipen autoinjector on the basis of an application that did not contain any preclinical, clinical or bioequivalence studies. Similarly, Twinject, another epinephrine autoinjector product, was approved without any such studies. King’s argument that clinical studies must be required in order to resolve safety issues raised by the Applicant’s product is entirely inconsistent with its application for the Epipen and with the Agency’s approval of that application. In section 2.1.2 of the 2007 Citizen Petition, King states that "FDA should establish new auto-injector dosage forms that distinguish among auto-injectors with significant differences in administration and physical appearance as well as distinguish autoinjectors from other injectable dosage forms." King further states that "differences among auto-injector release mechanisms would satisfy criteria under 21 C.F.R. § 314.127(a)(8) for refusing to approve an ANDA because ’there is a reasonable basis to conclude that one or more of the inactive ingredients of the proposed drug or its composition raises serious questions of safety or efficacy’" King cites 21 C.F.R. § 314.127(a)(8)(ii)(A)(2),(3), (5), and (6) and FDA’s Abbreviated New Drug Applications regulations at 57 Fed. Reg. 17950, 17969 (Apr 28, 1992), to argue that changes in release mechanism are comparable to other changes in inactive ingredients for the purpose of 21 C.F.R. § 314.127(a)(8). The obvious response to King’s argument is that the autoinjector component of the Applicant’s product is not an inactive ingredient, and there is nothing in the statute or regulations to suggest that it is. But even if the autoinjector component were somehow considered to be an inactive ingredient, then the applicant has met all the requirement of the statute and regulations. For example, section 505(j)(4)(H) of the FDC Act provides that one basis for disapproving an ANDA is "information [which] shows that.., the inactive ingredients of the drug axe unsafe." Of course, if the information provided to FDA shows that the inactive ingredients are safe, as is the case here, then FDA must approve the generic product. The FDA regulations and Federal Register notice cited by King are entirely consistent with the statute. Thus, 21 C.F.R.§ 314.127(a)(ii)(A) identifies situations where the inactive ingredient will be found to be unsafe, including where the inactive ingredient "does not comply with an official compendium," "a change in composition to include an inactive ingredient that has not been previously approved in a drug product for human use by the same route of administration," changes to include inactive ingredients that have not been previously approved in the dosage form proposed by the ANDA applicant or the use of inactive ingredients at levels not previously approved or in a way that might increase absorption of toxic ingredients, and the "use of a delivery or modified delivery mechanism never before approved for the drug." The Federal Register preamble cited by King restates some of these same criteria. Although one would have to stretch beyond recognition the meaning of inactive ingredient to include an autoinjector device, the principles in the regulation on which King relies support approval of the Applicant’s ANDA. In contrast to the situations identified in the regulations, which would be the basis for a safety concern, the device component in the Applicant’s product has previously been approved by FDA and it will deliver the active drug to the body at the same rate as the reference listed drug. Thus if King were correct that the autoinjector is an inactive ingredient, then under King’s argument the mere fact that the Applicant’s autoinjector has minor differences from the device component of the RLD would not be a basis for denying the ANDA. In Sec 2.3 of the 2007 citizen petition, King states that an in-vivo bioequivalence waiver should apply to drug products containing auto-injectors only in the presence of "other data" in the form of comparative performance testing. According to King, such testing should show that the auto-injector used in a proposed drug product will (i) deliver the same amount of drug (ii) to the same area (iii) in the same amount of time (iv) with the same force (v) under similar conditions. King, for once, cites an applicable requirement, which is in line with requirements set forth in the ISO 11608:2000 standard and used by the FDA to clear 510(k) premarket notifications. Where the ANDA applicant can establish performance equivalence to the device of the reference product, the ANDA 8 product may be approved without the requirements of clinical testing, particularly if the drug contained in the autoinjector device is a parenteral solution that is qualitatively and quantitatively similar to that contained in the reference product. 3. Requiring the Applicant to use the identical autoinjector would be requiring use of an autoinjector that does not meet ISO standards" that FDA has" recognized, is more difficult to use than Sun % injector, and lacks" certain saJ~ty features. Section 514(c) of the FDC Act gives manufacturers explicit authority to use FDArecognized standards to meet the requirements of the act.4 It directs FDA to recognize national and international standards by publication in the Federal Register and allows manufacturers, if they elect to conform to any of these standards, to submit a declaration of conformity to FDA or a statement of conformity to FDA. When FDA cleared the autoinjector included in the Applicant’s combination product, it relied on such a recognized ISO standard. If FDA were to accept King’s argument and require the Applicant to use the autoinjector device in Glaxo’s product, then the device would no longer meet that recognized standard because the autoinjector device used in the reference product, Glaxo’s Imitrex STATDose®, does not meet all of the requirements set forth in the ISO 11608:2000. Specifically, the Glaxo device does not have a cutout window to permit inspection of the syringe prior to injection. Substitution of the autoinjector device of the reference product with the improved autoinjector device ensures that safer and easy-to-use devices are made available to the patient. While we are not suggesting that the failure of the Glaxo device to meet ISO requirements would be a basis for withdrawing the product from the market, FDA’s policy should encourage applicants to improve device products as new materials and techniques become available; it surely should not prohibit the adoption of such improvements which would be the effective result of accepting King’s arguments. The Applicant’s autoinjector device is safer than the autoinjector device in Glaxo’s reference product in other respects as well. The advantages include ¯ ¯ The risk of needle stick injuries and needle phobia is reduced in the device, since the needle is not visible to the user and the needle is never left uncovered (the needle cover automatically locks in its extended position after injection in the device). In the Glaxo device, after the injection, the needle is visible and there is a risk of needle stick injury. The device is a single-use disposable device, and hence eliminates the risk of malfunction that may arise upon multiple-use, as well as the confusion associated with the same. For example, in the Glaxo device there is a risk that user may load the used syringe again. 4 See also, Guidance for Industry and for FDA Staff: Use of Standards in Substantial Equivalence Determinations (March 2000). The device is convenient for the user since it eliminates the preparation and disposal steps associated with the Glaxo device. As a result, the training time, as well as the time required to dispense and administer the injection is significantly less for the device. These improved safety features are a result of the improved design of the Applicant’s autoinjector device. King does not dispute that the patient will benefit from a better device that is equivalent in performance to the device of the reference product. Yet its claim that an ANDA applicant must use an "identical" device, if accepted, would deny the patient the benefits associated with the improved devices. In fact, the Applicant’s autoinjector device is a safer and better alternative to the Glaxo autoinjector device, which falls below current ISO standards. Since a generic combination product is developed much later than the reference product, it should have the benefit of being able to use a newer and improved autoinjector device, which has advantages and conveniences. Accepting King’s petition would freeze technology in place, force generic manufacturers of combination products to copy outmoded device components, and deny patients better alternatives that are a result of research into developing user-friendly, safer, convenient and cost-effective autoinjector devices. 4. The labeling on the autoinjector used in the Applicant % sumatriptan succinate product meets" the FDA-recognized ISO standards" requiring clear instruction of patients and is" consistent with safe use of the product by patients. In Section 1.4 of the 2007 citizen petition, entitled "Substitution of Auto-Injectors is Potentially Unsafe", King argues that patients will not read the labeling of a substituted autoinjector product and will use it improperly. Section 2.2 of the 2007 petition argues that FDA’s labeling regulations do not permit differences in operating instructions or graphic illustrations. As set forth above, FDA has permitted the device portion of a combination device to be different from the reference product. For example, a generic fluticasone nasal spray product was approved although the device used in the generic product is different from that of the reference product in that it has a safety clip, and the label for the generic has illustrations and instructions that are different from the label of the reference product. Thus, FDA does permit differences in the device portion of the labeling to account for these differences. King’s concerns on improper use of the Applicant’s sumatriptan injection are therefore unfounded. In addition, as described below, the Applicant’s inserts meet the ISO standards. Moreover, a pharmacist dispensing the Applicant’s sumatriptan injection would provide demonstration and explanation on the use of the device to the patient, as necessary. These careful instructions by the pharmacist assure 10 that the patient will use the device in the proper manner suggested in the Applicant’s package insert, and thus remove any risks associated with the improper use. The ISO standard applicable to the autoinjector, ISO 11608.2000, requires clear instructions to the patient on how to use the device. Specifically, the standard includes requirements regarding information to be provided by the manufacturer, and states that the pen-injector shall be accompanied by sufficient information to use it safely, taking into account the training and knowledge of the potential users. Section 15.3 of this standard provides requirements related to instructions for use. These requirements relate to instructions to be included in the package insert, and require inclusion of, among others, the following particulars ¯ any warnings and/or precautions to be taken ¯ any risks associated with its normal use ¯ sufficient details of its characteristics to identify the pen-injector and related equipment in order to obtain a safe combination ¯ details on any preparation needed before the pen-injector can be used, e.g. the need to prime before each injection, how to assemble/disassemble the product, replace the cartridge and attach the needle ¯ description of the method of use, e.g. the injection procedure as step-by-step operations ¯ time to wait before removing the needle from the injection site ¯ description of special features ¯ details allowing the medical staff to brief the user on any contraindications and any precautions to be taken. The package insert accompanying the Applicant’s sumatriptan injection provides detailed and pictorial description on use of the device, as required under ISO 11608:2000. The issue raised by King is whether the patient will be given, and can properly receive training when a generic product having a different autoinjector device is dispensed by a healthcare professional or a pharmacist. In the dispensation of medications, the dispensing healthcare professionals are known to exercise due care. In the case of the Applicant’s product, the autoinjector component is already on the market, and thus pharmacists and healthcare professionals will already be familiar with it and how to instruct patients on the products’ use. initial training is provided to the patient to ensure that he or she can use the alternate autoinjector device as required. The patient can also exercise his or her choice for the reference product. However, if the patient is comfortable with the generic product, which has the same performance, and if the patient is comfortable that he or she can learn how to use the generic product, then the patient should not be denied access to a more affordable, safer generic product. As mentioned above, the ISO standard requires that the package insert for the proposed device include instructions for use of the device that may be used by the healthcare professional to provide training to the patient. Hence, the graphic/pictorial illustrations and the written description on the steps to use the device would ensure that the healthcare professional 11 would provide the necessary training, and thereby address any contusion that King alleges may arise. 5. King hasJktiled to show that delay of approval of the Applicant’s ANDA is" necessary to protect the public health. Section 505(q) of the FDC Act provides that FDA shall not delay approval of a pending ANDA application because of any request in a citizen petition to take any form of action relating to the application, either before or during consideration of the request, unless the requested delay is necessary to protect the public health. Because King is effectively arguing that FDA should require the use of an autoinjector that falls below ISO consensus standards and lacks certain safety features, there is no basis to conclude that FDA should delay approval of the Applicant’s ANDA because such delay is necessary to protect the public health. In fact, in the unusual circumstances of the Applicant’s ANDA, such a delay would be inconsistent with the public health. Conclusion Contrary to King’s arguments, nothing in the law requires the autoinjector in the Applicant’s generic combination product to be identical to the reference drug’s autoinjector. In tact, if, as King argues, FDA must require an ANDA applicant to use an autoinjector that is identical to the one used in GSK’s product, it in effect would be requiring use of an autoinjector that does not meet ISO standards that were adopted by Agency. The autoinjector in the Applicant’s product has been cleared by FDA and is safer than the reference drug product’s autoinjector. FDA should promptly deny the King petitions and proceed to approve the Applicant’s ANDA. In any event, FDA should reach a decision within 180 days of January 29, 2009, the date King filed its citizens petition, as required by section 505(q) of the FDC Act. Zuckerman Spaeder LLP 12 VERIFICATION STATEMENT UNDER 21 U.S.C. § 355(q)(1)(I) I, Margaret M. Dotzel, certify that, to my best knowledge and belief: (a) I have not intentionally delayed submission of this document or its contents; and (b) the information upon which I have based the action requested herein first became known to me on or about February 10, 2009. If I received or expect to receive payments, including cash and other forms of consideration, fbr the time required to file this information or its contents, I received or expect to receive those payments in the form of standard hourly rates from the tbllowing persons or organizations: Sun Pharmaceutical Industries, Ltd. and its affiliates. I verify under penalty of perjury that the foregoing is true and correct as of the date of the submission of this petition. 13