4. Page 10, lines 6-14. The June 2 draft provides for denial of ANDA approval if the information submitted in the application or other information available to the Secretary shows that the inactive ingredients of the drug are unsafe or the composition of the drug is unsafe due to the type or quantity of inactive ingredients or the manner in which the inactive ingredients are included in the new drug. We had suggested such a revision, but our suggested revision also included, as a ground of denial, the failure of the information submitted to provide sufficient information to establish the safety of the inactive components or the composition of the new drug for its intended uses. Because it is the applicant's obligation to provide the information needed to support ANDA approval, the provision should be revised to provide for denial of ANDA approval if the information submitted is insufficient to show the safety of the inactive ingredients or composition of the product for its intended use. The following revision is suggested: (H) information submitted in the application 5. Page 11, lines 1-5. The June 2 draft continues to provide that the 180 day period for ANDA approval or disapproval runs from the initial receipt of the application. Consistent with the statutory provision for full NDAS, the period should run from the filing of the application, rather than the time of submission. There should be no implication that FDA may not refuse for filing an ANDA that is facially deficient nor should the agency be required to develop different procedures to deal with such problems than those already established for full NDAs. The provision should be revised to read as follows: (4)(A) Within 180 days of the filing of 6. Page 11, line 6 et. seq. The June 2 draft continues to condition the effective date of ANDA approval on the patent information field for pioneer drugs and on the patent status of pioneer drugs. FDA would continue to be required to consider whether an ANDA is the "first application which contains" a certification, to hold application approvals pending applications for preliminary injunction to district courts, to hold the approval of applications pending a request for a reexamination of patentability to the Patent Office, and to hold the approval of subsequent applications until the first application involved in a patent dispute has been marketed for 180 days. As pointed out previously, the provisions which key the effective date of ANDA approval to the patent status of the pioneer product would impose burdensome requirements upon the agency. Although the requirements are not intended to require judgmental determinations by the agency with respect to patent status, the complexisty of the recordkeeping requirements and effective date of ANDA approval provisions will be burdensome and will be inconsistent with the kind of recordkeeping for which the agency is currently responsible. From a pracatical viewpoint, moreover, a successful litigant in a patent suit would learn of a court decision before FDA could be officially notified and could attempt to pressure the agency to issue an approval prior to the official notification. As also pointed out previously, the patent status of the pioneer product would be adequately protected through a notice provision like that already incorporated in the revised bill. See page 5, lines 10-22 (ANDA applicant required to notify patent owner of application which applicant believes does not infringe a valid patent). Notification of the pioneer firm by the applicant, which would precede ANDA approval in every case by six months or more, would enable the pioneer manufacturer to protect its patent rights through judicial remedies and would not require FDA to divert its limited resources to issues that are peripheral to its primary public health protection responsibilities. The complex effective date provisions, which would impose a burdensome requirements on FDA, ovbiously are intended to prevent duplicate product marketing before issues concerning the pioneer's patent status are resolved. Those provisions should be replaced by a provision which prohibits the duplicate applicant from marketing the duplicate product even if it has received ANDA approval -- until the patent issues are resolved. Since the patent issues will already be involved in litigation before the courts, a statutory prohibition on marketing could be easily enforced as part of the litigation. Note that the patent term extension provisions already authorize a court to establish by order the effective date of approval for a duplicate product involved in a patent infringement suit (page 44, line 25 et. seq.). Under such an approach, FDA would be relieved of complex administrative responsibilities and it would be permitted as it is now to act on ANDAS without regard to patent controversies. - 7. Page 20, lines 2-6. The June 2 draft continues to provide for the amendment of section 505(e) to authorize the withdrawal of pioneer NDA approval if the patent information for the pioneer product was not filed "within 30 days after the receipt of written notice from the Secretary specifying the failure to file such information." The agency continues to be concerned that the provision may impose additional burdens on the agency if it contemplates that FDA would be expected to take affirmative action to require pioneer manufacturers to supply information to the agency conerning the patent status of their products. 8. Page 23, line 9 et. seq. The June 2 draft continues to establish effective dates for the approval of paper NDAS based on the applicant's certification of the patent status of the pioneer drug product. Although paper NDAS may be less attractive to generic manufacturers if a post-1962 ANDA procedure were available, the new provisions would impose additional burdens on the agency that could be resolved by a less burdensome procedure, discussed above, which would require notification by the paper NDA applicant to the pioneer NDA holder and a statutory prohibition on market introduction pending the resolution of the pioneer product's patent status. Patent Extension Provisions 9. Page 34, line 17. The June 2 draft continues to require the applicant to submit the Commissioner of Patents a brief description of the applicant's activities during the regulatory review period and the significant dates applicable to such activities. The Commissioner of Patents would be required to send a copy of the application containing the information to the Secretary who would be required within 30 days to determine the applicable regulatory review period. See page 35, lines 9-19. These burdens could be eliminated if the applicant were required to determine the regulatory review period in its application to the Commissioner of Patents. The applications could be made available to the FDA for inspection or audit at FDA's discretion, on the same enforcement basis that other reports, such as income tax filings, are regulated. Since the patent term extension is tacked on to the end of the patent term FDA continues to believe that there is no public health reason to require the agency to determine the regulatory review period under a restrictive 30-day time schedule. The validity of the regulatory review period may be adequately addressed through applicant determination and a discretionary enforcement approach. 10. Page 35, line 20 et. seq. The June 2 draft continues to provide for a due diligence determination to be made by the Secretary if petitioned to do so within 180 days after the publication of the patent extension determination. The June 2 draft, despite our earlier comment, also continues to provide that the authority to make the due diligence determination may not be delegated to an office below the Commissioner of Food and Drugs. FDA had objected that the agency did not have an adequate perspective to make a due diligence determination. This objection was raised with respect to the first draft, which would have permitted the due diligence determination to be made by the FDA organizational component directly responsible for the application. As pointed out previously, the due diligence determination will be even more difficult if the determination may be made only by the Office of the Commissioner. In effect, the revised bill would require a de novo review by personnel who have not had any prior familiarity with the application or with the problems associated with the development of the product or its investigation and approval. Since patent term extension is subject to a 14 year cap, counts only 1/2 of the investigational period, and is limited to a 5 year extension in any event, it continues to be FDA's view that a requirement for a de novo due diligence determination would clearly impose a burdensome resource requirements on the agency with little, if any, public benefit in the earlier availability of generic drug products. In FDA's experience, based on the latest year for which calculations were made, the average new chemical entity gaining NDA approval would have been entitled, under the proposed formula, to the maximum 5 years of patent term restoration (based only on review time). Assuming that the average application was pursued with diligence, it would seem unlikely that the 5 year maximum extension would ever be reduced for lack of due diligence. Nonetheless, FDA will have been required to promulgate regulations, review petitions, and prepare due diligence determinations. As a practical matter, therefore, it appears that a complex system is being established that will require FDA resources to implement and maintain for no public benefit. 11. Page 36, line 8 et. seq. The due diligence determination is required to be published in the FEDERAL REGISTER with a statement of the factual and legal basis for the determination. The June 2 draft still provides that any interested person may require the Secretary to hold an informal hearing on the determination. The owner of the patent involved is entitled to notice and may participate in the hearing. The Secretary is provided only 30 days after the completion of the hearing to affirm or revise the determination of due diligence. There is no provision that would limit judicial review. See page 36, line 20 et. seq. The FDA continues to regard the due diligence provision as imposing unnecessary and burdensome requirements on the agency. While the petition requirement may limit the number of determinations, the procedural restrictions imposed on the agency would provide no public health benefit and may divert scarce resources from more important matters, especially the review of other new drugs. In view of the limitations associated with patent term restoration, as noted above, the due diligence provision should be deleted on the ground that it will provide no public health benefit. |