Janssen T. October 31, 2016

Transcription

1 Docket No. FDA-2011-P /CP Janssen Research & Development, LLC Trenton-Harbourton Road, P.O. Box 200 Titusville, NJ Janssen T October 31, 2016 Division of Dockets Management (HF A 305) Food and Drug Administration Department of Health and Human Services 5630 Fishers Lane, Room 1061 Rockville, MD Re: Fourth Supplement to Citizen Petition, Docket No. FDA-2011-P /CP Dear Sir or Madam: As you are aware, Janssen Research & Development, LLC ("Janssen" or "the Company"), a company of Johnson & Johnson, 1 has made numerous attempts to engage the U.S. Food and Drug Administration ("FDA") on the complex issues associated with demonstrating bioequivalence of risperidone long-acting injection, including through the submission of a Citizen Petition (Docket No. FDA-2011-P /CP) and comments to various iterations of FDA's "BioequivalenceRecornrnendations for Risperidone; Draft Guidance for Industry" (the "Draft Bioequivalence Guidance"). 2 1 Janssen is the authorized regulatory agent for Janssen Pharmaceuticals, Inc. ("JPI"). JPI is the holder of the New Drug Application ("NDA'') for RIPSERDAL CONSTA (risperidone) Long-Acting Injection. The former holder of the NDA, Ortho-McNeil-Janssen Pharmaceuticals, Inc., was renamed JPI. Janssen was formerly named Johnson & Johnson Pharmaceutical Research & Development, L.L.C. ("J&JPRD"). 2 FDA issued the first version of the Draft Bioequivalence Guidance in February 2010 (Docket No. FDA-2007-D- 0369), and Janssen submitted comments to the docket in September of In February 2011, the Company submitted a Citizen Petition requesting that FDA implement certain additional pharmacokinetic ("PK") standards when measuring the bioequivalence of any potential follow-on versions of RISPERDAL CONSTA (risperidone) (Docket No. FDA-2011-P /CP). In August 2013, FDA released a revised Draft Bioequivalence Guidance, which did not address all of the concerns the Company had raised in prior comments to the docket or in the Citizen Petition. Accordingly, Janssen submitted comments to the docket in October 2013 and subsequently cross-filed those comments in a supplement to the Citizen Petition in December In May 2015, FDA issued a further revised Draft Guidance that again failed to address all of the concerns previously described by the Company. As a result, in July 2015, Janssen submitted to the docket another set of comments regarding FDA's proposed methodology for determining bioequivalence and cross-filed those comments in a second supplement to the Citizen Petition. Finally, in February 2016, Janssen submitted a third supplement to the Citizen Petition, which discussed _7

2 To date, FDA has neither responded to Janssen's submi~sions referenced in this letter nor adopted the recommendations conveyed therein. Most recently, we submitted comments to the version of the Draft Bioequivalence Guidance that FDA issued in August 2016 (Docket No. FDA-2007-D-0369). We hereby request that those comments, which are attached hereto, be considered a fourth supplement to the Citizen Petition. The undersigned makes the following verification for this submission, as required by 21 U.S.C.. 355(q)(1)(1): I 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 August 30, 2016, the date FDA released the Draft Bioequivalence Guidance. If I received or expect to receive payments, including cash and other forms of consideration, to file this information or its contents, I received or expect to receive those payments from the following persons or organizations: N/ A. I verify under penalty of perjury that the foregoing is true and conect of the date of the submission of this petition. Sincerely, Joseph Massarella, PhD Scientific Director, Clinical Phrumacology cc: Mitchell V. Mathis, M.D., CAPT., USPHS, Director, FDA Division of Psychiatry Products, Office of Drug Evaluation I, Office of New Drugs, CDER Ann Sohn, Pharm.D., LCDR, USPHS, Regulatory Project Manager, FDA Division of Psychiatry Products, Office of Drug Evaluation I, Office ofnew Drugs, CDER the concerns associated with demonstrating bioequivalence to RlSPERDAL CONSTA as applied to L Y003004, an intramuscular risperidone injectable product developed byluye Pharma Group Ltd _7-2-

3 Docket No. FDA-2007-D-0369 Janssen Research & Development, LLC Trenton-Harbourton Road, P.O. Box 200 Titusville, NJ "-- Janssen T PHARMAC"E.lJTl-c'.AL cor,'lp.anies OF 9of'l",fol"OU-4ffofnt.W1l October 31, 2016 RLD Application Number: NDA Division of Dockets Management (HFA 305) Food and Drug Administration Department of Health and Human Services 5630 Fishers Lane, Room 1061 Rockville, MD c Re: Docket No. FDA-2007-D-0369: Bioequivalence Recommendations for Risperidone; Draft Guidance for Industry, Revised August 2016 Dear Sir or Madam: On behalf of Janssen Research & Development, LLC ("Janssen" or "the Company"), a company of Johnson & Johnson, 1 we are providing the following comments in response to the Food and Drug Administration ("FDA") guidance entitled, "Bioequivalence Recommendations for Risperidone; Draft Guidance for Industry," as revised in August 2016 (the "Draft Bioequivalence Guidance"). Janssen has made numerous attempts to engage FDA on the significant issues associated with demonstrating bioequivalence of any potential follow-on versions of RISPERDAL CONSTA (risperidone). 2 RISPERDAL CONSTA has a complex pharmacokinetic("pk") profile, 1 Janssen is the authorized regulatory agent for Janssen Pharmaceuticals, Inc. ("JPI''). JPI is the holder of the New Drug Application ("NDA'') for RISPERDAL CONSTA (risperidone) Long-Acting Injection. The former holder of the NDA, Ortho-McNeil-Janssen Pharmaceuticals, Inc., was renamed JPI. Janssen was formerly named Johnson & Johnson Pharmaceutical Research & Development, L.L.C. ("J&JPRD"). 2 FDA issued the first version of the Draft B ioequivalence Guidance in February 2010 (Docket No. FDA-2007-D- 0369), and Janssen submitted comments to the docket in September of In February 2011, the Company submitted a Citizen Petition requesting that FDA implement certain additional pharmacokinetic standards when measuring the bioequivalence of any potential follow-on versions ofrisperdal CONSTA (risperidone) (Docket No. FDA-2011-P /CP). In August 2013, FDA released a revised Draft Bioequivalence Guidance, which did not address all of the concerns the Company had raised in prior comments to the docket or in the Citizen Petition. Accordingly, Janssen submitted comments to the docket in October 2013 and subsequently cross-filt;d those comments in a supplement to the Citizen Petition in December In May 2015, FDA issued a further revised Draft Guidance that again fitiled to address all of the concerns previously described by the Company. As a result, in July 2015, Janssen submitted to the docket another set of comments regarding FDA's proposed

4 which causes the drug to be released in three distinct phases: (i) an initial release phase ( <1% of the dose) following injection, (ii) a 3-week lag.phase, and (iii) a main release phase. As fully described in our prior submissions, to avoid potentially significant safety and efficacy issues associated with de novo treatment with a follow-on product or in a product-switching scenario, it is essential that FDA's methodology for determining bioequivalence adequately evaluate and control for all three release phases of RISPERDAL CONSTA. If patients are treated with a follow-on product that releases an excessive amount of risperidone during the initial release phase (known as dose dumping), patients may experience significant dose-related adverse effects. Similarly, a follow-on product that releases risperidone too early (i.e., accelerated main release after a shortened lag phase) may expose patients to excessive risks. To assure bioequivalence of any follow-on product to RISPERDAL CONSTA, Janssen requested in its Citizen Petition that FDA require applicants to conduct, at a minimum, a 2- strength single dose study that, in addition to the traditional bioequivalence metrics of Crnax, AUCo-t. and AUC 0 _oo, utilizes the following PK metrics to evaluate bioequivalence: 1) pauc 0 _24h: to ensure that the early systematic exposure due to the initial release of risperidone immediately following injection does not exceed that of RISPERDAL CONSTA ; 2) pauc 0 _24d: to ensure that any follow-on product does not release an excessive amount of drug during the expected lag phase; and 3) pauc 24 d-t: to ensure that any follow-on product does not release a substantially lower amount of drug during the expected main release phase. Janssen has also repeatedly requested that FDA consider specific revisions to prior iterations of the Draft Bioequivalence Guidance in the event the agency chose not to adopt the approach proposed in the Citizen Petition. To date, FDA has neither responded to the Company's various submissions nor adopted the recommendations conveyed therein. Indeed, after evaluation of the recently released 2016 Draft Bioequivalence Guidance, Janssen continues to believe that FDA's proposed methodology does not adequately evaluate the safety and efficacy issues surrounding the release of risperidone and may pose a potential public health risk. The Company has previously described in considerable detail its concerns with FDA's approach and will not repeat them in full here. Rather, Janssen incorporates by reference all of the prior submissions referenced in this letter, and requests that FDA reconsider the Draft Bioequivalence Guidance in light of Janssen's prior comments to this docket and the Citizen Petition and supplements thereto. 3 Thank you for the opportunity to review and comment on the Draft Bioequivalence Guidance. The Company also plans to submit a fourth supplement to the Citizen Petition to raise these methodology for determining bioequivalence and cross-filed those comments in a second supplement to the Citizen Petition. Finally, in February 2016, Janssen submitted a third supplement to the Citizen Petition, which discussed the concerns associated with demonstrating bioequivalence to RISPERDAL CONSTA as applied to LY003004, an intramuscular risperidone injectable product developed by Luye Pharma Group Ltd. 3 In addition to proposing detailed recommendations for FDA to consider in selecting an appropriate methodology for determining bioequivalence of a follow-on risperidone product, note that we have also previously requested that the Center for Drug Evaluation and Research Division of Psychiatry Products and the Office of Clinical Pharmacology be consulted in reviewing the Draft Bioequivalence Guidance and our prior submissions. -2-

5 concerns. Should you have any questions or comments, please contact me directly at Sincerely, James Tan, Ph.D. Global Regulatory Leader cc: Mitchell V. Mathis, M.D., CAPT., USPHS, Director, FDA Division of Psychiatry Products, Office of Drug Evaluation I, Office of New Drugs, CDER Ann Sohn, Pharm.D., LCDR, USPHS, Regulatory Project Manager, FDA Division of Psychiatry Products, Office of Drug Evaluation I, Office of New Drugs, CDER -3-