~'u"'"'•
`
`( ~ DEPARTMENTOFHEALTHANDHUMANSERVICES
`'~~~
`...... ~
`
`BLA 125427/0
`
`Genentech, Inc.
`Attention: Erica J. Evans, Ph.D.
`Regulat01y Program Management
`1 DNA Way
`South San Francisco, CA 94080-4990
`
`Dear Dr. Evans:
`
`Food and Drug Administration
`Silver Spring MD 20993
`
`BLA APPROVAL
`
`Please refer to your Biologics License Application (BLA) dated August 24, 2012, received
`August 27, 2012, submitted under section 351(a) of the Public Health Service Act for Kadcyla
`(ado-trastuzumab emtansine).
`
`We acknowledge receipt of your amendments dated June 12, and 25; July 11 and 31; August 24,
`and 27; September 12, 18(2), 21 , 25(2), 26(2), and 28(2); October 8(2), 9(2), 11(2), 17(2), 18(2),
`23(2), 24, 25, 29, 30, and 31; November 1, 2(3), 5, 6, 8(2), 12(3), 13(3), 14(2), 16, 20(2), 26, and
`30(2); December 5(2), 6, 7(6), 13, 14, 19, 20, 21(2) and Janua1y 2, 3, 4, 7, 11, 15(2), 17(2), 18,
`22, 23, 24,(3), 25(3), 28(2), 30(2) and Febma1y 5, 6, 7, 8, 12, and 15, 2013.
`
`LICENSING
`
`We have approved your BLA for Kadcyla (ado-trastuzumab emtansine) effective this date. You
`are hereby authorized to introduce or deliver for introduction into interstate commerce, Kadcyla
`(ado-trastuzumab emtansine) lmder your existing Depmi ment of Health and Human Services
`U.S. License No. 1048. Kadcyla (ado-trastuzumab emtansine) is indicated, as a single agent, for
`the treatment of patients with HER2-positive, metastatic breast cancer who previously received
`trastuzumab and a taxane, sepm·ately or in combination.
`
`MANUFACTURING LOCATIONS
`
`Under this license, you m·e aQ roved to manufacture ado-trastuzumab emtansine bulk
`41
`dmg substance at
`, and ado-trastuzumab emtansine fmal
`(b)C
`(bH~Y. Drug product labeling and packaging
`dmg product at
`will be done at Genentech Hillsboro FilfFiiiish Facifity m Hillsboro, Oregon.
`
`You may label your product with the proprieta1y name, Kadcyla, and will market it as a
`lyophilized product in two single-use presentations of 100 mg per 15 mL vial and 160 mg per
`20 mL vial.
`
`Reference ID: 3265306
`
`IMMUNOGEN 2181, pg. 1
`Phigenix v. Immunogen
`IPR2014-00676
`
`

`
`BLA 125427/0
`Page2
`
`Trastuzumab intennediate will be manufactured at Genentech, Inc., Vacaville, CA and Roche
`Sin~ore Technical Qperations Pte. Ltd, Sing2£ore. DMI intetmediate will be manufactured at
`(b) (45.
`
`DATING PERIOD
`
`The dating period for ado-trastuzumab emtansine dmg product (160 mg/vial) shall be 36 months
`from the date of manufacture when stored at 2°C to soc. The dating period for ado-trastuzmnab
`emtansine dmg product (I 00 mg/vial) shall be 24 months from the date of manufacture when
`stored at 2°C to S°C. The date of manufacture shall be defined as the date of
`(b) <-11
`the formulated dmg_P.roduct. The dating period for your trastuzumab intetmediate
`(b}(4~ The dating_.period for your ado-trastuzumab emtansine
`
`drug substance shall be
`
`(bl <4l
`
`We have approved the stability protocols in your license application for the purpose of
`extending the expiration dating period of the dmg substance and dmg product under
`21 CFR 601.12. Data supp01ting extension of the expiration dating period should be
`submitted to the BLA Annual Rep011.
`
`Consistent with 21 CFR 601.12, Genentech must inf01m FDA about each change in the
`product, production process, quality controls, equipment, facilities, responsible personnel,
`or labeling established in the approved application.
`
`FDA LOT RELEASE
`
`You are not cunently required to submit samples of future lots of ado-trastuzumab emtansine to
`the Center for Dmg Evaluation and Research (CDER) for release by the Director, CDER, under
`21 CFR 610.2. We will continue to monitor compliance with 21 CFR 610.1, requiring
`completion of tests for conf01mity with standards applicable to each product prior to release of
`each lot.
`
`Any changes in the manufacturing, testing, packaging, or labeling ofKadcyla (ado-trastuzumab
`emtansine ), or in the manufacturing facilities, will require the submission of inf01mation to your
`biologics license application for our review and written approval, consistent with
`21 CFR 601.12.
`
`APPROVAL & LABELING
`We have completed our review of this application, as amended. It is approved, effective on the
`date of this letter, for use as recommended in the enclosed agreed-upon labeling text.
`
`We note that your Febmaty 13, 2013, submission includes fmal printed labeling (FPL) for your
`package insert. We have not reviewed this FPL. You are responsible for assuring that the
`wording in this printed labeling is identical to that of the approved content of labeling in the
`structured product labeling (SPL) f01mat.
`
`Reference ID: 3265306
`
`IMMUNOGEN 2181, pg. 2
`Phigenix v. Immunogen
`IPR2014-00676
`
`

`
`BLA 125427/0
`Page 3
`
`
`
`CONTENT OF LABELING
`
`As soon as possible, but no later than 14 days from the date of this letter, submit, via the FDA
`automated drug registration and listing system (eLIST), the content of labeling [21 601.14(b)] in
`structured product labeling (SPL) format, as described at
`http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm.
`Content of labeling must be identical to the enclosed labeling (text for the package insert, text for
`the patient package insert, Medication Guide). Information on submitting SPL files using eLIST
`may be found in the guidance for industry titled “SPL Standard for Content of Labeling
`Technical Qs and As” at
`http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/U
`CM072392.pdf.
`
`The SPL will be accessible via publicly available labeling repositories.
`
`In addition, within 14 days of the date of this letter, amend any pending supplement that includes
`labeling changes for this BLA with content of labeling in SPL format to include the changes
`approved in this supplement.
`
`CARTON AND IMMEDIATE CONTAINER LABELS
`
`We acknowledge your January 30, 2013, submission containing final printed carton and
`container labels.
`
`ADVISORY COMMITTEE
`
`Your application for Kadcyla (ado-trastuzumab emtansine) was not referred to an FDA advisory
`committee because outside expertise was not necessary; there were no controversial issues that
`would benefit from advisory committee discussion.
`
`REQUIRED PEDIATRIC ASSESSMENTS
`
`Under the Pediatric Research Equity Act (PREA) (21 U.S.C. 355c), all applications for new
`active ingredients, new indications, new dosage forms, new dosing regimens, or new routes of
`administration are required to contain an assessment of the safety and effectiveness of the
`product for the claimed indication(s) in pediatric patients unless this requirement is waived,
`deferred, or inapplicable.
`
`We are waiving the pediatric study requirement for this application because necessary studies are
`impossible or highly impracticable. Breast cancer is on the list of conditions that do not occur in
`pediatric patients and qualify for a full waiver.
`
`Reference ID: 3265306
`
`IMMUNOGEN 2181, pg. 3
`Phigenix v. Immunogen
`IPR2014-00676
`
`

`
`BLA 125427/0
`Page4
`
`POSTMARKETING REQUIREMENTS UNDER 505(o)
`
`Section 505(o)(3) of the Federal Food, Dmg, and Cosmetic Act (FDCA) authorizes FDA to
`require holders of approved dmg and biological product applications to conduct postmarketing
`studies and clinical trials for certain pmposes, if FDA makes ce1tain findings required by the
`statute.
`
`We have determined that an analysis of spontaneous postmarketing adverse events rep01ted
`under subsection 505(k)(1) of the FDCA will not be sufficient to assess signals of serious risks of
`emb1yo-fetal toxicity and of increased toxicity due to a variable antibody dmg ratio and to
`41
`identi unexpected serious risks of increased toxicity due to
`(b)(
`
`Furthe1more, the new phannacovigilance system that FDA is required to establish lmder section
`505(k)(3) of the FDCA will not be sufficient to assess this serious risk.
`
`Therefore, based on appropriate scientific data, FDA has dete1mined that you are required to
`conduct the following:
`
`1. Establish a Pregnancy Regist:Iy to collect and analyze inf01mation for 10 years on pregnancy
`complications and bnth outcomes in women with breast cancer exposed to ado-u·astuzumab(cid:173)
`emtansine within 6 months of conception or during pregnancy. Submit yearly interim rep01ts,
`which may be included in your annual rep01ts, on the cumulative findings and analyses from
`the Pregnancy Regist:Iy.
`
`The timetable you submitted on Febmmy 15, 2013, states that you will conduct this study
`according to the following schedule:
`
`Draft Protocol Submission:
`Final Protocol Submission:
`Interiin Report # 1 :
`Interiin Rep01i #2:
`Interiin Rep01i #3:
`Interiin Report #4:
`Interiin Report #5:
`Interiin Report #6:
`Interiin Rep01i #7:
`Interiin Rep01i #8:
`Interiin Report #9:
`Study Completion:
`Final Rep01i Submission:
`
`03/13
`05/13
`05/14
`05/15
`05/16
`05/17
`05/18
`05/19
`05/20
`05/21
`05/22
`05/23
`05/24
`
`Reference ID: 3265306
`
`IMMUNOGEN 2181, pg. 4
`Phigenix v. Immunogen
`IPR2014-00676
`
`

`
`BLA 125427/0
`Page 5
`
`2. Perf01m a multivariate characterization study to supp01i the implementation of a
`
`during manufacture ofT-
`~~----------------------------------------~
`DMI.
`
`The timetable you submitted on Febmmy 15, 2013, states that you will conduct this study
`according to the following schedule:
`
`Final Protocol Submission:
`Study Completion:
`Final Rep01i Submission:
`
`03/13
`05/13
`06/13
`
`(b) c41method to use as a dm~bstance and dm g product
`3. Develop and validate an
`41 content and propose a
`regulat01y method for monitorin the
`4 content based on clinical and commercial
`specification limit for the
`batch data.
`
`(b)(
`
`(b)(
`
`The timetable you submitted on Febmmy 15, 2013, states that you will conduct this study
`according to the following schedule:
`
`Final Protocol Submission:
`Study Completion:
`Final Rep01i Submission:
`
`05/13
`11113
`12/ 13
`
`4. Provide qumterly rep01is on the status of an
`
`r - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - ,(b}(4l
`
`These rep01is should include, at a minimum, a sUIIllnmy of the root cause analyses,
`---·.•
`associated con ective actions, and disposition of all affected DM1 batches. Also, provide the
`disposition of any potentially affected finished product batches using these affected DM1
`batches. Submit an interim rep01i documenting that the manufacturing processes have been
`appropriately controlled at the manufacturing facilities according to Genentech 's evaluation.
`The interim rep01t should include a request for follow-up ins ection~. Submit a final rep01t
`41 issues during the
`with a statement conceming the follow-up perf01m ed on the
`(b)(
`course of the FDA inspection(s), an update on whether there have been any further instances
`41 managed by each site 's
` and a proposal to prevent
`o
`(b)(
`(bJC
`quality system.
`
`4\
`
`The timetable you submitted on Febmmy 15, 2013, states that you will conduct this study
`according to the following schedule:
`
`Qumierly Rep01i # 1 :
`Qumierly Rep01i #2:
`Qumierly Rep01i #3:
`Qumierly Rep01i #4:
`Interim Report:
`
`05/13
`08/13
`11113
`02/14
`04/14
`
`Reference ID: 3265306
`
`IMMUNOGEN 2181, pg. 5
`Phigenix v. Immunogen
`IPR2014-00676
`
`

`
`BLA 125427/0
`Page 6
`
`
`
`Quarterly Report #5: 05/14
`Quarterly Report #6: 08/14
`Quarterly Report #7: 11/14
`Quarterly Report #8: 02/15
`Final Report Submission: 04/15
`
`Finally, we have determined that only a clinical trial (rather than a nonclinical or observational
`study) will be sufficient to assess a signal of a serious risk of increased toxicity in patients with
`hepatic impairment.
`
`Therefore, based on appropriate scientific data, FDA has determined that you are required to
`conduct the following:
`
`5. Conduct a clinical trial to evaluate the impact of hepatic impairment on the pharmacokinetics
`of Kadcyla (ado-trastuzumab emtansine), total trastuzumab, and DM1-containing catabolites.
`Based on the results of this trial, update the approved Kadcyla labeling with
`recommendations for appropriate use of Kadcyla in patients with hepatic impairment.
`
`The timetable you submitted on February 15, 2013, states that you will conduct this trial
`according to the following schedule:
`
`
`Trial Completion:
`Final Report Submission:
`
`Submit the protocol(s) to your IND 071072, with a cross-reference letter to this BLA. Submit all
`final report(s) to your BLA. Prominently identify the submission with the following wording in
`bold capital letters at the top of the first page of the submission, as appropriate: “Required
`Postmarketing Protocol Under 505(o)”, “Required Postmarketing Final Report Under
`505(o)”, “Required Postmarketing Correspondence Under 505(o)”.
`
`Section 505(o)(3)(E)(ii) of the FDCA requires you to report periodically on the status of any
`study or clinical trial required under this section. This section also requires you to periodically
`report to FDA on the status of any study or clinical trial otherwise undertaken to investigate a
`safety issue. Section 506B of the FDCA, as well as 21 CFR 601.70 requires you to report
`annually on the status of any postmarketing commitments or required studies or clinical trials.
`
`FDA will consider the submission of your annual report under section 506B and 21 CFR 601.70
`to satisfy the periodic reporting requirement under section 505(o)(3)(E)(ii) provided that you
`include the elements listed in 505(o) and 21 CFR 601.70. We remind you that to comply with
`505(o), your annual report must also include a report on the status of any study or clinical trial
`otherwise undertaken to investigate a safety issue. Failure to submit an annual report for studies
`or clinical trials required under 505(o) on the date required will be considered a violation of
`FDCA section 505(o)(3)(E)(ii) and could result in enforcement action.
`
`
`06/14
`06/15
`
`Reference ID: 3265306
`
`IMMUNOGEN 2181, pg. 6
`Phigenix v. Immunogen
`IPR2014-00676
`
`

`
`BLA 125427/0
`Page 7
`
`POSTMARKETING COMMITMENTS NOT SUBJECT TO THE REPORTING
`REQUIREMENTS UNDER SECTION 506B
`
`We remind you of your postmarketing commitments:
`
`6. Transfer the methodology for validated dye ingress testing developed by Genentech to
`Conduct a study to confmn filling and crimping conditions for container closure integrity
`using the validated u·ansfened dye ingress method and provide a fmal rep01i in the 2014
`annual rep01i.
`
`The timetable you submitted on Febmmy 15, 2013, states that you will conduct this study
`according to the following schedule:
`
`Study Completion:
`Final Rep01i Submission:
`
`03/13
`04/14
`
`7. Conduct a study to assess the risk of, . . . - - - - - - - - - - - - - - - - - .(b>C41
`usm&__~~~~----~~---~- ~~--~~-~-~.--.---,~-,---0 .--~----~
`the lyophilization process. Submit a fmal rep01i that includes updated specifications as a
`Prior Approval Supplement.
`
`(b) (4)
`
`The timetable you submitted on Febmmy 15, 2013, states that you will conduct this study
`according to the following schedule:
`
`Final Rep01i Submission:
`
`03/13
`
`(b)(4~ is observed in the dmg product after lyophilization, develop an
`8. If
`altemative method to quantitate
`(bJC4l in the fmished ado-u·astuzumab emtansine dmg
`product after lyophilization using routine production conditions. Submit a fmal rep01i on any
`changes in the analytical methods as a Prior Approval Supplement.
`
`The timetable you submitted on Febmmy 15, 2013, states that you will conduct this study
`according to the following schedule:
`
`Final Protocol Submission: 09/13
`Final Rep01i Submission:
`12113
`
`4
`J for ado-u·astuzumab emtansine dmg product manufacture
`9. Dedicate
`(bJT
`
`(bH4Y validation and 3 media fill
`and submit a fmal rep01i of the results from
`simulations as a Changes Being Effected Supp ement [CBE-0).
`
`The timetable you submitted on Febmmy 15, 2013, states that you will conduct this study
`according to the following schedule:
`
`Final Rep01i Submission:
`
`06/13
`
`Reference ID: 3265306
`
`IMMUNOGEN 2181, pg. 7
`Phigenix v. Immunogen
`IPR2014-00676
`
`

`
`BLA 125427/0
`Page8
`
`10. Conduct cleaning verification after each change-over prior to manufacture of
`(b)(41 is implemented and rep01i the
`ado-trastuzumab emtansine until use of
`updated change-over procedures in the 2014 Annuaf RepOii.
`
`The timetable you submitted on Febmmy 15, 2013, states that you will conduct this study
`according to the following schedule:
`
`Study completion:
`Final Rep01i Submission:
`
`06/13
`04/14
`
`11. Conduct r----------------------------,(bn~l
`
`The timetable you submitted on Febmmy 15, 2013, states that you will conduct this study
`according to the following schedule:
`
`Final Rep01i Submission:
`
`05/13
`
`12. Develop a validated, sensitive, and accurate assay for the detection ofneutmlizing antibodies
`to ado-trastuzumab emtansine, including procedures for accurate detection of neutmlizing
`antibodies to ado-tmstuzumab emtansine in the presence of ado-tmstuzmnab emtansine levels
`that are expected to be present in the sennn or plasma at the time of patient sampling. The
`assay final rep01i will be submitted as a Prior Approval Supplement by Jlme, 2015.
`The timetable you submitted on Febmmy 15, 2013, states that you will conduct this study
`according to the following schedule:
`
`Final Rep01i Submission (Assay and Methodology) Date: 06/15
`
`13. Reassess release and stability specifications for ado-tmstuzmnab emtansine dmg substance
`and dmg product through the end ofFebmmy 2015. Submit the final rep01i as a Changes
`Being Effected-30 Supplement (CBE-30).
`
`The timetable you submitted on Febmmy 15, 2013, states that you will conduct this study
`according to the following schedule:
`
`Final Rep01i Submission: 05/15
`
`14. Provide a material compatibility assessment r---------------~(0> <4>
`
`Reference ID: 3265306
`
`IMMUNOGEN 2181, pg. 8
`Phigenix v. Immunogen
`IPR2014-00676
`
`

`
`BLA 125427/0
`Page 9
`
`r---------------------------------.(b)(41
`
`Provide a
`~--~-~~-~-~~·~---~--~~~-
`toxicological risk assessment of the safety of the leachables that could be present in the DM 1
`inte1mediate. If significant leachables are identified during these assessments, initiate action
`to Initigate the source(s) of risk to product quality.
`
`The timetable you sublnitted on Febmmy 15, 2013, states that you will conduct this study
`according to the following schedule:
`
`04/13
`Material Compatibility Assessment Completion:
`Leachable Assessment and Toxicological Risk Assessment: 05/13
`Final Rep01i Sublnission:
`06/13
`
`15. Conduct ado-trastuzumab emtansine exposure-response analyses for progression-free
`survival, fmal overall survival, and safety utilizing data from trial B025734/TDM4997
`(TH3RESA). The results of the exposure-response analyses from both TH3RESA and
`B021977/TDM4370g (EMILIA) will be used to dete1mine whether a postmarketing trial is
`needed to optilnize the dose in patients with metastatic breast cancer who have lower
`exposure to ado-trastuzumab emtansine conjugate at the approved dose (3.6 mg/kg q3w).
`Submit a final rep01i of the exposure-response analyses based on TH3RESA and EMILIA.
`
`The timetable you sublnitted on Febmmy 15, 2013, states that you will conduct this study
`according to the following schedule:
`
`Trial Completion:
`Final Rep01i Sublnission:
`
`06/16
`12116
`
`Submit clinical protocols to your IND 071072 for this product. Sublnit nonclinical and
`chemisuy, manufacturing, and conu·ols protocols and all postmarketing fmal reports to this BLA.
`In addition, under 21 CFR 601 .70 you should include a status surnmmy of each commitment in
`your annual progress rep01i of postmm·keting studies to this BLA. The status sunnna1y should
`include expected sunnna1y completion and fmal rep01i sublnission dates, any changes in plans
`since the last mmual rep01i, and, for clinical studies/u·ials, number of patients entered into each
`study/u·ial. All submissions, including supplements, relating to these postmarketing
`cormnitments should be prominently labeled "Postmarketing Commitment Protocol,"
`"Postmarketing Commitment Final Report," or "Postmarketing Commitment
`Correspondence."
`
`PROMOTIONAL MATERIALS
`
`You may request advis01y comments on proposed inu·oduct01y adveliising and promotional
`labeling. To do so, sublnit, in u·iplicate, a cover letter requesting advis01y comments, the
`
`Reference ID: 3265306
`
`IMMUNOGEN 2181, pg. 9
`Phigenix v. Immunogen
`IPR2014-00676
`
`

`
`BLA 125427/0
`Page 10
`
`
`
`proposed materials in draft or mock-up form with annotated references, and the package insert
`to:
`
`Food and Drug Administration
`Center for Drug Evaluation and Research
`Office of Prescription Drug Promotion
`5901-B Ammendale Road
`Beltsville, MD 20705-1266
`
`
`As required under 21 CFR 601.12(f)(4), you must submit final promotional materials, and the
`package insert, at the time of initial dissemination or publication, accompanied by a Form FDA
`2253. For instruction on completing the Form FDA 2253, see page 2 of the Form. For more
`information about submission of promotional materials to the Office of Prescription Drug
`Promotion (OPDP), see http://www.fda.gov/AboutFDA/CentersOffices/CDER/ucm090142.htm.
`
`REPORTING REQUIREMENTS
`
`You must submit adverse experience reports under the adverse experience reporting
`requirements for licensed biological products (21 CFR 600.80). You should submit
`postmarketing adverse experience reports to:
`
`
`Food and Drug Administration
`Center for Drug Evaluation and Research
`Central Document Room
`5901-B Ammendale Road
`Beltsville, MD 20705-1266
`
`Prominently identify all adverse experience reports as described in 21 CFR 600.80.
`
`You must submit distribution reports under the distribution reporting requirements for licensed
`biological products (21 CFR 600.81).
`
`You must submit reports of biological product deviations under 21 CFR 600.14. You should
`promptly identify and investigate all manufacturing deviations, including those associated with
`processing, testing, packing, labeling, storage, holding and distribution. If the deviation involves
`a distributed product, may affect the safety, purity, or potency of the product, and meets the other
`criteria in the regulation, you must submit a report on Form FDA-3486 to:
`
`
`Food and Drug Administration
`Center for Drug Evaluation and Research
`Division of Compliance Risk Management and Surveillance
`5901-B Ammendale Road
`Beltsville, MD 20705-1266
`
`Reference ID: 3265306
`
`IMMUNOGEN 2181, pg. 10
`Phigenix v. Immunogen
`IPR2014-00676
`
`

`
`BLA 125427/0
`Page 11
`
`
`
`
`Biological product deviations, sent by courier or overnight mail, should be addressed to:
`
`
`Food and Drug Administration
`Center for Drug Evaluation and Research
`Division of Compliance Risk Management and Surveillance
`10903 New Hampshire Avenue, Bldg. 51, Room 4206
`Silver Spring, MD 20903
`
`
`MEDWATCH-TO-MANUFACTURER PROGRAM
`
`The MedWatch-to-Manufacturer Program provides manufacturers with copies of serious adverse
`event reports that are received directly by the FDA. New molecular entities and important new
`biologics qualify for inclusion for three years after approval. Your firm is eligible to receive
`copies of reports for this product. To participate in the program, please see the enrollment
`instructions and program description details at
`http://www.fda.gov/Safety/MedWatch/HowToReport/ucm166910.htm.
`
`POST-ACTION FEEDBACK MEETING
`
`New molecular entities and new biologics qualify for a post-action feedback meeting. Such
`meetings are used to discuss the quality of the application and to evaluate the communication
`process during drug development and marketing application review. The purpose is to learn
`from successful aspects of the review process and to identify areas that could benefit from
`improvement. If you would like to have such a meeting with us, call the Regulatory Project
`Manager for this application.
`
`If you have any questions, call Lisa Skarupa, Regulatory Project Manager, at (301) 796-2219.
`
`
`Sincerely,
`
`{See appended electronic signature page}
`
`Richard Pazdur, M.D.
`Director
`Office of Hematology and Oncology Products
`Center for Drug Evaluation and Research
`
`
`
`
`
`ENCLOSURE(S):
`Content of Labeling
`Carton and Container Labeling
`
`Reference ID: 3265306
`
`IMMUNOGEN 2181, pg. 11
`Phigenix v. Immunogen
`IPR2014-00676
`
`

`
`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`RICHARD PAZDUR
`02/22/2013
`
`Reference ID: 3265306
`
`IMMUNOGEN 2181, pg. 12
`Phigenix v. Immunogen
`IPR2014-00676