DEPARTMENT OF HEALTH AND HUMAN SERVICES FOOD A1\'D DRUG ADMINISTRATION DIS TRlCT ADDRESS A>IO PHONE NUMBER DATE($) Of' INSPECTION 11/12/2019~11/26/2019* Food and Drug Administration - New Jersey F EJ NUMBER 3002889358 District, 10 Watervi ew Blvd, 3rd Floor, Parsippan y, NJ 07054 973-331-4900

lndustrv In formation: www.fda. e:ov/oc/industrv N ...v e AND Tilt.I:' OF INDIVIDUAL TO WHOM REPORT ISSUED Nellie D. Clark Eliza, VP Site Head of Manufacturing FIRM NAME STREET ADDRESS ImCl one Systems, L.L.C. 33 ImClone Drive CITY, STATE. ZIP CODE, COUNTRY TYPE ESTABLISHMENT INSPECTED Branchburg, NJ 08876-3904 Biological Drug Substance Manufacturer

This document lists observations made by the FDA representative(s) during the inspection ofyour facility. They are inspectional observations. and do not represent a final Agency determination regarding your compliance. If you have an objection regarding an observation, or have implemented, or plan to implement. corrective action in response to an observation. you may discuss the objection or action with the FDA representative(s) during the inspection or submit this information to FDA at the address above. If you have any questions, please contact FDA al the phone numbt!r and address above.

DURING AN INSPECTION OF YOUR FIRM WE OBSERVED: OBSERVATION 1

Appropriate controls are not exercised over computers or related production systems.

Specifically, electronic data obtained from manufacturing process or related equipment are not appropriately controlled. For example,

A. We observed from the audit trails of the( b) (4) units that electronic files identified as Calibration Study, Qualification Study and Verification Study have been deleted. These~ 5)(4) 1 units are used for the equipment qualifications, involving [(5) 14) I processes. The deleted incidents and related audit trail were not reviewed by the quality unit. For example, the following are some of the actions observed in the audit trail obtained from the{6) (4) ~b) (4) , units.

--- --·- -- - .. - (b) (4) Unit DatWiime Actions - 31-Jan-2018 Qualification Study J b) (4) 1deleted by at 15:57:48 User ID i(b) (6j". User Name: t b) (6)

0l-Feb-2018 Qualification Study : l(b} (4 ) f' deleted by at 09:22:17 User ID : [(b) (6)'. User Name: (b) (4)

EMPLOYEE{S) SIGNATURE OATE ISSUED l y t°\., ~~- SEE REVERSE Tamil Arasu, I nvestigator .·I.L I 0.. '(V\..'. f-\ 11/26/ 2019 OF THIS PAGE Guerlain Ulysse, Investigator~ .. VLu_,. c~ u FORM FDA 483 (0?i08) ~REVIOUS EDITION OBSOLl!Tc INSPECTION AL OBSERVATIONS PAGE I OF 5 PAGES DEPARTMENT OF HEALTH AND HUMAN SERVlCES FOOD AND DRUG ADMJNJSTRATION DISTRICT ADDRESS AND PliONE NUMBER OATE(S) OF INSPECTION 11/12/2019- il/26/2019* Food and Drug Administration - New Jersey FEINIJMBER District, 10 Waterview Blvd, 3rd Floor, 3002889358 Parsippany, NJ 07054 973-331-4900

lndust Information: www.fda.eov/oc/indust NAME AND TITLE OF INOIVIDUAl TO ""'10M REPORT ISSUED Nellie D. Clark Eliza, VP Site Head of Manufa-cturing

FIRMAAME STREET A~ESS I mClone Systems, L.L.C. 33 ImClone Drive CITY. STAlE. ZiP cooe. COONTAY TYPE ESTABLISHMENT INSPECTED Branchburg, NJ 08876-3904 Bi ological Drug Substance Manufacturer

05-Feb-2018 Verification Study: (b) (4) "deleted by at 14:15:14 User ID : (b) (6)". User Name: (o) (6)

05-Feb-2018 Calibration Study : (b) (4) " deleted by at 14:17:03 User ID : (b) (4)!'. User Name: (b) (4)

05-Feb-2018 6J (4 at 14:17:19 05-Feb-2018 at14:17:38

05-Feb-2018 Verification Study: (b) (4) deleted by at 14:18:05 User ID:' o) (4). User _.__15 4__ _ ,, 05-Feb-2018 at 14:20:22

22-Feb-2018 at 07:06:39

23-Mar-2018 Qualification Study : 15 4 deleted at 09:01 :04 by User ID : (b) (6) User Name: ~b) (6) 13-Apr-2018 Qualification Study : "~~----- b 4 - at 09:57:49 deleted by User JD : (o) (6),,_ User Name: (b) (6)

EMPLOY&($) SlGNATIJRE DA'T€1SSUED SEE REVERSE Tamil Arasu, Investigator 11/26/2019 OF THIS PAGE Guerlain Ulysse, Investigator ,,,I c,,\5.

FORM FDA 48J (09:0&) PREVIOUS romoN OBSOLETE INSPECTlONAL OBSI<:RVA TIONS PAGE 2 OF 5 PAGES DEPARTMENT OF HEALTH AND HUJ\tlAN SERVICES FOOD AND DRUG ADM!NISTRA1'10N DISTRICT ADDRESS ANO PHONE NUM81:R DA'('E (S) OF INSPECTION ll/ 12/201 9-11/26/201 9* Food and Drug Admi nistration - New Jersey FEI NUMBER District, 10 Waterview Blvd, 3rd Floor, 3002889358 Par sippany, NJ 07054 973 - 331-4900

Indus!! Information: www.fda. ov/oc/indust NAME AND TITLE OF INDIVIDUAL TO WHOM REPORT ISSUED Nellie D. Clark Eli za, VP Site Head of Manufacturing FIRM NAME STREET ADORESS ImClone Systems, L.L.C . 33 I mClone Drive CITY. STATE. ZIP CODE. COONTRY TYPE ESTABLISHMENT INSPECTED Branchburg, NJ 08876 - 3904 Biological Drug Substance Manufacturer

16-Aug-2018 Qualification Study : b 4 deleted by 1 at 13:49:53 User ID : b 6 • User Name: (b) (6)

at 14: 15: 14

05-Feb-2018 Calibration Study: (b) (6) deleted by at 14:17:03 User JD: (b) (6). User Name (t:5) (6)

05-Feb-2018 at 14: 17:19

o) 4) 05-Feb-2018 at 14:17:38

05-Feb-2018 at 14: 18:05

05-Feb-2018 Qualification Study:~~~,_,.. (b) (4) ___ _ at 14:19:51 deleted by User· ID: (b) (6) User Name: (b)(6)

13-Apr-2018 at 09:57:49 User Name:

* Full name withheld. and only initials shown

EMPLOYEE(S) S IGNATURE DATE ISSUED SEE REVERSE Tamil Arasu, Investigator 1 1/26/2019 OF THIS PAGE Guerlain Ulysse, Investigator

FORM FDA 483 (09108) PRE VlOUS EDITIOI< 06S01.ETI; lNSPEC."TIONA L OBSERVA TlONS PAGE; OF S PAGES DEPARTMENT OF HEALTH AND HUMAN SERVICES FOOD AND DRUG ADMlNISTRATION DISTRICT ADDRESS ANO PHONE NUMBER DATE(S)OF INSPECTION ll/12/2019 - 11/26/2019* Food and Drug Administration - New Jersey FENUWBER District, 10 Waterview Blvd, 3rd Floor, 3002889358 Parsippany, NJ 07054 973 - 331-4900

Industry Information: www.fda.e:ov/oc/industrv NAM!< ANO mLE Of' INDIVIDUAL TO WHOM REPORT ISSUED Nellie D. Clark Eliza, VP Site Head of Manufacturing FIRM NAME STREET ADDRESS I mClone Systems, L.L.C . 33 ImClone Drive CITY, STATE. ZIP CODE. COUNTRY TYPE ESTABLISHMENT INSPECTED Branchburg, NJ 08876-3904 Biological Drug Substance Manufacturer

B. Review of the :(b)(4) unit's (Serial Nol(b) (4) I) audit trail also indicated users had logged into the system on multiple occasions to do Audit Trail operations followed by adjusting the system clock. For example, the following table shows three sequential actions recorded in the audit trail: - (b) (4) Dateffim,.e Actions - 28-Sep-2018 User Id : [(b) (6)) Logged in to System. at 10:50:13 28-Sep-2018 User Id : [(b) {6Yi . User Name: ll>><6l,* logged in to ('11 at 11 :03:47 to do "AuditTrail" operation in [(b)(4)Jt l b) (4 ) screen I 28-Sep-2018 I (b)(4] Clock adjusted from at 10:48:59 28/09/2018 11:03:47 to 28/09/2018 10:49:00 by User Id : (b) (6)). User Name:(b) (6)

* Full name withheld. and only initials shown

Similar actions were observed in [(b) (4) , units, OC b) 4 ) J and[(b) (4) as well. The firm's quality unit did not review the audit trails from these 15f(4) I units. Operators were assigned administrative privileges. In addition, the finn does not have sufficient controls to prevent the deletion of electronic data stored in these systems, which is not backed-up on a periodic basis.

C. We observed that test runs have been aborted fro b) (4) I Test Instruments and the aborted tests were not logged in the user logs, documented or reviewed. For example, review of the run history on th~(l5f(4) _ Test Instruments (ID: :(15 (4) .) indicated an error message "Test aborted by the operator" on multiple occasions. However., these events were not

EMPI.OYEE(S) StGNATURE OATEISSUEO SEE REVERSE Tamil Arasu, Investigator @ 11/26/2019 OF THIS PAGE Guerlain Ulysse, Investigator Gcu t'ORM FDA ~83 (0,/08) PRcVJOUS eomoN OBSOLETE INSPECTIONAL OBSERVATIONS PAGE 4 OF S PAGES DEPARTMENT OF HEALTH ANO HUMAN SERVICES FOOD AND DRUG ADMJNJSTRATION DISTRICT AOO!lESS ANO PHONE NUMBER OATE{S) OF INSPECTION 11/12/201 9 -ll/26/2019* Food and Drug Administration - New Jersey FEINUMBER 3002889358 District , 1 0 Waterview Blvd, 3rd Floor, Par sippany, NJ 07054 973-331-4900

Industry Information: www.fda.12ov/oc/industrv NAME AND Tm.E OF INDIVIDUAL TD WHOM REPORT ISSUED Nellie D. Clark Eli za, VP Site Head o f Manufacturing FIRM NAME STREET ADDRESS ImClone systems, L.L.C. 33 ImCl one Drive CITY, STATE, ZIP CODE, COUNTRY TYPE ESTA8l1Sl

documented in the user logs and reviewed by the quality unit. We were unable to ascertain why the operators had aborted the runs. These (b) (4) J Test Instruments are used to conduct [(b) (4)) and [(b) (4) 'J testing of [(b) (4) .t that are used in the manufacturing processes of biological drug substances such as , , and , which are utilized in the production of drug products that are distributed in the U.S. market.

OBSERVATION 2

Appropriate controls are not exercised over computers or related laboratory systems.

Specifically, Quality Control (QC) laboratory data stored on multiple stand-alone equipment computer systems are not secured from modification or deletion. We observed that QC laboratory personnel could delete an entire fo lder found within the firm's shared drive '1(b) (4) I where data derived from stand-alone QC laboratory equipment computer systems are stored. For example, a QC laboratory employee demonstrated that they could create a test data folder and delete that folder from the computer system attached to the UV spectrometer (Software: [(15) (4) Other computer systems where data is not secured include, Plate Reader (Software: (b) (4) .), UV-Vis (Software: [(b) (4) J), qPCR (Software~~) (4) qPCR (Software: b 4) I), [(b) (4) I Densitometer (Software: (b) (4) 1) and FTIR (Software: (b) (4) ). These laboratory jnstruments are routinely used for testing of drug substances such as Cetuximab, Ramucirurnab, Necitumumab and Galcanezumab, which are utilized in the production of drug products that are distributed in the U.S. market.

*DATES OF INSPECTION l l/12/2019(Tue), I 1/l3/2019(Wed), I J/ 14/20!9(Thu), I l/!5/20l 9(Fri), 11/18/2019(Mon), l l/l9/2019(Tue), 11 /20/20 l 9(Wed), 11/21/20 I 9(Thu), 11/25/20 l 9(Mon) and I 1/26/20 I 9(Tue)

EMP1.OYEE(S) SIGNATURE DATE ISSUED SEE REVERSE Tamil Arasu, Investi gator ~tl-~·\ ft Y v~~~ 11/26/201 9 OF THIS PAG E Guerlain olysse, Investigator Cv.J..l,I.,{_, iu./\?> J-IZ.._ V f'ORM FOA 483 (09/08) PR\:\qQl/S EOITID~ 00SOI.E11! INSPECTIONA L OBSERVATIONS PACE 5 OF 5 PACES The observations of objectionable conditions and practices listed on the front of this form are reported: 1. Pursuant to Section 704(b) of the Federal Food, Drug and Cosmetic Act, or 2. To assist firms inspected in complying with the Acts and regulations enforced by the Food and Drug Administration.

Section 704(b) of the Federal Food, Drug, and Cosmetic Act (21 USC 374(b)) provides:

"Upon completion of any such inspection of a factory, warehouse, consulting laboratory, or other establishment, and prior to leaving the premises, the officer or employee making the inspection shall give to the owner, operator, or agent in charge a report in writing setting forth any conditions or practices observed by him wh ich, in his judgment, indicate that any food , drug, device, or cosmetic in such establishment (1) consists in whole or in part of any filthy, putrid, or decomposed substance, or (2) has been prepared, packed, or held under insan itary conditions whereby it may have become contaminated with fi lth , or whereby it may have been rendered injurious to health . A copy of such report sha ll be sent promptly to the Secretary." ,.