DISTRICT ADDRESS AND P"IONE NUMBER

1431 Harbor Bay Parkway Alameda, CA 94502-7070 (520) 337-6700 Faxo (510) 337-6702

Industry Information: www.fda.gov/oc/industry

DATE(S)Of INSPECTION

09/02/2011 - 09/27 /2011* I FEI NUMBER

2927293 1

NAME AND TITLE OF INDIVIDUAL TO WHOM REPORT ISSUED

TO: Andrea J. Goddard, Senior Director and SSF Site Quality Head FIRM NAME

Genentech Inc CITY, STATE, ZIP CODE. COUNTRY

South San Francisco, CA 94080-49l8

STREET ADDRESS

1 DNA Way TYPE ESTABLISHMENT INSPECTE:D

Manufacturer

DEPARTMENT OF HEALTH AND HUMAN SERVICES

FOOD AND DRUG ADMlNlSTRATION

This document lists observations made by the FDA represemative(s) during the inspection of your facility. 1l1ey 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 wiih ihe FDA representative{s) during the inspection or submit this information to FDA at the address above. If you have any questions, please contact FDA at the phone number and address above.

DURING. AN INSPECTION OF YOUR FIRM WE OBSERVED:

OBSERVATION 1

Written records of investigations into unexplained discrepancies and the failure of a batch or any of its components to meet specifications do not include the conclusions and follow-up.

THIS IS A REPEAT OBSERVATION FROM 06/201 I

Specifically,

A) During our review ofDeviation Report #506'273 on 09/02/11 , opened due to disint gaskets on the vial washer in Are on February 21, 2011, we noted that the investigation failed to include instructions to compare particulates isolated from culled Avastin finished drug product vials (packaged L Fill Lo with the disintegra gasket material identified and recovered after identification of the discrepancy.

The investigation report, dated 07/26/11 states that a total of 12 isolated particulates fro ltered Avastin vials were sent for analyticaJ anal ahd/or . However, the investigation failed to include analysis and comparison with the recovered 1 aLJHt; gasket material, in order to rule out potential contamination of this lot, which is currently in Quarantine status to failing urotal Critical Particulates" via Automated Inspection.

B) During our review ofDeviation Report 11464179 on 09/12/11, opened due to an Are capper power oulage dming. the fill of A vastin Lo (Packaged Lot #879296) on July 21, 2010, we noted that the investigation failed to describe:

1) Actions taken to address the capper oil leak discovered during the investigation 2) Disposition of the in process vials on the manufacturing line during the our shutdown and repair period

There is no documentation to provide assurance that the capper oil leak was addressed/repaired prior to the resumption of manufacturing. Additionally, there is no documentation to provide assurance that the in-process filled/stoppered vials were

required per section 11.0 of SOP 1630.011.

l PATE ISSUED

09/27/2011

,-~'""-~ ~I Peter E. Baker, InvestigatorJeffrey M. V~atson, Investiga r

Henry K. Lau, Investigator

Min-Shan-Ma "m.,,

Liu, Investigator

SEE REVERSEO''""eAG>

_

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FORM FDA 483 (09/08) PREV!OtJS EDITION OBSOlETE INSPECTIONAL OBSERVATIONS PAGE I OF 4 PAGES

(b) (4)(b) (4)

(b) (4)(b) (4) (b) (4)

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(b) (4)

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(b) (4)

(b) (4)

www.fda.gov/oc/industry

DEPARTMENT OF HEALTH AND HUMAN SERVJCES FOOD AND DRUG ADMINISTRATION

DATE(SIOf INSPECTION

~N~AMwE~A~N~D~TIT~L"E~OF~Iu.NDThiV~ID~U~&•TAO"-W~HO~M·~R~EP~O~RTT~~S~U~ED~---~~~-~------~------~---------------- ------~

TO: Andrea J. Goddard, Senior Director and SSF Site Quality H~ad ~F""IR:;-;M-c;N~A'M=E-----------------'------------~ STREET AOOR=.SS

Genentech Inc I 1 DNA Way~c=IT~Y~S~~~TE~.~ZI~P~CO~D~E.~C~OU~~=R~Y~------·----·------------·~TYP~E=EsC-T~~~LI~S~~~E~NT~IN~S~PE~C~TE~D~--------------------~

South San Francisco, CA 94080-4918 Manufacturer

DISrRICT ADDRESS AND PHONE NUMBER

1431 Harbor Bay Parkway Alameda, CA 94502-7070 (510) 337-6700 Fax: (510) 337-6702 Industry Information: www.fda.gov/oc/industry

09/02/2011 - 09/27/2011* FEI NUM6ER -----~--1

2917293

documented example, during

ntF·CTT''h' of the

OBSERVATION 2

Equipment used in the manufacture, processing, packing or holding ofdrug products is not ofappropriate design to facilitate operations for its intended use.

Specifically,

nr'""'',,. assurance that the conveyance and capping of product-filled Avastin vials is performed in a . as described in section 3.2.P.3.3 ofyour firm's Bevacizumab BLA (#125085).

The current design ofthe capping area, as observed during our tour of Area n 09/21111, appears to allow a gap between

the end ofthe HEPA filter coverage and the semi-permanent plastic baniers. This gap appears to permit the influx of air

from the Cla work environment, which would then be passed over the vials during the conveyance and capping process.

Additionally, your firm uses displaced stopper detector (DSD) equipment located the vial capping equipment in

Room to verify the displacement between the stopper and viaL The parameter settings for the DSD equipment were

derived from Document No. TRI 0-050 vol I titled "Defining the Reject Limit for the Displaced Stopper Detectors for

studies perfonned by a contract laboratory. Your firm lacks adequate studies performed by your contract laboratory. For

studies, were used to implement a pre-defined displacement between stopper and vial of study vials. There is no assurance that the thickness ofthe as reported were verified and accurate.

OBSERVATION 3

There was a failure to handle and store closures at all times in a manner to prevent contamination.

Specifically,

There is no data to provide evidence that the current procedures and practices in place, including the contract manufacturing, shipment, handling, and administration ofthe caps do not result product adulteration.

Notably, these caps are received in "folded" plastic bags caps/bag) inside cardboard boxes. The firm has no data and/or controls to provide assurance that this shipment in non-sealed plastic bags does not ·adversely affect the cap integnty, specifically with regard to cap bioburden.

EMPLOYEE(S) SIGNAllJRE

Peter E . Baker, Investigator r1>

Jeffrey M. Watson, Investigator _,...___

11SEE REVERSE Henry K. Lau, Investigator ~OF THIS PAGE William V. Millar, Investigator~£t/~

Min-Shan-Ma Liu, Investigator

FORM FDA 483 (0~/081 PREVlOUSFDJTION OBSOLETE INSI'ECTIONAL OBSERVATIONS PAGE 2 OF 4 PAGES

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(b) (4) (b) (4)(b) (4)

(b) (4) (b) (4)(b) (4)

(b) (4)

(b) (4)

www.fda.gov/oc/industry

DEPARTMENT OF HEALTH AND HUMAN SERVICES

DISTRICT ADDRESS AND PHONE NUMBER FOOD AND DRUG ADMTNISTRATJON

OATE(S)OF INSPECTION

1431 Harbor Bay Pa:r-kway

Alameda-, CA 94502-7070 (510) 337-6700 Fax' (510) 337-6702

09/02/2011 FEI NUMBER

2917293

09/27/2011*

Industry Information: www.fda.ge~o~v~/~o~cc~/~i~n=d~uc:s~t~r~y~---------L----------------------------------~ NAME AND TITLE OF INDIVIDUAL TO WHOM REPORT TSSlif':O

TO: Andrea J. Goddard, Senior Director and SSF Site Quality Head FIRM NAME STREET ADDRESS

Genentech Inc 1 DNA Way CITY, STATE. ZIP CODE, COUNTRY TYPE ESTABLISHMENT INSPECTED

South San Francisco, CA 94080--4918 Manufacturer

EMPLDYE.E(S) SIGNATURE I DATE ISSUED

Peter E. Baker, Investigator \-'l> Jeffrey M. Watson, Investigator

SEE REVERSE Henry K. Lau, Investigator ~ 09/27/2011OF THIS PAGE William V. Millar, Investigatorft

--

DEPARTMENT OF HEALTH AND HUMAN SERVICES

FOOD AND DRUG ADMINISTRATION

DISTRICT ADDRESS AND PHONE NUMBER DATE(S) OF INSPECTION

1431 Harbor Bay Parkway 09/02/201i - 09/27/2011* FEI NU!)IBER Alameda, CA 94502-7070

( 510) 337-6700 Fax; (510) 337-6702 2917293 Industry Information: www_fda.gov/oc/industry NAME AND TITLE OF INDIVIDUAL TO WHOM REPORT ISSUED

TO; Andrea J. Goddard, Senior Director and SSF Site Quality Head FIRM NAME

Genentech Inc CITY-, STATE, ZIP CODE. COUNTRY

South San Francisco, CA 94080-4918

STREET AODRE.SS

l DNA Way TYPE: ESTABLISHMENT INSPECTED

Manufacturer

0 DATE ISSUED EMPLOYEE(S)SIGNATURE ' _.-;:

Peter E. Baker, Investigator I

Jeffrey ·M. Watson, Investigato~~~

SEE REVERSE He.nry- K. Lau, Investigator c -~ ~..,___g_ OF THIS PAGE William V. Millar, Investigator Uv---- I 09/27/2011

Min-Shan-Ma Llu, Investigator

I

FORM FDA 4g3 (09/08) PREVIOUS EDITION OBSOLETE INSPECTIONAL OBSERVATIONS PAGE40F4PAGES

*DATES OF INSPECTION;

09/02/201l(Fri), 09/06/2011 (fue), 09/07/2011 (Wed), 09/08/2011 (Thu), 09109/2011 (Fri), 09112/2011 (M on), 09114/2011 (Wed),

09115/2011 (11m), 09/1912011 (Mon), 09;20/2011(Tue), 09/21/2011 (Wed), 09/2212011 (Thu), 09/27/2011 (Tue)

http:AODRE.SS