DEPARTMENT OF HEALTH AND HUMAN SERVICES

FOOD AND DRUG ADMINISTRATION

DISTRICT ADDRESS AND PHONE NUMBER DATE(S) OF INSPECTION

1431 Harbor Bay Parkway 7/24/2017-8/3/2017*

Alameda, CA 94502-7070 FEI NUMBER

(510)337-6700 Fax:(510)337-6702 3004888063

NAME AND TITLE OF INDIVIDUAL TO WHOM REPORT ISSUED

Sunita Zalani , VP of Regulatory Affairs and Quality Assurance

FIRM NAME STREET ADDRESS

Intarcia Therapeutics, Inc. 24670 Industrial Blvd

CITY, STATE, ZIP CODE, COUNTRY TYPE ESTABLISHMENT INSPECTED

Hayward, CA 94545-2234 Drug Manufacturer

This document lists observations made by the FDA representative(s) during the inspection of your 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 at the phone number and address above.

The observations noted in this Form FDA-483 are not an exhaustive listing of objectionable conditions. Under the law, your
firm is responsible for conducting internal self-audits to identify and correct any and all violations of the quality system
requirements.

DURING AN INSPECTION OF YOUR FIRM WE OBSERVED:

OBSERVATION 1
There is a lack of written procedures describing in sufficient detail the methods, equipment and
materials to be used for sanitation.

Specifically, we observed the daily cleaning process performed in the ISO 5 Transfer Room beginning
on 7/27/2017. This room is cleaned per SOP VV-01609, "Cleaning and Sanitization of the Transfer
Suite Within the Hayward One Manufacturing Facility". Your SOP lacks adequate detail regarding how
often the cleaning personnel shall re-wet their mops while performing cleaning operations in order to
ensure the disinfectant is applied to the surfaces for the minimum contact time (b) (4) ) required per
VV-01609. The cleaning disinfectant contact time is not documented during cleaning operations.

OBSERVATION 2
Aseptic processing areas are deficient regarding the system for cleaning and disinfecting the room and
equipment to produce aseptic conditions.

Specifically,

EMPLOYEE(S) SIGNATURE DATE ISSUED

SEE REVERSE Ashar P Parikh, Investigator ʖ 8/3/2017

OF THIS PAGE Eileen A Liu, Microbiologist Ashar P Parikh
Investigator
James A Lane, Investigator X
Signed By: Ashar P. Parikh -S
Date Signed: 8/3/2017

Chengjiu Hu, FDA Center Employee or

Employee of Other Federal Agencies

FORM FDA 483 (09/08) PREVIOUS EDITION OBSOLETE INSPECTIONAL OBSERVATIONS PAGE 1 OF 8 PAGES
 DEPARTMENT OF HEALTH AND HUMAN SERVICES
FOOD AND DRUG ADMINISTRATION
DISTRICT ADDRESS AND PHONE NUMBER DATE(S) OF INSPECTION

1431 Harbor Bay Parkway 7/24/2017-8/3/2017*

Alameda, CA 94502-7070 FEI NUMBER

(510)337-6700 Fax:(510)337-6702 3004888063

NAME AND TITLE OF INDIVIDUAL TO WHOM REPORT ISSUED

Sunita Zalani , VP of Regulatory Affairs and Quality Assurance

FIRM NAME STREET ADDRESS

Intarcia Therapeutics, Inc. 24670 Industrial Blvd

CITY, STATE, ZIP CODE, COUNTRY TYPE ESTABLISHMENT INSPECTED

Hayward, CA 94545-2234 Drug Manufacturer

A. Your firm has not established the efficacy of disinfectants used in the aseptic processing areas. For
example,(b) (4) , (b) (4) and (b) (4)
are used to clean various clean room and equipment surfaces. Your firm has not
demonstrated the disinfectants used are effective for the inactivation or removal of microorganisms on
the surfaces where they are used.

B. Your firm uses pre-saturated sterile (b) (4) and (b) (4) wipes for the disinfection of surfaces
during aseptic processing. However, the integrity of these sterile wipes cannot be assured. On 7/24/2017
we observed one pack of the (b) (4) and one pack of the (b) (4) wipes stored on a cart inside the
Grade D Material Transfer Room (b) (4) . We observed both packs were partially open exposing pre-
saturated sterile wipes to the room air. Additionally, we observed there was no open date or expiration
date written on either package.

OBSERVATION 3
Written records of investigations into unexplained discrepancies do not always include the conclusions
and follow-up.

Specifically,

A. During our review of your firm's building automation system which monitors pressure differential
and room temperatures, we observed your firm does not always review alarms as required per SOP
#VV-00754, "Building Automation System Response Procedure for the Hayward One Facility SOP"
section 5.2 which states, "Manufacturing will complete the alarm response form VV-01058 for all
critical action level alarms as identified in Table 1 Critical Building and Facility Alarms in VV-00728."
Furthermore, VV-00728, "Building and Facility Alarm Management SOP" section 5.4.2 states, "Log
into any BAS workstation and check Alarm Manager (as in FIGURE 8). Acknowledge the alarm."

EMPLOYEE(S) SIGNATURE DATE ISSUED

SEE REVERSE Ashar P Parikh, Investigator ʖ 8/3/2017

OF THIS PAGE Eileen A Liu, Microbiologist Ashar P Parikh
Investigator
James A Lane, Investigator X
Signed By: Ashar P. Parikh -S
Date Signed: 8/3/2017

Chengjiu Hu, FDA Center Employee or

Employee of Other Federal Agencies

FORM FDA 483 (09/08) PREVIOUS EDITION OBSOLETE INSPECTIONAL OBSERVATIONS PAGE 2 OF 8 PAGES
 DEPARTMENT OF HEALTH AND HUMAN SERVICES
FOOD AND DRUG ADMINISTRATION
DISTRICT ADDRESS AND PHONE NUMBER DATE(S) OF INSPECTION

1431 Harbor Bay Parkway 7/24/2017-8/3/2017*

Alameda, CA 94502-7070 FEI NUMBER

(510)337-6700 Fax:(510)337-6702 3004888063

NAME AND TITLE OF INDIVIDUAL TO WHOM REPORT ISSUED

Sunita Zalani , VP of Regulatory Affairs and Quality Assurance

FIRM NAME STREET ADDRESS

Intarcia Therapeutics, Inc. 24670 Industrial Blvd

CITY, STATE, ZIP CODE, COUNTRY TYPE ESTABLISHMENT INSPECTED

Hayward, CA 94545-2234 Drug Manufacturer

Alarms are not consistently acknowledged in BAS or on the printout log. We observed alarms including
(b) (4) on 7/12/2017 10:53:43 were not acknowledged.

B. Your firm failed to follow SOP VV-00229 Version 4.0, Section 7.2.1 regarding initiating a CAPA.
The SOP states your firm is to initiate a CAPA promptly after identifying any non-conformance
observations resulting from Deviations, Product Complaints, Environmental Monitoring, Out of
Specifications, Regulatory Audits (FDA, MHRA, ISO, BSI, and/or other regulatory agencies), Internal
Audits, Supplier and/or Partner Audits, Management Review, Quality Periodic Review, Returned
Product, Serious Adverse Events, Other Quality Systems (e.g. training), Data Trending. Your firm has
been initiating CAPAs following the closure of a Deviation report. For example, Deviation D15-097 was
opened on 13 July 2015 and closed on 17 Aug 2015. CAPA D15-097-01 was opened on 17 Aug 2015 at
the close of the deviation. Your firm was aware of the root cause prior to closure of the deviation report
but failed to open a CAPA until the deviation report was completed and signed.

C. The review of your CAPA procedures, logs and CAPAs revealed numerous incidents where you
failed to complete CAPAs within set timelines and or have failed to file appropriate extensions. Similar
deficiencies were also observed during the review of your deviation reports.

D. Corrective and preventive action activities and/or results have not been adequately documented.

x CAPA-D15-097-01 – The preventative action plan stated your firm would evaluate all other (b) (4)
series stainless to (b) (4) stainless contact surfaces for galling. Your firm failed to provide
documentation that the preventative action plan was complete and effective.

x CAPA-2016-058 – During an experimental fill using the (b) (4) filler, your firm experienced pump
(b) (4) (b) (4)
failures on pump and pump . Your CAPA failed to include a preventative action to mitigate
future pump failures.

EMPLOYEE(S) SIGNATURE DATE ISSUED

SEE REVERSE Ashar P Parikh, Investigator ʖ 8/3/2017

OF THIS PAGE Eileen A Liu, Microbiologist Ashar P Parikh
Investigator
James A Lane, Investigator X
Signed By: Ashar P. Parikh -S
Date Signed: 8/3/2017

Chengjiu Hu, FDA Center Employee or

Employee of Other Federal Agencies

FORM FDA 483 (09/08) PREVIOUS EDITION OBSOLETE INSPECTIONAL OBSERVATIONS PAGE 3 OF 8 PAGES
 DEPARTMENT OF HEALTH AND HUMAN SERVICES
FOOD AND DRUG ADMINISTRATION
DISTRICT ADDRESS AND PHONE NUMBER DATE(S) OF INSPECTION

1431 Harbor Bay Parkway 7/24/2017-8/3/2017*

Alameda, CA 94502-7070 FEI NUMBER

(510)337-6700 Fax:(510)337-6702 3004888063

NAME AND TITLE OF INDIVIDUAL TO WHOM REPORT ISSUED

Sunita Zalani , VP of Regulatory Affairs and Quality Assurance

FIRM NAME STREET ADDRESS

Intarcia Therapeutics, Inc. 24670 Industrial Blvd

CITY, STATE, ZIP CODE, COUNTRY TYPE ESTABLISHMENT INSPECTED

Hayward, CA 94545-2234 Drug Manufacturer

OBSERVATION 4
Aseptic processing areas are deficient regarding the system for monitoring environmental conditions.

Specifically,

A. Your firm has not performed airflow pattern evaluations (smoke studies) under dynamic conditions to
verify the unidirectional airflow and potential air turbulence within the ISO classified areas of your
facility including the inside of isolators and cleanrooms where sterile drug products are manufactured
and processed.

B. Your firm’s passive viable air sampling is inadequate. For example, on 7/24 and 7/26/2017 during
process simulation testing of batch(b) (4) inside (b) (4) , we observed settling plates
(b) (4)
were placed (b) (4) of the isolator approximately feet away from where
process simulation activities were occurring.

C. (b) (4) media is used to obtain environmental monitoring and personnel monitoring
samples in the aseptic processing areas. Your firm has not validated the(b) (4) incubation of
(b) (4)
media (b) (4) to demonstrate the optimal recovery of a
range of microorganisms including bacteria, yeast, and mold species.

OBSERVATION 5
Aseptic processing areas are deficient regarding systems for maintaining any equipment used to control
the aseptic conditions.

Specifically,

EMPLOYEE(S) SIGNATURE DATE ISSUED

SEE REVERSE Ashar P Parikh, Investigator ʖ 8/3/2017

OF THIS PAGE Eileen A Liu, Microbiologist Ashar P Parikh
Investigator
James A Lane, Investigator X
Signed By: Ashar P. Parikh -S
Date Signed: 8/3/2017

Chengjiu Hu, FDA Center Employee or

Employee of Other Federal Agencies

FORM FDA 483 (09/08) PREVIOUS EDITION OBSOLETE INSPECTIONAL OBSERVATIONS PAGE 4 OF 8 PAGES
 DEPARTMENT OF HEALTH AND HUMAN SERVICES
FOOD AND DRUG ADMINISTRATION
DISTRICT ADDRESS AND PHONE NUMBER DATE(S) OF INSPECTION

1431 Harbor Bay Parkway 7/24/2017-8/3/2017*

Alameda, CA 94502-7070 FEI NUMBER

(510)337-6700 Fax:(510)337-6702 3004888063

NAME AND TITLE OF INDIVIDUAL TO WHOM REPORT ISSUED

Sunita Zalani , VP of Regulatory Affairs and Quality Assurance

FIRM NAME STREET ADDRESS

Intarcia Therapeutics, Inc. 24670 Industrial Blvd

CITY, STATE, ZIP CODE, COUNTRY TYPE ESTABLISHMENT INSPECTED

Hayward, CA 94545-2234 Drug Manufacturer

The Performance Qualification of the (b) (4) , Document #VP-5238 (protocol)

and #FR-5238 (report) (effective February 17, 2016) for your firm's (b) (4) qualification
fails to adequately document the locations and quantities of materials included as part of the
qualification cycles. For example, the (b) (4) Load Verification" was performed using (b) (4)
in SOP VV-00276, "(b) (4) ". However the actual
quantities of the items and their locations are not documented in VP-5238 or FR-5238. Furthermore,
(b) (4)
VP-5238 indicates the (b) (4) reservoirs that are part of reservoir load (b) (4) are placed on a total of
different shelves. VP-5238 does not state how many reservoir trays need to be placed on each shelf. SOP
(b) (4) (b) (4)
VV-00276, Section 9.0 number 6 states, "Up to trays (Up to trays per shelf) of Reservoirs may be
(b) (4)
(b) (4)
processed in an load". Neither VP-5238 nor FP-5238 specifically state trays were placed on each
shelf during the qualification runs.

OBSERVATION 6
Laboratory controls do not include the establishment of scientifically sound and appropriate
specifications and test procedures designed to assure that drug products conform to appropriate
standards of identity, strength, quality and purity.

Specifically, your firm failed to validate the bacterial endotoxin test method for ITCA-650. During
bacterial endotoxin testing, the finished products are sonicated to achieve endotoxin recovery however
your firm lacks the data to demonstrate the extraction method can adequately recover endotoxin if it is
present in the drug product.

OBSERVATION 7
Procedures designed to prevent microbiological contamination of drug products purporting to be sterile
are not established and followed.

EMPLOYEE(S) SIGNATURE DATE ISSUED

SEE REVERSE Ashar P Parikh, Investigator ʖ 8/3/2017

OF THIS PAGE Eileen A Liu, Microbiologist Ashar P Parikh
Investigator
James A Lane, Investigator X
Signed By: Ashar P. Parikh -S
Date Signed: 8/3/2017

Chengjiu Hu, FDA Center Employee or

Employee of Other Federal Agencies

FORM FDA 483 (09/08) PREVIOUS EDITION OBSOLETE INSPECTIONAL OBSERVATIONS PAGE 5 OF 8 PAGES
 DEPARTMENT OF HEALTH AND HUMAN SERVICES
FOOD AND DRUG ADMINISTRATION
DISTRICT ADDRESS AND PHONE NUMBER DATE(S) OF INSPECTION

1431 Harbor Bay Parkway 7/24/2017-8/3/2017*

Alameda, CA 94502-7070 FEI NUMBER

(510)337-6700 Fax:(510)337-6702 3004888063

NAME AND TITLE OF INDIVIDUAL TO WHOM REPORT ISSUED

Sunita Zalani , VP of Regulatory Affairs and Quality Assurance

FIRM NAME STREET ADDRESS

Intarcia Therapeutics, Inc. 24670 Industrial Blvd

CITY, STATE, ZIP CODE, COUNTRY TYPE ESTABLISHMENT INSPECTED

Hayward, CA 94545-2234 Drug Manufacturer

Specifically,

Your firm does not perform isolator glove leak test to ensure the integrity of the gloves has not been
breached. Furthermore, your firm’s isolator gloves and sleeves visual inspection procedure lacks
adequate details. For example, SOP VV-00141, version 3.0, entitled “Daily Cleaning and Inspection of
Isolator gloves and Sleeves SOP” Section 7.1.1.1 states to “Examine gloves and sleeves for damage or
holes”. However, it lacks necessary details to explain how to perform visual examination or inspection
of gloves and sleeves. In addition, your firm was unable to provide training documentation to
demonstrate operators are adequately trained to perform glove and sleeve inspections.

OBSERVATION 8
Control procedures are not established which monitor the output of those manufacturing processes that
may be responsible for causing variability in the characteristics of in-process material and the drug
product.

Specifically,

A. The blend uniformity test is currently performed during the (b) (4) of the exenatide
suspension from (b) (4) . The samples for the uniformity test of
exenatide are collected “prior to filling the (b) (4) , in between filling each(b) (4) , and after
filling the (b) (4) ” and then tested for drug content (Batch record Step 16.11). This sampling plan fails
to demonstrate the uniformity of exenatide in each bowl for the top, middle and bottom layers to ensure
the drug product mixture has not experienced any separation after transfer.

B. Your firm has not adequately validated the (b) (4) test method which is used to ensure air bubbles are
not included in the final drug product for ITCA-650. The potential of air bubbles trapped in the

EMPLOYEE(S) SIGNATURE DATE ISSUED

SEE REVERSE Ashar P Parikh, Investigator ʖ 8/3/2017

OF THIS PAGE Eileen A Liu, Microbiologist Ashar P Parikh
Investigator
James A Lane, Investigator X
Signed By: Ashar P. Parikh -S
Date Signed: 8/3/2017

Chengjiu Hu, FDA Center Employee or

Employee of Other Federal Agencies

FORM FDA 483 (09/08) PREVIOUS EDITION OBSOLETE INSPECTIONAL OBSERVATIONS PAGE 6 OF 8 PAGES
 DEPARTMENT OF HEALTH AND HUMAN SERVICES
FOOD AND DRUG ADMINISTRATION
DISTRICT ADDRESS AND PHONE NUMBER DATE(S) OF INSPECTION

1431 Harbor Bay Parkway 7/24/2017-8/3/2017*

Alameda, CA 94502-7070 FEI NUMBER

(510)337-6700 Fax:(510)337-6702 3004888063

NAME AND TITLE OF INDIVIDUAL TO WHOM REPORT ISSUED

Sunita Zalani , VP of Regulatory Affairs and Quality Assurance

FIRM NAME STREET ADDRESS

Intarcia Therapeutics, Inc. 24670 Industrial Blvd

CITY, STATE, ZIP CODE, COUNTRY TYPE ESTABLISHMENT INSPECTED

Hayward, CA 94545-2234 Drug Manufacturer

exenatide suspension in the final drug device assembly is critical to ensure accuracy of the dose and
consistency of the drug release rate from the final drug product device.

C. There is no fixed formulation for the exenatide suspension used for ITCA-650. The formulation
varies per batch depending on (b) (4) . Furthermore, the (b) (4) used
(b) (4)
for the subsequent formulation adjustment is based on an average of randomly sampled
subassemblies. The representability and adequacy of the sampling plan (sample size and location) for
(b) (4) is not scientifically justified.

OBSERVATION 9
Written procedures are not followed for the receipt, storage, handling and sampling of components.

Specifically,
(b) (4)
A. During the walk through of your firm's GMP warehouse, we observed items including autoclave
tape and (b) (4) test packs which require specific storage conditions were being stored in this
uncontrolled and unmonitored warehouse. Your firm's SOP VV-00242, "Receipt, Storage and Handling
of Incoming Items SOP" requires all materials to be stored at required storage conditions as defined by
the Intarcia Quality Specifications or manufacturer's specifications.

*DATES OF INSPECTION
7/24/2017(Mon),7/25/2017(Tue),7/26/2017(Wed),7/27/2017(Thu),7/28/2017(Fri),8/01/2017(Tue),8/02/
2017(Wed),8/03/2017(Thu)

EMPLOYEE(S) SIGNATURE DATE ISSUED

SEE REVERSE Ashar P Parikh, Investigator ʖ 8/3/2017

OF THIS PAGE Eileen A Liu, Microbiologist Ashar P Parikh
Investigator
James A Lane, Investigator X
Signed By: Ashar P. Parikh -S
Date Signed: 8/3/2017

Chengjiu Hu, FDA Center Employee or

Employee of Other Federal Agencies

FORM FDA 483 (09/08) PREVIOUS EDITION OBSOLETE INSPECTIONAL OBSERVATIONS PAGE 7 OF 8 PAGES
 DEPARTMENT OF HEALTH AND HUMAN SERVICES
FOOD AND DRUG ADMINISTRATION
DISTRICT ADDRESS AND PHONE NUMBER DATE(S) OF INSPECTION

1431 Harbor Bay Parkway 7/24/2017-8/3/2017*

Alameda, CA 94502-7070 FEI NUMBER

(510)337-6700 Fax:(510)337-6702 3004888063

NAME AND TITLE OF INDIVIDUAL TO WHOM REPORT ISSUED

Sunita Zalani , VP of Regulatory Affairs and Quality Assurance

FIRM NAME STREET ADDRESS

Intarcia Therapeutics, Inc. 24670 Industrial Blvd

CITY, STATE, ZIP CODE, COUNTRY TYPE ESTABLISHMENT INSPECTED

Hayward, CA 94545-2234 Drug Manufacturer

James A Lane Eileen A Liu

Investigator Microbiologist
X Signed By: 2000428665
Date Signed: 8/3/2017 X Signed By: 2000427259
Date Signed: 8/3/2017

ʖ ʖ . . . . .

EMPLOYEE(S) SIGNATURE DATE ISSUED

SEE REVERSE Ashar P Parikh, Investigator ʖ 8/3/2017

OF THIS PAGE Eileen A Liu, Microbiologist Ashar P Parikh
Investigator
James A Lane, Investigator X
Signed By: Ashar P. Parikh -S
Date Signed: 8/3/2017

Chengjiu Hu, FDA Center Employee or

Employee of Other Federal Agencies

FORM FDA 483 (09/08) PREVIOUS EDITION OBSOLETE INSPECTIONAL OBSERVATIONS PAGE 8 OF 8 PAGES
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 which, 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 insanitary conditions whereby it may have become
contaminated with filth, or whereby it may have been rendered injurious to health. A copy
of such report shall be sent promptly to the Secretary."