PH1066_III

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SECTION III

DOCUMENT/REPORT EXAMPLES

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QUALITY ASSURANCE DOCUMENTS

Section III-1

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NORTHERN RESEARCH, INC.

QUALITY ASSURANCE

MASTER SCHEDULE

PROJECTIONS:

QAU Inspections I

Protocol Issued P

Final Report R

Interim Report r

Test Study Test Study Study Nature of Study and Current

Article Identity System Initiation Director Status/Final Report M A M J

AC-123 99-322 Mouse 01/07/00 Smith Acute PO Tox/In-Preparation R

AC-123 00-107 Rat 03/09/00 Robbins One-Month IV Tox/In-Process I I R

BD-149 99-257 Dog 09/19/99 Robbins Three-Month IV Tox/

Issued 3/26/00 R

BD-149 99-314 Monkey 12/17/99 Williams Six-Month IV Tox/In-Process I I

RS-160 00-059 Rat 03/25/00 Smith Acute IV Tox/Protocol P I R

RS-160 00-103 Rat 04/09/00 Smith One-Month IV/Protocol P I

TM-172 99-337 Salmonella 03/05/00 Gentry Ames Test/In-Preparation I R

VW-178 99-157 Dog 08/20/99 Robbins Twelve-Month Diet/In-Process IST-205 98-145 Mouse 08/06/98 Williams 2-Year Carcinogenicity Diet

In-Process r I

ST-205 98-147 Rat 09/20/98 Harris 2-Year Carcinogenicity Diet

In-Process I r I

WS-310 99-258 Dog 10/02/99 Anderson Three-Month PO Tox/In-Preparation R

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QUALITY ASSURANCE

STUDY INSPECTION RECORD

Study Title: Three-Month Intravenous Toxicity

Test Article: BD-149

Study Identity: 99-257

Study Species: Dog

Route: IV

Study Director: G. Robbins, Ph.D.Study Inspection Signature/ Inspection Corrective Action

Phase Dates Date Report No./Date Acceptance Date

Initiation 9/19, 20/99 A.D. Moulchin 9/20/99

9/24,25/99 A.D. Moulchin 9/25/99

In-Process 10/8, 1517/99 A.D. Moulchin

10/17/9910/2325/99 A.D. Moulchin 99-093 10/25/99 11/6/99

10/25/99

11/1215/99 A.D. Moulchin 11/15/99

Completion 12/1720/99 A.D. Moulchin 99-112 12/20/99 1/8/00 12/20/99

1/13,14/00 A.D. Moulchin

1/14/00

2/5/00 A.D. Moulchin2/5/00

Reporting 2/28/00 A.D. Moulchin2/28/00

3/46/00 A.D. Moulchin3/6/00 00-027 3/6/00 3/20/00

Version 1

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QUALITY ASSURANCE

STUDY INSPECTION RECORD

Study Title: Three-Month PO Toxicity

Test Article: WS-310

Study Identity: 99-258

Study Species: Dog

Route: PO

Study Director: J. B. E. Anderson, Ph.D.Study Inspection Signature/ Inspection Corrective Action

Phase Procedure Dates Date Report No./Date Acceptance Date

Initiation PRO 10/2/99 P. Verke10/2/99

AWS 10/2/99 P. Verke10/2/99

FOR 10/9/99 P. Verke10/9/99

In-Process AWS 10/7/99 P. Verke

10/7/99DOS 10/9/99 P. Verke 99-097 10/9/99 10/17/99

10/9/99FOR 11/12/99 P. Verke

11/12/99BCN 12/2/99 P. Verke

12/2/99OBS 12/6/99 P. Verke

12/6/99DOS 12/10/99 P. Verke

12/10/99Completion NEC 1/2, 3/00 P. Verke

1/3/00CCH/HEM 1/2,7/00 P. Verke 00-002 1/7/00 1/23/00

1/7/00MJC 2/19/00 P. Verke

2/19/00Reporting RPJ 4/7-9/00 P. Verke

4/9/004/16/00 P. Verke

4/16/00 00-017 4/16/00 4/27/00

Version 2

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QUALITY ASSURANCE

INSPECTION REPORT

To:______________________________ and ________________________

______________________________ ________________________

Please respond to the observation below, and return this report to theQuality Assurance Unit by 9/6/99.

__________________________

__________________________ __________________________

__________________________ __________________________

This is a CONFIDENTIAL legal document that is to be maintained by Quality Assurance for the pe-riod of time as prescribed by the Good Laboratory Practice Regulations.

STUDY PHASE(S) INSPECTED INSPECTION DATE(S)

Initiation:

In-Process:

Completion:

Reporting:

B. W. Herrick B. W. Herrick 8/6/99

OBSERVATION: The scale used in measuring body weights had an expired calibration date. Weigh-ings were done 8/2/99; the labeled calibration expiration date of this scale, Asset#434, was 7/25/99.

RESPONSE: All the scales and balances within this facility are in a scheduled calibrationprogram. The Calibration Record for the above scale indicates that it was calibratedon 7/24/99; however, the calibrator had failed to replace the calibration tag withone having the correct information. Metrology had been contacted and will makethe correction.

Prepared By: H. James Date: 8/8/99

Approved By: K. Bellows Date: 8/9/99

Proposed Completion Date(s): 8/14/99

Study Director: W. Harris Date: 8/12/99

QAU REVIEW:

Action Plan Acceptance Date: August 13, 1999

By: B. W. Herrick

Completed: 8/19/99

W. Harris, PhD

STUDY DIRECTOR

K. Bellows, DVM

MONITOR

Report Number: 99-092

Study Number: 98-147

Test Article: ST-205

Page: 1 of 1

Date: 8/6/99

5/24; 6/12, 20; 7/8; 8/2/99

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QUALITY ASSURANCE UNIT STATEMENT

Periodic Inspections of Study Number 99-257 entitled Three-Month IV Toxicity Study of BD-149 inDogs were conducted on all phases by the Quality Assurance Unit of Northern Research, Inc.

The study was inspected on the following dates:

September 19, 20, 24, 25, 1999

October 8, 1517, 2325, 1999

November 1215, 1999

January 13, 14, 2000

February 5, 2000

February 28, 2000

March 4, 6, 2000

Results of inspections were reported to Management and the Study Director on 10/25, 12/20/99, and3/6/00.

To the best of the signators knowledge there were no significant deviations from the Good LaboratoryPractice Regulations that affected the quality of integrity of the study.

______________________________ __________________________

James A. Kensington Date

Manager, Quality Assurance

James A. Kensington 3/6/00

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INSPECTION REPORT EXAMPLES

Section III-2

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QUALITY ASSURANCE

INSPECTION REPORT

To:______________________________ and ________________________

______________________________ ________________________


__________________________

__________________________ __________________________

__________________________ __________________________



Initiation:

In-Process:

Completion:

Reporting:

A. V. Moulchin A. V. Moulchin 3/26/00

OBSERVATION: The study protocol did not include the following information as required by theGLP (58.120):

The procedure for identification of the test system

The statement of the proposed statistical methods to be used

RESPONSE: Protocol Change #2 has been approved and issued. It includes both the procedurefor identification of the rats and the proposed statistical methods to be used.

Prepared By: R. Derich Date: 3/26/00Approved By: W. C. Jones Date: 3/27/00


Study Director: J. C. Smith Date: 3/27/00

QAU REVIEW:

Action Plan Acceptance Date: March 30, 2000

By: A. V. Moulchin

Completed: 3/30/00

J. C. Smith, PhD

STUDY DIRECTOR

W. C. Jones, DVM, PhD

MONITOR



Test Article: RS-160

Page: 1 of 1

Date: 3/26/00

3/25/00

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QUALITY ASSURANCE

INSPECTION REPORT

To:______________________________ and ________________________

______________________________ ________________________


__________________________

__________________________ __________________________

__________________________ __________________________



Initiation:

In-Process:

Completion:

Reporting:

P. Verke P. Verke 3/6/00

OBSERVATION: SOP 43-74A, Subcutaneous Injections of Primates, requires the use of a 23-gaugeneedle for administration of the test article mixture or control substances for a2-minute duration. A 20-gauge needle was being used, and the mixtures were ad-ministered for a duration of 1 minute.

RESPONSE: For these larger primates (4.55.5 kg) the increased cannula size and administra-tion rates are appropriate. The SOP will be modified, reflecting the increases incannula size and administration rates correlated with primate weight averages.

Prepared By: W. Strykowski Date: 3/12/00Approved By: K. Bellows Date: 3/14/00


Study Director: D. Williams Date: 3/17/00

QAU REVIEW:

Action Plan Acceptance Date: 3/20/00

By: P. Verke

Completed: 4/16/00

D. Williams, PhD

STUDY DIRECTOR

K. Bellows, DVM

MONITOR




Page: 1 of 1

Date: 3/6/00

12/17, 18, 24/99; 3/2, 6/00

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QUALITY ASSURANCE

INSPECTION REPORT

To:______________________________ and ________________________

______________________________ ________________________


__________________________

__________________________ __________________________

__________________________ __________________________



Initiation:

In-Process:

Completion:

Reporting:

A. D. Moulchin A. D. Moulchin 12/23/99

OBSERVATION: During necropsy, spinal fluid was collected from each animal. No departmentalSOP existed describing this procedure.

RESPONSE: The method describing this procedure has been written and will be documented ina new SOP.

Prepared By: J. Rodriguez Date: 12/27/99

Approved By: L. Kannal Date: 1/2/00

Proposed Completion Date(s): 1/17/00Study Director: G. Robbins Date: 1/3/00

QAU REVIEW:


By: A. D. Moulchin

Completed: 1/21/00

G. Robbins, PhD

STUDY DIRECTOR

L. Kannal, PhD

MONITOR




Page: 1 of 1

Date: 12/20/99

12/1720/99

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QUALITY ASSURANCE

INSPECTION REPORT

To:______________________________ and ________________________

______________________________ ________________________


__________________________

__________________________ __________________________

__________________________ __________________________

This is aCONFIDENTIAL

legal document that is to be maintained by Quality Assurance for the pe-riod of time as prescribed by the Good Laboratory Practice Regulations.


Initiation:

In-Process:

Completion:

Reporting:

A. D. Moulchin A. D. Moulchin 3/9/00

OBSERVATION: The following were observed in the appended Statistical Report:

In Table 2, Urinanalysis, the mean pH of the T2 females and T3 males are respec-tively recorded as 6.5 and 7.3. Calculations associated with the raw data indicate re-spective mean pH of 6.7 and 7.0.

In Table 5, Absolute and Relative Animal Organ Weights, the mean kidney weightof the T4 males is recorded as 44.23 g. Calculations associated with the raw data in-dicate a mean of 47.57 g.

RESPONSE: The errors noted above in Tables 2 and 5 of the Statistical Report have been cor-rected and the database changed to reflect the raw data.

Prepared By: R. Chin, PhD (Statistician) Date: 3/12/00

Approved By: B. Murphy, PhD (Stats. Mgr.) Date: 3/17/00


Study Director: G. Robbins Date: 3/18/00

QAU REVIEW:


By: A. D. Moulchin

Completed: 3/23/00

G. Robbins, PhD

STUDY DIRECTOR




L. McCarley, MS

MONITOR

Page: 1 of 1

Date: 3/6/00

2/28; 3/4, 6/00

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QUALITY ASSURANCE

AUDIT REPORT

Report Number: 99-105 Page 1

Date: 11/26/99

Department Audited: Analytical Chemistry

Location: Coeur dAlene, ID

Date(s) Audited: 11/1821/99

Auditors: M. Simpson M. Simpson 11/26/99

OBSERVATION: 1The Test Method validation file for determining the potency of test articleST-211 had been approved by the department manager on 10/16/99. Animals in

study 99-125 were dosed with this compound seven days prior to approval of the

validated test method on 10/9/99.

2SOP 796-35.02, MS-345 Determination-HPLC, approved 5/3/97, requires thatfor each standardization and test, the chromatographic system components be

identified on the charts.

Examination of the applicable HPLC charts, run 11/06/99, indicate that only the

column has been identified.

RESPONSE: 1The Test Method for the determination of potency for ST-211 includes more

than three determinations consistently using the same methodology and performed

by the same scientist. This had been reviewed in Dr. Shaws Laboratory Notebook,accepted and acknowledged by management on 10/3/99. The formal Test Method-

ology Report was signed, as indicated, on 10/16/99. An explanation will be written,

filed both in the validation file and with the documentation for study 99-125.

2These identity requirements had inadvertently been excluded; however, they

had been recorded in the scientists Laboratory Notebook, and have now been tran-scribed to the proper charts. This individual and other members of the department

have been cautioned to be more meticulous.

Prepared By: R. Shaw, PhD, Methods Development Date: 11/28/99

Approved By: W. Kimura, PhD, Laboratory Manager Date: 12/4/99

QAU REVIEW:

Report Return Date: 12/5/99

Accepted By: J. A. Kensington Plan Accepted Date: 12/6/99

Title: Manager QA

Auditor: M. Simpson Plan Completed Date: 12/18/99

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QUALITY ASSURANCE

AUDIT REPORT

Contract Laboratory

Report Number: 00-030 Date: 6/18/00

Facility Audited: Southwestern Laboratories (SWL)

Location: Albuquerque, NM

Date(s) Audited: 6/11/00

Auditors: B. E. Anderson B. E. Anderson 6/18/00AUDIT SCOPE: At the request of Drug Safety Evaluation (DSE), the QAU evaluated the

organization, facilities, operations, and SOPs of SWL with intensive sur-veillance of their QAU.

AUDIT COVERAGE:Facilities: There are four buildings at this site, three used for nonclinical studies. Primates

were in Bldg. B; observed building and room maintenance, cage washing, and fa-

cility security. Bldg. A contained the QAU, the archives, and computer opera-tions. Evaluated QAU facilities and files. Observed raw data, report retention,

and histology tissue storage.

Operations: Observed technicians IM dosing, measuring body weights and food consump-

tion, recorded by clinical signs; general facility animal husbandry and computer

operations. Concurrently reviewed the QAU auditors documentation process.

Documentation: Reviewed the SOPs of the study function groups and the QAU. Also reviewed the

Master Schedule, CVs of personnel, pest applicators log, cage wash equipmentlog, instrument calibrations, and primate TB treatment test records.

Recommendation: Our evaluation of SWL indicates that it has an excellent staff of scientific and

technical personnel. Their management personnel stress total compliance and

administer the most stringent international standards to all of their contracted

regulated studies. We would recommend contracting with SWL, contingent ontheir acquiring a remote secondary backup tape storage facility.

Observation: SWL stores its computer backup tapes within the computer operations facilities

of Bldg. A. It does not have off-site location for the secure storage of secondary

backup tapes.

Response: In my phone conversation of 6/22/00 with Dr. Simmons, President of SWL, he

informed me they have a project commencing on 7/1/00, providing for second-ary computer tape storage in a local bank vault.

Prepared By: K. Patel, DVM, Toxicologist Date: 6/23/00

Approved By: R. Schubert, PhD, Director DSE Date: 6/25/00

QAU REVIEW:

Report Return Date: 6/23/00

Accepted By: J. A. Kensington Plan Accepted Date: 6/24/00

Title: Manager QA

Auditor: B. E. Anderson Plan Completed Date: 7/6/00

PH1066_III

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