reduce risks and costs for laboratory equipment qualification … · costs for laboratory equipment...

Reduce Risks and Costs for Laboratory Equipment Qualification

Gary Powers Global Compliance Program Manager

1

Aspects of Instrument Qualification

4 Q Model for Instrument Qualification

PQ DQ OQ IQ

Does it Meet your USER

REQUIREMENTS

Design Qualification

Installation Qualification

Has it been INSTALLED CORRECTLY

Operational Qualification

Performance Qualification

Does it WORK as YOU

EXPECTED

Will it CONTINUE to

work CORRECTLY

But there are no set rules, and people do not agree on:

WHAT content is in each of the stages HOW often an OQ should be performed WHO performs the stages (OQ / PQ) WHAT needs to be done during the lifecycle

Company Confidential

4

DQ

Use OQ

IQ Maintenance

Re-Qualification (Justification)

Breakdown

Repair Re-Qualification (Justification)

Is the instrument suitable for use?

Is it installed correctly?

Is there an SOP? Are people trained? Calibrated? Validated method?

Maintenance Routine?

Failure management Impact of failure CAPA?

Re-Qualification / Calibration

What do you want the system to do?

- Write it down - Why is it suitable?

Does it work?

- Installed correctly - In your laboratory

What about the future?

Audit Focus



Frequent Questions

Justification:

OQ – How Often RQ – What to include


Instrument Lifecycle

Search “FDA Warning Letters”

5

http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/default.htm

Basic Search Engine


http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/default.htm

Search for “HPLC”

6

A B C

D E


FDA Warning Letters by Technique

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• KF – 2 • NMR - 2 • FTIR – 3 • FT-IR – 7 • Infrared – 47 • GC – 14 • Chromatography - 26 • Dissolution – 38 • UV – 43 • HPLC – 60 • Qualification – 303 • Calibration – 405 • Training – > 1,000 • Agilent - 0

• Pharmaceutical Manufacture

• Medical Devices

• Food Imports (3,000, 128,000, 48,000,000) (Updated M. Hamburg Speech, 4th Oct. 2011)

• Neutraceuticals (Fundamental cGMP)

• Cosmetics

• Tobacco Products

Searched 26 Feb 2013

Manufacturing Process Qualification

Supplier Qualification


8

725

535 538 471 445 474

673

1720

0

200

400

600

800

1000

1200

1400

1600

1800

2000

2200

2400

2600

2800

3000

2002 2004 2006 2008 2010 2012 2014

2767 www.fda.gov/downloads/ICECI/EnforcementActions

Margaret Hamburg joins FDA

FDA

War

ning

Let

ters

Trend down to flat

Trend sharply up

FDA Audits: 97 % of US Facilities [pharmaceutical, every 2 years]

FDA Audits: 7 % of Non US Facilities [pharmaceutical every year]

[Source: Journal of Validation Technology; D. W. Vincent, Winter 2012 edition]

Mutual recognition audits [Tougher “National” Audits]

Risk-based audit triggers…… Whistle blowers….


FDA Warning Letters FY 2004-2012

http://www.fda.gov/downloads/ICECI/EnforcementActions

FDA HPLC Warning Letters

9

0 1 2 3 4 5 6 7 8 9 10 11 12

Data Integrity - No Electronic Review

Data Integrity - Security

Data Integrity - Incomplete Records

Data Integrity - Data Deletion

Deficient HPLC Method

HPLC Method Validation

Chromatography - Unknown Peak

Problems With System Suitability

Repeat Work - No Justification

Repair Impact Assessment

OOS Problems

N/A

No Data Backup

No Calibration

Calibration Defeciencies

No HPLC - But Chromatograms !

1

7

3

1

5

8

3

3

1

2

2

4

1

8

10

1

92% related to Data Integrity

0 1 2 3 4 5 6 7 8 9 10 11 12

Data Integrity - No Electronic Review


Data Integrity - Incomplete Records

Data Integrity - Data Deletion

Deficient HPLC Method

HPLC Method Validation

Chromatography - Unknown Peak

Problems With System Suitability

Repeat Work - No Justification

Repair Impact Assessment

OOS Problems

N/A

No Data Backup

No Calibration

Calibration Defeciencies

No HPLC - But Chromatograms !

1

7

3

1

5

8

3

3

1

2

2

4

1

8

10

1

Calibration: Biggest Single Category (30 %)

Decisions & Justification

Using the Method

Data Integrity

Capability of the Method

Would you trust these data ?

Poor Compliance SOP’s

Poor HPLC Use / Training

HPLC Methods


From 2001


Most concern validity of analytical results

FDA “HPLC” Warning Letters last 12 years

10

More HPLC warning letters issued than any other year!

0

1

2

3

4

5

6

7

8

99

5

6

3

4 4

3

2 2

4

5 5

Year

FDA HPLC Warning Letters


FDA GC Warning Letters

11

Most concern validity of analytical results 86% related to Data Integrity

Read Evaluate Risks Categorize Knowledge

0 1 2 3 4 5 6

Data Integrity - No Raw Data


N/A

Defecient GC Method

GC Method Validation

System Suitability

Calibration Deficiencies

No Calibration

No GC

1

1

2

1

1

1

2

4

1

0 1 2 3 4 5 6

Data Integrity - No Raw Data


N/A

Defecient GC Method

GC Method Validation

System Suitability

Calibration Deficiencies

No Calibration

No GC

1

1

2

1

1

1

2

4

1

Poor GC Use / Training

GC Methods

Calibration: Biggest Single Category (43 %)

Using the Method

Data Integrity

Capability of the Method




HPLC/GC FDA Warning Letters vs. Lifecycle

12

Calibration 24

Method Use 7

Method Capability 15

Data Integrity 14

Impact Assessment 2


What are the most common deficiencies in

calibration / qualification?

Review of FDA Warning Letters what OQ / Calibration Problems does FDA Find ?

• OQ not good enough - Critical parts of system not qualified adequately or did not qualify range of use [27 % HPLC, 36 % GC of warning letters on these techniques] Example:

• People not adequately trained – FDA observe people doing the work [High feature in EIR Data Review]

• No raw data for the work – Firm could not show inspectors the raw data [More common in India and China] Example:

• Tools used were not calibrated – Tools used in an OQ must be calibrated. Example:

• OQ failures not detected – By person doing the work or managers checking it. Example:

• Data integrity – Data not assured or not secure - could have been tampered with [Most significant area, includes all the above]. Example:

http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/2009/ucm183410.htm [Ion Labs. 2009]

http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/2010/ucm249641.htm [Nanjing Pharmaceuticals, 2010]

http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/2010/ucm236841.htm [Yuki Gosei Kogyo, 2010]

http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/2009/ucm136661.htm [Time-Cap Labs., 2006]

http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/2010/ucm249641.htm [Nanjing Pharmaceuticals, 2010]

http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/2012/ucm298187.htm [UNAM, 2012]

http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/2009/ucm183410.htm







Laboratory Compliance Risk

15

“Too Little” Compliance

(High Risk)

Laboratory Compliance Risk is about “getting it right ”

• Damage to reputation • Loss of accreditation

• Cost of “Cost Savings” • What are “Real Costs” Many companies don’t know

“Too Much” Compliance

(High Cost)

Risk Implications to consider:

• High “visibility” of non-compliance + “risk rating” • Low Risk – Faster Review / High Risk - AIP (FDA - Application Integrity Program)

• Now much wider than laboratory cost savings……

Laboratory Compliance


May 15, 2014 Confidentiality Label

16

Data Integrity

Data

Prove your data are not fraudulent

• ALCOA…. (understand) • Build lab workflow • Compare results to electronic • Data Integrity audits

• All electronic • Not tampered with • Implement reviews

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• Scientific “Validity” • ICH Q9, Q10, Q11 support

• FDA Part 11 “add-on” Audits • Jan. 2011

• Data Integrity has always been an FDA focus

• 1997 Implementation • 2003 Guidance

Science Based GMP Decisions

(e.g. cGMP for 21st Century)

Fundamental Data Integrity

21 CFR Part 11

Part 11 Add on Audits

FDA focus on data integrity

[ PAI, Consent Decree, Data Integrity Training… etc. ]


Data Integrity drives Harmonization

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1. Sample Receipt

2. Booked into LIMS

3. Schedule Tests

4. Sample Preparation

5. Chromatograph Sample

6. Calculate Results

8. Compare Against Specification

7. Check / Report Results

“21 CFR Part 11 = Good Document Practice for Electronic Data”

A ttributable [Who did it]

L egible [Can you read it]

C ontemporaneous [Done in “Real Time”]

O riginal [Is it original]

A ccurate [Is it Accurate]

Electronic Log Vs. Ink Signature

Print Vs. Handwriting

Electronic Log Vs. Written Data

Secure Electronic File Vs. Paper “Photocopy”

Validated Electronic Output Vs. Paper….

Electronic Vs. Paper

Greater Risk (easier to manipulate) ?

More Secure (harder to manipulate) ?


How to Balance – Costs Vs. Risks

19

Costs

Costs

As long as laboratory compliance is perceived as a cost burden, a cost saving mind set will prevail

Generally, compliance risks are based on perceptions, while costs savings are based on a spreadsheet

Costs Compliance


Laboratories that Follow Compliance Best Practice:

20

Good Defense

Robust, well structured, understood, rehearsed “why are your results valid”?

this is the starting point….

Are Aware and Manage

Any gaps around their history, use, origins, qualification, problems “show me…..” ?

Can explain and defend instrument control strategy

Are Proactive

Prepared for future compliance trends that will affect them “what if…..”?

Perform gap analysis against those trends


Laboratories that Follow Compliance Best Practice:

21

Minimize

Instrument down time using efficient, coordinated maintenance and qualification processes such as Agilent Enterprise Edition

ROI for LC-MS, GC-MS and UHPLC

Range of Use

Qualify the range where their instruments are used no additional awkward qualification or justification

Linked to the methods they use

Understand

Traceability of raw data in their qualification reports and can demonstrate this

Supported by fully integrated electronic reports


Agilent Enterprise Edition

22 Agilent Confidential

Agilent Enterprise Edition analytical instrument qualification is automated, paperless and compatible with instruments from all leading vendors

Innovation in Compliance

Enterprise Edition reduces regulatory risk: • Harmonization across instruments • Flexibility to configure testing to SOP requirements • Full automation to assure adherence to protocol • Electronic reports and signatures

Equipment Qualification Plan – Universal Protocol


Harmonization

• Single protocol per technique

• Protocols compatible with systems from all leading vendors – Waters, PerkinElmer, Thermo, Shimadzu, Dionex, many more

• One protocol for QA to approve saves time

Testing Flexibility

• Specify set points/limits, add/remove tests without interfering with test design

• Specify testing based on your SOP requirements

Configurable Testing


Agilent Enterprise Edition Innovation

Paperless Reports


Single locked .pdf report • More secure GxP record • One single signature required

All-electronic information • Legible data entries, results and signatures • Electronic Routing for review • Export to external ECM and data bases

Reports burned to CD-ROM • Total integrity, 21 CFR Part 11, ISO compliant format • Less storage space and lower archival costs


Automated Compliance Engine



ACE efficiently enforces compliance to procedure

• Fully automated protocol

• Validated calculations

• Simultaneous qualification

• Results fully traceable to raw data

• Reports free of transcription errors

• Automated pass/fail report

ACE Partner Edition


• Access to all Agilent-developed and -tested protocols: (IQ, OQ, RQ, MQ, PQ, FV, PM)

• Assurance of auditability following approved and locked test methodology

• Customize protocol using the EQP Editor • ACE qualifies the latest technologies

including GC, LC, MS, Disso, UV, ICP-MS, AA, more

• Training and support for more effective teams

• Agilent-mentored deliveries help ensure success

• Far more robust compared to smart pdf’s and spreadsheets, especially in an audit

Agilent Compliance Innovation

ACE Partner Edition


• Simple OQ setup typically takes less than 10 minutes move immediately to protocol execution

• Multiple sessions run simultaneously easy to duplicate, restore • Previous session recall without fear of losing past work • Parallel services run multiple simultaneous compliance services • Parallel processes complete documentation while running OQ • Task-based working instructions now include GC and GC/MS • Direct data retrieval from PC


Process Data

Run Qualification

Documentation

Attachments

Agilent Compliance



Questions? For more information

please visit us online at

www.agilent.com

http://www.chem.agilent.com/en-US/products-services/Services/Analytical-Instrument-Services/Pages/default.aspx

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