Preparing Your Analytical Lab For A Regulatory Audit

Preparing Your
Analytical
Laboratory for a
Regulatory Audit
Live Webinar
Paul Smith
paul_smith@agilent.com
Confidentiality Label
May 2, 2014
1
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May 2, 2014
2
PREPARING YOUR ANALYTICAL LABORATORY
FOR A REGULATORY AUDIT
May 2, 2014
3
Possible Audits You May Face
Laboratory
May 2, 2014
4
Environmental
Health &
Safety
Financial
Accreditation Body
ISO: Internal
13485 / 17025 / 9001 (Self-Audits)
Customs &
Excise Laboratory Customers
May 2, 2014
5
Environmental
Health &
Safety
Financial
Pharmaceutical
Regulatory
Accreditation Body
ISO: Internal
13485 / 17025 / 9001 (Self-Audits)
Customs &
Rules Applied
& Possible Actions..
Vary Between Audits.... Industries
May 2, 2014
6
Environmental
Health &
Safety
Financial
Pharmaceutical
Regulatory
Accreditation Body
ISO: Internal
13485 / 17025 / 9001 (Self-Audits)
Customs &
CORPORATE
(Sometimes the Hardest !)
Rules Applied
Vary Between Audits.... Industries
May 2, 2014
7
Environmental
Health &
Safety
Financial
Pharmaceutical
Regulatory
Accreditation Body
ISO: Internal
13485 / 17025 / 9001 (Self-Audits)
Customs &
CORPORATE
Rules Applied
But, many of the same principles apply to
Vary Between Audits.... Industries ALL AUDITS..
May 2, 2014
8
Possible Audits You May Face Audits Preparation is
a Strategic Priority !
Environmental Run as a Project !

Health &
Safety
Financial
Pharmaceutical
Regulatory
Accreditation Body
ISO: Internal
13485 / 17025 / 9001 (Self-Audits)
Customs &
CORPORATE
Rules Applied
But, many of the same principles apply to
Vary Between Audits.... Industries ALL AUDITS..
Prepare Well Once Then Update / Apply

May 2, 2014
9
Compliance Drivers All Industries
Analytical Service
Commercial
Are Your Results Valid ?
Reasons
Compliance Reasons
May 2, 2014
10
Compliance Drivers All Industries
Analytical Service
Commercial
Are Your Results Valid ?
Reasons
Compliance Reasons
Pharmaceutical GXP ISO 9001 ISO 17025
Influenced by Where you: Quality Management System Testing & Calibration

- Manufacture - Manufacture Laboratories
- Supply - Supply
National Pharmacopeia's Influenced by: Influenced by:

USP - Scope of Accreditation - Scope of Accreditation
EP
Clauses
JP 4.13.1.2
4.2.4 Control of Records 5.2.1
EU GMP 7.4.3 - Materials 5.2.3
7.6 Measurement 5.3.1
CFR Equipment 5.4.6.1
(Code of Federal Regulations) 5.4.7.1
8.5.2 - Corrective Actions 5.5.2
8.5.3 - Preventative Actions 5.5.4.Etc.
May 2, 2014
11
How Do You Know Your Results are Valid ?
Correct Reference Materials Were Used

Training Records - The Analyst Was Trained
System Suitability The Method Was Working Correctly
Method Limits Were Validated

Instrument Was Qualified / Calibrated. Etc.
May 2, 2014
12
How Do You Know Your Results are Valid ?
Correct Reference Materials Were Used

Training Records - The Analyst Was Trained
System Suitability The Method Was Working Correctly
Method Limits Were Validated

Instrument Was Qualified / Calibrated. Etc.
The above align with United States

Pharmacopeia (USP) general
chapter 1058 on Analytical
Instrument Qualification (AIQ).
The Principles of This Data Triangle
Apply to All Labs!
May 2, 2014
13
Managing The Audit What to Expect
Who Has Been in an FDA Audit ?
Official Role
Inspector
Host Broad
Knowledge
- stay with inspector
Fronter
Technical
Experts
Scribe - Subject
Runner Records
- Time asked
supplied
Gets what's
asked
(Info. / People)
May 2, 2014
14
Strategic Role
Inspector
Reads
Host Inspector
Fronter Believable
Scribe
Runner Records
- Actions
issues..
Spy
(In Out)
May 2, 2014
15
The Control Room is Staffed
by experienced personnel who:
Keep calm under pressure
Know site & company systems well
Documentation Experts
Audit
Control
Suppliers
Room
Inspector
Runner
Host
Information
Fronter
Scribe
Runner
May 2, 2014
16
The Control Room is Staffed
by experienced personnel who:
Keep calm under pressure
Know site & company systems well
Documentation Experts
Audit
Control
Suppliers
Room
Inspector
Runner
Host
Information
Fronter
Scribe
Runner
Audit Decisions: Live Software Vs. Presentations / Simulated
FDA Now LIVE (Agilent is Supporting Customer FDA Audits)
Electronic or Paper Request System
May 2, 2014
17
Managing Document Requests
Have to Remain Compliant During The Audit
With some inspections, such as the FDA, there may be SEVERAL
Inspectors
Original Approved Master Document provided to Inspectors
Requests from Audit ..

Requests from Control Room.
What is requested?
Time of Request
Who is required (to Front/Present the Information)
White Copy Stays in Audit

Pads Blue Copy Stays in Control Room
Of
Green Copy Attached to
Request 1. Information
Forms 2. Pink Copy Left in the
Filing System
3. (in case someone
requests original)
4.
May 2, 2014
18
Audit Preparation Focus Area..
Area Subject Comments
A. Debarment
People A. Training
B. Demographics
Suitable for Use ?
Equipment Life Cycle Management
Return to Use
Validation / Change Mgt.

Methods Training / Uncertainty (ISO)
Data Integrity
Data Life Cycle
Internal
Audits Observations
Actions from Audits

Observations Customer Complaints
May 2, 2014
19
Audit Preparation Focus Area..
Area Subject Comments
A. Debarment A. FDA Web Site

People A. Training B. Structure / Proof
B. Demographics C. Justification of Resource
Suitable for Use ? Expected <1058> Changes

Equipment Life Cycle Management USP General Chapters
Return to Use GAMP USP Harmonisation
Validation / Change Mgt. USP Stimulus Paper (QbD)

Methods Training / Uncertainty (ISO) (Method Validation & QbD
Pharmacopeiai Forum)
Data Integrity FDA Focus Area
Data Life Cycle 21CFR Part 11
Chapter 4 / Annex 11
Internal Are you doing them ?

Audits Observations
Resolution of Observations
Actions from Audits Have you resolved them?
Observations Customer Complaints HPLC FDA Warning Letters (62)
(28% Repeat, 38% Poor Response (CAPA)
May 2, 2014
20
Audit Preparation Focus Areas + Data Integrity
Job Description / Training Records

People Demographics / Age / Qualifications
Expertise / Skills Map
Audit Risk ? Validation Status
Analytical Methods Technology Transfer
Registration
Suitability for Use Review (e.g. OOS)
Analytical Equipment Maintenance
Qualification / Calibration
Training (Technique / Instrument / SOP)
Validation / Reviews
Qualification Software / Computer Systems Change
Configuration Mgt. Control
Approved
Procedures In Date
Is the Ink Wet !
Housekeeping Justification
Infrastructure Electricity
Location of Instruments Audit
Questionnaires
Supplier Approval Lab. Supplier Approval
Quality Agreement
May 2, 2014
21
What did You Mean ?
May 2, 2014
22
What did You Mean ?
Terms Used:
1. Calibration [21 CFR 211.160 (b) (4), FDA]
2. Qualification [USP, e.g. <1058>]
3. Validation [Method, Process, Software]
4. Verification [GAMP 5, ASTM E2500]
May 2, 2014
23
TYPES OF AUDIT
May 2, 2014
24
How The Audit is Performed.
Records Trace Pedigree / History
Hierarchical
Examine the Manufacturing Records
Examine the Lab. Results
Hierarchical Examine the Analyst Training Records
Examine the Instrument Details... Etc.
Emphasis Identify areas of non-compliance in the INFORMATION
Scope Limited by where the inspection starts (e.g. which batch)
May 2, 2014
25
How The Audit is Performed.
Records Trace Pedigree / History
Hierarchical
Examine the Manufacturing Records
Examine the Lab. Results
Hierarchical Examine the Analyst Training Records
Examine the Instrument Details... Etc.
Emphasis Identify areas of non-compliance in the INFORMATION
Scope Limited by where the inspection starts (e.g. which batch)
System Based Inspection Examine Your Quality System

Examine Your - Analyst Training Process
Generic System Instrument Selection and Qualification
Batch Failures / Out of Specification Results
Questions: Your Trending and Quality CAPA System
Emphasis Identify areas of non-compliance in your QUALITY SYSTEM
Scope Your whole quality system everything WIDER RANGING
Hierarchical Some Element of Luck System-Based Inspection

(depending on where it starts)
Prepare, Prepare, Prepare
May 2, 2014
26
Kinds of Audit
Quality Management System
Is it Effective ?
Some Component
- Quality Mgt.
Early Observation.
ISO 9001 CAPA follow up
Emphasis Evaluate if Quality System is Effective for - SCOPE of ACCREDITATION
May 2, 2014
27
Kinds of Audit
Is it Effective ?
Some Component
- Quality Mgt.
Early Observation.
Is it Valid Technical Review of What You Do

Examine Your Systems
- Technical Evaluation
Uncertainty of Measurement (not just pass / fail)
ISO 17025 CAPA
Accredited Calibration ISO 13485 Medical Devices Adverse Effects
Accredited Services Control
Emphasis Problems & Technical Evaluation of What You Do Scope of A..
May 2, 2014
28
Kinds of Audit
Is it Effective ?
Some Component
- Quality Mgt.
Early Observation.
Is it Valid Technical Review of What You Do

Examine Your Systems
- Technical Evaluation
Uncertainty of Measurement (not just pass / fail)
ISO 17025 CAPA
Accredited Calibration ISO 13485 Medical Devices Adverse Effects
Accredited Services Control
Emphasis Problems & Technical Evaluation of What You Do Scope of A..
Now Assume - You Are Fraudulent

Is it Fraudulent ? Until You Can Prove Otherwise
Data Integrity (electronic data)
FDA Independent Data Integrity Auditing
Emphasis We dont Trust / Believe You - EVIDENCE
May 2, 2014
29
PREPARE YOUR PEOPLE
May 2, 2014
30
Prepare Your People
Some inspectors
are HOSTILE,
The Future of
this site depends..
ALL inspectors can be

Intimidating.
May 2, 2014
31
Prepare Your People
People who talk to the auditor must:
BE CONFIDENT in what they say

ONLY answer questions on what they are knowledgeable
ONLY answer QUESTIONS ASKED (dont provide additional information)
SOME PEOPLE find audits very stressful and/or FIND 1 to 3 difficult
An inspector will:
ASK you to describein your own words (to check you understand)
CHECK what you say Vs. the Standard Operating Procedure (SOP)
OBSERVE YOU doing the work
CHECK records of previous examples
CROSS-CHECK with other departments
ASK QUESTIONS
May 2, 2014
32
Prepare Your People
Everyday phrase . Inspectors impression.
I think this is what happens
Normally, we would..
To be honest..
Thats not my problem
Thats too expensive
May 2, 2014
33
Prepare Your People
Everyday phrase . Inspectors impression.
I think this is what happens I would expect you to know what

happens
So what happens when its not

Normally, we would.. normal
To be honest.. Suggests you are not always

honest !
Thats not my problem Care this implies you dont care
Thats too expensive If you cant afford to have proper controls,

you shouldnt be doing this
Provide a rational reason !
May 2, 2014
34
Training
Personnel Training
Documented (Training File)
Background / Experience (CV / Resume)
GMP (Annual)
Job / Task Specific
Training Certificates
Testing of Knowledge (Demonstration of Understanding)
Personnel must have the proper

education, background, training and
experience to perform their job function.
May 2, 2014
35
INSTRUMENTATION
May 2, 2014
36
4 Q Model for Instrument Qualification
Installation Performance
Qualification Qualification
DQ IQ OQ PQ
Design Operational
Qualification Qualification
May 2, 2014
37
4 Q Model for Instrument Qualification
Does it Does it
Meet your USER Installation WORK as YOU Performance
REQUIREMENTS? Qualification EXPECTED? Qualification
DQ IQ OQ PQ
Design Has it been Operational Will it
Qualification INSTALLED Qualification CONTINUE to work
CORRECTLY? CORRECTLY?
There are no Set Rules on:
WHAT Some of The Stages Contain

HOW Often an OQ should be Done
WHO Performs Some of The Stages (OQ/PQ)
May 2, 2014
38
What will an Auditor Look at ?
What about:
- The future

What do you Re-Qualification
want it to do:
(Justification)
- Write it down
- Why is it suitable
IQ Maintenance

DQ Use
OQ
Breakdown
Does it Work:

- Installed correctly Re-Qualification Repair
- In your laboratory (Justification)
May 2, 2014
39
What will an Auditor Look at ?
Audit Focus
What about:
- The future Is the Instrument
Suitable for use
What do you Re-Qualification Accuracy / Uncertainty
want it to do:
(Justification) Sensitivity / Science
- Write it down Is it installed

- Why is it suitable Correctly
IQ Maintenance
Is there an SOP
Are people Trained
Is it Calibrated
DQ Use Method Validation
OQ
Breakdown Failure Mgt.
Impact of Failure
CAPA ?
Does it Work:
Maintenance
Routine ?
- Installed correctly Re-Qualification Repair
- In your laboratory (Justification)
Re-Qualification
/ Calibration
As Found
May 2, 2014
40
Laboratory Instrumentation .. Inventory Critical Instruments List
System URS DQ IQ OQ PQ Rationale Problems Actions

FT-IR
GC
HPLC
Dissolution
LC-MS
NIR
KF
pH Meters
Balances
. etc
List all your Critical Instruments
Review the Qualification Status /
History (Maintenance / System Log Book) of Each Instrument
May 2, 2014
41
User Requirements Specification Qualification Any What is Your

/ Design Qualification Rationale Problems ? Strategy ?

FT-IR
GC
HPLC
Dissolution
LC-MS
NIR
KF
pH Meters
Balances
. etc
May 2, 2014
42
User Requirements Specification Qualification Any What is Your

/ Design Qualification Rationale Problems ? Strategy ?

FT-IR
GC USP <1058> Includes Definitions of:

Roles:
HPLC User
QA
Supplier
Dissolution Responsibilities
DQ / IQ / OQ / PQ
LC-MS
NIR
KF
Work Flow Mapping / Data Integrity Output to Source File
pH Meters Independent Data Integrity Review sample / check
Data Integrity Detection Training
Balances
. etc
May 2, 2014
43
Laboratory Instrumentation. Status
What is Your
Does Your Laboratory Have These Rationale Any Strategy ?
[or their equivalent steps ?] - Monitoring Problems ? [about problems]

Calib. SSC
FT-IR B test site. Too Good !! Avoid in Audit ?
GC X X X USP, SSC URS, DQ, IQ Do OEM

HPLC X X Caffeine GAPS Do IQ Review
Dissolution OEM, USP Sets Std USE in Audit
LC-MS X X X X X Non Routine From R & D Move
NIR X Calibration No URS Retrospective

KF X X X Daily Test IQ, PQ only System Suit.
pH Meters X X X X In House PQ only Hide !

Balances OEM Calib. Fail Review Results
. etc ! ! X X Fragmented Mixture Panic !
= Present X = Absent
May 2, 2014
44
Laboratory Instrumentation. Status Decisions What do you do about
What is Your
Does Your Laboratory Have These Rationale Any Strategy ?
[or their equivalent steps ?] - Monitoring Problems ? [about problems]

Calib. SSC
FT-IR B test site. Too Good !! Avoid in Audit ?
GC X X X USP, SSC URS, DQ, IQ Do OEM

HPLC X X Caffeine GAPS Do IQ Review
Dissolution OEM, USP Sets Std USE in Audit
LC-MS X X X X X Non Routine From R & D Move
NIR X Calibration No URS Retrospective

KF X X X Daily Test IQ, PQ only System Suit.
pH Meters X X X X In House PQ only Hide !

Balances OEM Calib. Fail Review Results
. etc ! ! X X Fragmented Mixture Panic !
= Present X = Absent
May 2, 2014
45
Laboratory Instrumentation People / Contacts
System Owner User Expert 2nd Expert Supplier (s)
FT-IR (1) Paul John Paul Derek A
GC (4) Clare Peter Ted Mark B
HPLC (11) James Mark Carole Mike A
Dissolution (1) Dave R John Derek Rob C

LC-MS (1) James R&D Mike Rob D
NIR (1) Paul Paul Paul Derek A
KF (3) James Andy Derek Mark E
pH Meters (2) Dave R Mark Mark Andrew E

Balances (6) Clare Richard Derek Andrew F
. Etc Manager 7 5 4 7
Holiday Too Busy Company Closed !
Relationship with supplier in an Audit. (what would yours do ?)
May 2, 2014
46
DATA INTEGRITY
May 2, 2014
47
So, What is Integrity
Data Data Integrity ?
May 2, 2014
48
You have it electronically

Prove Your Data is Not Fraudulent ! It is not tampered withLabel
Confidentiality
Implement reviewsMay 2, 201449


ALCOA. (understand)
Build lab workflow
Check results to electronic
Data integrity audits
Data
Data Traceability is Essential
In Data Integrity.
You have it electronically

Prove Your Data is Not Fraudulent ! It is not tampered withLabel
Confidentiality
Implement reviewsMay 2, 201450

Example Identification by FT-IR
Sample
FT-IR Sample Infrared Spectrum Result

Preparation Spectrum Comparison
May 2, 2014
51
Sample

Only compare spectra recorded under the
ATR
same conditions
Nujol Mull
[equivalent scan and sample preparation
KBr Disk defined by Pharmacopeia Requirements]
Film Etc.
Sample Preparation
Influences:
1. Spectrum Appearance
2. Variability [Skill]
3. Quality of Spectrum
[subjective decision]
USP
EP
Registration
Procedures
May 2, 2014
52
Spectrum Quality:
[of the sample preparation not the identification]
Sample 1. Is the Quality of the sample
prep good enough ?
2. How managed / documented ?
[ OOS for sample prep. or procedure explaining
poor spectrum quality & how documented ]

ATR
Instrument Performance: same conditions
Nujol Mull
[How Do You Manage It ?] [equivalent scan and sample preparation
Film Etc. 1. Wavenumber [Accuracy]
2. Resolution [of Instrument]
3. Interference [contamination or water
Sample Preparation vapour]
Influences: 4. Reproducibility [of Spectra JP]
1. Spectrum Appearance 5. % T [Scale Not Linear]
2. Variability [Skill] 6. EP / JP / USP / IP / CP .. Etc.
[subjective decision] Spectra Do You:
1. Saved electronically or
USP 2. Define print out as raw data
EP [ FDA Data Integrity, Tamper Evident, Print
Registration Scan Conditions, Analyst cGMP, Etc.]
Procedures
Complete Data
May 2, 2014
53
Spectrum Quality: Spectral

[of the sample preparation not the identification] Comparison:
Sample 1. Is the Quality of the sample 1. Electronically or
prep good enough ? 2. Using Print Outs
2. How managed / documented ? [ Reference material or Spectra ]


ATR
Nujol Mull
3. Interference [contamination or water Reference Spectra:
Sample Preparation vapour] 1. Approval of FT-IR Identification Test
Influences: 4. Reproducibility [of Spectra JP] 2. Management of Suitability
6. EP / JP / USP / IP / CP .. Etc. [ of the Reference spectra & Materials Used ]
[subjective decision] Spectra Do You: File Management:
1. Saved electronically or Can Files Be:
USP 2. Define print out as raw data 1. Re-named ?
EP [ FDA Data Integrity, Tamper Evident, Print 2. Manipulated ?
Registration Scan Conditions, Analyst cGMP, Etc.] 3. Deleted ?
Procedures
Complete Data
May 2, 2014
54
Spectrum Quality: Spectral Validation

[of the sample preparation not the identification]
Comparison: [for intended use]
Sample 1. Is the Quality of the sample 1. Electronically or
prep good enough ? 2. Using Print Outs
[ Reference material or Spectra ]
Training
2. How managed / documented ? [& SOP]

ATR
Nujol Mull
3. Interference [contamination or water Reference Spectra:
Sample Preparation vapour] 1. Approval of FT-IR Identification Test
Influences: 4. Reproducibility [of Spectra JP] 2. Management of Suitability
6. EP / JP / USP / IP / CP .. Etc. [ of the Reference spectra & Materials Used ]
[subjective decision] Spectra Do You: File Management:
1. Saved electronically or Can Files Be: Differences:
USP 2. Define print out as raw data 1. Re-named ? 1. How Manage and
EP [ FDA Data Integrity, Tamper Evident, Print 2. Manipulated ? 2. Documented
Registration Scan Conditions, Analyst cGMP, Etc.] 3. Deleted ? [ What level is significant ]
Procedures
Complete Data
May 2, 2014
55
THE LABORATORY TOUR
May 2, 2014
56
Plan The Lab. Tour
KF
Office
Sample Storage / Weighing

Area
LIMS
HPLC
Fume
Write Up
Hoods
Write Up
Write Up
Sample
Receipt
May 2, 2014
57
Plan The Lab. Tour
KF
Office

Area
LIMS
HPLC
Fume
Write Up
Hoods
Write Up
Write Up
Sample
Receipt
May 2, 2014
58
Plan The Lab. Tour
KF
Office

Area
LIMS
HPLC
Fume
Write Up
Hoods
Write Up
Write Up
Clipboard with Flow Charts

Sample Receipt Paperwork Etc Sample
Receipt
May 2, 2014
59
Strategy For The Laboratory Tour
Plan the Lab Tour

Walk the route
Where would you like to stop ?
Where will you explain your Instrument Control (Calibration)?
What did your audit reveal ?
Look in cupboards!
What is Visible Housekeeping Etc.
Before the Audit EMPTY Tree CYCLERS / Bins Etc.
May 2, 2014
60
Strategy For The Laboratory Tour
Plan the Lab Tour

Walk the route
Where would you like to stop ?
Where will you explain your Instrument Control (Calibration)?
What did your audit reveal ?
Look in cupboards!
What is Visible Housekeeping Etc.
Before the Audit EMPTY Tree CYCLERS / Bins Etc.
Care Over Material in Waste Bins !
found unofficial batch records for approximately 75 batches of injectable

finished drug products torn in half in the waste area ucm361928
The investigator found a certificate of analysis (COA) for (b)(4) oz, lot number (b)(4),
dated January 19, 2011, in a trash container in the office used by QC personnel
ucm311326
May 2, 2014
61
Questions ?
May 2, 2014
62
Thank You!
May 2, 2014
63
APPENDIX
ADDITIONAL INFORMATION
May 2, 2014
64
During The Audit
As the audit progresses Concerns are documented by the Auditor (s):
These
Are Discussed The site will WORK on these
OOS At the Daily Issues - to try and get them
CAPA Wash Up off the chart.
Etc
Establishment
Flip Chart Inspection Warning
Report (EIR) Letter
Wall Chart..
Form 483
2 Tier Wash up System
Inspector (s) Site / Company

Valuable if they will do Brief site management
Limited the no of people Communication update off site
Plan Next Day What Went Well
Clarify Concerns Plan Next Day
Work on Concerns ..overnight
May 2, 2014
65
Compliance - A Service Providers Perspective.
Customer Statement Lab. Managers Will Often Say: Comments
We dont supply to the US, so we Actually, you may have to..

dont have to worry about the FDA.. How familiar are you with the term Mutual Recognition
We are an R&D laboratory, so we Is your company involved in manufacturing generics

dont have to work to GMP How is your company implementing QbD
Did you know QbD will be applied to methods
Appropriate GMP in R&D
We have never had a problem with Data Integrity is a different kind of audit
our paper qualification in audits before, A good audit is good news for a site, but a perfect
so why should consider moving to audit may not be ideal - as its harder to justify
electronic now ? investment do you ever find that a problem ?
How do you justify new equipment / improvements
We use System Suitability, so we Routine analytical tests do not constitute OQ testing

dont have to perform Qualification USP <1058>
or Calibration ! - Justification Over Result Validity
Partnership Relationship Required.
May 2, 2014
66
Who Owns The Audit Preparation ?
You NEED everyone to CARE about AUDIT PREPARATION .

Motivation of Managers and all Personnel is Critical
The ability to motivate and inspire others is a Leadership Quality
IN OUR AUDIT
PLAN
The AUDIT PLAN is owned by the TEAM NOT the MANAGER
May 2, 2014
67
Example Sample Life Cycle. Electronic Vs. Paper
21 CFR Part 11 = Good Document

Sample Receipt Practice for Electronic Data
1.
2. Booked into LIMS AAttributable

[Who did it]
Electronic Log Vs. Ink Signature
3. Schedule Tests LLegible Print Vs. Handwriting

[Can you read it]
4. Sample Preparation CContemporaneous Electronic Log Vs. Written Data

[Recorded in Real Time]
5. Chromatograph Sample OOriginal [Is it original]

Secure Electronic File Vs. Paper Photocopy
6. Calculate Results AAccurate [Is it Accurate]

Validated Electronic Output Vs. Paper.
7. Check / Report Results More Secure Electronic Greater Risk

(harder to manipulate) ? Vs. Paper (easier to manipulate) ?
8. Compare Against Specification
May 2, 2014
68
Laboratory Instrument Check List
Calibration History Documentation

o Status Labelling ? o SOP
o On time / Gaps o Calibration
o Records o Training
o Log Book o USP Status
o Method Validation
Gap Analysis Holiday

Appearance
User / Expert
o Clean Leaks / Powder
CAPA o Reagent Labels
o Waste Container
Life Cycle o Excessive Stickers
o PM Fail
o Repair
o Change
Impact
Day
Definitions
Qualification o Dates
o URS Current Use o Critical Int. Week
o Vs Range of Use o Grace.....
o Talk Through (VMP) Month
May 2, 2014
69
Knowledge Management
Data Structure
Data
Data
Data Experience
Data Information
Data
Knowledge
Store
Search Organise
Meaning Apply
Decisions
of the Audit Preparation Process
May 2, 2014
70
What Questions Will The FDA Ask Software ?
1. Do you have your source electronic data or are your deleting it ?

- Electronic files should be retained they are the source data, paper is not
2. Do you review your electronic source files ?

- Data integrity check visibility of repeat work, integration and sequence files data not reported
3. Does review include a review of meaningful metadata ?

- Authenticity of data
4. Does your system configuration include clear segregation of duties ?

- Independence of Administrator and User Roles, Shared Passwords Etc.
5. If COTS software Is it validated for your intended use ?

- Vendor documentation (including qualification) must be reviewed and may need augmenting
May 2, 2014
71

Preparing Your Analytical Lab For A Regulatory Audit

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Preparing Your Analytical Lab For A Regulatory Audit

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Preparing Your

If you are experiencing technical problems with viewing or hearing the

Environmental Run as a Project !

Prepare Well Once Then Update / Apply

Pharmaceutical GXP ISO 9001 ISO 17025

Influenced by Where you: Quality Management System Testing & Calibration

National Pharmacopeia's Influenced by: Influenced by:

Correct Reference Materials Were Used

Method Limits Were Validated

Correct Reference Materials Were Used

Method Limits Were Validated

The above align with United States

Requests from Audit ..

White Copy Stays in Audit

Area Subject Comments

Validation / Change Mgt.

Actions from Audits

Area Subject Comments

A. Debarment A. FDA Web Site

Suitable for Use ? Expected <1058> Changes

Validation / Change Mgt. USP Stimulus Paper (QbD)

Internal Are you doing them ?

Job Description / Training Records

1. Calibration [21 CFR 211.160 (b) (4), FDA]

2. Qualification [USP, e.g. <1058>]

3. Validation [Method, Process, Software]

4. Verification [GAMP 5, ASTM E2500]

Emphasis Identify areas of non-compliance in the INFORMATION

Scope Limited by where the inspection starts (e.g. which batch)

Emphasis Identify areas of non-compliance in the INFORMATION

Scope Limited by where the inspection starts (e.g. which batch)

System Based Inspection Examine Your Quality System

Emphasis Identify areas of non-compliance in your QUALITY SYSTEM

Scope Your whole quality system everything WIDER RANGING

Hierarchical Some Element of Luck System-Based Inspection

Is it Valid Technical Review of What You Do

Is it Valid Technical Review of What You Do

Now Assume - You Are Fraudulent

ALL inspectors can be

BE CONFIDENT in what they say

Everyday phrase . Inspectors impression.

I think this is what happens

Thats not my problem

Thats too expensive

Everyday phrase . Inspectors impression.

I think this is what happens I would expect you to know what

So what happens when its not

To be honest.. Suggests you are not always

Thats not my problem Care this implies you dont care

Thats too expensive If you cant afford to have proper controls,

Personnel must have the proper

There are no Set Rules on:

WHAT Some of The Stages Contain

- Write it down Is it installed

System URS DQ IQ OQ PQ Rationale Problems Actions

User Requirements Specification Qualification Any What is Your

System URS DQ IQ OQ PQ Rationale Problems Actions

User Requirements Specification Qualification Any What is Your

System URS DQ IQ OQ PQ Rationale Problems Actions

GC USP <1058> Includes Definitions of:

System URS DQ IQ OQ PQ Rationale Problems Actions

GC X X X USP, SSC URS, DQ, IQ Do OEM

NIR X Calibration No URS Retrospective