DATA INTEGRITY, OOS, OOT,

UNEXPECTED RESULTS
Karen Ginsbury
PCI Pharmaceutical Consulting Israel
Lab Week San Diego, Dec 2016
DISCLAIMER

■ KAREN GINSBURY IS A CONSULTANT

■ Your company has a Quality System and Quality Unit
■ Karen will make you think about things once again,
but you MAY NOT change anything from approved
SOPs because “Karen said so”
■ Any changes must go through the change control /
change management process and be discussed and
agreed internally with your Quality Unit

2
Keywords – List…
■ ALCOA+
■ Compliance
■ Notification
■ Trust
■ Patient safety
■ Dollar signs – silly stuff
OOS Keywords
■ OOS ■ Batch release
■ OOT ■ Investigation
■ Questionable / unusual / ■ Laboratory error
atypical result ■ Production error
■ Reportable result ■ Sampling error
■ Retest ■ Data integrity
■ New test ■ Data quality
■ Invalid test ■ Averaging
■ Aborted test ■ Training, qualification, education
■ New test ■ COA
■ Resample ■ Reporting Results
■ Data Integrity
Objective

■ Understand why Data Integrity is BURNING hot

■ Understand what an OOS, OOT, Unusual result is
■ Learn to BE objective

There is no place for emotions – put them aside

5
What are the two latest “hotties”
fresh off the press guidance?

■ Clue: November 2016

■ Clue #2: they were drafts…

6
What are the two latest “hotties”
fresh off the press guidance?

7
Metrics FDA is collecting
Tie in with: OOS, DI and Quality Culture

8
Shaming into compliance?
Or Rewarding the good?

9
Integrity …but I am HONEST

■ We don’t have data integrity issues here !!!

10
 How many opportunities for cheating?
…but she is an HONEST person!

Karen Ginsbury, MSc, BPharm (MRPharms????)

CEO, PCI Pharmaceutical Consulting Israel Ltd

■ Karen Ginsbury is a London, UK trained pharmacist with a second degree in Microbiology. With close to 30
years’ experience in the pharmaceutical industry, Karen is a quality practitioner with a passion for doing things
right and once only. She runs a boutique quality systems consultancy offering services to companies who want
to set-up, maintain and constantly improve their quality management systems. Regularly lecturing in Israel and
around the world, Karen also serves on international professional committees and is co-chair of PDA’s
pharmacopoeial interest group. In these and other capacities Karen benchmarks best practices around the
globe in order to share them with her audiences. Double space or single space? Cherry picking???

11
 Any resemblance to the previous slide?

…but she is a “good” person

■ Karen Ginsbury likes to do the right thing first time

■ I have been working in the pharmaceutical industry since 1986 and
remember the Barr court case
■ I lecture and consult for different companies
I ask lots of questions and am asked a lot of questions
■ I like to share best practices
■ That’s what I am doing in San Diego
(other than mani/ pedi, shopping and walking on the beach)

12
 Before… and After
Truth / Lie
Good/Bad

The obscuring of intended meaning in

communication, making the message
confusing, willfully ambiguous, or
harder to understand. 13
Conclusion #1: Personal Integrity

■ Is not enough
■ We need PREVENTIVE measures and
BARRIERs
■ LONG TERM only FULLY automated
systems will PREVENT data integrity
issues
‫ ל"ה – ל"ו‬:‫ ויקרא י"ט‬Leviticus 19:35 – 36
Calibrate your decision making process

‫ׂשּורה‬
ָ ‫תַ עֲׂשּו עָ וֶ ל בַ ִּמ ְׁשפָ ט בַ ִּמ ָדה בַ ִּמ ְׁש ָקל ּובַ ְׁמ‬-‫לה ֹלא‬
‫צֶ ֶדק אֵ יפַ ת צֶ ֶדק וְׁ ִּהין צֶ ֶדק יִּ ְׁהיֶה לָכֶ ם‬-‫לו מֹאזְׁ נֵי צֶ ֶדק ַאבְׁ נֵי‬

35 Do no unrighteousness in judgment, in weight, or in measure.

36 You shall have just balances, just weights…

15
)‫ יד‬,‫(יט‬ "‫ ויראת מאלקך‬,‫"ולפני עור לא תתן מכשול‬

■ Assume people are intrinsically good

■ Hierarchical and peer pressure, rush to get home, other
psychological factors can cause them to make foolish
decisions
■ The purpose of the controls you put in place are to avoid
making it easy
(putting a stumbling block before them)

16
It can’t be left to chance - Data Governance

■ The sum total of arrangements which

provide assurance of data integrity
■ ensure that data, irrespective of the
process, format or technology in which it
is generated, recorded, processed,
retained, retrieved and used
 will ensure a complete, consistent
and accurate record
 throughout the data lifecycle
17
STRATEGY – POLICY, EDUCATE, COMMUNICATE, CONTROL, AUDIT, IMPROVE

Elements of a data governance plan

■ Policy
■ Educate
■ Communicate
■ Technology and IT
■ Audit and CAPA

18
STRATEGY – DEFINE, EDUCATE, COMMUNICATE

ALCOA+

 Accurate  Accurate
 Legible  Complete
 Contemporaneous (real  Consistent
time)
 Original  Secure
 Attributable

19
 OOS / Data Integrity timeline

1993 Barr court case

2005 Able Laboratories

2011 - Warning letters…x x XX XXX

2015 – 2016 Guidance…..

1993 Barr

The New York Times

February 6, 1993
COMPANY NEWS; Judge Rules On Barr Labs
A generic drug manufacturer must recall batches of some of its medicines
and stop distributing others until the company completes studies of its
manufacturing process, a Federal judge ruled on Thursday. But United States
District Judge Alfred M. Wolin refused a request by Federal pharmaceutical
regulators to order a complete shutdown Saturday
 Barr: What happened in court

■ The judge heard experts from FDA and Barr on retesting

■ FDA wanted retesting to be banned under all
circumstances
■ After a long hearing at which five industry experts, an
FDA investigator, and several company employees
testified, Judge Alfred M. Wolin, U.S. District Judge for
the District of New Jersey, issued a 79-page opinion

22
 Barr: The outcome
Draft 1998; final 2006
■ FDA OOS Guide
■ OOS SOPs
■ Later…OOT etc.

23
And along came Able…
17/08/2005 –
■ Troubled generic drug manufacturer Able
Laboratories has conceded defeat in its
bid to get products back onto the market
and elected to sell off the assets of the
business
 FDA Stops Them Manufacturing

■ Able was forced to cease manufacturing and recall all of its

products in May after serious questions were raised about
quality control data used to obtain approval for products made
at its manufacturing facility in New Jersey
■ Able proposed FDA allow them to re-validate product
development data from the ANDA under new management
and with data verification by an independent outside
consultant
FDA refuse

■ FDA declined the proposal which is against its policy in

situations involving questions of data integrity
■ Able's only route back to market was to resubmit ANDAs with
new data for review. This could take 18 months for each case a
delay that was too long and costly and bankrupt the company
■ Able has determined that the best course of action would be to
immediately reduce overhead and expenses as much as
possible and to initiate the process of selling the company's
business and assets
 Able happened 11 years ago
WAKE UP INDUSTRY
The Quality Unit failed to:
■ Review computer audit trails in the Waters Empower Data
Acquisition System
■ Provide adequate training to analytical chemists
These practices led to:
– The QU releasing batches failing in-process, finished product
and stability specifications
– Submission of erroneous data in Annual Reports and Prior
Approval Supplements
– Ceasing manufacture, distribution and recall of all products
as of 13 May 2005 and withdrawal of at least 5 ANDAs
Able: Resample, Re-injection,
Reprocessing
 Able 483 findings
OOS substituted with passing
results
■ The substitution of data was performed by:
 cutting and pasting chromatograms
 substituting vials
 changing sample weights
 changing processing methods
 OOS results found in electronic data files not
documented in lab records
2011 Warning Letter – Turbo 483

1. Your firm has not thoroughly investigated the

failure of a batch or any of its components to meet its
specifications whether or not the batch has already
been distributed, and you failed to extend the
investigation to other batches of the same drug
product that may have been associated with the
specific failure or discrepancy [21 CFR. § 211.192]
 2011 Warning letter continued…

Your firm did not thoroughly investigate lot #1129BX014, when it

failed to meet the established specification for both the single largest
impurity and for total impurities amount.
■ Specifically, the laboratory test results had a single impurity at
RRT 0.8 minutes of 0.34 (specification limit NMT 0.3% and total
impurity result of 1.05% (specification limit NMT 1.0 %)
■ Your firm subsequently invalidated these results although your
investigation was unable to confirm a root cause of the failure
■ Your firm selectively used passing results from a different analysis
to approve the lot
 The Guidances – Harmonizsation?
TWO kinds: Culture / QS vs Q&A
Date Title Content
EMA: Good Manufacturing Guidance to Ensure the Integrity of
11 Aug 2016 23 Q&A
Data

PIC/s: Draft Guidance Good Practices For Data Management And

10 Aug 2016 41 pages
Integrity In Regulated GMP/GDP Environments

July 2016 MHRA: GXP Data Integrity Draft Guidance 14 pages

FDA: Draft Guidance: Data Integrity and Compliance with GMP

April 2016 13 pages
Q&A
WHO: Draft Guidance: Good Data and Record Management
Sept 2015 35 pages
Practices

March 2015 MHRA: Data Integrity Definitions and Guidance for Industry 16 pages
Altering time and date stamps

WHO guidance

33
Independent IT personnel as
administrators?

WHO guidance

34
QU evaluate configuration settings
data annotation tools…

WHO guidance

35
Rename, copy, delete local files
on stand alone system?

WHO guidance

36
Q#1 What is an OOS

■ Q#2 and is it a problem?

■ Hint: Stability testing and COA

■ Hint 2: Analytical methods validation
■ Hint 3: DI and regulatory submissions?
What is an OOS

■ Think reportable result

■ FDA metrics require invalidated
laboratory results BUT e.g. for content
uniformity if you went to stage two, you
would have tested 30 tablets but it
would be a single OOS result
■ Same for two injections on same sample
metrics guide good source of
information
38
What is an OOS
■ What is a specification? A document that lists all the
results and the limits that you are supposed to get
when testing a product or material or a component
■ A specification is a list of Critical Quality Attributes of
a material, component, product that must meet a
limit, range or specified value in order for the item
to perform its function as intended
■ A result which does meet the specification meaning
that the item deviations / does not meet the
requirements: ONE OR MORE OF THE CRITICAL
QUALITY ATTRIBUTES is NOT met which means the
item will not / cannot function as intended and IS
LIKELY to cause HARM
IF I have several OOS / OOT’s for a
product over time
■ I can’t and won’t know if the problem is in
the test method or the process
■ So I have to look at the validation file and at
PQR – product quality reviews annual
product review as well and trends – has the
process or the method moved? / changed
■ And I open the validation of the analytical
method and the process what should I look
for?
■ Extremes – where do I get extremes, ranges,
variations, reproducibility or lack of it
Q#3 What is an OOT?

■ Q#4 And is it a problem?

■ Q#5 Do we ALWAYS have to respond to
an OOT
What is an OOT: Out of Trend
■ Results that are close to the upper or lower limit
■ Results that are different from what we are used to
getting
■ Stability results that are out of the usual trend
■ Needs to be statistically based
■ The average and the limits are statistical

A RESULT CAN ONLY BE OUT OF TREND, IF I HAVE A

WRITTEN METHOD FOR COLLECTING AND
STATISTICALLY ANALYZING TRENDS
OOT in stability

■ Different to QC release or in process or

starting material test?
■ What is your POLICY?
■ Do analysts UNDERSTAND
■ What about new hires?
■ What about SUPERVISORS and approvers
■ What about OUTSIDE the lab?s

43
Q#6: What is an Unusual, Questionable, “Atypcial” Result

■ Q#7 Is it a problem?
What is an Unusual, Questionable, “Atypcial” Result

■ It is a result which the analyst

“doesn’t like”
■ Can you retest? Should you retest?
Warning Letter 19 October, 2016 China
Unstable baseline; cleaning hard drive
You do NOT want to go there…
DI Remediation
You do NOT want to go there…
Investigators are out of patience
GIGO: ALCOA+
nothing lost, changed or manipulated

Data Information Knowledge

49
STRATEGY – DEFINE, EDUCATE, COMMUNICATE,
COMMUNICATE VERIFY AND CHECK FROM TIME TO TIME

Performed by….
Defined in an SOP
■ To perform the action
■ 100% responsible for the action and all activities
associated with its performance and documenting
its performance (may be electronic documentation)

50
STRATEGY – DEFINE, EDUCATE, COMMUNICATE,
COMMUNICATE VERIFY AND CHECK FROM TIME TO TIME

Verified by…
Defined in an SOP
■ To verify that the action was performed according to
the current, written approved instructions
■ 100% responsible for verifying that the action was
performed correctly including all activities associated
with its performance and the documentation of these
■ MUST BE PRESENT THROUGHOUT AND WITNESS, THE
PERFORMANCE OF THE ACTION AND ITS
DOCUMENTATION before signing as verifier

51
STRATEGY – DEFINE, EDUCATE, COMMUNICATE, VERIFY AND CHECK FROM TIME TO TIME

The reviewer or approver

Defined in an SOP

■ Approves data and analysis of the data –

IS NOT PRESENT when the work is
performed
■ Should be provided with sufficient raw
data and analysis to enable a complete
and accurate review

52
STRATEGY – CULTURE, CLOSING THE DOOR OF OPPORTUNITY

Have you ever…

■ Back dated a document
■ Filled in missing data
■ Replaced a page in a controlled
document to correct a typo without
changing the version number…
BECAUSE YOU CAN and not because you
are a wicked person – unconscious…or
conscious incompetence?
53
WHO Guide pages 16 – 20
take a look
■ Risk based approach outlining the
particular risks for each aspect of
ALCOA+

54
PIC/s Guidance
Does have limited mention of PLCs

Restricting access to PLC nodules

(sic probably modules) , e.g. by
locking access panels.

PI 041-1 (Draft 2) 29 of 41 10 August 2016

55
Data Integrity

56
STRATEGY – EDUCATE, COMMUNICATE

Warning Letter: Lack of Basic Controls

■ c) A “File Note” dated February 10, 2014, signed by the QC Head,

established that the printed data used for batch disposition decisions from
the Metrohm Titrando Instrument MLG/QC/12/048 hard drive was not
necessarily the complete data for a batch. Our inspection found that data on
the instrument was selected for use and was not protected from change
and deletion. Notably, the audit trail capability of this QC “commercial”
laboratory instrument was not enabled, even after creation of the “File
Note.”

57
STRATEGY – EDUCATE, COMMUNICATE

Backdating
■ Our investigators found backdated batch production records
dated February 10 to February 25, 2014, signed by your
Production Manager and Technical Director in the “Batch
Manufacturing Record Reviewed by” section.
■ The Technical Director stated that he was not in the facility on
these dates and was “countersigning” for another person who
allegedly performed these review activities. However, these
records did not contain signatures (contemporaneous or
otherwise) of the alternate reviewer who purportedly
conducted the review.
■ Furthermore, the Technical Director backdated his own
signature to the date the quality unit (QU) reviewed and
released your drug product. You released these batches before
the Technical Director returned to the facility and backdated his
signatures.
58
STRATEGY – EDUCATE, COMMUNICATE
Failure to record activities at the time
they are performed and destruction of
original records
■ Specifically, your employees completed batch production records
entries days after operations had ended, released lots before the
proper approvals, and failed to maintain original manufacturing data
for critical steps in the batch production records. For example, Our
investigators found that some of your operators used “rough notes”
(unbound, uncontrolled loose paper) to capture critical
manufacturing data and then destroyed these original records after
transcription into the batch production records
■ For example, the (b)(4) chemist recorded original manufacturing data
as rough notes and left these rough notes for the (b)(4) chemist to
transcribe into the batch production records. The next morning, the
chemist signed the batch production records and destroyed the
original rough notes. We interviewed employees during the
inspection who confirmed your firm’s practice of transcribing data to
batch records and destroying original records.

59
STRATEGY – EDUCATE, COMMUNICATE

Shared Passwords
■ 6. Your firm failed to establish appropriate controls over computers and related
systems to assure that changes in master production and control records or
other records are instituted only by authorized personnel (21 CFR 211. 68(b))
■ You lacked audit trails or other sufficient controls to facilitate traceability of the
individuals who access each of the programmable logic controller (PLC) levels
or Man-Machine Interface (MMI) equipment. You had no way to verify that
individuals have not changed, adjusted, or modified equipment operation
parameters. Access to production equipment used in parenteral manufacturing
and solid dosage forms used a password shared by four or five individuals to
gain access to each individual piece of equipment and access level.
■ During our inspection, your Executive Production and QA manager confirmed
that the password was shared. During our inspection, firm officials also
confirmed that you had not established or documented a control program to
describe the roles and responsibilities of production equipment system
administrators. There was also no record documenting the individuals who
have access to the production equipment or the manner in which individual
personnel access production equipment.

60
STRATEGY – DEFINE, EDUCATE, COMMUNICATE

Data Integrity:
Paper / hybrid / Electronic
■ Data is precisely recorded. On retrieval, the data is the
same as when originally recorded, complete, consistent,
accurate, attributable throughout the lifecycle (archiving,
retrieval)
■ The accuracy and consistency of stored data, indicated by
an absence of any alteration in data between two updates
of a data record. Data integrity is imposed on a system at
its design stage through standard rules and procedures,
and maintained through error checking and validation
routines.
■ Critical aspect in the design, implementation and usage of
any system which stores, processes or retrieves data

61
STRATEGY – EDUCATE, COMMUNICATE

Data integrity issues:

■ Deletion – raw data
■ Change – raw data
■ Incomplete – raw data
■ Unofficial or trial testing
■ AA spectro – over 400 analyses – only 38 data files
■ Audit trails deleted
■ SOPs don’t include instructions for retention of raw data
■ Date of second signature – what does SOP say?
■ Disabled audit trail function
■ Unauthorized file folders e.g. for column wash data

62
STRATEGY – DEFINE, EDUCATE, COMMUNICATE

MetaData

■ is data that describe the attributes of other

data, and provide context and meaning.
Typically, these are data that describe the
structure, data elements, inter-
relationships and other characteristics of
data. It also permits data to be attributable
to an individual.
MHRA, Data Integrity Definitions and
Expectations and Guidance for Industry, January
2015

63
MetaData

Example: data (bold text)

3.5
and metadata, giving context and meaning, (italic text) are:
sodium chloride batch 1234, 3.5mg J Smith 01/07/14
Metadata forms an integral part of the original record.
Without metadata, the data has no meaning.

MHRA, Data Integrity Definitions and Expectations and Guidance

for Industry, January 2015

64
STRATEGY – DEFINE, EDUCATE, COMMUNICATE

Original record vs True copy

■ Original record: Data as the file or format in which it
was originally generated, preserving the integrity
(accuracy, completeness, content and meaning) of
the record, e.g. original paper record of manual
observation, or electronic raw data file from a
computerised system
■ True Copy: An exact copy of an original record, which
may be retained in the same or different format in
which it was originally generated, e.g. a paper copy of
a paper record, an electronic scan of a paper record,
or a paper record of electronically generated data

MHRA, Data Integrity Definitions and Expectations

and Guidance for Industry, January 2015

65
STRATEGY – DEFINE, EDUCATE, COMMUNICATE
Original record vs True copy
■ Raw data generated by electronic means may be retained
in a paper or pdf format. The data retention process must
be shown to include verified copies of all raw data,
metadata, relevant audit trail and result files, software /
system configuration settings specific to each analytical
run*, and all data processing runs (including methods and
audit trails) necessary for reconstruction of a given raw
data set. It would also require a documented means to
verify that the printed records were an accurate
representation. This approach is likely to be onerous in its
administration to enable a GMP compliant record.
■ * computerised system configuration settings should be
defined, tested and ‘locked’ as part of computer system
validation. Only those variable settings which relate to an
analytical run would be considered as electronic raw data.

MHRA, Data Integrity Definitions and Expectations

and Guidance for Industry, January 2015 66
STRATEGY - DEFINE
Have you defined (in an SOP)…
Educated and communicated…
Verified understanding of…
■ Data
■ Raw Data
■ Meta Data
■ Derived Data
■ Original Record
■ Primary Record
■ True Copy
■ Certified Copy
67
STRATEGY – COMMUNICATE, CONTROL, AUDIT, IMPROVE

Some risks
■ Paper based: missing signatures, details
■ Excel spreadsheets
■ Stand alone software
■ Log on / log off
■ Printouts vs unintegrated data

68
STRATEGY - CONTROL

Risk Mitigation

Might be better to move to VALIDATED electronic records

where QA review electronic record and cut out several
paper based risks:

Electronic data – printout – reduce size – paste in

notebook – QA review and sign notebook

Or one step?

69
STRATEGY – CULTURE – EDUCATE UP – RESPONSIBLE
MANAGEMENT – PROVIDE TOOLS (NO WRITING ROOM)

What are the Stumbling Blocks?

Credit to: Madlene Dole, Novartis
■ Performance and business pressure
■ Lack of awareness or capability
■ DI not (fully) integrated into our culture
■ Inadequate processes and technology
KG: there is no excuse for a balance without a printout
KG: after meeting with client x – it is not good
enough!!

70
STRATEGY – PLAN, DEFINE, IMPLEMENT, MAINTAIN, AUDIT

Audit trail and controls at two levels:

71
STRATEGY – SEGREGATE DUTIES
TO MAXIMIZE OBJECTIVITY
Minimize threats to DI by:
• Segregation of Duties (SOD)
• Configuration of systems
• Backing up data regularly
• Controlling access to data via security mechanisms
• Designing user interfaces that prevent the input of invalid data
• Using error detection and correction software when transmitting
data
• Audit trail Review

Segregation of duties
Roles and Responsibilities allowing a conflict of interest that
would allowalteration of data.
For example, the QC Lab Manager acting as system
administrator for Empower would violate segregation of duties 72
Data Governance Policy

■ Values:
The Officers of this company expect every employee
to provide accurate, complete and contemporaneous
(real-time) records of activities and to perform all
tasks with integrity especially when no one is looking
■ Tools:
Managers are expected to provide staff with the means
to allow them to perform their tasks with integrity, to
collect, analyze and report data accurately, completely
and on real-time including but not limited to:

73
Data Governance

■ Senior management is responsible for the

implementation of systems and
procedures to minimise the potential risk
to data integrity, and for identifying the
residual risk
■ Contract Givers should perform a similar
review as part of their vendor assurance
program

74
Data Integrity Code of Conduct

■ Annual signature of all employees that

they are aware of it and followed
it…what about MOST senior
management / officers of the
company???
■ Culture?

75
 Warning letters
a. The inspection documented that HPLC processing methods (including
integration parameters) and re-integrations are executed without a pre-defined,
scientifically valid procedure. Your analytical methods are not locked to ensure
that the same integration parameters are used on each analysis. A QC operator
interviewed during the inspection stated that integrations are performed and re-
performed until the chromatographic peaks are “good”, but was unable to provide
an explanation for the manner in which integration is performed. Moreover, your
firm does not have a procedure for the saving of processing methods used for
integration.

Your response did not include a description of the method by which

chromatograph integrations are to be performed (e.g., what constitutes a
chromatographic peak, how shoulder peaks are to be handled, etc.). In addition,
your response did not include an audit of past chromatographic data to determine
whether data used to support release and stability studies originated from
appropriately integrated chromatograms.

76
 Warning letters
• the use of the Excel® spreadsheets in analytical calculations are neither controlled nor
protected from modifications or deletion. The investigator noticed that the calculation
for residual solvent uses an Excel spreadsheet that has not been qualified. We are
concerned about the data generated by your QC laboratory from non-qualified and
uncontrolled Excel spreadsheets.

In response to this letter, provide a retrospective evaluation of the analytical values

reported where such Excel spreadsheets have been used.

CAN’T WE DO BETTER THAN EXCEL?

77
Computerized Spreadsheets

■ Error in / incorrect formula

■ Spreadsheet not protected or locked
■ Data loss through inadvertent or
intentional deletion, errors, computer issues
■ Omitted, added or altered information
■ Entry / transcription errors

78
STRATEGY – PDCA

Data integrity audits

■ Educate
■ Show others what is unacceptable
■ Show them how to correct bad practices
■ Integrate automated methods for data
integrity which are difficult to bypass
■ AUDIT, CORRECT, AUDIT, CORRECT, involve
management and measure – metrics – are
the number and seriousness of the findings
decreasing?
79
 In Conclusion: Strive for Truth

■ Know the basic concepts of Data Integrity

■ Keep a close eye on OOS and EDUCATE everyone –
up and down in the organization
■ Understand the use of audits
– Formal: internal audit program
– On-the-spot: sometimes and whenever a problem
is suspected
■ Recognize that the opportunity with data integrity is
to DESIGN controls INTO the computerized system
■ People based systems are stumbling blocks and will
ultimately fail
80
 In Conclusion: Strive for Truth

■ Traceability
■ Transparency – document, date and sign with
reason for ANY amendment recorded

81
Links to guides
■ EMA Data Integrity Guidance Q&A
http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/q_and_a/q
_and_a_detail_000027.jsp#section17
■ PIC/s Data Integrity Guidance
https://www.picscheme.org/useruploads/documents/PI_041_1_Draft_2_Gui
dance_on_Data_Integrity_2.pdf
■ MHRA: GxP Data Integrity Definitions and Guidance
https://www.gov.uk/government/uploads/system/uploads/attachment_data/f
ile/538871/MHRA_GxP_data_integrity_consultation.pdf
■ WHO: guidance on good data and record keeping
http://www.who.int/medicines/areas/quality_safety/quality_assurance/Guida
nce-on-good-data-management-practices_QAS15-624_16092015.pdf
■ FDA Data Integrity and Compliance with cGMP
http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinforma
tion/guidances/ucm495891.pdf
■ MHRA: GMP Data Integrity Definitions and Guidance
https://www.gov.uk/government/uploads/system/uploads/attachment_data/f
ile/412735/Data_integrity_definitions_and_guidance_v2.pdf

82
THANK YOU FOR PARTICIPATING
?
Questions ? ?

Find me
[email protected]

83