The document provides definitions and guidelines for quality control laboratory management. It discusses definitions of key terms, requirements for quality control documentation and records, personnel qualifications, sample management, use of reagents and reference standards, instrument calibration, analytical methods, and data review. The document emphasizes that quality control laboratories must meet regulatory requirements and operate according to good practices and management systems to ensure the quality of pharmaceutical products.

1. Dr. A. Amsavel
1

2. The Overview
 Definition
 Requirements
 QC Lab Management
 Documents & Records
 QC personal
 Sample Management
 Reagents & Reference standard
 Instruments and Calibration
 Computer System Validation
 Analytical method
 Analysis, analytical data & Review
 Reserve sample
 Purposes of GMP Documentation
 Tips to good documentation practices
 Warning letters and observations
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3. Definition (WHO)
 Quality Control
All measures taken, including the setting of specifications, sampling, testing
and analytical clearance, to ensure that raw materials, intermediates,
packaging materials and finished pharmaceutical products conform with
established specifications for identity, strength, purity and other
characteristics
 Quality Management System
An appropriate infrastructure, encompassing the organizational structure,
procedures, processes and resources, and systematic actions necessary to
ensure adequate confidence that a product or service will satisfy given
requirements for quality.
 Analytical test report
An analytical test report usually includes a description of the test
procedure(s) employed, results of the analysis, discussion and conclusions
and/or recommendations for one or more samples submitted for testing
3

4. Definition (WHO)
 Analytical worksheet
A printed form, an analytical workbook or electronic means (e-
records) for recording information about the sample, as well as
reagents and solvents used, test procedure applied, calculations
made, results and any other relevant information or comments .
 Measurement uncertainty
Non-negative parameter characterizing the dispersion of quantity
values being attributed to a measurand (analyte), based on the
information used
Metrological traceability
Property of a measurement result whereby the result can be
related to a reference through a documented, unbroken chain of
calibrations, each contributing to the measurement uncertainty.
4

5. Definition (WHO)
 Deviation:
Deviation from the prescribed procedure
 Out-Of-Specifi cation (OOS) result
All test results that fall outside the specifications or acceptance
criteria
established in product dossiers, drug master files, pharmacopoeias
or by the manufacturer
 Reference substance (or standard)
An authenticated, uniform material that is intended for use in
specified chemical and physical tests, in which its properties are
compared with those of the product under examination, and which
possesses a degree of purity adequate for its intended use
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6. GDP references
21 CFR 58 GLP:
All data generated during performing of a study, (except
automated data collection systems), shall be recorded
directly, promptly, and legibly in ink.
All data entries shall be dated on the date of entry and
signed or initialed by the person entering the data.
Any change in entries shall be made so as not to obscure
the original entry, shall indicate the reason for such
change, and shall be dated and signed or identified at the
time of the change.
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7. GDP references
21 CFR 211.194 (a)
Verification of laboratory test data for “Accuracy,
Completeness compliance with established
standards”
ICH Q7 : Chapter–6 & other GMP guidelines
Documentation and Records
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8. Why GMP Documentation ?
“If it hasn't been documented, then it hasn't done or
happened!”
“If it is not documented, it is a rumour!”
Famous FDA statement
The product considered as “Adulterated” if the procedure
not followed/ not documented properly.
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9. QC Lab Management
 Organization and management
 Quality management systems
 Control of documentation and records
 Data processing equipment
 Personnel
 Premises, equipment, instruments and other
devices
 Working procedures, documents and safety
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10. Organization and Management
 Function to meet Regulatory requirements
 Operate in accordance with Good Practice & standards
 Good Manufacturing Practices and Good Practices in
Quality control
 Personnel
 Adequately Qualified , experienced and competent
 Managerial and technical positions to ensure operation in
accordance with quality systems
 No conflict of interest
 Organizational chart and job descriptions
 Supervision and training
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11. Organization and Management
 Adequate information flow
 Traceability of the samples (from receipt to test
report completion)
 Procedures (SOP), Work instruction & documents
 Current specifications & test method
 MSDS
 Safety procedures
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12. Documents in QC
Procedures should ensure that:
 All specifications, sampling plans, and test
procedures should be scientifically sound
 Shall be current documents with Ref No. Version
and effective date
 Authorized SOPs are available near points of use
 Invalid documents are removed and replaced
 Revised documents refer to the previous document
 Documents are archived,
 Staff are trained for the new and revised SOPs
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13. Records
 Procedure for the identification, collection,
indexing, retrieval, storage, maintenance and
disposal of documents/records.
 All original observations, calculations and derived
data, calibration, validation and verification
records, etc. and final results must be retained on
record for an appropriate period of time, e.g.
 Records to contain sufficient information to permit
repetition of tests and traceability
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14. Records
 Legible, readily retrievable, stored and retained
 In a suitable environment that will prevent modification,
damage or deterioration and/or loss
 Secure, confidential. Access restricted to authorized
personnel.
 Electronic storage and signatures allowed - restricted
access and in conformance with requirements for
electronic records
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15. QC personal
 Organization chart
 Assess and ensure QC has sufficient people
 Personal shall have appropriate Qualification /education, experience
or trainings.
 Job description for each person
 Analyst qualification as per assigned work
 Training & retraining to analyst, reviewer, validation & computer
data evaluation
 Training on
 Quality system procedures
 Pharmacopeia General chapters
 Test methods
 Operation & calibration of Instruments
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16. General Requirement
 Water used in the Lab shall be suitable for indented use.
 Washing of glassware shall be ensured and validated
 Separate area for sample preparation
 Separate oven for drying of glassware ( 60°C)
 SOPs are available
 Any deviation, OOS shll be reported and investigated. CAPA
shall be implemented and relevet reports should be
maintained
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17. Work plan
Forwarding to testing / work allocation
 Sample for testing allocated to analyst or unit
 Should have competence, expertise, training
 Use specification and test procedure
 Verbal requests for testing followed up by written request
 Ensure the resources & reagents are available
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18. Sample Management
 Written procedures for sampling methods for in-process materials,
intermediates, and APIs.
 Sampling plans and procedures should be based on scientifically
sound
 Samples should be representative of the batch of material
 Sampling methods should specify the number of containers to be
sampled, which part of the container to sample, and the amount of
material in each container.
 Sampling should be conducted at defined locations and to prevent
contamination
 Containers from which samples are withdrawn should be opened
carefully and subsequently re-closed.
 Containers should be marked to indicate that a sample
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19. Sample Management
 Label affixed to each container of the sample
 Procedure for preparation of representative samples
 Sampling activity shall be recorded and maintained
 Storage of sample and prevent mix-up or contamination
 Registration number allocated for every sample
 Information recorded in a register and include e.g.:
– registration number of the sample, date of receipt, location of sample
sent
 In-process sample shall be obtained from production with
request and appropriate tests will analysis before testing
starts
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20. Reagents
 Reagents, chemicals, solvents and materials used
in tests and assays shall be appropriate quality –
with COA
 From reputable, approved suppliers
 Preparation of reagents:
 SOPs and as recommended in pharmacopoeia
 Clear responsibility in job descriptions
 Records for the preparation, and standardization
of volumetric solutions
 Storage & validity of based on established stability
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21. Reagents
 Reagents shall be clearly labelled:
 the contents, the manufacturer, the date received and
opened, concentration, storage conditions, expiry or re-
test date
 the name, date of preparation, initials of person, expiry
date, concentration
 Volumetric solutions:
 the name, molarity or concentration, date of preparation,
the date of standardization and Normality/factor.
 Transportation in original containers
 When subdivided – into clean, fully labelled containers
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22. Reference standard
Reference substances and reference materials
 Assign a person responsible
 Primary reference standards obtained from an officially
recognized source
 Pharmacopoeia reference substances / certified RS
 Used for testing, calibration, qualification of equipment,
instruments or other devices
Registration and labelling
 Ref / Identification number
 number marked on each vial and quoted on the analytical
worksheet at every use (batch number)
 Log or reconciliation
 Procumbent evidence/ record
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23. Record for reference standard
 Ref No /identification No. of the material
 Description of the material
 Source & date of receipt
 batch designation or other identification code
 Potency , LOD any other details as apprppriate
 Intended use of the material (e.g. as an infrared reference
material, as an impurity reference material for thin-layer
chromatography, etc.)
 location of storage in the laboratory, and any special
storage conditions
Reference standard
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24. In-house Reference standard /
Working standard
 Where a pharmacopeia RS is not available, in-house primary
standard should be established.
 Appropriate testing should be performed to establish fully the
identity and purity of the primary reference standard.
 Full characterization and assign potency or other quality attribute.
 Qualification , characterization recordshould be maintained.
 Secondary reference standards (working standard) should be
appropriately prepared, identified, tested, approved, and stored.
 The suitability should established by comparing against a primary reference
standard.
 Secondary reference standard should be periodically re-qualified
 Certificate of analysis with reference to PRS
 Store at recommended condition with expiry date or retest date
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25. Instrument & Testing devices
Qualification, Calibration, validation and verification of
equipment, instruments and other devices
 Control, weighing, measuring, monitoring, and testing
equipment critical for ensuring the quality of product should
be calibrated according to written procedures and an
established schedule.
 Calibration procedure can be used from Pharmacopiea
 Qualification / requalification DQ, IQ, OQ, PQ as necessary
 Performance verification at appropriate intervals
 Unique identification / code no for equipment, instruments,
devices used for testing, verification and/or calibration
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26. Instrument & Testing devices
 Schedule /plan for regular calibration & execution and record
 calibrations should be performed using standards traceable to
certified standards, if they exist.
 Display labels indicating status of calibration and due date
 Records of these calibrations should be maintained.
 Instruments that do not meet calibration criteria should not
be used.
 Deviations from approved standards of calibration on critical
instruments should be investigated to determine if these
could have had an effect on the quality of the intermediate(s)
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27. Records related to Instruments
Records kept of each item of equipment/ instrument
 Dates, results and copies of reports, verifications and
certificates of all calibrations, adjustments, acceptance
criteria and the due date of the next qualification,
verification and/or calibration
 Maintenance carried out, and the maintenance plan
 History of any damage, malfunction, modification or
repair
 Use and “remarks or observations” made at the time the
equipment, instruments or devices were used
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28. Analysis & record
Analytical worksheet
 Analyst shall record the information about the sample, the test
procedure, calculations and the results of testing
 Raw data shall ne controlled / issued by QA or as appropriate
 Provides documentary evidence either:
 to confirm that the sample is tested as per requirements
 to support an OOS result and investigation
 A separate analytical worksheet for each numbered sample
 Keep all the test data (different analysts/units) together.
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29. Analytical worksheet
 Dates (request, start of analysis, and completion), Time as required
 Name and signature of the analyst
 Description of the sample
 Reference to the specifications and test methods and limits
 Test equipment used
 Reference substance used
 Results of the system suitability test
 Reagents and solvents employed
 Results obtained
 Interpretation of the results and the final conclusions
 Deviations and other remarks
 Reviewed / Approved and signed by the supervisor
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30. Analytical worksheet
 Recording the data immediately on the analytical worksheet
 All graphical data attached or be traceable to an electronic record
 A complete record of all raw data generated during each test, in
addition to graphs, charts and spectra from laboratory instrumentation,
 Completed analytical worksheet signed by analyst(s), verified and
approved and signed by the supervisor
 Mistakes and amended results:
 old and new information available
 signed and dated by the person making the correction
 reason for the change given on the worksheet
 SOP for amending electronic worksheets and audit trail
 Follow ALCOA principles
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31. External testing Laboratory
 When specific tests are to be done outside the laboratory –
test request and samples transferred.
 Ensure the external Lab is qualified and approved.
 Ensure the Lab id approved by regulatory authority,
 Establish quality agreement
 Declaration on following the requirement
 Method validation, transfer as required.
 Ensure the sample and Test procedures detailed are provided
and followed
 Deviations/ OOS shall be investigated and documented
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32. Validation of analytical procedures
Validation of analytical procedures
 All analytical procedures used for testing should be suitable for
the intended use.
 Analytical method shall be validated as appropriately
 If validation in other Lab, perform method transfer
 Pharmacopoeial methods to be confirmed as suitable for use.
If adapted for another use then to be validated
 In case of a major change in analytical procedure , it shall be
revalidated
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33. System Suitability testing
Ensure to follow System suitability test as appropriate
 SS is an integral part of many analytical procedures
 Shows that equipment, electronics, analytical operations are
appropriate/suitable for the samples to be analysed
 To be performed prior to the analysis
 In case of a large number of samples analyzed in sequence -
then appropriate system suitability tests are to be performed
throughout the sequence
 Verification not required for basic pharmacopoeial methods
– E.g. pH, loss on drying and wet chemical methods
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34. Review of Analytical Results
Evaluation of test results
 All test results shall be reviewed and evaluated
 check that results are accurate , consistent and meeting
specifications
 Doubtful (atypical) and OOS results investigated (supervisor
with the analyst). Checks may include (not limited to):
 Appropriate procedures applied and followed correctly
 Discrepancies in raw data; calculations correct
 Qualified, calibrated equipment used; system suitability tests were
done and acceptable
 Glassware, reagents, solvents and reference substances used
 Original sample kept until the investigation is complete
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35. Review of Analytical record
 Proper review will prevent the Non-compliances/ observation;
 Sincere and effective review shall be done; not just signing as
reviewer;
 The following shall be reviewed but not limited to;
 Incomplete entries, signature
 missing records and out-prints
 Illegible entries / unacceptable corrections
 Traceability of relevant records /cross references
 Deviations, if any investigation the impact on the product
 Valid calibrations and service intervals of test equipment
 Compliance with specifications,
 Calculations
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36. Reserve sample
1. Pack & store the reserve samples is for the purpose of potential
future evaluation of the quality of batches of API
 Appropriately identified reserve samples of each API batch should
be retained for 1 year after the expiry date or for 3 years after
distribution of the batch, whichever is longer.
 The reserve sample should be stored in the same packaging system
in which the API is stored or in one that is equivalent to or more
protective than the marketed packaging system.
 Sufficient quantities should be retained to conduct at least two full
specification analyses
 Verify the reserve sample periodically and record for physical
attribute
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37. Computer System Validation
 GMP-related computerized systems should be validated.
 Appropriate installation and operational qualifications should
demonstrate the suitability of computer hardware and software to
perform assigned tasks.
 Commercially available software that has been qualified does not require
the same level of testing.
 Computerized systems should have sufficient controls to prevent
unauthorized access or changes to data. There should be controls to
prevent omissions in data (e.g., system turned off and data not captured).
 There should be a record of any data change made, the previous entry,
who made the change, and when the change was made.
 SOP for the operation and maintenance of computerized systems.
 Any critical data is manual, ensure an additional check on the accuracy of
the entry.
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38. Computer System Validation
 Incidents related to computerized systems that could affect the
quality of product or test results should be recorded and
investigated.
 Changes to computerized systems should handled thorough change
procedure.
 Record all changes, modifications and enhancements made to the
hardware, software, and critical component of the system to ensure
that the system is maintained in a validated state.
 Records shall be a backed up. Ensure data protection all
computerized systems.
 Data can be recorded by a second means in addition to the
computer system.
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39. Good Document practice
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40. Good Document practice
Data Integrity
ALCOA is an acronym representing the following data integrity
elements:
 Attributable – Who performed and when?
 Legible – Can it be read? Permanent Record
 Contemporaneous – Recorded at the time the activity
was performed
 Original – Original record or certified true copy
 Accurate – Error free
40

41. ALCOA principle
ALCOA is an acronym representing the following data integrity
elements:
 Attributable – Who performed and when?
 Legible – Can it be read? Permanent Record
 Contemporaneous – Recorded at the time the activity
was performed
 Original – Original record or certified true copy
 Accurate – Error free
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42. ALCOA Description
ALCOA Description/Explanation
A Attributable Who performed an action and when?
If a record is amended / changed, who did it and why?
Why- reason & explain in detail
Traceable to the source data.
L Legible Data shall be recorded permanently
Record shall be durable & readable.
C Contempora
neous
The data shall be recorded at the time the work is
performed. Signature / initial with date
O Original Is the information the original record or a certified true
copy?
A Accurate No errors or if editing shall be amended properly
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43. ALCOA +
ALCOA + Description/Explanation
1 Complete All data including repeat or reanalysis
performed on the sample.
2 Consistent Consistent application of data time stamps in
the expected sequence
3 Enduring & Recorded on controlled worksheets,
laboratory notebooks, or electronic media.
4 Available Available/accessible for review/audit for the
lifetime of the record.
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44. Tips to Good Documentation Practices
 All entries must be clear and legible
 Never make erasures or write overs.
 Do not scribble out or "white out" entries;
Thus, the integrity of the record will not be in question.
 Any written error must be crossed out in such a manner that the
original information is still legible.
 The crossed out section must be initialed and dated by originator.
Corrections must be made adjacent to the deleted entry. Write
reason for correction eg Transposition, Illegible entry, Scale zero error
 DO NOT USE “write-overs” (Don’t turn a “6” or “9” into an “8”.)
 Never vary your initials or signature
 Eg. Weight of material - 14.5 kg 14.75 kg Ams 13/12/07
44

45. Tips to Good Documentation Practices
• Pencil writing is not
acceptable,
Use only black or blue permanent ink.
The ink should not run or smear if the
record is splashed with liquid. All entries
must be permanent and able to be
photocopied.
Don’t use pens like gel pens, ink pens for
making entries. Don’t use pens like red,
green color ink.
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46. Tips to Good Documentation Practices
 When portions of a page or a complete page remain unused, a
single line must be drawn angularly across the unused portion. Sign
and date the crossed out section and provide an explanation
 Eg- Not applicable; Remining pages not used refer new note
book
 Ensure the pagination (all pages to be numbered; could be page X of
Y for loose sheets and page x.. For bound books)
 Make the required entries on the record as the work is performed.
Do not record information on a
separate piece of paper /temporary
entry and enter on the record later
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47. Tips to Good Documentation Practices
 Use correct rounding off procedures and significant figures
 When a comment or explanation is required, make all statements
objective. Avoid personal comments and opinions.
 When dating a signature, use the actual day the signature was
signed.
 If the activity being recorded occurs on more than one day, the
record must clearly indicate where the "break" occurred. This
can be accomplished by drawing a horizontal line through the
procedure at the break" and indicating the new date or making
entries that are initiated and dated appropriately.
47

48. Observations on poor
documentation practices
 Document error correction not signed/dated, and didn’t include a reason
for the correction
 Write-overs, multiple line-through and use of "White-out" or other
masking device
 Sample sequence table and audit trail not documented (if its not
documented, it didn’t happen)
 SOP related to production, calibration, storage and maintenance not
authorized by the QA head
 The delegation for the batch release, in case of absence of the QA
manager, not recorded / documented
 Out-of-specification (OOS) procedure not detailed enough; flow chart and
/or check-list not available.
48

49. “ I swear to follow the good documentation
practice and document the actual
information and on line…..”
49

50. Data integrity issues
 Backdating/Postdating/Missing Signatures
• Fabricating/faking data
• Copying existing data as new data
• Releasing failing product
• Hiding/obscuring SOP or protocol deviations
• Not saving electronic or hard copy data
• Inadequate reporting of failure and deviation
• Use of non-validated software
• Mismatch between reported data and actual data
• No links/traceability to source documents or original data
50

51. Data integrity issues
• Re-running samples / Test until release/ No /Inappropriate Audit Trail
• Inadequate Access Authorization/ Privileges
• Discarding Deleting of data/ omitting negative data (like OOS or eliminating
outliers)
• Not reporting failing results /stability failures
• Conducting unofficial analysis
• Disabling audit trails in electronic data capture systems
• Fabricating training data
• Having unofficial batch sheets and analytical reports
This is not related to training or understanding a particular technical or
quality concept but mainly related to honesty and ethical issues.
51

52. Typical content in WL
 Firm did not identify, report, or investigate the out-of-
specification (OOS) results.
 Firm did not retain any raw data related to sample weights and
sample solution preparations for the HPLC assays….
 Repeated the analysis next day using a new set of sample
solutions, and reported the retest results in COA
 Firm deleted /disregarded OOS data without investigations,
and selectively reported only passing results.
 During inspection, QC Chemist admitted that, under the
direction of a senior colleague, he had recorded false data in
the logbooks for reserve samples
52

53. Typical content in WL
 QC analyst label sample “trial” injections as standard rather than by the
actual sample batch numbers”
 Creating passing test results without performing the test
 Access control is not implemented in GC, FTIR and HPLC to prevent
unauthorized access and control
 Lack of records demonstrating who performed analysis
 Raw data not recorded contemporaneously nor by the performing analyst
 Failed injections of QC standards (SS) deleted, repeated and inserted into
the analytical sequence without explanation.
 Falsification of batch records (re-writing clean records) Non-
contemporaneous recording of lab data Recording of sample weights on
scraps of paper Missing raw data

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54. Thank You
Q&A
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