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Good Laboratory Practices- Pharma QC Lab_Dr.Amsavel


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 – PowerPoint PPT presentation

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Title: Good Laboratory Practices- Pharma QC Lab_Dr.Amsavel

Good Practices for QC Laboratories in Pharma
  • Dr. A. Amsavel

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

Definition (WHO)
  • Quality ControlAll measures taken, including
    the setting of specifications, sampling,
    testingand 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 SystemAn appropriate
    infrastructure, encompassing the organizational
    structure,procedures, processes and resources,
    and systematic actions necessary toensure
    adequate confidence that a product or service
    will satisfy givenrequirements for quality.
  • Analytical test reportAn 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

Definition (WHO)
  • Analytical worksheetA 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 uncertaintyNon-negative parameter
    characterizing the dispersion of quantity values
    being attributed to a measurand (analyte), based
    on the information usedMetrological
    traceabilityProperty 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.

Definition (WHO)
  • Deviation
  • Deviation from the prescribed procedure
  • Out-Of-Specifi cation (OOS) resultAll test
    results that fall outside the specifications or
    acceptance criteriaestablished 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

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
  • 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.

GDP references
  • 21 CFR 211.194 (a)
  • Verification of laboratory test data for
    Accuracy, Completeness compliance with
    established standards
  • ICH Q7 Chapter6 other GMP guidelines
  • Documentation and Records

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.

QC Lab Management
  • Organization and management
  • Quality management systems
  • Control of documentation and records
  • Data processing equipment
  • Personnel
  • Premises, equipment, instruments and other
  • Working procedures, documents and safety

Organization and Management
  • Function to meet Regulatory requirements
  • Operate in accordance with Good Practice
  • 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

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

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

  • 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

  • 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

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

General Requirement
  • Water used in the Lab shall be suitable for
    indented use.
  • Washing of glassware shall be ensured and
  • Separate area for sample preparation
  • Separate oven for drying of glassware ( 60C)
  • SOPs are available
  • Any deviation, OOS shll be reported and
    investigated. CAPA shall be implemented and
    relevet reports should be maintained

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

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
  • 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
  • Containers should be marked to indicate that a

Sample Management
  • Label affixed to each container of the sample
  • Procedure for preparation of representative
  • Sampling activity shall be recorded and
  • Storage of sample and prevent mix-up or
  • Registration number allocated for every sample
  • Information recorded in a register and include
  • 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

  • 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

  • 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
  • Transportation in original containers
  • When subdivided into clean, fully labelled

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

Reference standard
  • 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

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
  • 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

Instrument Testing devices
  • Qualification, Calibration, validation and
    verification of equipment, instruments and other
  • Control, weighing, measuring, monitoring, and
    testing equipment critical for ensuring the
    quality of product should be calibrated according
    to written procedures and an established
  • Calibration procedure can be used from
  • 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

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
  • 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)

Records related to Instruments
  • Records kept of each item of equipment/
  • 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

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
  • to support an OOS result and investigation
  • A separate analytical worksheet for each numbered
  • Keep all the test data (different
    analysts/units) together.

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
  • Deviations and other remarks
  • Reviewed / Approved and signed by the supervisor

Analytical worksheet
  • Recording the data immediately on the analytical
  • 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
  • reason for the change given on the worksheet
  • SOP for amending electronic worksheets and audit
  • Follow ALCOA principles

External testing Laboratory
  • When specific tests are to be done outside the
    laboratory test request and samples
  • Ensure the external Lab is qualified and
  • Ensure the Lab id approved by regulatory
  • 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

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
  • If validation in other Lab, perform method
  • 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

System Suitability testing
  • Ensure to follow System suitability test as
  • SS is an integral part of many analytical
  • 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

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
  • 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

Review of Analytical record
  • Proper review will prevent the Non-compliances/
  • Sincere and effective review shall be done not
    just signing as reviewer
  • The following shall be reviewed but not limited
  • Incomplete entries, signature
  • missing records and out-prints
  • Illegible entries / unacceptable corrections
  • Traceability of relevant records /cross
  • Deviations, if any investigation the impact on
    the product
  • Valid calibrations and service intervals of test
  • Compliance with specifications,
  • Calculations

Reserve sample
  • 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

Computer System Validation
  • GMP-related computerized systems should be
  • 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
  • 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.

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.

  • Good Document practice

Good Document practiceData 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
  • Accurate Error free

ALCOA Description
ALCOA 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 Contemporaneous 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
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.
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
  • 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 (Dont 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

Tips to Good Documentation Practices
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. Dont use pens like gel
pens, ink pens for making entries. Dont use pens
like red, green color ink.
  • Pencil writing is not acceptable,

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

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.

Observations on poor documentation practices
  • Document error correction not signed/dated, and
    didnt 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 didnt
  • 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 /
  • Out-of-specification (OOS) procedure not
    detailed enough flow chart and /or check-list
    not available.

I swear to follow the good documentation
practice and document the actual information
and on line..
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

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
  • Conducting unofficial analysis
  • Disabling audit trails in electronic data
    capture systems
  • Fabricating training data
  • Having unofficial batch sheets and analytical
  • This is not related to training or
    understanding a particular technical or quality
    concept but mainly related to honesty and ethical

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

Typical content in WL
  • QC analyst label sample trial injections as
    standard rather than by the actual sample batch
  • 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
  • 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

  • Thank You
  • QA
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