Challenges of the Quality

Control Laboratories
CHALLENGES AND SOLUTIONS
DATE : 21ST AND 22ND SEPT. 2019
BAXIMICO DHAKA , BANGLADESH
DR Deo Narain Dikshit
Director –AQEC PHARMASOLUTION PVT LTD
 01 Back ground

Agenda 02
Current Experiences from GMP Inspections in
QC Labs

cGMP Compliance Trends in Analytical

03 Labs

Modern Days Challenges and Analysis of

04 Cause

05 Defining Issues and Designing Actions for

Compliance and Productivity

Lean Quality Laboratory

06

Quality Matrices and benefits of Quality

05 Matrices
CURRENT EXPERIENCES IN GMP INSPECTIONS
OF QUALITY CONTROL
 Modern Day Challenges of a Quality Control
Laboratory
 Mounting Stress on Management for Regulatory Inspections always
in fire fighting mode
Plenty of conformance, but not much real control on Systems –
Compliance issues still remains even after Remedial Actions
Large backlogs of Samples (Routine , In-process and Stability )and
missed deadlines for deliverance
Analytical method issues , Analytical method validation of legacy
products
Method Transfers , Analytical Validations , and Regulatory filing
Documents preparations , which trigger fast-tracking or expediting of
work and further complicate scheduling
4
 Modern Day Challenges of a Quality Control
Laboratory
Compliance with Data Integrity CSV and Data Management , Compliance of
Legacy systems with Part 11
Variable demand and uneven workloads due to Change in Work Plans and
Sample Plans
 Resource management ,Knowledge Management , SKill Development and
control on expenses
 Complex scheduling that combines In process testing with Finished
Products and special tests and projects.
Individuals who are their own mini-silos; that is, they are set up to work to
their own schedule or “drumbeat” rather than to the rhythm of demand,
Different Verticals of laboratory working in Silos and lack of Visibility and
Controls.
483 on Laboratory Facility- Responsibility
19. [email protected] Regulation
20. CFR part 211 Regulation - 21 CFR 211.22(c) • The quality control unit shall have the
responsibility for approving or rejecting all procedures or specifications impacting on the identity,
strength, quality, and purity of the drug product.
483 citations related to 21 CFR 211.22(c) Cite Id Reference Number Short Description Long
Description Frequency 2014 2013 1098 21 CFR 211.22(c) Approve or reject procedures or specs
The quality control unit lacks responsibility to [approve] [reject] all procedures
or specifications impacting on the [identity] [strength] [quality] [purity] of drug
products. Specifically,
The responsibilities and procedures applicable to the quality control unit are not fully followed. Ref:
483 of Hospira Inc. (Mar-2013) 483 citations related to 21 CFR 211.22
29. • The responsibilities and procedures applicable to the quality control unit are
not fully followed. Ref: 483 of Hospira Inc. (Mar-2013) 483 citations related to 21
CFR 211.22
 483 on Laboratory Facility
16. CFR part 211 Regulation - 21 CFR 211.22 (b) Adequate laboratory facilities for the testing and approval
(or rejection) of components, drug product containers, closures, packaging materials, in-process materials,
and drug products shall be available to the quality control unit.
17. 483 citations related to 21 CFR 211.22(b) Cite Id Reference Number Short Description Long Description
Frequency 2014 2013 1086 21 CFR 211.22(b) Adequate lab facilities not available Adequate lab
facilities for testing and approval or rejection of [components] [drug product
containers] [closures] [packaging materials] [in- process materials] [drug products] are
not available to the quality control unit. Specifically, *** 7 12
18. Warning letter observations -2013 - 21 CFR 211.22(b) Your firm failed to have an adequate
laboratory facility available for the testing and approval (or rejection) of components,
drug product containers, closures, packaging materials, in-process materials, and drug
products (21 CFR 211.22(b)). For example, assay methods used by your contract testing
laboratory to test your finished products (e.g. Instaclean and PeriShield) for release have not been
validated. Ref: WL: 14-NWJ-02 (Ameriderm Laboratories, Ltd. 12/2/13)
Recent Inspections 483 Observations on Quality
Control- Inadequate Quality Management System and
Controls
Another example read s as follows:
“Failure to perform at least one identity test of each batch of incoming material.
For example, the starting material [deleted] lot [deleted], used for the production
of [deleted] USP, API lot [deleted] was not tested for identity.”

And yet another violation is described here:

“Failure of your quality unit to evaluate raw materials prior to release and use in drug
production operations. The inspection revealed that your firm recovers [deleted]
from the purification processes and reuses the recovered solvent without
performing any test to ensure the purity and quality of the recovered solvent.”
Recent Inspections 483 Observations on Quality
Control – In adequate Quality Management
System Control – Vendor management
And again:
“Failure to have a system in place to evaluate suppliers, and failure to adequately test
each batch of incoming materials intended to be used in drug production. For example,
the inspection found that you have not evaluated the suppliers of [deleted],
[deleted], and [deleted], all used in the manufacturing process of [deleted].
Your firm currently accepts certificates of analysis (COA) from unevaluated
suppliers in lieu of testing each batch of an incoming component to ensure
conformity with the established specifications.”
“
Recent Inspections 483 Observations on Quality
Control – Inadequate Document Review
Failure of your quality unit to conduct review of completed batch production and laboratory control
records before release for distribution. For example, your firm lacks raw data to
demonstrate that the [deleted] test for the lots of [deleted] shipped to the United
States met the acceptance criteria. Your firm sends samples of [deleted], produced
by your firm, to your contract laboratory [deleted] for [deleted] testing. The
material is released without adequate review of laboratory control records. Instead
the results used for release are summary results accepted via text messaging, e-
mail, or phone. In addition, your contract testing laboratory [deleted] for proton-nuclear
magnetic resonance (HNMR) only provides you with a partial spectra zoomed in on the range for
[deleted] and [deleted]. It is important for your firm to review the entire spectrum for other
potential impurities or contaminants. All documents related to the testing of your [deleted] should
be reviewed and approved by your quality unit according to established procedures. Contract
laboratories are an extension of your operations and, as such, your quality unit is responsible for all
data acquired at the contract laboratories you choose to use.”
Recent Inspections 483 Observations on Quality Control-
Inadequate Quality Management System and Controls – CMO
supplied Products
Warning letter observations -2013 - 21 CFR 211.22 b) Your finished drug products have
been released by your warehouse manager, not signed off by your QCU. In
addition, your unapproved procedure, SOP-01-05 “Finished Product Release,
Storage and Distribution” addresses how your warehouse releases materials for
shipping, not how your finished product is examined, and approved by your QCU.
c) Your QCU failed to establish SOPs to examine and ensure the suitability of
incoming raw materials, components, container, closures, or labels. d) Your firm
contracted out the manufacturer of STRONG WOO LOK GAO to an external party.
Your firm is the owner of this drug product, but did not adequately evaluate
whether the CMO (contract manufacturing organization), which is an extension of
your operations, can consistently produce product that is suitable for distribution
Recent Inspections 483 Observations on Quality Control-
Inadequate Quality Management System and Controls – Data
Integrity and CSV
The inspector found “Data reports in uncontrolled, loose handwritten
notebooks” and unsigned reports about sterile operations. The plant’s
investigations into data discrepancies didn’t often get to the root cause. The
report said that out of 112 cases during a 16-month period, in 39 (nearly 35%)
data were missing or incomplete.
Computers were not secure and cleaning protocols were not being followed,
the report says. And then there were those four buckets half-full of air
conditioner condenser water sitting in laboratories with no indication that
they were being emptied regularly
Compliance –
Regulatory Perspective of Quality Control
Regulatory Guidance – • European Guidance – Eudralex –Volume 4
• WHO good practices for pharmaceutical ,
quality control laboratory TRS 957 • ICH Q2 R1 Validation of Analytical
• FDA’s GUIDE TO INSPECTIONS OF Methods
PHARMACEUTICAL QUALITY CONTROL • ICH Guidance on Tecnology Transfer ICH
LABORATORIES 7/93 Q10 ( Pharmaceutical Quality System
• Good laboratories Practices 21 CFR Part • ICH Guidance for Stability Q1A
58 (and 210 , 211 for cGMP) • WHO good practices for pharmaceutical
• 21 CFR Part 11 , 21 CFR 22 quality control - Microbiology laboratory
• Guidance for Data Integrity TRS 957 Annexure 1
• WHO Guidance -on Computer System
Validation Annexure 5, PICs Guidance
and GAMP
 Challenges – COMPLIANCE
 COMPUTER SYSTEM VALIDATION – Inadequate or Un available
System Security Policy in compliance with 21 CFR Part 11- Control on
Manual Data Recording – Not Contemporaneous, Use of Post it slips , note
papers for recording data
Inadequate information, Missing Information or about samples in
Laboratory paper and Electronic Records ,
Un authorized Changes – Alter Samples , Deletion or Un intentional Data
Processing due to lack of understanding
 Archived Data Security and Data Reliability- Review of the Back up projects
Internal Audit observations – Not addressed in Time
 Long due Open Records – Deviations ,Investigations , CAPA , Change Controls
 Challenges – COMPLIANCE
 Over Due Samples - Microbiology , and Instrumental Analysis
Over Due Calibration and standardization
 Repeated Failures and Root Cause un identified or Multiple causes
Batches Released even with Incomplete Investigations of Deviation/ OOT /
OOS – Reason for Pending Investigation not addressed
CAPA implementation Pending - committed in Response report of Last
Inspection , Over due after Repeated extension of the Date
No Risk Mitigation implemented after observation of System failures or
Critical Deviations
No Quality Over sight for Out sourced tests , Out sourced services not
audited and certified for Quality Systems
 Challenges at Glance-
Analytical Methods and Related
 Analytical Methods – Un- validated Method in Use , Pending Analytical
Method Validation and Poor of Performance of Validated Methods ,
Analytical Method transfer
Laboratory _Data Handling - Generation , Processing , Data Review , Errors ,
Deviations
 High Percentage of Invalidated OOS
 Calibration and Validation of Analytical Systems – Application Software
Validation , Computerized System Validation , IQ, OQ and PQ of the System
Management of Primary Standards , Impurities – Reference Standards –
Working standards , Stability and Validation of Working standards
 Challenges at Glance- Analytical
Methods and Related
 Out of Trend and anticipation of failures in future at time of Release
and During Stability testing
 OOS observed in Stability of Batches Live in Market
FDA Picked samples failed to Comply with Files Specification in
Marketing Authorization , Registration Dossiers
FAR and Investigation – Impact analysis on Live Batches
Recalls
 Three Key Focus Areas

The Modern Challenges of the Quality Control Laboratory are Critical to Business
of the Pharmaceutical Industry , Hence the It becomes the important to have an
effective strategy for handling the Laboratory issues with effective tools –
Documentation Control , Validation ,Compliance , Training ,and Lean Quality
Laboratory Management
Three Critical Challenges
Improvement Strategy

Implement Lean Reduce the Improve

01 Management 02 Cost 03 Compliance
Improve
and Meet
KPI
What’s is needed ? Top 10 Golden Priorities
1. Improve Productivity - The top-down, managed work of standardizing
processes, of analyzing the nature of demand and how it matches with
resources, and of finding a better way to effectively manage flow and
scheduling;
2. The bottom-up, self-managing processes of visual management and lab
organization,.
3. Reduce The Cost by Automation , Software Based QMS Solutions , Reduce
Documentation , Reduce Non Value Added Activities , Improve The Processes
performance and Reduce Time (Cycle Time)
4. Improve Compliance and Meet KPI -Continuous Improvement on -Identified
Indicators of Poor Controls , Laboratory Management Performance
(Productivity and Quality Attributes, such as Quality Matrices)
5. Integrated Compliance – Quality Risk Management and Data Governance
Strategy
21
What’s is needed ? Top 10 Golden Priorities
6. Develop Center of excellence – Simplify the Procedures , Update the
Systems , Monitor the Implementation of excellence such as
Harmonization of SOPs , Improvement of Analytical Methods and Trouble
Shooting
7. Integrate the Analytical Development , Technology transfer and Quality
Unit (QA&QC)
8. Training and skills development, and teamwork, Identify the Changing
Training Need and Develop SME
9. Set Realistic achievable and Progressive KPI at all Levels – Chemists , Lab
Managers , General Managers and Heads
10. Quality Review Meeting and Escalations of the Issues to QRB and Senior
Management
IMPROVE PRODUCTIVITY –
THE IMPETUS = THE NEED FOR SPEED
To illustrate how a specific strategic change can serve as the springboard for
transformation, - It is “Lean Laboratory Strategy ”
There are two broad dimensions in a lean lab Transformation-
A) The first is improvement of Performance of the whole value
stream for different Sample Families – Chemical (wet testing )
Instrumentation samples , Microbiological analysis Samples ,
Specialized test using Advance technologies such as MS –MS , LC-MS , AAS ,
CE etc. , from receipt of Samples to delivery of Results and test report with all
completed test records in compliance with applied Guidance and standards .

23
 .

THE IMPETUS = THE NEED FOR SPEED & COMPLIANCE

B) The Second dimension is “Transformation operations” which includes –

Establish a lean scheduling system for both people and machine time,
based on a clear understanding of volume and demand variation;
 Reduce changeover time between running sequences of assays, RS
and other tests on HPLC and other Equipments for high Ques
 Improve workplace organization and create standards;
Establish visual flow management;
 Develop effective performance management systems, and
 Create a team and problem-solving culture
24
IMPROVING SPEED
Three steps-
1. Creating stability in the workplace and in processes; 5 S strategy

1. Linking processes in flow; to set the order which saves the idle
hours and

2. Managing the workload visually and Monitoring the Efficiency

25
CREATING STABILITY-5 S Strategy
The 5S system is a working tool for ISO
9001:2015 that was developed to help
mangers and work personnel
systematically achieve greater
organization, standardization, efficiency
and safety in the workplace.
CREATING STABILITY-5 S Strategy

1. SHORT ;- The goal is to filter through all workplace inventories of

the sample , Pending activities , Pending documentations and
make the sample receipt , work bench , documentations in order
so needless items, redundancies and hazards can be sorted out of
the workplace. .

27
CREATING STABILITY-5 S Strategy
2. SET IN ORDER : This step is dedicated to helping the work force to
set every item( Chemicals , Impurities , Glass wares , Reagents ,
Solvents ) in proper place for quick retrieval and storage at a shop
floor , for day to day operations at the chemical and regents selves ,
to find permanent storage locations for every item and visually
identifying their locations
3. Shine,:This refers to the critical cleaning and basic maintenance
duties of the employees incorporated into their daily routines.
Once in place, shine becomes an invaluable step in this system.
Reductions in utensils, glass wares , papers and unwanted things
around equipment and workplaces allows for improved work area
safety and personnel efficiency. Clean the workplace. Every one
should be a janitor.
28
CREATING STABILITY-5 S Strategy
4. Standardize, Create a set of standards for both organization and processes. In
essence, this is where you take the first three S's and make rules for how and
when these tasks will be performed.
These standards can involve benchmarking of the Analytical testing Times ,
scheduling and adherence , Work Monitoring Dashboard ,Quality Matrices for
QC Performance and Compliance
5. Sustain ;Make 5S part of daily work so it becomes a habit.Perform a 5S audit
regularly to maintain standards and measure progress."Don't slip back into old
habits"
Monitor Instituting an audit process is a key tool to not only measure but also
manage 5S performance and the continuous improvement process. In
the life sciences industry audits are not unusual and, therefore,
instituting a 5S audit process is typically not very difficult.
29
2.0 LINKING PROCESSES IN FLOW
• The work of QC labs can be extremely complex, especially in labs that
handle a variety of different types of testing. Creating an appropriate
scheduling system on a case-by-case basis is a must to optimize the time
of both people and machines in different environments. Labs can have
short machine cycle times and long manual times, the opposite, or a
combination. The process of creating a simplified scheduling system can be
quite challenging.
• Creating a schedule based on the pull of demand begins with
understanding the true nature and volatility of that demand, usually by
analyzing it over a given time period, and then creating routines that help
level out the peaks and valleys. Combined with a multi-skilled staff and a
visual method for tracking progress, labs can see big improvements in
throughput times and on-time releases
30
MANAGING THE WORKLOAD VISUALLY
1. A visual planning board can be used to allocate incoming assays in a
standardized way to a leveled lab schedule. That provides a way to manage the
workload visually. At a glance, staff can see lab capacity, can see the work in
process and work to be done, and can see whether they are working to
demand. People become used to working to the demands of the process and
their internal customers, rather than in silos.

A lab schedule that handles complexity visually. This board was developed from a kaizen event to review process delays.
Availability of the right person at the right time was a problem. The team split the day into 15-minute increments and used
color-coding to denote types of activities. The value stream of the process (green activities) takes priority; other activities
have to be scheduled around it; and the staff can easily keep track visual of what needs to be done. 31
MANAGING THE WORKLOAD VISUALLY- Activity mapping and
Resource allocation
• Through standardized visual scheduling, one lab was able to increase the number
of HPLC Tests performed in a 10-day period from two to three. Because two
technicians are required in the process—one to perform the tests and one to
prepare and feed ,
So schedule was revamped to assign two technicians rather than one to the core
process. Each technician now worked half-time on HPLC assays and half-time on
other duties. The result was a 50 percent improvement in HPLC productivity with
no additional staff hours

32
 Optimize Scheduling
 Prioritize Linked Activity
 Consider dedicated Equipment for Frequent Samples or
Complex Analysis techniques
 Align Different Analytical Works

Activities 1 2 3 4 5 6 OFF
Media Preparation
Culturing
Miro Assay
Sterility
SterMon
Peso Monit
EM samples
 Reduce The Cost
• Operation Cost –
1. Standardize the Consumption : Standardize the Volume of Mobile Phase ,
Buffers , dissolution Media , Freshly prepared Standard Volumetric Solutions ,
Impurities for Preparing Impurity Solution.
2. Standardize and Centralize the Purchase Quantity : Rationalize the Purchase
Quantity based on trend of Consumption – Frequently used , Commonly used ,
rarely used and Special Cases , so that the best price could be achieved while
bargaining . Reduce the number of brands of HPLC Solvents unless specified .
3. Map the activity Flow and Space : The Best way of achieving the operational
efficiency is by Mapping activity Flow to adopt -sequencing / or Parallel
Activity Flow to reduce the wastage of time .
4. Bring the Supporting activity Closer to Testing Area – Such as Weiging ,
Solution Preparation , Filtration, Sonication etc to HPLC testing Room , so that
we can avoid the travel time .
 Reduce The Cost
• Operation Cost –
1. Standardize the Consumption : Standardize the Volume of Mobile Phase , Buffers ,
dissolution Media , Freshly prepared Standard Volumetric Solutions , Impurities for
Preparing Impurity Solution.
2. Standardize and Centralize the Purchase Quantity : Rationalize the Purchase Quantity
based on trend of Consumption – Frequently used , Commonly used , rarely used and
Special Cases , so that the best price could be achieved while bargaining . Reduce the
number of brands of HPLC Solvents unless specified .
3. Map the activity Flow and Space : The Best way of achieving the operational efficiency is
by Mapping activity Flow to adopt -sequencing / or Parallel Activity Flow to reduce the
wastage of time .
4. Bring the Supporting activity Closer to Testing Area – Such as Weiging , Solution
Preparation , Filtration, Sonication etc to HPLC testing Room , so that we can avoid the
travel time .
5. Make the Resources Available at/ near Work bench Assuring Availability of preparatory
the Glass wares , Chemicals , Columns ,Reagents , Solvents for Day Consumption in Lab
strategic changes to optimize workflow
• Improve productivity and throughput
• Streamline processes to manage growing
workload
• Reduce turnaround time and ensure
quality, standardized results for client
satisfaction
• Reduce or eliminate errors
• Ensure staff skills are directed to most
appropriate activities
• Reduce movement strain and increase
safety
• Reduce stress and raise staff satisfaction
Bring Automation
• The automation must always be based on an improvement of the process.
Thus, the goal of a successful automation project must be to change the way
in which the laboratory’s work is done. This involves changing not only tools
and processes, but also jobs, structure, and ultimately, the way people think
about their work .
• Automation and Software Based Tools reduces not only documentation but
also brings the efficiency in works –
• Examples – Use Auto tester for Multiple Physical tests – Weight Variation ,
Hardness , Dimensions and Statistical Evolution of Process efficiency
• Use serial Automated Dilution and CFU concentration measurement for
Micro organism Specimens
• Use Auto sampler for Long run Dissolutions in case of Extended release
products and can be further automated analysis by integrating On line UV
measurement robotics
Bring Automation- Advancement
• Use Artificial Intelligence in Training the Workforce for visualizing the Activities posing
Contamination Risk in Microbiology
• Use Server Based Quality Management Tools – Trackwise , LMS , NOVATECK ,
• Use sample management and Data management aligned with progress of testing activity in
full compliance of ALCOA , use LIMS
• Use Data Base and Think Clients to manage the Document Flow from Stand alone PCs
• NuGenesis Lab Management System uniquely combines synergistic data, workflow, and
sample management capabilities to support the entire product lifecycle from discovery
through manufacturing.
• The user-centric platform encompasses NuGenesis SDMS, a compliant-ready data
repository, NuGenesis ELN, a flexible analytical electronic laboratory notebook, and
NuGenesis Sample Management. NuGenesis seamlessly links data from the lab to the
business operations of the enterprise with functionality such as sample submission and
results review, stability testing, scientific search, multi-vendor software connection,
laboratory inventories, data retention and legal hold, and laboratory execution methods
 Improve Compliance and Meet KPI -
Continuous Improvement on - Actions- To be done
• Repetitions :Aborted Run, Acquisition • Routine maintenance , predictive
Failure ,Lab Errors and System maintenance, Root cause analysis of
Breakdown communication error
• Productivity • Allocate the Productivity KPI for
No of Work Units / sample analyzed Instrumental , Microbiological and
/Chemist/day (25 days /450 to 480 Wet Chemistry Tests based
minutes per shift basis) • Monitor all unit operation Time for
each sample and allocate the Cycle
Time for each type of samples
 Improve Compliance and Meet KPI -
Continuous Improvement on - Actions- To be done
• Laboratory Deviation : The Objective • Measure the trend of the deviation in
should be identify the Common Sample type , Activity Type and
Technology of test Type
Laboratory Incidence which are
• Use Statistical Tools to measure Control
related to – in Process Efficiency and inherent
o Inadequate information in analytical Limitations by techniques -
Analysis of Variance , Student T , Control
Procedures (SOPs / STPs) Chart , % RSD etc
o Skill Gaps in Work force
o Performance of Analytical Method
o Performance of analytical Systems
 Improve Compliance and Meet KPI -
Continuous Improvement on - Actions- To be done
• Do not Ignoring failing results donot repeat without
• Invalidated OOS rate : The Objective documentation and investigation
should be identify the causes of high %
of invalidated OOS rate and reduce • Do not over look report &only passing results without
month by month or atleast sustain and justification for failing In process measurement such as pH ,
then Reduce
PSD,
o Malfunctioning of Analytical System –
Equipment , Column , Incorrect • Use Scientific tools such as Brain storming , RCA , C&E analysis
measurement, , Other Statistical tools
o Human Errors – Skill Gap , Lack of • Donot settle early for CAPA without right Root Cause specially
Understanding , Lack of Attention , Lack recurring problems .
of inadequate Resource and fatigue
o Poor Performance of Analytical Methods• Follow the Current Guidance for OOS handling and document
accordingly
• Study systemic failures _ Poor Controls in Lab management ,
continued over stretched working, Training
• Send back poor performing methods to Analytical
development
• Keep Routine Maintenance of Equipment and in state of order
 Improve Compliance and Meet KPI -
Continuous Improvement on - Actions- To be done
• Data Reliability : The Objective Institutionalize Data Governance for
should be identify the factors
influencing the Data Integrity. real time Assurance to Data Security , Availability
• Evaluate lagging practices and Traceability , and meets to ALCOA principle
Impact on Compliance in Implement Robust Computer system Validations
GXP Practices Program
Product Development – EB Analytical o Implement Quality IT Strategy for – Internal
data Audit of the implementation of SOPs of IT
Analytical Method Development data systems in QC and QA
Stability Data o Investigation Root cause analysis
Investigational Analysis Data o Validation Documentation Compliance
Tech transfer Data
 Develop Center of excellence – Objective
• Decrease implementation and platform support costs for Improvement
projects
• Accelerated deployment of Highly skilled and Experiences SME , reference
procedures , and best practices at Selected Sites of Company
• Mitigated risk due to deep rooted Gaps in System and Procesees
• Increased agility with resources who are able to respond rapidly to issues and
requests
• Optimum solution for each problem
• Quality and predictability from institutionalized best practices
• Established standards and guidelines derived from regulatory publication ,
Learning from Regulatory Inspections by sharing information Centrally to
right person for evaluation of current status at QC and other Operations Area
and implementation of Improvement Strategy
Develop Center of excellence – Objective
• Update the Systems : There is continuous change in information
pertaining to regulatory guidance with respect to compliance and system
requirement , Pharmacopeia Monographs and MOA , Hence there should
be a team at Corporate QA and Analytical Development to study evaluate
the impact of changes , and Risk Mitigation for Implementation
• If there are Changes in analytical method , AMV or Method Performancxe
Verification must be done
• There should evaluation of Method suitability by actual analysis to judge
the Compliance of the Product Quality with new / changed method
• If there is Change in Guidance the QC Team of Experts must go through the
guidance and evaluate the impact of existing Procedures , Processes and
working and escalate to management
Monitor the Center of excellence –
Performance
• Monitor the Implementation Progress of Projects taken by Centre of
excellence in Quality Review Meeting or dedicated meeting at least
once in Quarteer
• Initiate the Simplification and Harmonization of SOPs across the
Laboratories – Main QC Lab , Stability Testing , and Other QC laboratory
of Organization

• Implement of Analytical Methods Trouble Shooting cell to identify and

work to improve the Methods
Integrated Compliance- Quality Risk Management
• The Quality Control
Compliance
Laboratory should have
Excellence Team which
are well integrated with – Analytical
Analytical Development , Development
and Tech
Centre of
Excllence
Business Development , Transfer
Quality
Data Governance , Control
Corporate Compliance Excellence
strategy and Centre of
Excellence Data
Business
Governance
Quality Control Excellence Cycle
 Management of Computetrised system

Identify Controls

Computer Create Data Flow Diagram and Assess Risks

Systems
Controls Reconcile the Computer Systems Life Cycle and the
Data Life Cycle
Collaborate with vendors to manage controls
20TH ANNUAL COMPUTER AND IT SYSTEMS VALIDATION
4
8
Computer System Controls

DATA GOVERNANCE DATA CONTROLS COMPUTER SYSTEMS

CONTROLS

20TH ANNUAL COMPUTER AND IT SYSTEMSVALIDATION 3

 Data Governance
•Management Oversight and Commitment
•Clear objectives and expectations
• Continuous and consistent reinforcement from all levels of Management
•Data Governance Policies and Procedures
•Organization‐wide
•Site Level
•System Level
•Knowledge of Business Models and Technologies
•On‐premise
•Hosted services (SaaS)
•Shared Services

20TH ANNUAL COMPUTER AND IT SYSTEMSVALIDATION

50
 Data Governance
• Training
•Initial training on data integrity
• Continuous reinforcement of data governance training through periodic training
•Retraining (as needed)
•Monitoring
•Detection Processes
•Periodic Reviews
•Quality Audits

20TH ANNUAL COMPUTER AND IT SYSTEMSVALIDATION

51
 Computer Systems Controls
• Validation of Systems
•Risk‐based testing based on intended use
•Change Control Programs
•Impact Assessment of Changes
•Actions taken to maintain system in a validated state
•Security
•User Roles
•User Groups
•Periodic Reviews
•Administrative Controls
•Policies and Procedures

20TH ANNUAL COMPUTER AND IT SYSTEMSVALIDATION

52
 Computer Systems Controls
•Configuration Controls
•Configuration needed to implement intended use of system
•Verification of configuration in both validation and production environments
•Access Controls
•Access to data
•Ability to make modifications
•Electronic Recordkeeping Controls
• Operational system checks to enforce sequencing of events
•Identification of data and metadata
•Certified (or true) copies of original data

20TH ANNUAL COMPUTER AND IT SYSTEMSVALIDATION

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 Data Controls
•Procedures defining use of system and management of data
•Data entry
•Data review
•Audit Trail Review
•Types of records requiring review
• Frequency of review
•Backup and Archival Requirements
•Backup frequencies
•Ability to restore
•Archival processes
•Disaster Recovery
•Disaster Recovery Plan
•DRP Test 20TH ANNUAL COMPUTER AND IT SYSTEMSVALIDATION
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 Exercise –
Define Requirements for Audit TrailReview
•Quality Management System
•Corrective and Preventive Action Records
•Laboratory System
•Chromatography Data

•Electronic Data Capture System

•eSource Data System
• Manufacturing Execution System
•Electronic Batch Record

20TH ANNUAL COMPUTER AND IT SYSTEMSVALIDATION

55