introduction to lims & 21 cfr part 11

8/19/2019 Introduction to LIMS & 21 CFR Part 11

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IntroductionIntroductionLaboratory Information ManagementLaboratory Information ManagementSystem (LIMS)System (LIMS)


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What is LIMS?What is LIMS?

Laboratory I nformation Management S ystem

designed specifically for the analytical laboratory• Research & Development

• In-process testing

• Quality Assurance• Quality Control

• other laboratories

to gain control over the laboratory processes andprovide visibility throughout the organization


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What is LIMS?What is LIMS?

Industries:

• Pharmaceutical• Food and Beverage

• Petrochemical

• Chemical & Industrial

• Metals

• Mining

• Forensics

• Healthcare


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Evolution of LIMSEvolution of LIMS

In-housesinglecentralizedminicomputer

Use of RDBMSClient-SeverWeb-enabled

21 CFR Part 11(1997, 2003,

2007)

- cards, files- spreadsheets

- Sample tracking,- Inventory

- Regulatorycompliance


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Batch/Sample

MethodMgmt

Document

Mgmt

Chain ofCustody

InstrumentCPM

DataEntry

WorkloadMgmt

Instrument &ApplicationIntegration

AuditMgmt

Reports

Statistical

Analysis

QA/ QC/R&D

Evolution of LIMSEvolution of LIMS

EnvironmentalMonitoring

StabilityMgmt


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Why OneWhy One --LIMS for allLIMS for alldoesndoesn ’’t reallyt really ……

LIMSGeneric

Customization

EM

Stability

DocumentManagement

system


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• Risk management tools

• Optimize current manufacturing processes

• Increase productivity

• Significantly enhance compliance

• Improve quality measurement

• Meet turn around times (TAT)and holding times

• Prevent missed sampling events• Lost time searching for or checking data

• Increase efficiency and effectiveness

Why LIMS?Why LIMS?


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• If a laboratory wants to remain competitive it needs to have a plan to doso and constantly look for areas that processes can be improved upon.

Data Quality + Cost Reduction = LIMS

Why LIMS?Why LIMS?• Through the use of proper systems and process a laboratory can

produce and manage data of high quality.

• In today’s world, this must be accomplished while working underheavy budget constraints.

• As a result, the laboratory must consider how to achieve high data

quality without destroying the budget.• Customer expectation and the laboratory business environment are

changing constantly, to the point that current, efficient processes canrapidly become obsolete.


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• The ability to enforce Quality Assurance

and Regulatory goals• An integrated LIMS will allow for the

specification of required methods.

• Integration of regulatory requirementsinto the processes.

• An integrated LIMS will also allow the laboratory:• communicate• generate work lists• expedite the generation of reports• Graphical Trending• Statistical analysis

Benefits of a LIMSBenefits of a LIMS


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Benefits of a LIMSBenefits of a LIMSIncreased Efficiency

• Paperless environment

• Customizable reporting options• Archiving• Fast data entry

Increased Accuracy• Significantly minimization of human error• Avoid missing deadlines• Maximal Security and Control• OOS Notification & Custom Alert Controls

Increased Productivity

• LIMS adapts to the laboratory routine• Scheduling and tracking• Increased throughput• Real Time Data Processing & Handling


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Understanding Regulations forUnderstanding Regulations forElectronic Records; Electronic SignaturesElectronic Records; Electronic Signatures21 CFR Part 1121 CFR Part 11


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•Legacy Systems- Pre 1997

•Spreadsheets/ Access

-Non-compliant

•In-house Systems-Maintenance, Upgrade, Regulatory Changes

Outdated PracticesOutdated Practices


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Today, the FDA believes:Today, the FDA believes:

• Manual systems can not be validated.Data integrity requires administrative controls andredundant checking.

• If it is not documented , It was not done .

• If it was not done using an approvedprocedure, It was not done properly .


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NonNon --compliancecompliance

• Failure to maintain system with validated program

- No testing after installation at operating site

- No ‘worst’ case testing

- Lacks provisions to show correct functioning ofsoftware

- Mentions ‘historical’ experience with terminalsbut doesn’t specify terminal model

- Lacks change control program

- Protocol execution predates protocol approval


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The Paperless LaboratoryThe Paperless Laboratory

Finally a RealityFinally a Reality ……

• Leading pharmaceutical companies must improve

productivity while ensuring compliance under moreand more demanding regulations.

• The FDA is committed to electronic filings and audits,21 CFR Part 11 defines how electronic records canmeet or exceed today’s paper based records

• Several years of automation and IT innovation haveset the stage for the paperless laboratory

• The technology is available today and affordable


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Cost ofCost of

NonNon --compliancecompliance

FDA requires further details regarding steps that are being

taken to bring e-records into conformance with requirements of21 CFR Part 11. Deviations include:

• An audit trail (important)

• No procedures to hold individuals responsible for actionstaken under e-signatures (vital)

• No documentation or testing of system’s ability to discerninvalid or altered records (significant)

• Copies of e-records can not be generated (serious)• No safeguards to prevent unauthorized access when an

employee leaves a terminal logged on (serious)


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Benefits of aBenefits of a

Compliant SystemCompliant System

• All data is managed and contained in one system(for all sites)

• All data can be easily analyzed expediting

problem detection

• Data integrity and security

• Regulatory compliance; No 483s


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What are the requirements in aWhat are the requirements in aCompliant Software System?Compliant Software System?


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User RequirementsUser Requirements

• Specific (easily understood)

• Attainable (realistic)

• Prioritized• Traceable – requirement ~ design ~ validation

• Compliant to 21 CFR Part 11


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Subpart ASubpart A

General ProvisionsGeneral Provisions

11.1 (a)…. Electronic records

to be trustworthy,reliable, and generallyequivalent to paperrecords.

Visual cue

Locked down ofcompleted andapproved data

Data Locks


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11.1 (e)Computer systems (includinghardware and software), controls,and attendant documentationmaintained under this part shall bereadily available for, and subject to, FDA inspection.

Subpart ASubpart A

General ProvisionsGeneral Provisions

Source Code


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Subpart BSubpart B

Electronic RecordsElectronic Records

11.10 (a)

Validation of systems toensure accuracy, reliability,consistent intendedperformance, and the abilityto discern invalid or alteredrecords .

Installation Qualification

Operation Qualification

Performance Qualification

Built-in Traceability Matrix

Standard OperatingProcedures (Backup,Recovery, Passwords)

Full-documentation

execute the validation at theuser’s site(s).

Validation


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11.10 (b)The ability to generateaccurate and completecopies of records in bothhuman readable andelectronic form suitablefor inspection, reviewand copying by theagency.

Subpart BSubpart B

Electronic RecordsElectronic RecordsAccurate Records

Log of user activity

All information shouldbe printable


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Subpart BSubpart B


11.10 (c)

Protection of records toenable their accurate andready retrieval throughoutthe records retention period .

Archiving Strategies

Archiving utility

Access the data on demand

Storage of past dataAudit trail

Version control


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Subpart BSubpart B


11.10 (d)

Limiting system access toauthorized individuals.

Login required.No users may enter the systemwithout using a two component

signature.

Security


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Subpart BSubpart B


11.10 (e)

Use of secure, computer- generated, time-stamped audittrails to independently recordthe date and time of operator

entries and actions that create,modify, or delete electronicrecords. Record changes shallnot obscure previouslyrecorded information. Such

audit trail documentation shallbe retained for a period at leastas long as that required for thesubject electronic records andshall be available for agencyreview and copying.

Change Control


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Subpart BSubpart B


11.10 (f)Use of operationalsystem checks toenforce permitted

sequencing of stepsand events asappropriate.

Sequential Access

Internal systemchecks.


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Subpart BSubpart B


11.10 (g)

Use of authority checks toensure that only authorizedindividuals can use thesystem, electronically sign arecord, access the operationor computer system input oroutput device, alter a record,or perform the operation athand.

Security Access Privileges

User access rights

User responsibilities


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11.10 (h)

Use of device (e.g.,terminal) checks todetermine, as appropriate,the validity of the source ofdata input or operationalinstruction.

Subpart BSubpart B


Data Input

Automated verification ofinput from any device

Start End

3 6 9

2005 3 01010000101 6 290192123

Checksum


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Subpart BSubpart B


11.10 (i)

Determination that personswho develop, maintain, or useelectronic record/ electronicsignature systems have theeducation, training, andexperience to perform theirassigned tasks.

Training


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11.10 (j)

The establishment of, andadherence to, written policiesthat hold individualsaccountable and responsiblefor actions initiated undertheir electronic signatures, inorder to deter record and

signature falsification.

Subpart BSubpart B


SOPs/ Document Tracking

SOPs are in place priorto the system going “live”.

Document trackingnumbers for these SOPsare included in thevalidation document.


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11.10 (k)Use of appropriate controls oversystems documentation including:

(1) Adequate controls over the

distribution of, access to, and useof documentation for systemoperation and maintenance.

(2) Revision and change controlprocedures to maintain an audittrail that documents time- sequenced development andmodification of systemsdocumentation.

Document Tracking

Document control system: – user guides – training manuals – SOPs – user requirements, and – design specifications

Subpart BSubpart B



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Subpart BSubpart B


11.50 (a)

Signed electronic records shallcontain information associatedwith the signing that clearlyindicates all of the following:

(1) The printed name of thesigner;

(2) The date and time when thesignature was executed; and

(3) The meaning (such as review,approval, responsibility, orauthorship) associated withthe signature.

11.50 (b)

The items identified inparagraphs (a)(1), (a)(2) and(a)(3) of this section shall be tothe same controls as forelectronic records and shall be

included as part of any humanreadable form of the electronicrecord (such as electronicdisplay or printout).

Signatures

Complete tracking of data to user.

Username and person’s namedisplayed on all printoutsgenerated by the system.

Timestamps on the printout.


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Subpart BSubpart B


11.70Electronic signatures andhandwritten signaturesexecuted to electronic

records shall be linked totheir respective electronicrecords to ensure that thesignatures cannot beexcised, copied, orotherwise transferred tofalsify an electronic recordby ordinary means.

Signatures

Complete tracking of data to user viathe user log and audit trail.

Username displayed on all printoutsgenerated by the system.

Timestamps on the printouts


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Subpart CSubpart C

Electronic SignaturesElectronic Signatures

11.100 (a)Each electronic signature shallbe unique to one individual andshall not be reused by, orreassigned to, anyone else .

11.200 (a)

Electronic signatures that arenot based upon biometrics

shall: (1) Employ at least two distinctidentification components suchas identification code andpassword.

disallow the duplicationof a username

username and password

Unique Identification


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11.300

Controls for identificationcodes/ passwords.

Subpart CSubpart C

Electronic SignaturesElectronic Signatures

User name cannot be used twiceeven if the username is de-activated.

System configurable passwordexpiry time limit

All data modifications require apassword be entered.

System lockout after aconfigurable number of times

Email notification

Signatures


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Compliant StatisticsCompliant Statistics

Built-in statisticalpackages keep yourdata compliant.

Records should not be

exported from thesystem.


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Statistical OutputStatistical Output

Trend Basis

User

Product Lot

Stability Study

Raw Material

Location

Test type and Location


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Linear RegressionLinear Regression

Control/Specification levels

Upper and lowerconfidence levels

Regression line

Time points


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Multiple RegressionMultiple Regression

Select multiplestudies

Select multiplelocations

Trendseparately

Trend together


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Multiple RegressionMultiple Regression

Manipulate x-axisand y-axis

Set desired timevalues

Upper limit met?

Lower limit met?


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Percentage distribution ofidentified microorganisms

Bar chart of CFUs found in aspecific location over time

Pie & Bar ChartsPie & Bar Charts

HistogramsHistograms


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PP --ValueValue

Calculate withdifferent criticalvalues

Proper data pooling

Validated statisticalpackage


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Arrhenius EquationArrhenius EquationWhen multiple studies areselected, the first ratedegradation equations areused.

When a single study isselected, the estimated Q10method is used for calculation.


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Free Format QueryFree Format Query

Manipulate systemdata as neededwhile remaining in acompliant state.

21 CFR P 1121 CFR P t 11


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Audit trail and User logElectronic signatures

Data concurrency security

ApprovalsConfiguration of User Rights &Privileges

21 CFR Part 1121 CFR Part 11

CompliantCompliant


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• To remain competitive in the ever changing laboratorylandscape, organizations must embrace principles ofcontinual improvement to reduce waste and functionmore effectively.

• Employees are constantly being asked to do more withfewer resources.

• Continual P rocess Improvement is the key

• Laboratories that effectively manage change andimplement CPI can realize substantial cost savings through:

• Enhanced data quality• Laboratory safety• Improved customer satisfaction• reduction in turnaround times• elimination of waste

• elimination of duplication of efforts.

ConclusionConclusion


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IndustryIndustry ’’s Way Forwards Way Forward

“The sector across the ASEAN region is facing radicaltransformation movement: the cost of compliance and the ever-

increasing standards of quality throughout the life sciencesindustry pushes out of the game many medium to small size

players who have been reacting too little or too late.”

Reference: Executive Country Reviews (September 2006)


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