WHO- Self Inspection & Quality Audit_2012.ppt

WHO guidelines are required for self inspection in Pharma Industry

1. Module 7 |Slide 1of 17 2012
Production, Self-
Inspection and quality
audits
Basic Principles of GMP

2. Module 7 |Slide 2of 17 2012
Self-Inspection
Objectives
To identify the role of self-inspection in the quality management
system
To review the way in which a self-inspection programme should
be carried out
To discuss what to inspect and verify in a company’s self-
inspection system

3. Module 7 |Slide 3of 17 2012
PRODUCTION
PROCEDURES

4. Module 7 |Slide 4of 17 2012
Startingmaterials-testedandapprovedaccordingitsspecification
Productionequipment-cleaned,safe,appropriateinsize,andappropriateforproduct
typetobemanufactured
Operationondifferentproductsshouldnotbecarriedoutsimultaneouslyinthesame
room,unlessthereisnopotentialriskofmix-upandcontamination
Allmaterialsshouldbearclearlabelsandbatchnumbers
Limitedaccessinproductionarea,onlyauthorizedpersonnel
Handlingofmaterialsandproductsshouldbebasedonwritteninstruction/procedure,
andwherenecessary,recorded
Allworkinstructions/proceduresshouldbewrittenandapproved
Batchmanufacturingrecords(BMR)shouldbewellrecordedbyqualifiedandresponsible
personnel.
BASIC PRODUCTION
PRINCIPLES

5. Module 7 |Slide 5of 17 2012
Thereareseveralguidelinesthatshouldbefollowedprior,duringandaftereach
productionactivities.Theseare:
Areaclearanceorlinesclearanceshouldbedone,toavoidmixupofstarting
materialsorfinishedproducts
In-processandenvironmentalcontrolsshouldbecarriedoutandrecorded.
Indicationoffailureofequipmentorservicesshouldbemonitoredandonly
equipmentsingoodconditionshouldbeavailableintheproductionarea.
Cleaningproceduresshouldbewrittenandapproved
Containersshouldbecleanedpriortouse
Anydeviationfromrequirementsandexpectedresultshouldberecordedand
investigatedpriortostartofproductionandpriortoreleaseofthefinishedproduct
PROCESSING GUIDANCE
(1)

6. Module 7 |Slide 6of 17 2012
Anysignificantdeviationfromtheexpectedyieldshouldberecordedand
investigated.
Checksshouldbecarriedouttoensurethatpipelinesandotherpiecesof
equipmentusedforthetransportationofproductsfromoneareatoanotherare
connectedinacorrectmanner.
Measuring,weighing,recording,andcontrolequipmentshouldbeserviced
andcalibratedatpre-specifiedintervalsandrecordsaremaintained.
Repairandmaintenanceoperationsshouldnotpresentanyhazardtothe
qualityoftheproducts.
PROCESSING GUIDANCE
(2)

7. Module 7 |Slide 7of 17 2012
( Company name)
QUARANTINELABEL
Formula Number
ProductName
Manufacturing No
Batch Size
Processing Date
Transfer date & Time
Bulk transferred to
Bulk Valid until
:
:
:
:
:
:
:
:
Chemical Microbioogical
Approval Approval
Sample Finished Product
Micro
( )Yes
( )No
HOLD
BULK QUARANTINE
LABEL

8. Module 7 |Slide 8of 17 2012
Both labels should be attached to theBMR
EQUIPMENT
LABEL
Cleaning Status ofEquipment
CompanyName :
EQUIPMENT :
STATUS :
SANITIZE
D
Checked and Verified by: Date :
Validuntil :
Cleaning Status ofEquipment
CompanyName
EQUIPMENT :
STATUS :
CLEANED
Checked and Verifiedby: Date :
Validuntil :

9. Module 7 |Slide 9of 17 2012
Weighingshouldbecarriedout:
-indefinedareas
-usingcalibratedequipment.
Allweighingandmeasurementcarried
outshouldbe:
-recorded
-counterchecked
WEIGHING &
MEASUREMENT

10. Module 7 |Slide 10of 17 2012
:
Donewithintheproductionareaandbyproduction people and/or Quality Control
Should be recorded and done as per approved/written SOP
Sampling done to verify:
physical aspects (weight, volume, amount, etc)
text on labels
other performance requirements
Sampling maybe conducted based on need:
during processing activity
during packaging (filling & packing) activities
•random,
•sequential, or
•statistical
Samples takenaway fromthepackaginglineshouldnotbereturned
ifcontainerswereopened
Recordofin-processcontrolshouldbepartofthe BMR
IN-PROCESS
CONTROL

11. Module 7 |Slide 11of 17 2012
Anydeviationfromtheproceduresshouldbeavoidedasmuchaspossible.If
deviationsoccur,theyshouldbeapprovedinwritingbyadesignatedperson,
withtheinvolvementofthequalitycontroldepartment.
Checksonyieldsandreconciliationofquantitiesshouldbecarriedoutas
necessarytoensurethattherearenodiscrepanciesoutsideacceptable
limits.
Thesearesomepointstobeconsideredinthereconciliationofthebatch:
quantityofstartingmaterials,outputoffinishedproducts,machineefficiency
Allactivitiesconcerningreconciliationshouldbeconductedbasedonwritten
standardoperatingprocedures.
RECONCILIATION

12. Module 7 |Slide 12of 17 2012
A product identification number/batch number should be assigned
to:
every finished product
every bulk and semi finished product
which enables the history of the product to be traced.
A batch numbering system should be unique
specific for the product
non repetitive for the same product
Creation of batch number should be based on written guideline
(SOP)
BATCH NUMBERING SYSTEM
(1)

13. Module 7 |Slide 13of 17 2012
The batch number should be printed on:
primary packaging
secondary packaging (as necessary)
A batch number may give informationon :
date and year of production
country, manufacturer or subcontractor
sequence of production
Records of batch number should be kept and maintained
for every finished product
until at least 1 year after the expiry date
for traceabilityfactor
BATCH NUMBERING SYSTEM
(2)

14. Module 7 |Slide 14of 17 2012
Example of batch number: M001S09A
The1stprefix-MrepresentforMALAYSIAProducts
The2nd-4thdigit–BatchNumber
The5thalphabet-Productformatcode:S(Sachet),C(Capsule),T
(Tablet),P(Powder)andL(Liquid).
The6th–7thdigit-Yearofproductmanufactured:08(Year2008),
09(Year2009),10(Year2010),etc
Thelastalphabet-Monthofproductionmanufactured:A
(JANUARY),B(FEBRUARY),C(MARCH),etc.

15. Module 7 |Slide 15of 17 2012
REPROCESSING
Reprocessingisadelicate/tediousactivityforarejectedproduct.
Thereshouldbeawrittenpolicywhichclearlystatesthatsuchactionisallowedto
bedone.
Reprocessingofrejectedproductshouldonlybedoneinexceptionalcases.
Itshouldonlybeallowedifthequalityoftheproductisnotnegativelyaffected
andtheproductqualitystillcomplieswiththespecifications.
Itshouldconsideradditionaltestingofreprocessedproduct,e.g.stabilitytesting
ofthebatch.
Completerecordsshouldbemaintainedforreprocessedproduct
Areprocessedproductshouldbegivenanewbatchnumber.

16. Module 7 |Slide 16of 17 2012
Liquidsandcreamsshouldbeproducedinsucha
wayastoprotecttheproductfrommicrobialand
othercontamination.
Theuseofclosedsystemsofproductionandtransfer
isrecommended.
Wherepipe-linesareusedfordeliveryofingredients
orbulkproducts,careshouldbetakentoensure
thatthesystemsareeasytoclean.
WET PRODUCT
HANDLING

17. Module 7 |Slide 17of 17 2012
While awaiting approval, finished products should
be placed & kept under quarantine area at
the finished product warehouse.
Quarantine label indicates :
Date
Product name
Batch No
Quantity
Number of pallets
FINISHED GOOD
PRINCIPLES

18. Module 7 |Slide 18of 17 2012
Alllabelconcerningwiththestatusoffinished
productsshouldbeshownclearly
Quarantinestatuscanbeintheformof:
•physical(rope,rackslayers,pallet)
•computersystem
Rejectedproducts:
•identifiedandphysicallyseparated
•takenoutfromthestock
•furtherprocess(destruction,reworked,etc)
FINISHED PRODUCT
STATUS

19. Module 7 |Slide 19of 17 2012
Type ofAudits
•Self-Inspection
(Internal) Audit
1
stParty
Audit
2
nd Party
Audit
•External provideraudit
•Other interested party
audit
3
rd
Party
Audit
•Certification and/or
accreditation audit
•Statutory, regulatory and similar
audit

20. Module 7 |Slide 20of 17 2012
Self-Inspection
Principle (1)
Purpose of self-inspection is to evaluate whether a company’s
operations remain compliant with GMP
Assists in ensuring quality improvement
The programme should
cover all aspects of production and quality control
be designed to detect shortcomings in the implementation of
GMP
recommend corrective actions
set a timetable for corrective action to be completed
8.1

21. Module 7 |Slide 21of 17 2012
Self-Inspection
Principle (2)
Performed routinely
Also on special occasions such as
Recalls
Repeated rejections
When a GMP inspection is announced by the
national drug regulatory authority
8.1

22. Module 7 |Slide 22of 17 2012
Self-Inspection
Principle (3)
Self-inspection team should consist of personnel who:
Are objective and have no revenge in mind
Have no conflict of interest (That is, normally not from the
same department as the one being inspected)
should have experience as observers of a self-inspection
team before becoming a team member
The team should be led by an experienced person
Procedure should be documented
Effective follow-up programme (CAPA implemented)
8.1

23. Module 7 |Slide 23of 17 2012
Self Inspections/ InternalAudits
•Performed in-house most often by a
team and involve people with
different expertise
•Could be carried out within a single
facility or organised by Head Office to
be done over a range of facilities

24. Module 7 |Slide 24of 17 2012
Inspectorattributes
•Knowledgeable
•Being able to identify and focus on areas
of high risk
•Being well trained in inspecting
•Having appropriate personal skills

25. Module 7 |Slide 25of 17 2012
Self Inspections/ InternalAudits
Self Inspections done by externalexperts
Could be full self audit of a facility or
system specific audit
External expertise, a fresh set of eyes
No
politics

26. Module 7 |Slide 26of 17 2012
Self-Inspection
1.Self-inspection -informal
(daily) Immediate correction
2.Self-inspection -formal
(quarterly) Improve systems
3.QC -Internal Confirm compliance
(half-yearly)

27. Module 7 |Slide 27of 17 2012
8.2
Self-Inspection
Items for Self-Inspection (1)
Written instructions provide minimum and uniform standard
Covering all aspects of GMP:
personnel
premises including personnel facilities
maintenance of buildings and equipment
storage of starting materials and finished products
equipment
production and in-process controls
quality control

28. Module 7 |Slide 28of 17 2012
8.2
Self-Inspection
Items for Self-Inspection (2)
documentation
sanitation and hygiene
validation and revalidation programmes
calibration of instruments or measurement systems
recall procedures
complaints management
labels control
results of previous self-inspections and
any corrective steps taken

29. Module 7 |Slide 29of 17 2012
8.3, 8.4
Self-Inspection
The Self-Inspection Team
Team appointed by management, with:
authority
sufficient experience
may be from inside or outside the company
experts in their own field
familiar with GMP
Frequency should be at least once a year
Depends on company size, requirements, actrivities
Often, departments are inspected according to a calender –
one department per month over a one year cycle

30. Module 7 |Slide 30of 17 2012
8.5, 8.6
Self-Inspection
Self-Inspection
Report prepared at completion of inspection, including:
results
evaluation
conclusions
recommended corrective measures
Follow-up action
Effective follow-up programme
Company management to evaluate both
the report and corrective actions

31. Module 7 |Slide 31of 17 2012
8.7
Quality Audit
This is an examination of all or part of quality system
The aim is to improve it
Usually conducted by outside experts or team
appointed by management
Useful to supplement self-inspection programme with
quality audits
May be extended to suppliers and contractors

32. Module 7 |Slide 32of 17 2012
External Audits –RegulatoryAudits
•Carried out by national auditing/
inspecting authorities
•Verify compliance with the ISO
Standards and other national legal
requirements
•Could be product specific or system
audits
•Could be triggered by a product recall
or other undesired events
(unannounced?)
•Detailed in scope

33. Module 7 |Slide 33of 17 2012
External Audits –Contractor Audits
•Carried out to determine manufacturer’s
technical capability
•Carried out by a group of experts from
contract giver
•Establish line of communications and
priorities between involved parties

34. Module 7 |Slide 34of 17 2012
External Audits –Supplier Audits
•Carried out on suppliers of
critical raw materials and
packaging materials
•Verify materials specifications
•Could be used to justify reduced
raw materials testing

35. Module 7 |Slide 35of 17 2012
8.8, 8.9
Suppliers’ audits and approvals
Quality Unit (e.g. QA or QC) responsible together with other
relevant departments for approving suppliers
Ensure that suppliers can reliably supply materials that meet
established specifications
Suppliers should be evaluated and approved before they are
included in approved supplier's lists
Should take into account the supplier’s history and nature of
materials to be supplied
Evaluation may also lead to an audit to assess compliance, e.g.
with GMP
Quality Audit

36. Module 7 |Slide 36of 17 2012
Inspecting the Self-Inspection Programme (1)
GMP inspectors should preferably check self-inspection
programme at end of an inspection
Evaluate:
SOP, team composition
Annual program / schedule
Checklists used by the company (are these up to date?)
Check that inspections are done as schedules
Reports are available
CAPAs are taken, implementation is verified, management
involvement
Quality Audit

37. Module 7 |Slide 37of 17 2012
Auditing the Self-Inspection Programme (2)
The SOP should describe teams, process, items covered, and
the frequency of self-inspection
Company policy may not permit GMP inspector to see actual
deficiency reports and corrective actions
GMP Inspectors should be looking for compliance with the self-
inspection SOP -not necessarily at actual deficiencies
recorded
Seek objective evidence of reports and action
Quality Audit

38. Module 7 |Slide 38of 17 2012
Auditing the Self-Inspection Programme (3)
Ensure company is not just doing housekeeping or safety
audits
Check there are “Vertical” as well as normal “Horizontal”
audits; both play valuable role in self-inspection
Quality Audit

39. Module 7 |Slide 39of 17 2012
AuditReport
•Brief description of the
company and its activities.
Introductio
n:
•Ensure that you briefly
document major changes
since the last audit.
Change
s:

40. Module 7 |Slide 40of 17 2012
Auditfindings:
Keyforclassificationofobservations/reportare:
 Critical:Adeficiencywhichhasproducedorleadstoasignificantriskofproducing
productsthatharmfultoconsumersormanufacturerisinvolvedwithfraudorfalse
advertising.
 Major:Adeficiencywhichhasproducedwhichdoesnotcomplytospecificationsor
whichindicatesamajordeviationfromEUGoodManufacturingPracticeorwhich
indicatesafailuretocarryoutsatisfactoryproceduresforreleaseofbatches.
 Other:AdeficiencythatisnotclassifiedasmajororcriticalbutdeviatesfromGMP.
 Recommendation:NoGMPviolation.
AuditReport

41. Module 7 |Slide 41of 17 2012
●The name of the organization,
department, process or function
being audited.
●The address of the site
audited.
●Date and duration of audit.
●Reason for performing the
audit.
●Standard used for
assessment during audit.
●Name of the audit host
and their contact details.
●Names of auditors.
●People at opening and
closing meeting.
●Statement of
confidentiality.
●Audit programme or
agenda.
●Obstacles
encountered.
●An overview of all
areas observed during
the audit.
●Any non-
conformities or
observations that
were raised.
●Any unobserved
areas.
●A description of any
grading of any non-
conformities.
●Conclusion.
●Instructions for the
department or
organization to
comply upon receipt
of the report in
order to respond to
any non-
conformities raised.
AuditReport