valuable for m.pharm students...

1. A
SEMINAR ON
VALIDATION OF SOLID
DOSAGE FORMS
Babu Banarasi Das
University, Lucknow
PRESENTED BY-
Naincy Gupta
M.PHARM (IInd Sem)
PHARMACEUTICS

2. INTRODUCTION
Solid Dosage Forms-
 Asubstance having definite shapeand
volumemanufactured forthe
administration ofactive and/or inert
ingredient(s).
 Solids include
tablets, capsules, powders, granules and
certainsuppositories.

4. Disadvantages of Solid Dosage Forms
1) Difficult to swallow.
2) patients cannot swallow pills.
3) Takes longer to absorb in the body.
Advantages of Solid Dosage Forms
1) More accurate dosing.
2) Releases medication over a longer period of
time.

5. VALIDATION
DEFINITION - :
 QUALITY ASSURANCE DEPT; API DEFINITION -
VALIDATION Validation word derived from ‘valid’
which means “can be justified or defended”.
 Validation is a systematic approach to identifying,
measuring, evaluating ,documenting,& reevaluating a
series of critical steps in manufacturing process that
require control to ensure are producible final product.

7. Validation is an established
documented evidence which
provides high degree of
assurance that a specific
equipment, process, method
or system will consistently
produce results meeting its
predetermined
specifications and quality
characteristics”.

9. VALIDATION OF RAW
MATERIALS
1) Validation begins with the raw
materials, active pharmaceutical
ingredients excipients.
2) Raw materials, major causes of product
variation or deviation from specification.
3) Most uncontrollable component in the
complete product/process validation
scheme because morphology particle
size/surface area not be completely defined
this early.

10. It includes validation of both active
ingredients& excipients.
Characteristics - particle size, surface
area, color, density.
Chemical characteristics- water content
residue on ignition & heavy metals.
Variables: Flow, blend uniformity, granulation
solution/binder uptake
compressibility, lubricant efficiency.

11. Example
1) Mg sterate (lubricant). Its action
depends on particle size.
2) dyes (color)
variation in material occur depending
upon...
a) Method of transportation chosen.
b) Exposure of material to undesirable
conditions (heat and humidity)

12. RAW MATERIALS & ITS
IMPORTANCE
• Chemical characteristics : Drug
impurities can affect the stability.
• Physical properties: Drug morphology,
solubility & particle size/surface area may
affects drug availability.
• The particle size, shape , and density can
affect material flow and blend uniformity.
• The hygroscopic drug caring in handling the
material and the reproducibility of the
manufacturing process.

13. STEPS FOR RAW
MATERIALS VALIDATION
1. Each raw material validated by testing at least 3 batches
from primary & alternate supplier ; representing the
ranges, both high and low.
2. Depending on the susceptibility aging, physical, chemical,
and/or microbiological stability should be assessed.
3. If under acceptable range, especially for materials
sensitive to small changes; then appropriate to use
several lots of raw material with low and high ends of the
specification.
4. The final step of raw material validation should involve
an on-site inspection of the vendor’s to review the
manufacturing operations, controlling & conforming to
regulatory requirements.

14. ANALYTICAL METHOD OF
VALIDATION
Prior to any validation program analytical criteria must be
assessedare-
Accuracyofmethod: truevalue
Precisionofmethod:estimatereproducibility
Specificity: accurately measure a SPECIFIC analyte in the
presenceofothercomponents.
•out-of-dayvariation:
•operatorvariation
•instrumentvariation
•laboratoryvariation

15. NEED OF ANALYTICAL
METHODS VALIDATION
Analytical methods need to be validated, verified, or
revalidatedinthefollowinginstances-
1) Before initial use in routine testing.
2) When transferred to another laboratory.
3) Whenever the conditions or method parameters
for which the method has been validated change
(for example, an instrument with different
characteristics or samples with a different
matrix) and the change is outside the original
scope of the method.

16. DEVELOPMENT OF
ANALYTICAL METHOD
Cognizant of the laboratory conditions
development of analytical method
routinely run
ensuring the validity & ruggedness
if less than optimum or if deficient
re- evaluation
method modified---- high accuracy , greater efficiency &
high reproducibility
preferred if automated--- expertise training

17. CONTROL OF PROCESS
VARIABLES
Defination
A process variable, is the current status of a
processundercontrol.
The process variable is a dynamic feature of
theprocess which maychange rapidly.
Accuate measurementvof process variable
is important for the maintanance of accuracy
inaprocess.

18. • Anexampleofthiswouldbethe
temperatureofa furnace.Thecurrent
temperatureis calledtheprocess
variable,whilethedesiredtemperature
isknownas the set-point.

19. Importance
1) Measurementofprocessvariablesareimportant
incontrollingaprocess.
2) The process variable is a dynamic feature of the
process which may change rapidly. Accurate
measurement of process variables is important
forthemaintenanceofaccuracyinaprocess.
3) There are four commonly measured variables
which affect chemical and physical
process:pressure,temperature,levelandflow.

20. Process variables:
Isforconsistentproduction;
by challenging a process during development to
determinevariablestobecontrolled.
(forasqualitymeans&specificationcompliance)
Stepsindevelopmentofvalidationprogram-
1) Obtaining test data to determine the
numericalrangeofeachparameter.
Example-Assess the tablet hardness over a
series batches.

21. 2) Establishings pecification limits from the test data
derivedforagivenparameter.
3) Determine how well the specification limit Indicates
thattheprocessisundercontrol.
4) Certifytheeqipmentoperatingcondition.
Example- rpm,temp are within specification
limits.

23. Process Validation is defined as the collection and
evaluation of data, from the process design stage
throughout production, which establishes scientific
evidence that a process is capable of consistently
deliveringqualityproducts.
It is an establishing documented evidence which
provides a high degree of assurance that a specific
process will consistently produce a product
meeting its predetermined specifications and
quality characteristics.”
CONTROL OF PROCESS
Validation
Defination

25. PARAMETERS FOR
ESTIMATION OF PROCESS
VALIDATION
Process validation is generally done with three
consecutive batches.
 All the critical parameters were evaluated for fixing
the optimum process parameters.
 Every processing step is validated for all the three
batches and the results obtained must be present
within the acceptance criteria, such that the product
can be forwarded for the commercial production.
All the problems that arise during validation are
overcome and the product will be kept ready for the
commercial batch production.

26. CHANGE CONTROL
• Must be a review procedure for
validated processes
• From time to time changes may be
necessary
• Documented change control procedure
needed
• changes do not require re-validation

27. • Written procedures should be in place to
describe the actions to be taken if a change is
proposed to a product component, process
equipment, process environment, processing
site, method of production or testing or any
other change that may affect product quality
or support system operations.
• All changes must be formally
requested, documented and accepted by the
validation team. The likely impact / risk of the
change on the product must be assessed and
the need for the extent of re-validation should
be determined.

28. General view of process validation

29. Schematic diagram of processing steps and
respective in-process variables during tablet
manufacture
CAUSE-AND-EFFECT OR "FISHBONE DIAGRAM

30. 1)The"fishbone" diagram represents all possible relationships
and interrelationships that may exist among the various
processvariables(possiblecauses)andthesingleresponseor
product attribute (effect) affected during the manufacture of
atabletdosageform.
2)Thecentrallineofthecauseandeffectdiagram isa
composite of all the possible factors that may influence the
qualityandconsistencyofdoseuniformityofthetablet.
3) Branches off the central line represent the influence of the
sixunitoperationsorprocesssteps.
4)Theprincipleprocessvariablesforeachprocessstepthatcan
cause or influence the final outcome are depicted as sub-
branchesoffeachofthesixmainbranches.

31. BENEFITS
1) Helpsdeterminerootcauses.
2) Encouragesgroupparticipation.
3) Uses an orderly, easy-to-read format to diagram
causeandeffectrelationships.
4) Indicatespossiblecausesofvariation.
5) Increasesknowledgeoftheprocessbyhelping
everyonetolearnmoreaboutthefactorsatworkand
howtheyrelate.
6) Identifiesareasforcollectingdata.

32. GUIDELINES FOR
PROCESS VALIDATION
SOLID DOSAGE FORMS (TABLETS):
A) TabletComposition:
1) Normal properties
2) Density
3) Particle size distribution
4) Surface area
5) Flow properties
6) Moisture content
7) solubility

33. • B) Process evaluation & selection
1) Blending operation
2) Determine time of un mixing
3) Characteristics of blend
 Bulk density
 Particle size distribution
4) Color uniformity
C) Wet granulation
1)Evaluation of binder
 Binder concentration
 Solubility in granulating solution
2)Evalution of mixed granulation
3)Evalution of drying

34. D)Tablet compression
1)Appearance
2)Color quality
3)Powder flow
4)Speed of tablet machine
E)Tablet coating
1)Evaluate coating procedure in different
size pans
2)Coating speed
3)Amount of material required application

35. D) Equipment evaluation
1) Blending equipment
2) Granulating equipment
3) Tablet equipment
4) Tablet coating

36. Check list of Validation and Control
Documentation
Sr. No. Selection of cGMP Validation and control documentation
1 Introduction Establishing of QA & PV functions
2 Organization and personnel. Establishment and facility installation and
qualification
3 Buildings and facilities Plant and facility installation qualification
Maintenance and sanitation
Microbial and pest control
4 Equipment Installation and qualification cleaning methods.
5 Air and water quality Water treatment and steam systems air, heat,
and vacuum handling.
6 Control of raw material, in-process
material, product
Incoming components
Manufacturing non-sterile products
7 Production and process controls Process control systems (instruments and
computers)
8 Packing and labeling controls Depyrogenation, sterile packing, filling, and
closing.
9 Holding and distribution Facilities
10 Laboratory controls Analytical methods
11 Records and reports Computer systems
12 Returned and salvage drug products Batch processing