Download - QC & Ass
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QUALITY CONTROLQUALITY CONTROLANDAND
ASSURANCEASSURANCE
QUALITY CONTROLQUALITY CONTROLANDAND
ASSURANCEASSURANCE
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CONCEPT OF QUALITY
CONTROL Refers to the process of striving to
produce a perfect product
Requires a series of measures requiringan organized effort
Prevent or eliminate errors at every
stage in the production
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When? Quality must be built in to product during
Process and product design
Influenced by
Physical plant design Space,ventilation
cleanliness and sanitation
Begins at R&D
Includes
Preformulation Physical,chemical ,therapeutic and toxicologic
considerations
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Steps Material q.c
Inprocess q.c
Product q.c
Specifications and tests for Active ingredients
Excipients Product itself
Stability procedures
Freedom from microbial contamination
Storage and labelling
Containers Provision for cross referecing
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Quality assurance
Assuring the quality of the product
Manufacturing unit prime
responsibility Quality assurance essential from the
start up to the finished
pharmaceutical.
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Sources of quality variation
Raw materials
In-process
Packaging material
labeling
Finished product variables
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Control of quality
variation Can be done by
Raw material control
In-process items control
Packaging materials control
Label control
Finished product control
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Raw material control
Raw material specifications must be Complete
Provide specific details of test methods
Type of instruments Manner of sampling
Properly identified.
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Raw material QA
monograph Raw material (name)
Structural formula,MW
Chemical names Item number
Date of issue
Date of superseeded , if any new material
Signature of writer Signature of approval
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Raw material QA
monograph Samples
Safety requirement
Sample plan and procedure
Sample size and container to be used Preservation sample required
Retest program Retesting schedule
Reanalysis to be performed to assure identity,strength ,quality and purity
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Raw material QA
monograph Specifications (whereever applicable)
Description
Solubility
Identity Specific chemical tests such as related alkaloids,organic
nitrogen bases etc.
Infrared absorption
UV absorption
Melting range
Congealing point
Boiling point or range
TLC,Paper,liquid chromatography
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Raw material QA
monograph Purity and quality
General completeness of solutions,pH,SR,nonvolatile residue,ash ,acid soluble ash etc.
Special quality tests ,particle size,crystallinitycharacteristics and polymorphic forms.
Special purity tests in ferric and ferroussalts,peroxides and aldehydes in ether andrelated degradation products
Assay calculated either on hydrous oranhydrous basis
Microbial limits especially for raw materialsof natural origin
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Raw material QA
monograph Test procedures
Compendial,USP or NF references
Non compendial if any
Approved suppliers
List of prime suppliers and other approved
alternate suppliers if any
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RAWMATERIALS Classified in general into
Active or therapeutic
Antibiotics Other active materials
Inactive or inert
Flavors
Colorants Sweetening agents etc.
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ANTIBIOTICS Analytical methods appear in CFR 21
Parts 436-436.517 and 442-455
Specifications for all the antibiotics Chemically, microbiologically or
biologically
Sampling in dry ,dust free,contaminant free environment.
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ANTIBIOTICS Minimal time of sampling
Two separate weighings on each of
three different days(six different assaysusing six different weighings)
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Other active materials USP and NF contains monograph on
most therapeutically active substances
Degree of purity of each raw material
97% according to compendium
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Other active materials Specifications normally include
Solubility
Identification Melting range
Loss on drying
Residue on ignition
Special metal testing Specific impurities
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Other active materials Analytical methods
Spectrophotometry
Potentiometric titrimetry
GLC,HPLC,polarography,X-ray diffraction
,radio tracer techniques
Microbiological assay Pharmacologic assay
Safety testing
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Inactive or inert materials Major portion of the dosage form
Color,odor and foreign matter
Chemical purity
Particle size
Heavy metal content arsenic, selenium
Water limit
Microbial limit
Residue on ignition
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Colorants
FDA approved Identity tests
tests of volatile materials
Heavy metalsWater insoluble matter
Synthetic impurities
Arsenic,lead Total color
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F,D&C LAKES Additional tests for
Chloride
Sulfate
Organic matter
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Flavors
Refractive index
Specific gravity
Solubility
Alcohol content
GLC can be used
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Sweetening agents
Furfuraldehyde in lactose
Reducing sugars in mannitol
Water content,heavy metals,residue on
ignition, arsenic
Specific rotation
Melting range
Selenium
Readily carbonizable matter
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In-process items control Identify critical steps in mfg process
Controlling them within defined limits
Batch to batch variation
GMP emphasizes on good
environmental conditions
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In-process items control Quality assurance before start up
Quality assurance at start up
Packaging material contol
Labels control
Finished product control
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QA before start up
Environmental and microbiologic control andsanitation
Sanitation program at all facilities
Control insects and rodents
Personal sanitation Floors,walls ,ceilings resistant to external forces
Adequate ventilation
Temperature
Humidity
Air quality monitoring
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QA REVIEWS Sanitation
Cleaning of building and equipment
Ventilation
water
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Master working formula
procedures (MWFP) Documentation of component
materials
Processing stepsWith production operation
specifications
Equipment to be used
Prepared for each batch
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QA REVIEWS
Working formula procedures for eachbatch before,during and afterproduction for the following details
Signature and date of issue given by a QA
employee Proper identification by name and dosage
form
Item number
Lot number
Effective date of the document
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QA REVIEWS Reference version if any
Amount
Lot
Code numbers of each raw material utilized
Calculations of both active and inactive material
Start and finish times of each operation
Equipment to be used and specificaation of its
setup.
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QA REVIEWS Proper labeling of released components
and equipment
Product name Strength
Lot number
Item number
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QA at start upi. Raw materials processing
ii. Compounding
iii. Packaging materials control
iv. Labels control
v. Finished product control.
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Raw materials control Only labelled enterin processing
QA-should maintain temperature &humidity within area of specified limits.
-should check in process procedure with SOP.
Verify & document the properequipment,addition of ingredient,mixing &drying time meshsize of sieves used inscreening.
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Cont.. Samples to be taken at certain points
for potency assay& batch purity &
uniformity.
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Compounding Check labelled r.m staged in compounding
staging area(for cleanliness,manufacturingequipment,item no.,lot no.,)
QA-manufacturing process performed acc.,to SOP
-Checks tests toproduct(thickness,disintegration,etc)
-documentation to maintained thro;out allstages of manufacturing
If deviation-corrective action by resampling.
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Packaging materials
control Container closure system
Properties
1.properties of container tightness 2.moisture & vapor tightness regardless of
container construction
3.toxicity & phy/chem characteristics of
materials needed in container constructions
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Cont.. 4.Phy /chem chages of container upon
prolonged contact with product
5.compatibility b/w container & product
Packaging material should not interactphy/chem with ff
Specifications & test methods for lightresistance,tightly & well closed,
Submit stability data of ff in same containerclosure system.
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Labels control Production control issues a packaging
form that carries-(name,item no.,lot
no., no., of labels,packaging inserts &material operations,quantity to bepacked
1.copy to supervisor of label control
2.packaging dept.
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Cont.. Supervisor of label
control Counts required no., of labels
>identified & kept in separate
container
>sent to packaging dept>(accounts to
be maintained if excess destroyed)
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Cont.. Packaging dept Product & its components
(labels,cartons,insert & packaging
material,stopper ,cap,seal,shipcases)are supplied & operation done.
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Cont QA-all materials are clean,identified
-all materials of previous packaging
operation removed.
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Finished product control Specification: Final testing in QC labs-Why? To
determine compliance with SOP prior to packaging& distribution.
+ In process testing: Stable in ccs. Compare-label with product-> available for
complete absorption.
Test (GMP) parameter done during product dev ->no toxic foreign and substance detected.
Results to statistical analysis
Product specifications -> additional productionexperience
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Bulk product testing Each lot tested for -> ensuring identity, quality,
potency, purity.
QA -> further processing based on actual phy, chem,
bio, laboratory testing.
Accurate, specific, economical and acc to
pharmacopeia
Analytical procedure -> not required until quality of
the product is equal to compendia requirement
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QA during packing QA, QC confirm product ->sent to packing dept ->
QA observes for product & labeling SOPs visual ->automated testing high speed equipment & visual.
1. QA audit indicates that manufacturing operationsare satisfactory. The bulk product is released topacking dept and production control notified
2. QA personnel periodically inspects packing linesand should check filled and labeled containers for
compliance and written specification.
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Contd 3. QA should perform independent inspection and
select finished preservation samples at random from
each lot.
4. QA personnel should also select an appropriatesize sample of FF package product and send to
analytical control lab for final testing.
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Auditing GMP compliance documented.
QA should evolutes batch records for in process
controls and of all tests of final product to determine
whether they conform to specifications
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Contd Areas of record keeping:
1. Individual components, r.m and packagingmaterials MWF and procedures.
2. Batch production 3. Lab in process and finished control testing
4. Proper signing and dating -> by at least 2individuals independently for each operations inproper spaces,
5. Reconciliation of materials supplied and amts oftabs produced, taking in to account allowable losslimits.