Transcript
QUALITY CONTROL QUALITY CONTROL AND AND ASSURANCE ASSURANCE
QUALITY CONTROL QUALITY CONTROL AND AND ASSURANCE ASSURANCE
CONCEPT OF QUALITY CONTROL
• Refers to the process of striving to produce a perfect product
• Requires a series of measures requiring an organized effort
• Prevent or eliminate errors at every stage in the production
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
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
Quality assurance
• Assuring the quality of the product• Manufacturing unit – prime
responsibility• Quality assurance essential from
the start up to the finished pharmaceutical.
Sources of quality variation• Raw materials• In-process• Packaging material• labeling• Finished product variables
Control of quality variation
• Can be done by– Raw material control– In-process items control– Packaging materials control– Label control– Finished product control
Raw material control• Raw material specifications must
be– Complete– Provide specific details of test
methods– Type of instruments– Manner of sampling– Properly identified.
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
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
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
Raw material QA monograph
• Purity and quality– General completeness of solutions,pH,SR,non
volatile residue,ash ,acid soluble ash etc.– Special quality tests ,particle size,crystallinity
characteristics and polymorphic forms.– Special purity tests in ferric and ferrous
salts,peroxides and aldehydes in ether and related degradation products
• Assay calculated either on hydrous or anhydrous basis
• Microbial limits especially for raw materials of natural origin
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
RAW MATERIALS• Classified in general into
– Active or therapeutic• Antibiotics• Other active materials
– Inactive or inert• Flavors• Colorants• Sweetening agents etc.
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.
ANTIBIOTICS• Minimal time of sampling• Two separate weighings on each
of three different days(six different assays using six different weighings)
Other active materials• USP and NF contains monograph
on most therapeutically active substances
• Degree of purity of each raw material
• 97% according to compendium
Other active materials• Specifications normally include
– Solubility– Identification– Melting range– Loss on drying– Residue on ignition– Special metal testing– Specific impurities
Other active materials• Analytical methods
– Spectrophotometry– Potentiometric titrimetry– GLC,HPLC,polarography,X-ray
diffraction ,radio tracer techniques– Microbiological assay– Pharmacologic assay– Safety testing
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
Colorants
• FDA approved• Identity tests • tests of volatile materials• Heavy metals• Water insoluble matter• Synthetic impurities• Arsenic,lead• Total color
F,D&C LAKES• Additional tests for
– Chloride– Sulfate – Organic matter
Flavors
• Refractive index• Specific gravity• Solubility• Alcohol content• GLC can be used
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
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
In-process items control
• Quality assurance before start up • Quality assurance at start up• Packaging material contol• Labels control• Finished product control
QA before start up
– Environmental and microbiologic control and sanitation
– 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
QA REVIEWS• Sanitation • Cleaning of building and
equipment• Ventilation• water
Master working formula procedures (MWFP)
• Documentation of component materials
• Processing steps• With production operation
specifications• Equipment to be used• Prepared for each batch
QA REVIEWS• Working formula procedures for
each batch before,during and after production 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
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.
QA REVIEWS • Proper labeling of released
components and equipment – Product name– Strength– Lot number– Item number
QA at start upi. Raw materials processingii. Compoundingiii. Packaging materials controliv. Labels controlv. Finished product control.
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 proper
equipment,addition of ingredient,mixing & drying time meshsize of sieves used in screening.
Cont..• Samples to be taken at certain
points for potency assay& batch purity & uniformity.
Compounding • Check labelled r.m staged in compounding
staging area(for cleanliness,manufacturing equipment,item no.,lot no.,)
• QA-manufacturing process performed acc., to SOP
• -Checks tests to product(thickness,disintegration,etc)
• -documentation to maintained thro;out all stages of manufacturing
• If deviation-corrective action by resampling.
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
Cont..• 4.Phy /chem chages of container upon
prolonged contact with product • 5.compatibility b/w container & product• Packaging material should not interact
phy/chem with ff • Specifications & test methods for light
resistance,tightly & well closed,• Submit stability data of ff in same
container closure system.
Labels control• Production control issues a packaging
form that carries-(name,item no.,lot no., no., of labels,packaging inserts & material operations,quantity to be packed
• 1.copy to supervisor of label control• 2.packaging dept.
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)
Cont.. Packaging dept• Product & its components
(labels,cartons,insert & packaging material,stopper ,cap,seal,ship cases)are supplied & operation done.
Cont…• QA-all materials are
clean,identified• -all materials of previous
packaging operation removed.
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
production experience
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
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 operations are satisfactory. The bulk product is released to packing dept and production control notified
• 2. QA personnel periodically inspects packing lines and should check filled and labeled containers for compliance and written specification.
Contd…• 3. QA should perform independent
inspection and select finished preservation samples at random from each lot.
• 4. QA personnel should also select an appropriate size sample of FF package product and send to analytical control lab for final testing.
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
Contd…• Areas of record keeping:• 1. Individual components, r.m and
packaging materials MWF and procedures.• 2. Batch production• 3. Lab in process and finished control
testing• 4. Proper signing and dating -> by at least 2
individuals independently for each operations in proper spaces,
• 5. Reconciliation of materials supplied and amts of tabs produced, taking in to account allowable loss limits.
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