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QUALITY ASSURANCE AND QUALITY
CONTROL
CURRENT GOOD MANUFACTURING PRACTICE
- Not a sole responsibility of QC group but also of the production group
- Permits the use of precision automatic, mechanical or electronic equipment in the production and control of drugs when adequate inspection and checking procedures are used to assure proper performance
OBJECTIVE OF cGMP:
1. Safe2. Pure3. Effective
Non-compliance---contamination, mix-ups and errors
QUALITY ASSURANCE
- sum total of the organized arrangements made with the object of ensuring that products will be consistently of the quality required by their intended use
QUALITY CONTROL
Part of cGMP concerned with sampling, specifications, testing, organization, documentation and release procedures
Quality Assurance vs. Quality Control
Quality Assurance
An overallmanagement plan to guarantee theintegrity of data(The “system”)
Quality Control
A series of analytical measurements usedto assess thequality of the analytical data(The “tools”)
STANDARDS AND SPECIFICATIONS
a. FORMULA- concise and precise statement of the ingredient that comprise the product, with % /weight of each
b. RAW MATERIAL SPECIFICATIONS- enumerate characteristics of all materials that go into the product and the permissible range of purity of each ingredient
c. STANDARD OPERATING PROCEDURE- step by step method on how to go about the job
d. FINISHED PRODUCT SPECIFICATION- cover all characteristics that affect the proper performance, purity, safety and stability of the product
e. PACKAGING MATERIAL STANDARD- set for everything that goes around the product
f. TESTING METHODS- Testing procedures to that they yield
results of comparable precision and accuracy
DEFECTS
- Undesirable characteristic of a product
- Failure to confirm to conformance
DEFECTIVE-unit of a product which contains one or more defects
ACCDG. TO MEASURABILITY
a. VARIABLE DEFECT- Measured directly by instruments giving
dimension of length, weight, height, thickness etc.
b. ATTRIBUTE DEFECT- cannot be measured directly by instruments- odor or visual examination like color, clarity, cleanliness, smoothness etc.
ACCORDING TO SERIOUSNESS OR GRAVITY
1. CRITICAL DEFECT- a defect which may endanger life or property and may render the product nonfunctional
2. MAJOR DEFECT- defect which may affect the function of the object and therefore, may render the product useless
3. MINOR DEFECT- defect which does not endanger life or property nor will it affect the function but nevertheless remains a defect since it is outside the prescribed limits
ACCORDING TO NATURE
1. OCULAR DEFECT- defect that is visible
2. INTERNAL DEFECT- defect which is not seen although present
3. PERFORMANCE DEFECT- defect in function
SOURCES OF VARIATIONSOURCE/S EXAMPLE/S
MATERIALS -Between suppliers of same substances-Between batches from same supplier-Variation within a batch
MACHINES -Variation of equipment for the same process-Difference in adjustment of equipment-Aging and improper care
METHODS -Inexact procedures-Inadequate procedures-Negligence by chance
MEN -Improper working conditions-Inadequate training, and understanding-Dishonesty, fatigue and carelessness
QUALITY CONTROL ORGANIZATIONAL CHART
Quality Control Manager
Materials Inspection Section
Analytical Laboratory
Biological Testing Laboratory
Specifications and Analytical
DevelopmentQuality Coordinating
Office
CONTROL FUNCTIONS
a. Analysis Functionb. Monitor Functionc. Record Review and Release
Functiond. Audit Function
TERMS:
a. ACCURACY- closeness of test results to the TV
b. PRECISON- degree of agreement among individual test results when the method is applied repeatedly to multiple samplings of a homogenous sample
c. SPECIFICITY- ability to assess unequivocally the analyte in the presence of components such as: impurities, degradation pdts.
d. ROBUSTNESS- measure of its capacity to remain unaffected
TABLETS:
HARDNESS
EQUIPMENTS Stoke’s hardness tester (Monsanto)Strong –Cobb hardness testerPfizer testerErweka testerSchleuniger
ACCEPTANCE HARDNESS RANGE
4-10 Kg(ordinary compressed tab)2 Kg (Sublingual & chewable tab)10 Kg (Buccal & extended/modified release tab)
THICKNESS
EQUIPMENT Micrometer caliper
ACCEPTANCE CRITERIA ≤ 5 % of set std. thickness
FRIABILITY
EQUIPMENT Roche friabilatorSetting: 25 rpmTime: 4 mins. (100 revolutions)
ACCEPTANCE CRITERIA
STAGE/SAMPLE ACCEPTANCE LIMIT
1( 10/20) NMT 1 %
2(20/40) NMT 1 % (Average of 3 trials)
New formulation NMT 0.8 %
DISSOLUTION TESTING
Media Temperature
37 ± 2 ˚C ( 35-39 ˚C)
Equipment Basket Rack Assembly
Procedure Load 1 tablet or capsule in each of the tube and expose the product into the conditions specified. Overlay with sinker or 10 mesh wire cloth(as specified)
Time requirement Plain, coated tablet and capsules:-30 mins (H2O)Enteric coated tablet:5 mins soaking(H2O)1 hr(simulated gastric juice)1 hr(simulated intestinal juice)Buccal tablets:4 hrs(H2O)Sublingual tablets:3 mins (H2O)
Criteria Passed test- if none remained on the wireIf 1 or 2 did not disintegrate, perform 2 trialsNMT 2 of the 18 samples tested failed to disintegrate
DISSOLUTION TESTING
Media Temperature 37 ± 0.5 ˚C ( 36.5-37.5˚C)
Apparatus Consist of a vessel with cover, motor, H2O bath maintained at ( 37 ± 0.5 ˚C) metallic drive shaftType 1: Basket accessoryType 2: Paddle accessory
Criteria Stage 1: 6 samples Each unit should at least Q + 5 %**Q- % accdg. to label claimStage 2: + 6 samples Average of 12 units is ≥ Q & no unit is < Q-15%Stage 3: + 12 samples Average of 24 units is ≥ Q & NMT 2 units are < Q-15 % & no unit is < Q-25%
Formulas:Abs(sample) x Conc. (std) x dilution
factor
Abs(standard)
% label claim = -------------------------- x 100 Label claim
Average weight
Adjusted Label claim= % Label claim x ---------------------------
Weight (sample)
WEIGHT VARIATION TESTING & CONTENT UNIFORMITY TEST
CONTENT UNIFORMITY TEST -For tablets containing 50 mg or less of an active ingredient-Ensures potency of tablet products-USP limit: 85-115 %-Sample: NLT 30 tablets then assay 10 tablets individually
WEIGHT VARIATION TESTING - For tablets containing 50 mg or more of an active ingredient
ACCEPTABLE TABLET WEIGHT VARIATIO N
% VARIATION
< 130 mg ± 10 %
130- 324 mg ± 7.5 %
> 324 mg ± 5 %
SOLUTIONS, SUSPENSIONS, EMULSIONS & GRANULES
a. SOLUTIONS:- appearance- Stability
- Chemical- Physical(viscosity, color,
clarity, odor & taste)
b. SUSPENSIONS:
- Sedimentation volume- Redispersability- Particle size measurement- Rheological properties- Temperature and gravitational
stress
c. EMULSIONS:
- Tests for creaming, cracking, phase separation and phase inversion
- Particle size nos. analysis
d. GRANULES:
- Particle size distributions- Angle of repose- Bulk density- Moisture content- Content uniformity- ShapeTECHNIQUES:
- Sieving- Optical microscopy- Adsorption study- Light scattering technique- Sedimentation
ANGLE OF REPOSE:
ANGLE OF REPOSE INTERPRETATION
< 25 Excellent
25-30 Good
30-40 Fair (+ glidant)
>40 Poor
ANIMAL USED IN TESTING OF DRUGS:
DRUG ANIMAL EMPLOYED
DIGITALIS Pigeon
GLUCAGON INJECTION Cat
OXYTOCIN INJECTION Chicken
PARATHYROID INJECTION Dog
HEPARIN AND PROTAMINE SULFATE
Sheep blood plasma
VASOPRESSIN INJECTION Male rat
SAMPLING AND SAMPLING PLAN
INSPECTION STEPS:1. Interpretation of the specification2. Measurement of the product3. Comparison of the product with
specification4. Judgment as to conformance5. Disposition of the product6. Recording of the data obtained
SAMPLING
- Process of removing an appropriate number of items from a population in order to make inferences to the entire population
POPULATION- is the totaling of all actual or conceivable items of a certain class under considerations
SAMPLE
- A finite number of objects selected from a population
RANDOM SAMPLE- chosen such that one object has a good chance of being selected as another
MATERIALS TO BE SAMPLED
a. Raw materialsb. Packaging and printed materialsc. Intermediate productsd. Final products (before, during and
after packaging operations)
SAMPLING PLAN
- a definite working rule regarding size and frequency of sample and the basis for acceptance or rejection;
RECEPTIONQUARANTINE- yellowREJECTED- redAPPROVED- green
PACKAGING MATERIALS:
a. Primary packaging- direct contact with the product itself
b. Secondary packaging- not come in direct contact with the product and serve as accessory to the primary packaging
REASSAY DATES
- Date of retest- Periodic testing--done to revalidate
material
MANUFACTURING CONTROL
MASTER FORMULA RECORD- original document used as key in the production of products
BATCH
LOTBATCH NUMBER/LOT
NUMBER/CONTROL NUMBER
STABILITY
- Ability of a particular formulation in a specific container to remain within its physical, chemical and toxicological specifications
STABILITY STUDIES
STABILITY STUDY
STORAGE CONDITIONS MINIMUM PERIOD COVERED
Long-term 25 ± 2˚C 60 ± 5 % RH 12 months
Intermediate 30 ± 2 ˚ C 60 ± 5 % RH 8 months
Accelerated 40 ± 2 ˚ C 75 ± RH 5 months
WORLD CLIMATE CONDITIONS:
CLIMATE CONDITIO
NS
ZONE I(Temp-erate)
ZONE II(Mediterrane
an/Subtropical)
ZONE III(Hot, Dry)
ZONE IV(Hot, Humid/
Tropical)
Mean Annual
Temp (˚C)
20.5 20.5-24 24 24
Kinetic Mean Temp
(˚C)
21 26 31 31
Mean Annual RH
( %)
45 60 40 70
SAMPLE PROBLEMS:
**STABILITY COMPUTATIONS:FORMULATION:
ACTIVE 1 65 mg (limits:95-105%)
ACTIVE 2 15 mg (limits: 90-110%)
ACTIVE 3 122 mg (limits: 90-110%)
Results of analysis:
Initial 3 mos.
6 mos.
12 mos.
24 mos.
36 mos.
48 mos.
Active 1
67.00 67 66.80 65.40 63.06 61.98 61.79
Active 2
15.00 14.94 14.90 14.21 14.01 13.67 13.38
Active 3
128.30 126 124.10 117.76 113.30 110.60 109.50
Questions:
1. Determine the minimum and maximum limits of each active based on the specifications.
2. What is the shelf life of the formulation?
3. What would be the expiry date of a product manufactured on December 22, 1994?
----more problems….try to solved pls…tnx
2. Assay of 250 ml solution of Dopamine 200 mg injection resulted in the following data. Based on these, determine the amount of Dopamine in 100 ml solution.
Sample Volume: 5 mlSolution Volume: 250 mlAbsorbance (sample): 38259Absorbance (standard): 20163
FORMULA:
Absorbance(sx) 100 1
Conc’n (mg/ml) = ---------------------x---------- x ----
Absorbance(std) Vol’m(sx) 1000
THANK YOU!!!GODBLESS