production and control of drugs when adequate inspection and checking procedures are used to assure proper performance
OBJECTIVE OF cGMP:
1. Safe 2. Pure 3. Effective
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,
A series of analytical measurements used to assess the quality of the analytical data (The tools)
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
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.
-
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 VARIATION
SOURCE/S MATERIALS EXAMPLE/S -Between suppliers of same substances -Between batches from same supplier -Variation within a batch -Variation of equipment for the same process -Difference in adjustment of equipment -Aging and improper care -Inexact procedures -Inadequate procedures -Negligence by chance -Improper working conditions -Inadequate training, and understanding -Dishonesty, fatigue and carelessness
MACHINES
METHODS
MEN
Analytical Laboratory
Biological Testing Laboratory
CONTROL FUNCTIONS
a. Analysis Function b. Monitor Function c. Record Review and Release Function d. 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 Stokes hardness tester (Monsanto) Strong Cobb hardness tester Pfizer tester Erweka tester Schleuniger
ACCEPTANCE HARDNESS RANGE 4-10 Kg(ordinary compressed tab) 2 Kg (Sublingual & chewable tab) 10 Kg (Buccal & extended/modified release tab) THICKNESS EQUIPMENT ACCEPTANCE CRITERIA Micrometer caliper 5 % of set std. thickness
FRIABILITY EQUIPMENT Roche friabilator Setting: 25 rpm Time: 4 mins. (100 revolutions)
ACCEPTANCE CRITERIA STAGE/SAMPLE 1( 10/20) 2(20/40) New formulation ACCEPTANCE LIMIT NMT 1 % NMT 1 % (Average of 3 trials) NMT 0.8 %
DISSOLUTION TESTING
Time requirement
Criteria
DISSOLUTION TESTING
37 0.5 C ( 36.5-37.5C) Consist of a vessel with cover, motor, H2O bath maintained at ( 37 0.5 C) metallic drive shaft Type 1: Basket accessory Type 2: Paddle accessory Stage 1: 6 samples Each unit should at least Q + 5 % **Q- % accdg. to label claim Stage 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 < Q25%
Criteria
Formulas:
Abs(sample) x Conc. (std) x dilution factor Abs(standard)
% VARIATION
10 % 7.5 % 5%
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
d. GRANULES:
Particle size distributions Angle of repose Bulk density Moisture content Content uniformity Shape TECHNIQUES: - Sieving - Optical microscopy - Adsorption study - Light scattering technique - Sedimentation
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ANGLE OF REPOSE:
ANGLE OF REPOSE
< 25
INTERPRETATION
Excellent
25-30
30-40 >40
Good
Fair (+ glidant) Poor
ANIMAL EMPLOYED
Pigeon Cat
OXYTOCIN INJECTION
PARATHYROID INJECTION HEPARIN AND PROTAMINE SULFATE VASOPRESSIN INJECTION
Chicken
Dog Sheep blood plasma Male rat
SAMPLING
- Process of removing an appropriate number of items from a population in order to make
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 materials b. Packaging and printed materials c. Intermediate products d. 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; RECEPTION QUARANTINE- yellow REJECTED- red APPROVED- 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 LOT BATCH 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 2C
60 5 % RH
12 months
Intermediate
Accelerated
30 2 C
40 2 C
60 5 % RH
75 RH
8 months
5 months
24
21
26
31
31
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
Results of analysis:
Initial 3 mos. 6 mos. 12 mos.
67 14.94 126 66.80 14.90 124.10 65.40 14.21 117.76
24 mos.
63.06 14.01 113.30
36 mos.
61.98 13.67 110.60
48 mos.
61.79 13.38 109.50
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 plstnx
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 ml Solution Volume: 250 ml Absorbance (sample): 38259 Absorbance (standard): 20163
FORMULA:
Absorbance(sx) 100 1
THANK YOU!!!GODBLESS