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QUALITY ASSURANCE AND QUALITY CONTROL

Quality Assurance and Quality Control-final

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Page 1: Quality Assurance and Quality Control-final

QUALITY ASSURANCE AND QUALITY

CONTROL

Page 2: Quality Assurance and Quality Control-final

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

Page 3: Quality Assurance and Quality Control-final

OBJECTIVE OF cGMP:

1. Safe2. Pure3. Effective

Non-compliance---contamination, mix-ups and errors

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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

Page 5: Quality Assurance and Quality Control-final

QUALITY CONTROL

Part of cGMP concerned with sampling, specifications, testing, organization, documentation and release procedures

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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”)

Page 7: Quality Assurance and Quality Control-final

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

Page 8: Quality Assurance and Quality Control-final

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

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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

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DEFECTS

- Undesirable characteristic of a product

- Failure to confirm to conformance

DEFECTIVE-unit of a product which contains one or more defects

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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.

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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

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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

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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

Page 15: Quality Assurance and Quality Control-final

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

Page 16: Quality Assurance and Quality Control-final

QUALITY CONTROL ORGANIZATIONAL CHART

Quality Control Manager

Materials Inspection Section

Analytical Laboratory

Biological Testing Laboratory

Specifications and Analytical

DevelopmentQuality Coordinating

Office

Page 17: Quality Assurance and Quality Control-final

CONTROL FUNCTIONS

a. Analysis Functionb. Monitor Functionc. Record Review and Release

Functiond. Audit Function

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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

Page 19: Quality Assurance and Quality Control-final

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

Page 20: Quality Assurance and Quality Control-final

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 %

Page 21: Quality Assurance and Quality Control-final

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

Page 22: Quality Assurance and Quality Control-final

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%

Page 23: Quality Assurance and Quality Control-final

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)

Page 24: Quality Assurance and Quality Control-final

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 %

Page 25: Quality Assurance and Quality Control-final

SOLUTIONS, SUSPENSIONS, EMULSIONS & GRANULES

a. SOLUTIONS:- appearance- Stability

- Chemical- Physical(viscosity, color,

clarity, odor & taste)

Page 26: Quality Assurance and Quality Control-final

b. SUSPENSIONS:

- Sedimentation volume- Redispersability- Particle size measurement- Rheological properties- Temperature and gravitational

stress

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c. EMULSIONS:

- Tests for creaming, cracking, phase separation and phase inversion

- Particle size nos. analysis

Page 28: Quality Assurance and Quality Control-final

d. GRANULES:

- Particle size distributions- Angle of repose- Bulk density- Moisture content- Content uniformity- ShapeTECHNIQUES:

- Sieving- Optical microscopy- Adsorption study- Light scattering technique- Sedimentation

Page 29: Quality Assurance and Quality Control-final

ANGLE OF REPOSE:

ANGLE OF REPOSE INTERPRETATION

< 25 Excellent

25-30 Good

30-40 Fair (+ glidant)

>40 Poor

Page 30: Quality Assurance and Quality Control-final

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

Page 31: Quality Assurance and Quality Control-final

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

Page 32: Quality Assurance and Quality Control-final

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

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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

Page 34: Quality Assurance and Quality Control-final

MATERIALS TO BE SAMPLED

a. Raw materialsb. Packaging and printed materialsc. Intermediate productsd. Final products (before, during and

after packaging operations)

Page 35: Quality Assurance and Quality Control-final

SAMPLING PLAN

- a definite working rule regarding size and frequency of sample and the basis for acceptance or rejection;

RECEPTIONQUARANTINE- yellowREJECTED- redAPPROVED- green

Page 36: Quality Assurance and Quality Control-final

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

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REASSAY DATES

- Date of retest- Periodic testing--done to revalidate

material

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MANUFACTURING CONTROL

MASTER FORMULA RECORD- original document used as key in the production of products

BATCH

LOTBATCH NUMBER/LOT

NUMBER/CONTROL NUMBER

Page 39: Quality Assurance and Quality Control-final

STABILITY

- Ability of a particular formulation in a specific container to remain within its physical, chemical and toxicological specifications

Page 40: Quality Assurance and Quality Control-final

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

Page 41: Quality Assurance and Quality Control-final

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

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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%)

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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

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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

Page 45: Quality Assurance and Quality Control-final

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

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FORMULA:

Absorbance(sx) 100 1

Conc’n (mg/ml) = ---------------------x---------- x ----

Absorbance(std) Vol’m(sx) 1000

Page 47: Quality Assurance and Quality Control-final

THANK YOU!!!GODBLESS