Quality Control Lecture Notes PDF

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Quality Control in Manufacturing...

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QUALITY CONTROL LECTURE NOTES DEFECTS - A defect is an undesirable characteristic of a product. It is defined as a failure to conform to specifications. - A unit of a product which contains one or more defects is called a defective.

General Sources Causing Product Quality Variation during Manufacturing Sources of Variation 1. Materials

Classification : A. According to measurability : 1. Variable defect – a defect which can be measured directly by instruments giving dimensions of length, weight, height, thickness, concentration, volume, viscosity, pH or size particles. 2. Attribute defect – a defect which cannot be measured directly by instruments. This applies to many things that can be judged only by color or visual exam. Like color, clarity, sheen, cleanliness, smoothness, taste. B. According to seriousness or gravity : 1. Critical defect – a defect which may endanger life or property and may render the product non-functional. Absence of warning label for a potent drug is a critical defect. 2. Major defect – a defect which may affect the function of the object and therefore, may render the product useless. The presence of a crack in a bottle is a major defect. 3. Minor defect – a defect which does not endanger life or property nor will affect the function but nevertheless remains a defect since it is outside the prescribed limits. Slight deviation of the color of label from the color standards is a minor defect. C. According to nature : 1. Ocular defect – a defect that is visible, e.g. foreign particulate contamination 2. Internal defect – a defect which is not seen although present, e.g. a sub potent drug product. 3. Performance defect – a defect in function, e.g. a suppository that does not melt at body temperature.

2.

Machines

3.

Methods

4.

Men

Example a. Variation between suppliers of same subs. b. Variation between batches from same supplier. c. Variation within a batch. a. Variation of equipment for the same process. b. Difference in adjustment of equipment c. Aging and improper care a. Inexact procedures. b. Inadequate procedures. c. Negligence by chance a. Improper working conditions. b. Inadequate training, and understanding. c. Dishonesty, fatigue and carelessness.

CONTROL FUNCTIONS 4 CATEGORIES : 1. Analysis Function – continues even after distribution to the end user when selected lots are subjected to shelf life studies to confirm the expiration period of the finished product. 2. Monitor Function - Examine materials while they are being processed. - Environmental monitoring. 3. Record Review and Release Function - Batch records are all records generated during the course of producing a quality controlled product. - Record-review function is responsible for carefully reviewing the batch record for that lot and assuring that all necessary records are present, complete and accurate. 4. Audit Function

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Quality audit is designed to detect areas where the established SOPs are not being followed and to report these findings to the supervisor for appropriate action.

SAMPLING AND SAMPLING PLAN A basic quality function is that deciding whether the product conforms to specifications. This function is generally called “acceptance”. To arrive to a decision, the primary step is inspection. INSPECTION – is the comparison of certain attributes and dimensions of a product against specifications to find out if the product is within the prescribed limits.

4. Final products : before, during and after manufacturing and packaging operations. Sampling inspection is therefore used in lieu of 100% inspection for the following reasons : 1. The cost of 100% inspection is prohibitive. 2. 100% inspection is tiring and the probability that the inspector will commit error is high. 3. The inspection operation may involve destructive testing. 4. A statistical sampling plan well applied may give better quality assurance than 100% inspection. INSPECTION METHODS

Inspection consists of several steps : 1. Interpretation of the specification. 2. Measurement of the product. 3. Comparison of the product specification. 4. Judgment as to conformance. 5. Disposition of the product. 6. Recording of the data obtained.

The most common and distinct methods of inspection are the SINGLE and DOUBLE SAMPLING METHODS. with

ACCEPTANCE SAMPLING Much of acceptance inspection is by sampling. Sampling may be defined as the 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. A sample is a finite number of objects selected from a population. A random sample is a sample chosen in such a manner that one object has a good chance of being selected as another. Representatives of materials to be sampled : 1. Raw materials 2. Packaging and printed materials 3. Intermediate products

SINGLE SAMPLING – a decision is reached after only one sampling. DOUBLE SAMPLING – a decision is obtained after the result of the second sampling is known. SAMPLING PLAN In sampling, one must consider the LAWS OF PROBABILITY. There are certain risks involved; namely, the risk of error. A producer’s risk (∞) is the probability of rejecting a good batch, where as consumer’s risk (β) is the probability of accepting a bad batch. A sampling plan is a definite working rule regarding size and frequency of sample and the basis for acceptance or rejection. It is therefore a specification of sampling. SQUARE ROOT SYSTEM SAMPLING PLAN Which uses the formula : n = √ N + 1 . The acceptance number is specified by the AQL (Acceptable Quality Level) GOVERNMENT SAMPLING PLAN A sampling plan which has found wide acceptance throughout the industrial world.

It consists of master tables first developed in 1942 by a group of engineers from the Bell Telephone Laboratories. These tables are further developed and adopted by the US Department of Defense. Thus, they are now known as the Military Standards. MATERIAL CONTROL Material control is the main component of the process of material management.

utmost efforts should be made to minimize the wastage of raw materials. This is possible only by introducing an efficient materials control system. (d) To fix responsibility: A proper system of materials control also aims at fixing responsibility of operating units and individuals connected with the purchase, storage and handling of materials.

Control over materials is of utmost importance for smooth and uninterrupted functioning of an organization.

(e) To provide information: Another objective of materials control is to provide accurate information regarding material cost and inventory whenever needed by management.

In simple words, material control refers to the various measures adopted to reduce the amount of loss of materials at the time of receiving, storing and issuing the raw materials. Material control in practice is exercised through periodical records and reports relating to purchase, receipt, inspection, storage and issuing direct and indirect materials. Proper control over material can contribute substantially to the efficiency of a business.

Necessity and importance of material control: In a productive undertaking the need of materials control arises on account of the following reasons: 1. For keeping the stock of raw materials within limits in the stores i.e., to avoid overstocking and understocking of raw materials, materials control is significant.

Objectives of Material Control : (a) To enable uninterrupted production: The main object of material control is to ensure smooth and unrestricted production. Production stoppages and production delays cause substantial loss to a concern. (b) To ensure requisite quality of materials: The quality of finished products depends mainly on the quality of raw materials used. If quality of the raw materials is not up to desired standards, the end product will not be of desired quality which affects the sale of the product in the market resulting in loss of profits as well as goodwill of the concern. It is of vital importance to exercise strict control and supervision over the purchases, storage and handling of materials. (c) To minimize wastage: The loss of material may occur on account of rust, dust, dirt or moisture, bad and careless handling of materials, poor packing and many other reasons. The causes responsible for such losses must be brought to light and

2. It ensures proper storage of materials. For the proper preservation and safety of materials, adequate storage facilities are to be provided. With the help of proper storing of materials, quantity of materials as and when required can be issued to various jobs. 3. For knowing proper cost of production, control over materials is indispensable. 4. Certain techniques and methods are developed under the system of materials control thereby ensuring optimum utilization of materials. 5. In order to undertake continuous checking of materials, the necessity of a proper system of materials control cannot be ignored. RAW MATERIALS These are the ingredients intended for use in the manufacture of drugs and cosmetics, including those that may not appear in the final product.

The control of raw materials at different stage is handled in the following manner : A. Reception : 1. The receiving tally report is checked by a QC inspector for accuracy. 2. Each container of raw materials is examined visually for damage or contamination in transit, including breakage of seals when indicated. 3. Adequate number of samples are taken from a representative number of containers. a. Sampling plan is used to determine the number of raw material container to be sampled. b. Calculate for the total quantity of material required for a complete test to determine the amount of sample to be taken from each container. c. The composite sample should not be less than three times the amount required for one complete test. B. Quarantine : 1. The inspector checks that the raw material container has a “HOLD” or a quarantine sticker pasted by the receiving warehouse personnel to indicate that a decision to accept or reject is yet to be made by quality control. 2. Samples are submitted to the laboratory for testing. 3. The sample is subjected to tests such as : a. Physical and Organoleptic examination b. Identification tests c. Limits of impurities and degradation products d. Potency or assay e. Microbiological tests 4. If the test results indicate that the raw material meets monograph specifications, the material is approved for use; otherwise, it is

rejected. Decision stickers are then issued by QC. 5. The decision stickers are either placed on top of the quarantine sticker or the quarantine is first removed before the decision sticker is pasted. No two stickers of different dispositions must be present on the same container. At this stage, the raw material is transferred to either the rejected or approved materials area. C. Rejected : The material so marked is checked that it is held at a rejected materials area to prevent the possibility of use in any manufacturing or processing procedure. D. Approved : 1. The material marked as approved is checked that is brought to the approved materials area. 2. Approved materials are tested when reassay date is due to assure that they conform to appropriate specifications of identity, strength and purity at time of use. 3. Approved raw materials are audited to assure that they are rotated in such a manner that the oldest stock is used first. This is known as the FIFO (first in, first out) policy. Analytical Approach and Instrumentation Raw materials analysis requires a wide range of analytical chemistry expertise. The most common tests performed in a raw materials laboratory include titrations, loss on drying, Karl Fischer moisture determination, heavy metals limit tests, and infrared spectrophotometry. Full monograph testing often requires as many as seven different analytical techniques. For example, to perform full USP monograph testing for methylparaben, eight different tests using six analytical techniques ranging from infrared absorption to gas chromatography are required. Therefore, the most efficient organization of a raw

materials laboratories is by function so that analysts can specialize in specific techniques. To perform even basic monograph testing, laboratories must contain a wide spectrum of instrumentation. The most commonly specified instruments include ●pH meters/ion meters ●balances ●gas chromatographs (GCs) ●high-performance liquid chromatographs (HPLCs) ●infrared spectrophotometers ●UV-Visible & Fluorescence spectrophotometers ●Tintometer ●Karl Fischer moisture titrators ●Auto-titrators & titration apparatus ●Vacuum ovens ●Melting-point apparatus ●Thin-layer chromatography apparatus (TLC) ●Polarimeter ●Refractometer ●Viscometers (Capillary & Rotary) ●Muffle furnace To expand the number and variety of excipients that can be tested, additional instrumentation is required. These include ●Flame atomic absorption spectrophotometer ●Graphite furnace atomic absorption spectrophotometer ●Osmometer ●Inductively coupled Plasma Spectrometer ●Mass spectrometer STICKERS

Color codes : Yellow – for Quarantine Green – for approved Red – for rejected PRINTED AND PACKAGING MATERIALS 2 types of Packaging Materials : 1. Primary Packaging Components - Packaging materials which come in direct contact with the product itself; like bottles, tubes, ampoules, vials, carpules, caps, stoppers, plungers, stripping material jars, fillers and seals. 2. Secondary Packaging Components - Packaging material which do not come in direct contact with the product and serve as accessory to the primary packaging component. Most of these are labels, inserts, unit cartons, brochures, packer boxes and shippers. Printed Materials By official definitions, labeling includes all written, printed or graphic materials accompanying a product. They are subjected to inspections by an experienced proofreader for graphical errors, for compliance with specifications as to type and grade of stock printing quality and dimensional tolerance. Minimum criteria for acceptance of printed materials consists of : 1. Text 6. Sealability 2. Color 7. Cleanliness 3. Size 8. Surface finish 4. Thickness 9. Adequate paste 5. Grain direction 10. Shape

In order to avoid mix-ups, a material warehouse is subdivided into several sections. Accordingly, the materials are segregated and properly identified by the stickers attached on the individual containers, cage or pallet of materials. On the reception of materials, a quarantine sticker is pasted on the container of the material. The materials are held in a quarantine area while waiting for its release by QC.

LABELING CONTROL Below is a summary of labeling requirements for drugs and cosmetics.

Labels : 1. Name of drug or cosmetic 2. The strength or quantity of the substance contained per unit dosage form 3. Lot or batch number 4. Expiration date 5. Registration number 6. Storage condition 7. Name of the manufacturer, packer or distributor 8. Business address 9. Quantity of contents of package 10. Names and quantities of components in the preparation 11. Rx symbol (if necessary) 12. Warning or precaution 13. Adequate direction for use Package Insert : 1. Product name 2. Strength or quantity of the active substance contained per unit dosage form 3. Description 4. Action 5. Indication 6. Contraindications 7. Warnings 8. Precautions 9. Adverse Reactions 10. Dosage and Administration 11. Overdosage 12. How supplied 13. Manufacturer/packer/distributor 14. Business address To prevent mix-ups of inventories of printed labeling materials of similar color and shape, bar codes placed on edge have been found useful CONTAINERS 1. 2. 3. 4. 5. 6.

Glass and Glass Containers Metal and Metal Containers Plastics and Plastic Containers Paper and board Films, foils and laminates Rubber-based components

Classes of Containers 0 Well – Closed Containers 0 Tight Containers

0 0 0

Hermetic Containers Light-resistant Containers Child-resistant Containers

QC tests for Containers : 1. 2. 3. 4.

Physical Appearance Physical Tests Physico-chemical Tests Biological Tests

Physical Tests : 1. Light Transmission Test - Using Spectrophotometer - Max % of light transmitted at 290 – 450 nm LIMITS : - Type NP/IV – nmt 10% - Types I, II and III, and Plastic Classes I-VI – table for flamesealed and closure-sealed containers Physico-chemical Tests : 1. Chemical Resistance Test - Resistance to water attack - Degree of attack = amt of alkali released - Direct Acidimetry – 0.02 N H2SO4. 2 Methods: - Powdered Glass - Water Attack Test at 121° 2. Permeation Test / Moisture Permeability - Moisture permeability across the container 3. Heavy Metals - Titrimetry – complexometry - Atomic Absorption Spectrometry (AAS) 4. Non volatile Residue - Gravimetric method 5. Thermal Analysis - Use of DSC thermogram 6. Residue on Ignition (ROI) - Not necessary if non volatile results is not >5 mg

- Gravimetry 7. Buffering Capacity - Potentiometric titration Biological Tests : In-vitro : Mammalian Cell Cultures 1. Agar Diffusion Tests - For elastomeric closures - Agar layer – cushion to protect cells – will allow diffusion of leachable chemicals. 2. Direct Contact - Materials in a variety of shapes - Simultaneous extraction and testing - Not appropriate – very low or high density materials 3. Elution Test - Extracts of polymeric materials - At physiological or nonphysiological temperatures - High-density materials and dose-response evaluation In-vivo : Biological response of animals 1. Systemic Injection Test - Evaluate system responses 2. Intracutaneous Test - Local responses 3. Implantation Test - Direct contact with living tissue CLOSURES OR CAPS 0 Tin plates 0 Aluminum 0 Rubber 0 Thermoplastics Different Kinds: 1. Threaded Screw Caps - Preformed (Lug cap) - Formed during application (Roll-on, Pilferproof) 2. Push-on or Plug-type closures QC tests on Closures : 1. Torque Test

Tightness of the cap Torque – Circular force – loosen the cap - Application Torque – To tighten the cap - n = 10 bottles - Unit: inch-pound - Machine: Torque Tester 2. Water/Vapor Transmission Test - Efficiency of the closure system - n = 5 bottles - % weight loss – every month - Limit – nmt 3% loss in one year 3. Leak Test – ampoules and heatsealed containers -

Methods: a. Dye Bath – vacuum or pressure while in dye solution b. Liquid Loss – pulling a vacuum, without dye c. High Voltage Detection – across length of ampoule

Prepared by : Giuseppe C, Jumawan...