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Quality control is an essential operation of the pharmaceutical industry. Drugs must be marketed as safe and therapeutically active formulations whose performance is consistent and predictable. In this article, Common words being described which are generally used in pharmaceutical Quality Control.

Definition of Terms Used in Quality Control Laboratory

1.0   Description – Quality Control Tests:

• • Statements given under this heading are not to be interpreted in a strict sense and are not to be regarded as analytical requirements, although they may help in the preliminary evaluation of the integrity of an article.

• • Where, however, the description is included under the heading `STANDARDS’ the article shall comply with this requirement.

• • Where the substance is described as `odorless’, the following method of examination applies:

• • Examine a sample of not more than 25 g immediately after opening the package.

• • If any odor is noticeable, transfer the sample rapidly to an open container and re-examine after 15 minutes.

• • If the odor still persists, the sample fails with the description `odorless’.

• • Statements on taste are provided only in cases where this property is a guide to the acceptability of the material (for example, a substance used primarily for flavoring).

2.0   Solubility– Quality Control Tests:

• • Statements on solubility given under the heading `Solubility’ are not standards or tests for purity but are provided primarily as information.

• • Where, however, a quantitative solubility test is given under `STANDARDS’, the substance shall comply with this requirement.

• • Statements of solubility are indicated by a descriptive phrase and are intended to apply at 20^oC to 30^o C.

• • The following table indicates the meanings of the terms used in statements of approximate solubility in the Quality Control Laboratory.

3.0   Atomic weights:

• • The atomic weights adopted are the values given in the Table of Relative Atomic Weights1989 published by the IUPAC.
  • The values are based on the carbon-12 scale.

4.0   Chemical Formulae :

• • When the chemical structure of an official substance is known or generally accepted, the graphic and molecular formulae and the molecular weight are given at the beginning of the monograph.

• • This refers to the chemically pure substances and is not to be regarded as an indication of the purity of the drug.

• • From the statements of standards of purity and strength and in descriptions of processes of the assay,

• • It will be evident from the context that the formulae denote the chemically pure substances.

• • Where the absolute stereochemical configuration is specified, the International Union of Pure and Applied Chemistry (IUPAC) R/S and E/Z systems of designation have been used. If the substance is an enantiomer of unknown absolute stereochemistry, the sign of the optical rotation, as determined in the solvent and under the conditions specified in the monograph, has been attached to the systematic name. An indication of sign of rotation and/or configuration has also been given where this is incorporated in a trivial name that appears on an IUPAC preferred list.
• Abbreviated Statement in Monographs:
  • Incomplete sentences are employed in parts of the monographs for directness and brevity (for example, Iodine Value: Not more than…..; Wt. per ml: Between …..and…..). Where the tests are so abbreviated, it is to be understood that the appendix referred to provides the method to be followed and that the values specified are the required limits.
• Limits, Significant Figures and Tolerances:
  • When limits of content are given in a monograph they are determined by the method prescribed therein.
  • When limits are expressed numerically, the upper and lower limits of a range are inclusive so that the range consists of the two values themselves and all intermediate values, but no values outside the limits. The limits expressed in monograph standards and tests, regardless of whether the values are expressed as percentages or as absolute numbers, are considered significant to the last digit shown.
  • The limits stated in monographs are based on data obtained in normal analytical practice. No further tolerances are to be applied to the limits prescribed to determine whether the article being examined complies with the requirements of the monograph.
• Calculation of Results:
  • In determining compliance with a numerical limit in an assay or test, the result should be calculated to one decimal place more than the significant figures stated and then rounded up or down as follows: if the last figure calculated is 5 to 9, the preceding figure is increased by 1; if it is 4 or less, the preceding figure is left unchanged.
• Ingredients and Processes:
  • in Official preparations are prepared from ingredients that comply with the requirements of the compendial monographs for those individual ingredients for which monographs are provided. Where water is used as an ingredient it meets the requirements for Purified Water, for Water for Injection, or for one of the sterile forms of water covered by a monograph in this Pharmacopoeia.
  • A dosage form shall be formulated with the intent to provide 100% of the quantity of each ingredient stated on the label. Where the content of an ingredient is known to decrease with time, an amount in excess of that stated on the label may be added at the time of manufacture to assure compliance with the content requirements of the monograph throughout the life period of the product. The limits stated in the monographs allow for such overages, for analytical errors, for unavoidable variations in manufacturing and for deterioration to an extent considered insignificant under practical conditions. The specified tolerances are based on the assumption that good manufacturing practices have been followed in the production of an article from suitable raw materials.
  • Monographs for certain official preparations include a full formula together with, in some cases, directions for their preparation. Such full formulae and directions are intended for preparation of small quantities for short-term supply and use. When so prepared, no deviation from the stated formula and directions is permitted. If, however, such a preparation is manufactured on a larger scale with the intention that it may be stored and distributed, deviations from the formula and directions stated in the monograph are permitted provided that the ingredients used comply with the compendial requirements and with the general notice on Added Substances and that the final product meets the following criteria:
    • Compliance with all of the requirements stated in the monograph, and
    •  Retention of the essential characteristics of the preparation made strictly according to  the formula and directions of the Pharmacopoeia.
    • If a preparation is intended to be stored over a period of time, deterioration due to microbial contamination may be inhibited by the addition to the formula of a suitable antimicrobial preservative. In such circumstances the label states the concentration of the antimicrobial preservative and the appropriate storage conditions. It is implied that such a preparation will be effectively preserved according to the appropriate criteria applied and interpreted as described in the test for effectiveness of antimicrobial preservatives in a pharmaceutical preparation.
    •       The direction that a preparation must be freshly prepared indicates that it must be made not more than 24 hours before it is used.
  • Assay & Tests:
    • Apparatus: A specification for a definite size or type of container or apparatus in a test or assay is given merely as a recommendation. Where volumetric flasks or other exact measuring or weighing devices are specified, this or other equipment of at least equivalent accuracy may be employed.
    • In order to obtain solutions having concentrations that are adaptable to the working range of the instrument being used, solutions of proportionally higher or lower concentrations may be prepared, according to the solvents and proportions thereof that are specified in the procedure.
    • Water-bath: The term `water-bath’ means a bath of vigorously boiling water unless water at some other temperature is indicated.
    • Desiccator: The term `desiccator’ means a tightly-closed container of suitable size and design that maintains an atmosphere of low moisture content by means of silica gel or phosphorus pentoxide or other suitable desiccant.
  • Storage:
    • Statements under the heading `Storage’ constitute non-mandatory advice. The substances and preparations of the Pharmacopoeia are to be stored under conditions that prevent contamination and, as far as possible, deterioration. Precautions that should be taken in relation to the effects of the atmosphere, moisture, heat and light are indicated, where appropriate, in the individual monographs.
    • Specific directions are given in some monographs with respect to the temperatures at which Pharmacopoeial articles should be stored, where it is considered that storage at a lower or higher temperature may produce undesirable results. The conditions are defined by the following terms.
    • Cold – Any temperature not exceeding 8<sup>o</sup>C and usually between 2<sup>o</sup>C and 8<sup>o</sup> A refrigerator is a cold place in which the temperature is maintained thermostatically between 2<sup>o</sup>C and 8<sup>o</sup>C.
    • Cool – Any temperature between 8<sup>o</sup>C and 25<sup>o</sup> An article for which storage in a cool place is directed may, alternately, be stored in a refrigerator, unless otherwise specified in the individual monograph.
    • Room temperature – The temperature prevailing in a working area.
    • Warm – Any temperature between 30<sup>o</sup>C and 40<sup>o</sup>
    • Excessive heat – Any temperature above 40<sup>o</sup>
    • Protection from freezing – Where, in addition to the risk of breaking of the container, freezing results in loss of strength or potency or in destructive alteration of the characteristics of an article the label on the container bears an appropriate instruction to protect from freezing.
    • Storage under non-specific conditions – Where no specific storage directions or limitations are given in the individual monograph, it is to be understood that the storage conditions include protection from moisture, freezing and excessive heat.
  • Labeling:
    • In general, the labeling of drugs and pharmaceuticals is governed by the Rules made under the Drugs and Cosmetics Act, 1940. The statements that are given in the monographs under the heading `Labeling’ are included as recommendations. Practical considerations where the individual container is too small, as in certain vaccines, to accommodate the information stated under `Labeling’ may demand alternative means of making the required information available to the user. Such matters as the exact form of wording to be used and whether a particular information should appear in the label on the immediate container or the primary label as well as, or alternatively, on the package/leaflet/insert are, in general, outside the scope of the Pharmacopoeia.
  • Expression of strengths:
    • The term `per cent’ or more usually the symbol `%’ is used with one of four different meanings in the expression of concentrations according to circumstances. In order that the meaning to be attached to the expression in each instance is clear, the following notation is used.
    • Per cent w/w (% w/w) (percentage weight in weight) expresses the number of grams of solute in 100 g of product.
    • Per cent w/v (% w/v) (percentage weight in volume) expresses the number of grams of solute in 100 ml of product.
    • Per cent v/v (% v/v) (percentage volume in volume) expresses the number of milliliters of solute in 100 ml of product.
    • Per cent v/w (% v/w) (percentage volume in weight) expresses the number of milliliters of solute in 100 g of product.
    • Usually, the strength of solutions of solids in liquids is expressed as percentage weight in volume, of liquids in liquids as percentage volume in volume and of gases in liquids as percentage weight in weight.
    • When the concentration of a solution is expressed as parts per million (ppm), it means weight in weight, unless otherwise specified.
    •     When the concentration of a solution is expressed as parts of dissolved substance in parts of solution, it means parts by weight (g) of a solid in parts by volume (ml) of the final solution; or parts by volume (ml) of a liquid in parts by volume (ml) of the final solution; or parts by weight (g) of a gas in parts by weight (g) of the final solution.
    • When the concentration of a solution is expressed in molarity designated by the symbol M preceded by a number, it denotes the number of moles of the stated solute contained in sufficient Purified Water (unless otherwise stated) to produce 1 liter of solution.
  • Solvents:
    • Where the name of the solvent is not stated, the term `solution’ implies a solution in water and the water used complies with the requirements of the monograph on Purified Water. The term `distilled water’ indicates Purified Water prepared by distillation.
  • Pressure Measurements & Temperature:
    • Pressure has been indicated in terms of kilo Pascals (kPa).
  •    Temperatures:
    •    Unless otherwise specified, all temperatures in this Pharmacopoeia are expressed in degrees Celsius (centigrade) and all measurements are made at 25<sup>o</sup>
  •     Indicators:
    •   Where the use of an indicator solution is specified in an assay or test, approximately 0.1 ml of the solution shall be added, unless otherwise directed.
  • Ignition to Constant Weight:
    •    The specification `ignite to constant weight’ means that the ignition shall be continued at 800^o ± 25^oC, unless otherwise indicated, until two consecutive weightings do not differ by more than 0.50 mg per g of substance taken, the second weighing following an additional 15-minute ignition period.
  •    Loss on drying and water:
    •    Where absorbed water or water of hydration is determined by drying under specified conditions, the test is generally given under the heading `Loss on drying’. It must, however, be understood that the loss in weight also represents residual volatile constituents including organic solvents as well as water.
    •    Where the determination is done by the titrimetric method, the test is generally given under the heading `Water’.
  • Negligible:
    • This term indicates a quantity not exceeding 0.50 mg.
  • Cautionary Statements:
    • A number of substances described in the monographs and some of the reagents specified for use in the tests and assays may be hazardous to health unless adequate precautions are taken. Attention is drawn to particular hazards in certain monographs and in statements pertaining to certain reagents by means of a italicised statements; the absence of such a statement should not be taken to mean that no hazard exists.
  •     Ultra-violet Lamp:
    • The viewing of thin-layer chromatograms is done with the aid of a source of ultra-violet light such as a mercury vapour in  quartz lamp.  A suitable filter may be fitted to eliminate the visible part  of  the spectrum  emitted by the lamp. Where  the  monograph prescribes  viewing under ultra-violet light of wavelength 254 nm or 365 nm, an instrument consisting of a mercury vapour lamp  and a filter which gives  an  emission band with  maximum intensity  at about  254 nm or 365 nm should be used. The lamp  should  be capable of  revealing  without  doubt  a  standard spot of sodium  salicylate with  diameter of about 5 mm on a chromatographic plate  coated with  silica  gel G. For this purpose the following test may  be carried out.
    • Apply to a  plate coated  with silica gel G, 5 µl of a  04%  w/v solution  of  sodium  salicylate in ethanol  (95%)  for  lamps  of maximum output at about 254 nm and 5 ul of a 0.2% w/v solution of sodium  salicylate in ethanol (95%) for lamps of maximum output at about  365nm.  Examine  the spot in a  position normal  to  the radiation. The  distance between the lamp and  the  plate  under `examination  used in a pharmacopoeial test should not exceed  the distance used to carry out the above test.
  • Thermometers :
    • Unless otherwise specified, thermometers suitable for pharmacopoeial tests conform to Indian Standard 4825:1968 and are standardised in accordance with the Indian Standard 6274:1971, Method   of   Calibrating   Liquid-in-Glass       The  thermometers  are  of   the mercury-in-glass type and the column above the liquid is filled with nitrogen.  They   may   be standardised for total immersion or for partial immersion. To the extent possible, each thermometer should be employed according to the condition of immersion under which it was standardized. In the selection of a thermometer, it is essential to consider the conditions under which it is to be used.
  • Sieves :
    • Sieves for pharmacopoeia testing are of wire cloth woven from brass, bronze, stainless steel or other suitable wire and are not coated or plated. The wires are of uniform circular cross- section. There must be no reaction between the material of the sieves and the substance being sifted.
  • Water for Pharmaceutical Use:
    • Water is one of the most widely and abundantly used substances in pharmaceutical  It is required for a variety of purposes ranging from manufacturing processes to the preparation of the final dosage forms. The quality of water therefore  assumes considerable importance. The control  of the  chemical  and microbiological  quality  of  water  for  pharmaceutical use  is governed  by  many  factors of which the most  important  is  the variability of the basic source viz. municipal water or any other water. The starting material for most forms of water is  drinking water which should normally be subject to municipal or any  other local  regulations  is drawn from a private  well  or  reservoir. Water prepared from  other starting material  may  have  to  be processed to meet drinking water standards. Drinking water itself may be used in the manufacture of drug substances but not in the preparation of dosage forms, or in the preparation  of  reagents and test solutions.
    • Standards have been given in this Pharmacopoeia for the  various types  of water to be used in the)manufacture  of  pharmaceutical articles.
  • Purified water:
    • This article  represents  water  rendered  suitable  for  pharmaceutical  use  by  processes  such as  distillation,  ion-exchange  treatment (deionization or demineralization), or reverse osmosis. It meets the specifications  for chemical purity and  it contains no added substances. However, the different methods of producing it present different potential for contamination. Purified Water produced by distillation is sterile, provided the production equipment is suitable and sterile. Water obtained by ion-exchange treatment or by reverse osmosis may contain micro- organisms and it will be necessary to monitor the bacterial quality of the water frequently, particularly with the use of the purifying systems following periods of shutdown of more than a few hours.
  • Water for Injection:
    • This article is water purified by distillation or by reverse osmosis and it meets the purity requirements stated under purified water. It is not intended to be sterile but should comply with the test for pyrogens or with  the  test  for a limit of bacterial endotoxins. It must be produced, stored and distributed under conditions designed to prevent production of pyrogens or endotoxins.

• Sterile Water for Injection :
  • This article is water for injection which is sterilised within 12 hours of collection and distributed in sterile  It  is intended  mainly  for use as a solvent for inject able preparations such as powders for injection that are distributed dry because of limited stability of their solutions. It should be packaged only in single dose containers of not larger than 1-litre size.
• Guidelines for Microbial Control in water for Pharmaceutical use:
  • The criteria for controlling the microbial quality of Purified water and water for Injection vary according to the method of production, distribution and/or storage and use. The purification systems used for production of water of acceptable microbiological quality should be validated prior to production for [which purpose suitable microbiological, chemical, and operating controls should be evolved.
  • A total  aerobic  microbial count  that may  be  used  for  source drinking  water  is  less than  500 colony -forming units (CFU) per  Since Purified  Water is used  in the manufacture  of  a  variety of products, the limit  for this article should be  based  on  the intended  use of the water, the nature of the product to be made and the effect of the manufacturing process on  the  microbial  population. As a general guideline, a limit of Not More than 100 CFU per ml may be adopted for Purified water.
  • If the afore-mentioned limits are approached or exceeded, corrective  action  is called for. The actions to  be taken may include sanitisation of the system by for example, flushing with hot water, steam, or suitable disinfecting agents. This should be followed by extensive sampling and testing to ensure that the corrective action has resulted in conformance to desired standards
• Annexure (S)

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•         Reference (S)

Indian Pharmacopoeia

• Glossary           

SOP                     :  Standard Operating Procedure

QC                       :  Quality Control

IUPAC                 :  International Union of Pure & Applied Chemistry.

CFU                    :  Colony forming Unit