Description is general in nature and is not a standard in itself. It communicates the appearance of an article that complies with monograph standards.

The identification test is defined in General Notices and Requirements, 5.40. It is included in a monograph as an aid to confirm that the article contains the labeled drug substance by providing a positive identification of the drug substance or substances in a drug product.

One method of confirming the identity is to compare the retention time of the sample with that obtained for the standard injections in a chromatographic assay procedure. Other methods often used to orthogonally confirm the identity of the active ingredient are: Thin-Layer Chromatographic Identification Test 201, Spectrophotometric Identification Tests 197, Nuclear Magnetic Resonance 761, Near-Infrared Spectroscopy 1119,1 and Raman Spectroscopy 1120,1 among others. The analytical procedure must be able to distinguish the active ingredient from all excipients that are present or from potential degradation products likely to be present. Care must also be taken to ensure that the chromatographic system separates the article from other closely related drug substances, impurities, and additives. Infrared and ultraviolet absorption also can be used for identification (see 197), if the procedure has been demonstrated to be selective for the drug substance via an appropriate validation or verification study. The results of the identification test must be compared to the results obtained from a similarly prepared, suitable reference standard.

The assay is a specific and stability-indicating test to determine the potency (content) of the drug product. When a nonspecific assay (e.g., titration) is justified, other supporting analytical procedures should ensure that any interfering species can be detected. In general the a priori acceptance of ±10% variation in limits of a quality attribute (e.g., assay) from the target label claim (100%) in most cases is intended to account for manufacturing variability and shelf-life stability and is primarily based on the notion that such variation in a quality attribute is less likely to have any noticeable adverse impact on the desired clinical outcome. Acceptance criteria of 95.0%–105.0% are used with justification (e.g., for drug products with narrow therapeutic index). Activity assays and absolute content assays also are acceptable when justified.

Process impurities, synthetic by-products, and other inorganic and organic impurities may be present in the drug substance and in the excipients used in the manufacture of the drug product. These impurities are limited by drug substance and excipient monographs. During product manufacture and over the shelf life of the product, degradation products can form. These can be a result of degradation of the drug substance or from interactions between the drug substance and excipient(s), among other factors. The procedures and acceptance criteria should specifically limit toxic materials. See specific requirements in the USP General Notices, 5.60 Impurities and Foreign Substances. [Note—For additional information, see Impurities in Drug Substances and Drug Products 1086.1 ]

The test and the specific method depend on the nature of the article. Special consideration should be given to dosage forms for which water content has been shown to be a potential quality attribute and to products where solvent is used in the manufacture of the drug product.

When the presence of moisture or other volatile material may become critical, analysts must determine the amount of unbound volatile solvents or volatile matter of any kind that is driven off by Loss on Drying 731 or another suitable technique (e.g., water activity). For substances that appear to contain water as the only volatile constituent, the procedure given in Water Determination 921 may be appropriate. For drug products, analysts also should consult Residual Solvents 467.

Disintegration is an essential attribute of oral solids, except for those intended to be chewed before being swallowed and for delayed- or extended-release products. This test measures the time it takes for the dosage unit to disintegrate in an aqueous medium and is described in detail in 701. For certain dosage forms, e.g., effervescent tablets, disintegrating tablets, soluble tablets, etc., the European Pharmacopoeia describes the disintegration test in great detail. The disintegration test for some of the dosage forms in this chapter is included for completeness. For detailed procedures, please refer to 701 or the European Pharmacopoeia. The disintegration test, if included, is used only as a quality control test and not as a product performance test and should conform with the specifications in the monograph. Only when disintegration has been correlated with dissolution of a dosage form can a disintegration test be used as a product performance test (ICH Guidance Q6A, available at www.ich.org). In all other instances, a dissolution test should be considered as a product performance test.

The test procedure is applicable to most compressed, uncoated tablets. Friability determines the ability of tablets to withstand mechanical stresses and their resistance to chipping and surface abrasion. [Note—For additional information, see Tablet Friability 1216.1 ]

Tablet breaking force measures the mechanical integrity of tablets, which is the force required to cause them to fail (i.e., break) in a specific plane. [Note—For additional information, see Tablet Breaking Force 1217.1 ]

Uniformity of dosage units must be demonstrated by either content uniformity or weight variation. Content uniformity is based on the assay of the individual content of drug substance(s) in a number of dosage units to determine whether the individual contents are sufficiently close to label claim. Weight variation can be used as an alternative to estimate content uniformity under certain conditions (see Uniformity of Dosage Units 905).

These dosage forms will be discussed in a future new chapter, Mucosal Drug Products—Product Quality Tests 4. They are listed here for informational purposes and completeness.

Chewable tablets are not required to comply with the disintegration test. Chewable tablets (intact) should undergo dissolution testing, as a product performance test (if cited in the monograph), because they might be swallowed without proper chewing by a patient. In general, the dissolution test conditions for chewable tablets should be the same as for nonchewable tablets of the same active ingredient or moiety.

These are tablets intended to be dispersed in water before administration, giving a homogeneous dispersion.

Dispersion fineness: Place 2 tablets in 100 mL of water, and stir until completely dispersed. A smooth dispersion that passes through a No. 25 sieve (710 µm) is obtained.

Dispersion fineness: Place 2 tablets in 100 mL of water, and stir until completely dispersed. A smooth dispersion that passes through a No. 25 sieve (710 µm) is obtained.

When the liquid formulation is packaged in a multiple-dose container, compliance with Deliverable Volume 698 is required.

If the liquid formulation contains a quantity of alcohol, Alcohol Determination 611 should be included. The limits may be an absolute concentration, in percentage, or relative to a labeled content.

Liquid oral products typically are aqueous formulations that are susceptible to pH changes from exposure to atmospheric CO2. The uptake of atmospheric CO2 and pH change of oral liquid products is only relevant to aqueous based products. Although it is less critical than in ophthalmic preparations, the pH of a liquid formulation can affect flavor and stability. The pH range as outlined in pH 791 is indicated in the monograph.

The presence of certain microorganisms in nonsterile preparations may have the potential to reduce or even inactivate the therapeutic activity of the product and has a potential to adversely affect the health of the patient. Some liquid oral products can be subject to extreme microbiological control, and others require none. The needed microbial specification for a given liquid oral product depends on its formulation and use and is indicated in the monograph.

[Note—For additional information, see Microbiological Examination of Nonsterile Products: Acceptance Criteria for Pharmaceutical Preparations and Substances for Pharmaceutical Use 1111.1 ]

Release testing should be performed. Shelf-life testing may be unnecessary where justified by development and stability data (ICH Guidance Q6A).

Where development and stability data show no significant evidence of extractables, elimination of this test may be proposed. Where data demonstrate the need and acceptance criteria for oral solutions—rubber stopper, cap liner, plastic bottle—data should be collected as early in the development process as possible (ICH Guidance Q6A).

Tests of “for Solution” formulations are conducted on a well-mixed solution of the drug product constituted as described in the labeling.

Tests of “for Suspension” formulations are conducted on a well-mixed suspension of the drug product constituted as described in the labeling. Product quality tests for suspensions should include a test of suspendability.

After dissolution or suspension, they comply with monograph requirements for the final dosage form. Volatile content (731 and 921) may be an additional quality test for powders and granules for reconstitution.

Water Determination 921, Method Ia: Lyophilized oral products comply with the test. The limits are approved as indicated in the specific monograph.