Pharmacopeial methods

The ICH-EWG-Q produced two guidelines, Q6A and Q6B, dealing with specifications to support a new drug registration. Biotechnology-related specifications are treated by Q6B, and all others previously subject to EWG-Q guidelines are treated by Q6A. Pharmacopeial methods are intrinsic to these guidelines. 

All test containers should be incubated at temperatures specified by the pharmacopeial method for each test media for at least 14 days, regardless of whether filtration or direct inoculation test methodology is used. 

Direct quantification is carried out in situ rather than after spot elution. The simplest direct method involves visual comparison of sample zone size and/or intensity (color) variation according to concentration against reference standards developed on the same plate.f This qualitative/semiquantitative approach is specified in various pharmacopeias for the purity analysis of active raw materials and formulated products. These pharmacopeial methods are designed for analyses at several levels 1) simple detection of impurities as additional spots 2) detection and identification of impurities by comparison to the R( values distances of standards or 3) detection, identification, and estimation of amounts of impurities by comparing intensities between samples and standard dilutions of the same compounds. ... 

Pharmacopoeia (J) allow an individual laboratory, able to do the offieial method, to validate an alternative method of analysis. The latter is chosen usually for speed, convenience, or economy but also to incorporate an existing database when a new or revised pharmacopeial method is adopted. Under those provisions, a laboratory can validate a method from another pharmacopeia, thereby avoiding duplication of routine work. In all three cases, only the official method could be used in compliance or contest. One point of harmonization is to avoid even the more remote instances of duplicative testing, in addition to international product registration. 

The pharmacopeias have worked with the ICH process to facilitate the international environment of pharmaceutical research and product registration. On the other hand, the additional situation for compendia is that the standards that they have published now apply to all of the products already marketed. In that case, a company has testing history in their quality control (QC) departments. The QC departments are the most conservative elements within the pharmaceutical industry-an attribute necessary to their task. QC departments are reluctant to change methods when they feel that their products are properly represented by their current suite of tests. Thus, there is resultant tension between trying to develop harmonized standards that facilitates one area of activity in the world of pharmaceuticals and not disturbing a satisfactory market place. A vast amount of progress has been made in harmonization of pharmacopeial methods. 

In 1960, at the general assembly of the International Pharmaceutical Federation (FIP), the obsolescence of various national pharmacopeial methods for assaying pharmaceutical enzymes was demonstrated. An international commission on pharmaceutical enzymes was created to deal with this unsatisfactory situation and develop improved assay methods and guidelines for the preparation of pharmaceutical enzyme reference materials. The Center for Standards has a coordination function in organizing collaborative enzyme assays between academic, industrial, and national pharmaceutical control laboratories and in distributing FIP pharmaceutical enzyme standards. Since 1960, many FIP assay methods and standard preparations have been adopted by national and international pharmacopeias, such as the European Pharmacopoeia. The ultimate goal is to provide official, preferentially nonempirical, standardized assay methods by which comparison of commercially available pharmaceutical enzymes is made possible. The most desirable situation would be an international uniformity of enzyme standards and assay methods, which would allow physicians and clinicians to unambiguously compare the potencies of commercially available enzyme products. 

It should be stressed that the use of a general pharmacopeial method is not a reason not to validate the latter when analyzing a particular substance. The matrix effect, in particular, has to be investigated when using the static headspace mode of injection. 

The water used in pharmaceutical processes must conform to appropriate specifications detailed in the relevant pharmacopeias. In the past, pharmacopeial methods for the analysis of inorganic anions and cations utilized classical... 

E. palustre L., which contains the alkaloid palustrine, is also toxic to livestock. The German Pharmacopoeia requires examination of E. arvense for adulteration with other Equisetum species, especially E. palustre (frohne and pfander). a critical review of the German Pharmacopeial methods, along with... 

For pharmacopeial materials scientific data are not normally required in the application provided that the method of production is such that uncontrolled impurities will not be present in the material. Otherwise the impurities concerned should be declared and appropriate specifications and test methods put forward. 

J. Chayen, Cytochemical bioassay and its potential place in compendial definitions A method that offers sensitivity as well as specificity, in Hormone Drugs, U.S. Pharmacopeial Convention, Rockville, MD, 1982, pp. 48-58. 

United States Pharmacopoeia 27 (USP 27) National Formulary 22 (NF 22). United States Pharmacopeial Convention, Rockville. MD 2003 < 1225 > Validation of Compendial Methods 2662-2625. 

Volpe, A.D., Faustino, P.J., and Yu, L.X., Towards standardization of an in vitro method of drug absorption, Pharmacopeial Forum, 27, July-August, 2001. 

Articulating the three concepts for harmonization was particularly important. Prospective and retrospective clarify the distinction between work required to avoid conflict when establishing standards for pharmacopeial articles for which standards do not exist, or where few standards exist among the pharmacopeias, from work required to reconcile differences among well-established standards for articles that may have been in the pharmacopeias for considerable time. Prospective harmonization was inaugurated for biotechnology-derived products. Retrospective harmonization focused on pharmaceutical excipients and analytical tests and methods. Forward harmonization expresses a philosophy and environment for harmonization consistent with advances in pharmaceutical analysis. 

The sterility test is applicable for determining whether drug substances, preparations, or other pharmacopeial articles are sterile as defined by the compendial method. A satisfactory result only indicates that no contaminating microorganisms have been found in the sample examined rmder the conditions of the test. Therefore, the result is a function of the efficiency of the adopted sampling plan. Compendial references to sterility testing include USP 24 Chapter (71) Sterility Tests the Ph. Eur. 3rd ed.. Biological Tests 2.6.1, Sterility and the JP Xlll 45, Sterility Test. 

USP 24 Testing Chapters (51) Antimicrobial Effectiveness Testing, (61) Microbial Limit Tests and (71) Sterility Tests, United States Pharmacopeial Convention, Inc., Rockville, MD, 2000. USP 24 Informational Chapters (1116) Microbiological Evaluation of Clean Rooms and other Controlled Environments, (1111) Microbiological Attributes of Pharmaceutical Articles, (1151) Pharmaceutical Dosage Forms, (1225) Validation of Compendial Methods, and (1231) Water for Pharmaceutical Purposes, United States Pharmacopeial Convention, Inc., Rockville, MD, 2000. 

Pharmacopeial count limits for particulates in parenteral solutions is given in Table 39. The limit depends on the method used for the determination and also on the volume of the sample. Two different procedures for the determination are generally proposed light obscuration particle count test (LO) and microscopic particle count test (M), since neither is applicable to all kinds of samples. 

USP (1999), Validation of compendial methods, in The United States Pharmacopeia 24—National Formulary 19, General Chapter 1225 (Rockville, MD United States Pharmacopeial Convention, Inc.). 

General Chapter <1225> Validation of compendial methods. United States Pharmacopeia XXIII, National Formulary, XVIII. Rockville, MD U.S. Pharmacopeial Convention, pp. 1710-1612 (1995). 

As part of the international harmonization of test methods, a proposed change to the USP <905> content uniformity test has been made [12]. This test is more restrictive than the current USP test, especially as the batch mean deviates from target. It is also more restrictive for capsules, since both the tablets and capsules are required to meet the same requirements. A number of USP Pharmacopeial Forum articles have been written by the Pharmaceutical Manufacturers Association (PhRMA) statistics expert team discussing the proposal and their characteristics. An approved version of the proposal is eventually expected. In anticipation of this happening, appropriate modifications to the CuDAL approach have been determined to evaluate the newly proposed test. 

The most widely used chemical method is the antimony trichloride colorimetric method. The method is applicable to vitamins D2 and D3 for their analysis in pharmacopeial preparations. The reaction product of vitamin D3 with antimony trichloride is believed to be isovitamin D3 (46, See Scheme IV). Antimony trichloride reacts with vitamin A also. Vitamin A occurs along with D3 in many biological samples and is also an ingredient in many commercial products. Therefore, it is necessary to remove it and other interfering substances prior to reaction with... 

Comparison of three test methods for suppostories, Pharmacopeial Forum, 9/10 2427 (1991). 

United States Pharmacopeia 24, National Formulary 19, Section 1225 Vahdation of Compendial Methods United States Pharmacopeial Convention, Rockville, 2000. 

Two sets of standards are set for empty capsules, analytical and functional. Capsules, like all other pharmaceutical preparations, must comply with cGMP norms and must be made of materials that comply with pharmacopeial chemical and microbiological standards. However, these tests do not indicate whether a capsule will run well on a filling machine. Series of functional tests are applied by the manufacturers. The critical dimensions of a capsule (the lengths and diameters of the caps and bodies) are checked. It is a continuous production process, and there will be a very small proportion of visually defective capsules. Standard statistical sampling methods are used to estimate quality from samples. The manufacturers and users agree on acceptable quality levels (AQL). The faults are... 

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