Pharmaceutical products active ingredient

Medicinal products and bulk pharmaceutical chemicals are produced mainly in batch processes. Controlling these products and chemicals at the end of their manufacturing processes is not in line with the general principle of quality assurance, which is that quality should be built into the product. It is then necessary to ensure that appropriate good manufacturing practices are adhered to throughout the manufacture of both bulk pharmaceutical chemicals (active ingredients as well as excipients) and medicinal products. 

Many pharmaceutical compounds contain chromophores that make them suitable for analysis by UV/Vis absorption. Products that have been analyzed in this fashion include antibiotics, hormones, vitamins, and analgesics. One example of the use of UV absorption is in determining the purity of aspirin tablets, for which the active ingredient is acetylsalicylic acid. Salicylic acid, which is produced by the hydrolysis of acetylsalicylic acid, is an undesirable impurity in aspirin tablets, and should not be present at more than 0.01% w/w. Samples can be screened for unacceptable levels of salicylic acid by monitoring the absorbance at a wavelength of... 

Typical examples that fall in this group would be the determination of the active ingredients in analgesic tablets for pharmaceutical use, such as aspirin or codeine or the analysis of a food product such as margarine. Examples of both these analyses will be described to illustrate the sample preparation procedure. 

Similarly, low volume chemicals are classified according to whether they are sold primarily on the basis of specification or performance. Specialties are generally formulations that are sold on the basis of their performance and their prices reflect their value rather than cost of production. Producers of specialty chemicals often provide extensive technical service to their customers. Examples of specialty chemicals include pharmaceuticals, pesticides, flavours and fragrances, specialty polymers, etc. Fine chemicals, on the other hand, are produced to customer specifications and are often intermediates or active ingredients for specialty chemicals, e.g. pharmaceutical and agrochemical intermediates and bulk actives. 

Non-specific absolute assay methods, e.g. volumetric titration, can be applied to avoid the establishment of a reference substance. This is only appropriate, however, when the monograph describes a separation test for related substances. This approach is certainly valid for the determination of the content of pharmaceutical raw materials but less acceptable for the assay of content of pharmaceutical preparations where the employment of specific assay methods is recommended (ICH Guideline 1994) to take account of decomposition of the active ingredient during the shelf life of the product and to avoid possible interference from excipients. 

A pharmacopoeial reference substance is intended for the determination of the main component of a substance or for the active ingredient of a pharmaceutical formulation which is usually present at a high proportion of the total. The reference substance is to be used as a primary standard in a specific method validated as prescribed in the ICH Guideline Validation of Analytical Procedure Methodology" (Technical Guide for the Elaboration of Monographs 1996 ICH Guideline 1997). the reproducibility of which is known. This is taken into account when the limits of acceptance (tolerance) for the substance or product are fixed (Daas and Miller 1997,1998). 

Development pharmaceutics information is intended to cover a number of aspects related to the active ingredient(s), excipients, container-closure system, and the finished (drug) product. These aspects will be considered individually below. 

The development pharmaceutics section should also include consideration of possible overdosing of the active ingredient that might arise from normal use of the dosage form—e.g., deposition of drug substance from a metered dose inhalation product in the mouth. 

The development pharmaceutics section of the application should address the clinical need for a transdermal delivery system and the appropriateness of the active ingredient for this type of product based on... 

Additional guidance on the development pharmaceutics aspects of this type of product is included in document CPMP/QWP/604/96, adopted July 1999. This emphasizes the need for information on the rationale for the design of the product—e.g., therapeutic benefit, pharmacokinetics, and physical properties of the active ingredient. 

First, the pharmaceutical market failures mentioned above may be empirically inconsequential, which may either render their regulation unnecessary or make it advisable to use more flexible price control policies. For example, justifications for regulation that are based on the virtual absence of competition seem weak when one observes markets with products whose patent has expired. When a patent expires barriers to entry should disappear, since the composition of the active ingredient becomes public, and other companies should not have too many problems to reproduce the production process. The reasons brandished for price regulation when any company can manufacture a generic to compete with the brand product find no justification in theory. 

Method The authors use information on all non-hospital sales of pharmaceutical products in 1992 in a sample of countries consisting of the USA, Canada, Germany, France, Italy, Japan and the UK. The database was provided by Intercontinental Medical Systems (IMS). The empirical analysis is based on the calculation of the Paasche and Laspeyres price indexes and the ratio between them. The descriptive analysis is completed with the econometric analysis (quasi-hedonic model) of the determining factors of the variation in the relative prices of each active ingredient in each country taking the USA as the point of comparison. 

Fourth, we are interested in information on the various presentations of each product. The presentations differ in pharmaceutical form (tablets, capsules, injectables, creams and so on), the concentration of the therapeutic active ingredient (usually specified in milligrams) and the number of tablets, vials, or units in general, provided in each package. The Spanish data enable us to identify the number of units per package for all the observations. The... 

Table 4.3 Number of active ingredients, pharmaceutical products and pharmaceutical presentations...

There are three levels of equivalence for classifying products, each submitted to an identical maximum level of public financing chemical equivalence, pharmacological equivalence and therapeutic equivalence. The first level entails establishing groups for the same active ingredient, which at the same time include both generics and brand-name pharmaceuticals whose patent has expired. This is the system applied in Sweden, Denmark, Norway and Spain. It encompasses bio-equivalent products with identical qualitative or quantitative composition, pharmaceutical form, dose, administration method and presentation . 

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