Identity, active substance

Bioavailahility studies are used to compare different formulations of the drug product, or different batches of the same formulation and, as discussed in Chapter 8, generic copies of a reference drug. Their comparative value is based on the premise that, if similar amounts of identical active substance are delivered to the site of action at similar rates, then a similar biological response can be expected, which leads to the conclusion that the two preparations are bioequivalent. 

The guideline on chiral active substances states that particular attention should be paid to identity and stereochemical purity. It states that specifications for a racemate should include a test to show that the substance is indeed a racemate and this is a position supported by the requirements of the European Pharmacopoeia for drug substance monographs [16]. 

Application of the analytical techniques discussed thus far focuses upon detection of proteinaceous impurities. A variety of additional tests are undertaken that focus upon the active substance itself. These tests aim to confirm that the presumed active substance observed by electrophoresis, HPLC, etc. is indeed the active substance, and that its primary sequence (and, to a lesser extent, higher orders of structure) conform to licensed product specification. Tests performed to verify the product identity include amino acid analysis, peptide mapping, N-terminal sequencing and spectrophotometric analyses. 

A truncated version of PTH (tradenames Forsteo and Forteo) has been approved for the treatment of osteoporosis in postmenopausal women. This 4 kDa polypeptide is identical in sequence to the N-terminal residues 1-34 of endogenous hPTH, it binds to the native PTH receptor and triggers the same effects. The product is produced in E. coli, purified and presented as a sterile solution containing 250 pg active substance per millilitre. 

Validation parameter Confirmation of the identity of pure substances Determination of identity of unknown substances Amount single pure substance Amount active substance Limit test (semi- quantitiative) Amount impurities/ degradation products (quantitative) Dissolution speed of substances Bioequivalence studies... 

A placebo is an inert substance or dosage form which is identical in appearance, flavor and odour to the active substance or dosage form. It is used as a active control in a bioassay or in a clinical study (IUPAC). 

Subsequent to the discovery that the flavonone fraction of lemons exerted a therapeutic effect on abnormal capillary permeability and fragility, controversies arose concerning the identity of the active substance and the nature of its role in the body. 

Fogging This test is a special case of test chamber examination-SVOCs such as plasticizers and flame retardants are precipitated inside the chamber on a cooled surface. The method had initially been developed for examining automotive parts in order to determine the portion of fogging-active substances. It can also be used for examining other products used indoors. The fogging value (in Xg), usually determined over a 14-day period, is a characteristic for the SVOC quantity which can be expected to condense on cold indoor surfaces. The fogging method is based on a convention. If results are to be compared, the studies must be carried out in an identical manner (Uhde et al., 2001 Wensing, Uhde and Salthammer, 2005). 

While chemical galvanic colls are formed by a combination of two different types of electrodes, by a combination of two identical half cells which differ only in concentration of the electromotively active substances, the so called concentration cells are obtained. In such colls the electrical energy is generated by the spontaneous transfer of the active substance from a higher to a lower potential level (e. g. by transfer from the more concentrated to the more diluted solution). 

The first part of a dossier contains basic information about the active substance and the applicant. Here are some examples name, structure, and route of synthesis of the substance must be described. The typical purity of the technical material and the identity isomers and impurities is determined by the analysis of five production batches to assess the reproducibility of the process and to help to identify fake products. In the next chapter the chemical and physical properties are described, determined according to official guidelines published by the OECD and other organizations. This applies to the active substance, all significant metabolites, and all formulated products. Some of the required studies are listed in Table 11.11. 

One of them, that which comes from crystals of the double salt hemi-hedral to the right, deviates to the right, and is identical with ordinary tartaric acid. The other deviates to the left, like the salt which furnishes it. The deviation of the plane of polarisation produced by these two adds is rigorously the same in absolute value. The right acid follows special laws in its deviation, which no other active substance had exhibited. The left add exhibits them, in the opposite sense, in the most faithful manner, leaving no suspidon of the slightest difference. 

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