Active pharmaceutical ingredient purity

Fig. 17.16. Determination of the enantiomeric purity of an active pharmaceutical ingredient (main compound = MC). Conditions 30 mM sodium phosphate buffer, pH = 2.3, 10 mM trimethyl /i-cyclodextrin, 35 cm fused silica capillary (effective length 28.5cm) x 75 pm I.D., injection 10 s at 35mbar, 20°C, 20 kV (positive polarity) resulting in a current of approximately 65 pA, detection UV 215 nm.

The reasons behind the validation of cleaning procedures are the assurance of the safety and purity of the product (customer requirement), it is a regulatory requirement in active pharmaceutical ingredient product manufacture, and it assures the quality of the process from an internal control and comphance point of view... 

Complete Chemistry, Manufacturing, and Control (CMC) information provided, including evidence of purity, stability, toxicology testing, and integrity of active pharmaceutical ingredient (API), placebo, and final product. 

Conversion of cephalosporin C into 7-ACA of the purified aqueous extract to produce an aqueous solution followed by precipitation and isolation of 7-ACA of appropriate purity (c. 98%) for use in the preparation of advanced cephalosporin intermediates and/or active pharmaceutical ingredients. 

A more detailed discussion of the stationary phase types and mechanism of interaction and separation theory in relation to chiral compounds is given in Chapter 22. A large number of chiral stationary phases are currently available to meet the needs of the pharmaceutical industry for determination of the enantiomeric purity of active pharmaceutical ingredients, raw materials, and metabolites. As a consequence, there are a multitude of options in terms of columns, separation mode, and separation conditions to explore in achieving an enantioseparation. 

In the pharmaceutical industry, the issue of better control, desirable in itself, is reinforced by the need to assure the regulatory authorities that a continuing supply of active pharmaceutical ingredients (APIs) of high and reproducible quality and bioavailability can be delivered for formulation and finally to the patient. The product image (properties, purity, etc.) of this medicine must be the same as that used in the clinical testing carried out to prove the product s place in the therapeutic marketplace. Some additional comments on regulatory issues are included later in this chapter (Section 1.7). 

Since there are fundamental distinctions between the production of bulk active pharmaceutical ingredients and the formulation of finished pharmaceutical products, the strict application of GMP as set forth in the main part of this guide is not always practical or necessary. The present supplementary guidelines outline procedures and practices that manufacturers should employ to ensure that the methods, facilities, and controls used for the production of active pharmaceutical ingredients are operated or managed so that such products have the quality and purity appropriate for their use in finished pharmaceutical products. 

Each batch of finished active pharmaceutical ingredient must meet established specifications for quality, purity, identity, and potency, including, where applicable, specifications for tests and limits for residues of solvents and other reactants. 

Quality control Measures designed to ensure the output of batches of active pharmaceutical ingredients conforming to established specifications of identity, strength, purity and other characteristics. 

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