Pharmaceutical Technology Europe - February 2012 - (Page 15)

Evaluating impurities in drugs Part I To ensure the quality of APIs and finished drug products, impurities must be monitored carefully during process development, optimisation, and process changeover. The authors discuss what constitutes an impurity and the potential sources of such impurities, such as vendor scheme, solvents, and reagents for key starting raw material(s). Definition and sources of impurities An impure substance may be defined as a substance of interest mixed or impregnated with an extraneous or usually inferior substance. The greatest financial impact on the cost of a drug substance often is found in the final preparation process. Product yield, physical characteristics, and chemical purity are important considerations in the manufacture of the active ingredient, the formulation of the dosage form, and the manufacture of the finished drug product. Processes to control the preparation of the drug substance and drug product must be disclosed to most regulatory authorties as part of a new drug application. Any material that can affect the purity of an API or finished drug product is considered an impurity. Impurities arise from various sources, which commonly include starting material(s), intermediates, penultimate intermediates, byproducts, transformation products, interaction products, related products, degradation products, and tautomers. Starting materials Impurity control in starting materials used to manufacture APIs has long been expected by regulatory agencies. An API starting material is a raw material, intermediate, or API that is used in the production of an API and that is incorporated as a significant structural element into the API. API starting materials normally have defined chemical properties and structure. Intermediates Organic compounds formed during the synthesis of APIs are termed as intermediates. The compound in the synthetic chain before the production of the final desired compound is called the penultimate intermediate. Byproducts In synthetic organic chemistry, getting a single end product, 100% pure, seldom occurs because of the change into byproducts, which can be formed through a variety of side reactions, such as incomplete reactions, overreactions, isomerisation, or unwanted reactions between starting materials, intermediates, chemical reagents, or catalysts. For example, in the bulk production of paracetamol, diacetylated paracetamol may form as a byproduct. The full article text highlights the origination and classification of impurities and provides a perspective on impurities in drug substances and drug products. The impurity profile of a drug substance is of increasing importance for ensuring the quality of drug products. Whatever the class of impurity, its identification and adequate control is a tremendous challenge for process-development chemists. No two drugs are alike, consequently, neither are the development pathways. Each drug candidate poses a different challenge in terms of impurities, and establishing efficient ways for the isolation and control of impurities is a key task in process development. Read the full text at PharmTech.com/impuritiespart1 Kashyap R Wadekar, Mitali Bhalme, S. Srinivasa Rao, K. Vigneshwar Reddy, L Sampath Kumar and E. Balasubrahmanyam 2 SPECIAL FEATURE 12 INTERVIEW 7 NEWS BITES 13 COLUMN CRUNCH 9 BLOG 15 PEER REVIEW 11 CLOUD COMPUTING 16 TOP TECH http://www.PharmTech.com/impuritiespart1

Table of Contents for the Digital Edition of Pharmaceutical Technology Europe - February 2012

Pharmaceutical Technology Europe - February 2012
Contents
Innovations, drivers and trends in self-injection technology
News Bites, twitter and poll
Blogs Abridged
Focus: Cloud computing
Interview: Nanomedicine advances
Column Crunch: Servier scandal, Biomanufacturing, and more
Evaluating drug impurities
Top Tech

Pharmaceutical Technology Europe - February 2012