Pharmaceutical Technology Europe - April 2012 - (Page 17)

PEER REVIEW Evaluating impurities in drugs — Part III The term impurity reflects unwanted chemicals that are present in APIs or that develop during formulation or upon aging of the API in the formulated drug product. Several guidelines from the International Conference on Harmonization (ICH) address impurities in new drug substances, drug products and residual solvents. As per the ICH guidelines on impurities in new drug products impurities present below a 0.1% level do not need to be qualified unless the potential impurities are expected to be unusually potent or toxic. In all other cases, impurities should be qualified. I Metabolite impurities Metabolite impurities are byproducts formed in the body after a drug substance is ingested. During metabolism, the API and drug product in the body are exposed to various enzymes, from which metabolite impurities can be formed. Drug metabolism is traditionally divided into two phases: metabolic (i.e., hepatic) clearance, and the Phase I and Phase II process. The division is based on the observation that a drug substance first undergoes oxidative attack (e.g., benzene to phenol), and the newly introduced hydroxyl function will undergo glucouronidation (e.g., phenol to phenyl glucouronic acid). Some metabolites are formed as impurities during the development of a process. Control of these process- related metabolite impurities in the final API may not be necessary if control of other metabolites has already occurred and taken into consideration. Tightening the limits, therefore, may not be needed. methods, separation methods such as thin-layer chromatography, gas chromatography, HPLC, capillary electrophoresis and supercritical fluid chromatography, among others. Select analytical methodologies A new drug requires reliable analytical data to be generated at various steps of development. The drug also should exhibit excellent stability throughout shelflife. To meet these requirements, methodologies need to be developed that are sensitive enough to measure low levels of impurities. This has led to analytical methods that are suitable for determining trace and ultra-trace levels quantities of various chemical entities. Various methods are available including spectroscopic Read the full text at: PharmTech.com/impuritiespart3 This article is part of a 3-part series. Read the previous articles at: PharmTech.com/impuritiespart1 PharmTech.com/impuritiespart2 Degradation-related impurities Degradation products are compounds produced by decomposition of the material of interest or active ingredient. Several impurities may result because of API degradation or other interaction on storage, so stability studies need to be conducted to ensure drug product safety. Kashyap R. Wadekar, Ponnaiah Ravi, Mitali Bhalme, S. Srinivasa Rao, K. Vigneshwar Reddy, L Sampath Kumar and E. Balasubrahmanyam 2 SPECIAL FEATURE 14 MAGNETIC VECTORING 3 LYOPHILISATION EXPERTS 15 COLUMNS 12 BLOGS 17 DRUG IMPURITIES 14 MAGNETIC VECTORING 18 TOP TECH http://www.PharmTech.com/impuritiespart3 http://www.PharmTech.com/impuritiespart1 http://www.PharmTech.com/impuritiespart2

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

Pharmaceutical Technology Europe - April 2012
Contents
Thoughts and challenges connected to design space and Quality by Design for lyophilisation processes
News Bites
Blogs Abridged
Interview: Achieving localised delivery with magnetic vectoring
Column Crunch: Greek healthcare system, outsourcing, packaging and excipient portfolios
Evaluating drug impurities
Top Tech

Pharmaceutical Technology Europe - April 2012