API – Impurity Profile Generation
- Published on: Oct 27, 2017
I.INTRODUCTION
This SOP addresses those impurities in drug substances classified as degradation products of the active ingredient, impurities present in the drug substance as part of the manufacturing/storage process or reaction of the drug substance with an immediate container/closure system.
II.DEFINITIONS
A. Foreign substances: Materials introduced by contamination or cross contamination and are not consequences of the preparation of the drug substance.
B. Residual Solvents: Organic volatile chemicals that are used or produced in the manufacturing process. The solvents are not completely removed by practical manufacturing methods. Drug products should contain no higher a level of residual solvents than can be supported by safety data. For a classification of residual solvents, refer to the current USP <467>.
C. Toxic Impurities: Impurities that have significant undesirable activity. These require individual identification and quantitation by specific tests.
D. Concomitant Components: These are characteristic of many drug substances. Examples may include, but are not limited to, geometric and optical isomers or racemates.
E. Signal Impurities: Impurities that require individual identification and quantitation by specific tests. Signal impurities may include some process related impurities or degradation products that provide key information about the process.
F. Ordinary Impurities: Impurities that are innocuous by virtue of having no significant, undesirable activity in the amounts present. These impurities may arise out of the synthesis, preparation or degradation of the drug substance. For further information, refer to the current USP <466>.
G. Related Substances: These impurities may be identified or unidentified degradation products or impurities arising from the manufacturing process.
H. Degradation Study: A means of degrading a drug substance via several routes, usually involving acids, temperature, light, etc., in order to evaluate the routes and base of impurities. This information is used to generate the impurity profile of the product.
III.PROCEDURE
A. A protocol will be developed outlining the process for compiling an impurity profile for the drug substance. Included in the protocol will be the following information, at a minimum:
- a. Process description
- b. Drug Substance name
- c. Finished substance or compendia specifications
- d. Methodology for testing
- e. Process for degradation
- f. Any limits for identification
- a. Oxidation
- b. Hydrolysis
- c. Racemization
- d. Photo-chemical reactions
- e. Denaturation
- f. Temperature
- g. Humidity
-
- a. The toxicology of the drug substance containing typical levels of impurities
- b. The toxicology of the impurities relative to the drug substance
- c. The route of administration
- d. The daily dose of the drug substance
- e. The target population
- f. The pharmacology of an impurity, if appropriate
- g. The source of the drug substance
- h. Duration of administration
- i. Capability of removal
Author: Kazi Hasan
Kazi is a seasoned pharmaceutical industry professional with over 20 years of experience specializing in production operations, quality management, and process validation.
Kazi has worked with several global pharmaceutical companies to streamline production processes, ensure product quality, and validate operations complying with international regulatory standards and best practices.
Kazi holds several pharmaceutical industry certifications including post-graduate degrees in Engineering Management and Business Administration.
Related Posts
You may like to read these related posts.
Six steps procedure for corrective and preventive action
Calibration Practices of a GMP Site
Change control management – how to implement in 06 steps?