“The quality management system should also include a procedure to verify that each supplier of APIs, packaging materials or services is able to consistently meet the previously agreed requirements,” explains APIC. The responsibilities of independent quality units within that system should also be defined in the form of a contract or agreement. While APIC warns that the guidelines “should not be considered technical standards,” the Committee says they should serve as a starting point for internal discussions. EU GMP Essential requirements for active substances used as raw materials – The EUMP for APIs provides GMP guidelines for the manufacture of active substances as part of an appropriate quality control system. Based on the WHO Good Trade and Distribution Practice for Pharmaceutical Starting Materials (GTDP) directive, which APIC considers “the only directive that deals with API GDP”, the APIC guidelines invite API manufacturers and distributors to set up a quality management system that defines specific procedures and principles for interacting with suppliers. The Committee also calls for the establishment of an independent quality unit to ensure quality assurance (QA) responsibilities, such as documentation and traceability of API distribution activities. In addition to the CPO document, APIC has also published guidelines on aspects of validation of the cleaning of API production facilities. “The ICH Q7 Good Manufacturing Practice Guidance for Active Pharmaceutical Ingredients aims to provide Good Manufacturing Practices (GMP) guidelines for the production of pharmaceutical substances (APIs) as part of an appropriate quality management system.” – FDA Guidance for Industry: Q7 Good Manufacturing Practice Guidance for Active Pharmaceutical Ingredients – Questions and Answers. WHO Technical Complements to modelling guidance for the storage and transport of time- and temperature-sensitive pharmaceuticals “In this guide, the term `new excipients` refers to all inactive ingredients intentionally added to therapeutic and diagnostic products, but 1) we consider that they are not intended to exert therapeutic effects in the proposed dosage, although they are intended to improve the distribution of the product. (for example.B. improved absorption or control of release of the drug substance); and (2) are not fully qualified by existing safety data with respect to the proposed level of exposure, duration of exposure or route of administration. Examples of excipients are fillers, extenders, diluents, solvents, emulsifiers, preservatives, flavors, absorption enhancers, delayed-release matrices, and dyes.
APIC – Manufacture of sterile active pharmaceutical ingredients – guidance 1999 The IPEC Excipient Information Package (EIP) : Template & User guide 2012 APIC – Guide for auditing Registered Starting Material manufacturers ICH Q11 Guideline: Development and Manufacture of Drug Substances (Chemical Entities and Biotechnological Entities/ Biological Entities) Questions and Answers The US FDA has not presented a formal regulatory definition of the term “excipient”. Nevertheless, non-clinical safety studies on excipients provide some general information: PIC/S Guide to Good Manufacturing Practice for Medicinal Products (PE 009-14) Part II Annex 1 – Contract between Auditor and the API Compliance Institute FDA Guidance for Industry: Non penicillin Beta-Lactam Drugs: A CGMP Framework for Preventing Cross-Contamination An active pharmaceutical ingredient is defined in ICH Q7 as “any substance or mixture of substances intended for the manufacture of a medicinal product and which: when used in the manufacture of a medicinal product, become an active substance in the medicinal product. . . .