Safety & Quality of Excipients – IPEC

Apart from regulatory legislations, the pharmaceutical excipient industry has long been taking their own steps to ensure the safety and quality of excipients. Back in 1991, the industry formed the International Pharmaceutical Excipients Council (IPEC), an industry group focusing on harmonizing compendia, GMP and GDP standards for pharmaceutical excipients internationally. Its publication of IPEC-PQG (The Pharmaceutical Quality Group) GMP Guide 2006 and IPEC GDP Guide 2006 have been recognized as industry standards and applied in excipient manufacturing and distribution voluntarily.

The latest IPEC-PQG GMP guide was published in 2017.

The latest IPEC GDP Guide was published in 2017.

In general excipients are not treated as drugs. Different directives and guidelines have been established over the years.

• 2011 Falsified Medicines Directive 2011/62/EU Qualification of excipient suppliers
• 2014 Revision of EU GMP Part 1 Chapter 5 Production – starting materials, 5.29 excipients
• 2015 Guidelines on the formalized risk assessment for ascertaining appropriate good manufacturing practice for excipients of medicinal products for human use – to have been implemented by 21st March 2016

Directive 2011/62/EU , article 46 (f) :

‘The holder of the manufacturing authorisation shall ensure that the excipients are suitable for use in medicinal products by ascertaining what the appropriate good manufacturing practice is. This shall be ascertained on the basis of a formalised risk assessment…’

Revised EU GMP Guidelines chapter 5, section 5.27:

‘The selection, qualification, approval and maintenance of suppliers….should be documented as part of the pharmaceutical quality system. The level of supervision should be proportionate to the

risks…..The supporting evidence for each supplier / material approval should be maintained.’

2015-03-19 Guidelines on the formalized risk assessment for ascertaining appropriate good manufacturing practice for excipients of medicinal products for human use ……to have been implemented by the Manufacturing Authorisation Holder (MAH) by 21st March 2016

• To determine the GMP required the MAH (the user) has to evaluate the risks posed
  • by the excipient in terms of the nature of the substance and
  • by the approved suppliers who provide that substance
• These suppliers can be the Manufacturer of the excipient or a Distributor

Excipients are Drugs …. 

• Federal Food, Drug and Cosmetic Act Section 501(a)(2)(B) Adulteration Provision“A drug shall be deemed adulterated – if… the methods used in, or the facilities or controls used for, its manufacture, processing, packing, or holding do not conform to or are not operated or administered in conformity with current good manufacturing practice to assure that such drug meets the requirements of this Act as to safety and has the identity and strength, and meets the quality and purity characteristics, which it purports or is represented to possess.”
• Subject to inspection under FDA (Section 704 (a)(1) of the Act) however, inspections will only be conducted by special assignment or for cause.