07.08.2013 |

LOGFILE No. 11/2012 - GDPs for Excipients

USP and IPEC-Europe Weigh in on GDPs for Excipients

An article by IPQ Publications

USP and the European branch of the International Pharmaceutical Excipients Council (IPEC-Europe) have both released guidance for pharmaceutical companies on the evaluation and handling of excipient distribution.

USP published for comment in “Pharmacopeial Forum,” PF 37 (6), available on its website, a draft of a general chapter <1197> that has been developed on “good distribution practices for bulk pharmaceutical excipients” (link provided below). Comments were due by January 31.

Formed at the request of USP’s Excipients Expert Committee, the <1197> Expert Panel that developed the draft proposal was global in makeup with volunteers from the United States, China, Germany, and Jordan.

Excipients are used in virtually all drug products and are essential to product performance and quality. Typically, excipients are manufactured and supplied to comply with compendial standards.

The quality of pharmaceutical excipients can be affected by the lack of adequate control of activities including distribution, packaging, repackaging, labeling, and storage. “Improper or inadequately controlled trading practices,” USP cautions, “can pose a significant risk to the quality of pharmaceutical excipients and can increase the risk of contamination, cross-contamination, adulteration, mix-ups, degradation, or changes in physical or chemical properties.”

In the introduction to the draft, USP notes that the “proposed general information chapter provides key information to help assure excipient quality and help prevent economically motivated adulteration.”

The chapter outlines “key strategies necessary in the qualification of starting material of good quality, the maintenance of that quality throughout the distribution chain and the confirmation of the quality by the users of starting materials.”

The 56-page draft includes sections covering:

  • introduction and scope
  • quality, organization and documentation
  • premises, storage, repackaging and stability
  • returned goods, dispatch, transport, importation, adulteration and traceability, and
  • excipients used in pharmacy compounding.

An appendix is attached providing related definitions/acronyms.

USP Draft Sections

In the introduction and scope section, the draft stresses that “to maintain the original and intended quality” all activities should be carried out according to appropriate standards for good trade and distribution practices as outlined in the draft guide.

The importance of a quality management system (QMS) is emphasized in the quality, organization and documentation section.  It states that “a documented quality policy is the cornerstone of the QMS and formally describes the company's overall philosophy with regard to quality as authorized by top or senior management.”

Other important elements of a QMS, the draft notes, include:

  • an organizational structure capable of supporting the elements of the quality policy (QA)
  • documented procedures and relevant records that demonstrate that a product will meet established quality criteria
  • established procedures for approving suppliers of starting materials and verifying that they continue to meet agreed-upon requirements, and
  • a material-release testing procedure to confirm the quality of excipients for their intended purpose(s).

Regarding premises and packaging operations, the guide recommends that organizations should establish operating procedures for the use of buildings and facilities and should consider protective measures to ensure the security of the grounds (e.g., fencing or perimeter walls).  Also important are suitable equipment and procedures that minimize the potential for cross-contamination and mix-ups.

Returns of goods by users to suppliers should be reviewed on a case-by-case basis and the distributor should facilitate a root cause analysis and investigation of complaints, the fourth section of the draft recommends.  Measures should be taken to ensure that the integrity of the Pharmaceutical excipient is maintained by the appropriate storage and transport conditions as described in product labeling. Also discussed in the section are:

  • tamper-evident seals
  • damaged materials
  • where ownership begins, and
  • adulteration and economically motivated adulteration.

The section on excipients used in pharmacy compounding notes that in certain instances USP-NF handles compounded preparations differently than commercially manufactured lots – for example, expiration dates are assigned to commercially manufactured products and beyond-use dates are assigned to compounded preparations.

The draft advises that State Boards of Pharmacy regulate pharmacy compounding, and points to other USP chapters for guidance on compounding: Pharmaceutical Compounding – Nonsterile Preparations <795>, Pharmaceutical Compounding – Sterile Preparations <797>, and Quality Assurance in Pharmaceutical Compounding <1163>.

<1197> is USPs latest foray into the world of good distribution practices (GDPs).

Last fall, the standard-setting organization released for comment a wholesale revision of its chapter <1079> on “good storage and distribution practices for drug products.”  The World Health Organization (WHO) and PDA have also made substantial contributions recently to the international GDP guidance canon.  (See IPQ “In the News” September 27, 2011 for an analysis of the USP <1079>, WHO and PDA efforts.)

IPEC Europe Releases Revised GDP Audit Guideline

Meanwhile, IPEC Europe has released a new version of its audit guideline for pharmaceutical excipients, replacing its 2008 excipient auditing guideline.

The document is again designed in a questionnaire format to assist in evaluating the practices and quality systems of distributors who sell, store or repackage pharmaceutical excipients or any combination thereof. It is intended to be used as an audit tool in the evaluation of excipient distributors’ GDP compliance, in accord with the principles provided in IPEC’s GDP guideline for pharmaceutical excipients (2006).

For the purpose of these guidelines, “distributors” is a term which includes those parties involved in trade and distribution, (re)processors, (re)packagers, transport and warehousing companies, forwarding agents, brokers, traders, and suppliers other than the original manufacturer.

“Due to the fact that distributors and traders became an important group of excipient suppliers carrying out various GxP relevant processes in the supply chain, the guide tries to cover these specific processes,” said Frank Milek, chair of IPEC Europe's GDP Committee, in a press release.  “It therefore can be seen as a combination of good storage, good transportation, and good manufacturing practices tailor-made for parties in the supply chain of pharmaceutical excipients.”

A comparison with the 2008 version shows that all the questions in that version have been carried through to the 2011 revision, and the following questions have been added in the relevant sections:

  • Quality management: Are the good trade and distribution practices (GTDP) and hazard analysis and critical control point (HACCP) principles part of the quality system?
  • Premises: Are appropriate laboratory facilities available?  Do sampling processes ensure sufficient protection of product quality?
  • Equipment: Is controlled testing equipment available?
  • Repackaging and relabeling: Is mixing of lots from different manufacturers avoided?  Are written testing procedures in place for all tests carried out?  Are all test data recorded and archived in a traceable way?


<1197> draft (in USP PF 37 (6); access is free, password required)

IPEC-Europe GDP audit guideline

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EC Publishes Concept Paper on Safety Features to Support Falsified Medicines Legislation

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Ireland’s IMB Publishes Drug Transport and Storage Guide

New EU Draft Guideline Clarifies, Broadens and Deepens Expectations for GDPs

Multifaceted Falsified Medicines Directive Cleared in Europe; Implementation Will Pose Challenges for Industry and Regulators



This is an article from IPQ Publications. More Information about IPQ: www.ipqpubs.com