Harmonization—Pharmacopeial Discussion Group

Harmonization

USP participates in the Pharmacopeial Discussion Group (PDG) to work on pharmacopeial harmonization topics. Visit the links below to learn more about PDG and also see the pages listed on the left sidebar for information about current PDG activities.

The Pharmacopeial Discussion Group (PDG) was formed in 1989 with representatives from the European Directorate for the Quality of Medicines in the Council of Europe (the European Pharmacopoeia), the Ministry of Health and Welfare—now the Ministry of Health, Labor, and Welfare (MHLW) (the Japanese Pharmacopoeia), and the United States Pharmacopeial Convention, Inc., (the U.S. Pharmacopeia). In May 2001, PDG welcomed the World Health Organization as an observer. PDG generally meets twice a year and holds monthly status and technical teleconferences to advance harmonization work.

The purpose of PDG is to harmonize pharmacopeial standards (excipient monographs and selected general chapters) in three major regions of the world. Harmonization reduces manufacturers' burden of having to perform analytical procedures in different ways, using different acceptance criteria, in order to satisfy pharmacopeial requirements that vary across regions. At all times, PDG strives to maintain a consistent level of science across the three pharmacopoeias, with the shared goal of protecting the public health.  A pharmacopeial monograph for an active ingredient or excipient, preparation, or other substance used in the manufacture or compounding of a medicinal product generally provides a specification by way of a name, definition, description, tests, procedures, and acceptance criteria and sometimes packaging, labeling, and storage statements. For frequently cited procedures, or for broad-based guidance, a monograph may reference a general chapter.

Definition of Harmonization: PDG has defined harmonization of a pharmacopeial monograph or general chapter as follows:

“A pharmacopeial general chapter or other pharmacopeial document is harmonized when a pharmaceutical substance or product tested by the document's harmonized procedure yields the same results and the same accept/reject decision is reached.”
 

When using a fully harmonized pharmacopeial monograph or general chapter, an analyst will perform the same procedures and reach the same accept/reject decisions irrespective of which PDG pharmacopeia is referenced. This is called interchangeability, and each pharmacopeia will identify, in an appropriate manner, each fully harmonized monograph and general chapter.

When full harmonization of a pharmacopeial monograph or general chapter is not possible, the PDG uses an approach termed harmonization by attribute. In this approach, some elements of a monograph or general chapter are harmonized, but others are not. When a monograph is harmonized by attribute, interchangeability is achieved only with respect to the harmonized elements.  For nonharmonized attributes, compliance with the individual pharmacopeial requirements in each region is necessary.

Harmonization of pharmacopeial documents in PDG is based upon decisions of the expert bodies of each pharmacopeia, which are reached in accordance with the procedures followed by each pharmacopeia.  PDG works transparently in many ways, principally through the public notice and comment process of each pharmacopeia. The details are described below under PDG Working Procedures.

Implementation

The implementation of a harmonized document varies in the three PDG regions, depending upon their legal requirements, need for translation, and publication schedules. Each pharmacopeia generally allows some period of time after publication to implement official harmonized texts to allow manufacturers and other users to achieve conformity. Harmonization is not achieved until the text becomes official in all three pharmacopeias.

Revision of Harmonized Monographs

The PDG pharmacopeias have agreed not to revise unilaterally any harmonized document after publication. Should revisions be necessary for any appropriate reason, the initiating pharmacopeia notifies the PDG, and revision proceeds according to the PDG Working Procedures.

In November 2003, ICH Steering Committee established the Q4 Expert Working Group (EWG) to address 11 compendial general test chapters discussed during development of the ICH Q6A Guideline. The harmonization of these 11 chapters was deemed essential to obtain full utility of the ICH Q6A Guideline.

In November 2008, ICH SC expanded the scope of Q4B EWG to address five additional compendial general test chapters:

  • Analytical Sieving, Bulk and Tapped Density, Tablet Friability, Capillary Electrophoresis, Polyacrylamide Gel Electrophoresis.

PDG provided Q4B EWG with complete harmonization packages for these chapters including PDG-harmonized text, JP/Ph. Eur./USP draft version of how harmonized text will be implemented in their compendia, a briefing note highlighting any local differences or potential issues, and an anticipated timeline to move each pharmacopeia to official status. Q4B members brought the documents back to their constituents for independent evaluation and began the Q4B Annex Process to determine regulatory interchangeability.

In November 2010, Q4B EWG was disbanded by the ICH Steering Committee as it was concluded that essentially all chapters within its scope were completed. PDG will notify the ICH Secretariat of any future revisions to chapters previously assessed by ICH-Q4B.

Many USP staff members are involved in international harmonization through PDG. Currently, these include:

  • Catherine Sheehan, signatory and head of USP delegation to PDG, (cxs@usp.org)
  • Kevin Moore, scientific liaison to and primary contact to PDG, (ktm@usp.org)
  • Mario Sindaco, general coordination of PDG activities, (mys@usp.org)

In addition, the specific USP scientific liaison associated with each monograph or general chapter can be found on the General Chapters and Monographs pages.