Medical Device Link.

Originally Published PMPN September 2004

Regulatory Focus

The Pharmacopeial Discussion Group (PDG) has agreed to the final harmonization of several general chapters. The group made the announcement at its Washington, DC, meeting in June. 

The general chapters include “Extractable Volume of Parenterals” and “Particulate Matter in Injectables.” Both were recently revised and harmonized by the three pharmacopoeias: The United States Pharmacopeia (USP), the Japanese Pharmacopoeia (JP), and the European Pharmacopoeia (EP). The chapters were also cited in the International Conference on Harmonization (ICH) Q6A guidelines. 

“These two chapters are very important,” says Eric B. Sheinin, PhD, vice president for standards development at USP. “By harmonizing them, we have eliminated the need for triplicate development and testing.” 

Sheinin says the ICH Q4B Expert Working Group (EWG) is about to evaluate the chapter on extractable volume for regulatory interchangeability. The EWG includes regulatory and industry representatives, and is in charge of interchangeability evaluation under the guidance of the ICH Steering Committee.

A number of revisions have been made to both the extractable-volume and particulate-matter chapters. “We revised the extractable-volume chapter to allow for a flexible approach when using a small-volume article of 1 ml or 2 ml,” says Sheinin. “We made it clearer how to handle those. It was important to more specifically define large-volume versus small-volume parenterals.”

Regarding the particulate-matter chapter, Sheinin says the PDG revised the text slightly. “We changed some things regarding calibration of particles of a certain size,” he says. “The main thing is the harmonization. Companies were often in the dark about what to do in terms of calibration and volume, among other things.”

Indeed, ICH wrote in a 1999 guidance that “there is little international guidance on how to set such specifications with a result that regulators and manufacturers often find themselves setting or agreeing to conflicting standards for the same product, as part of the registration in different regions. This leads to increased expenses and opportunities for error, as well as a potential cause for interruption of product supply. Work is therefore underway to provide harmonized guidance in this area. The topic is divided into two parts: Chemical Substances (Q6A) and Biotechnological/Biological Substances (Q6B).”

In addition to extractable volume and particulate matter, the PDG harmonized chapters cover dissolution and disintegration. Those chapters will provide procedures acceptable for evaluating dosage form performance. The PDG hopes that will simplify development and product testing. 

A pharmacopoeia general chapter is harmonized when a substance or preparation tested by the harmonized procedure yields the same result and the same accept/reject decision is reached. The result is a basis for regulatory interchangeability.

That harmonization is a seven-stage process. It includes identification, investigation, proposal for expert committee review, public inquiry, provisional consensus, signoff, and regional adoption and implementation. 

The ICH Steering Committee considers the harmonization of about 10 compendial test chapters to be critical in attaining full utility of the ICH Q6A guideline. These chapters are at various stages of harmonization among the three pharmacopeial organizations. The PDG will meet again this November in Yokohama, Japan. 

Copyright ©2004 Pharmaceutical & Medical Packaging News