Minutes

PQRI Drug Substance Working Group

3. Impurities - Breakout Session

Members: John Carrano (chair), Kenneth Sigvardson, Christianah Moji Adeyeye, Yafei Zhang, Henry Drew, Chung Chow Chan, Todd Cecil, Matthew C. Gosnell, Zi-Qiang Gu, Patrick Faustino, Kasturi Srinivasacha

The meeting began with Patrick Faustino (FDA) familiarizing everybody with the background of the working group as stated in the points below;

• Appropriate specifications for quality by FDA includes 0.1% limit on impurities (as it is in ICH, BACPAC 1 and II)

• FDA’s perspective on regulatory science versus science and current approaches used to make both relevant

• Room to develop better approaches by establishing and executing research projects with the goal of relieving regulatory burden and shortening time line for review of NDAs

The working hypothesis (listed below) was formulated after extensive discussion:

• Appropriate methods are available to quantitatively and qualitatively determine impurities

  • Impurities are defined as per ICH Q3A plus enantiomeric isomers and polymorphic species

  • Qualitative determination includes structural characterization where appropriate

• Should there be classification for methods based on drug impurities or classes of drugs/impurities (this was discussed but not formalized, and thus not included with the above hypothesis during the overall group report)

Questions asked:

Modification of the given questions was made and new ones were added as listed below:

1. What constitutes structural characterization?
2. How will the stages of development impact method development and structural characterization?
3. What are the criteria for developing appropriate methods for impurities?
4. What determines the applicability of different methods?
5. How do you ensure that impurities are reliably determined?
6. By what criteria is one analytical method judged to be sufficient?
7. When should a different method be developed?

Suggested critical regulatory research projects:

Some discussion was done, however it was decided that an in-depth discussion would be done during our first teleconference. Some projects were suggested as shown below:

1. The use of mixed resolution standards for confirming system suitability of HPLC impurity methods.

2. Impact of technology on impurity profile methods.

A teleconference meeting was tentatively scheduled for April. April 18, 19 and 20 were suggested as possible dates and the meeting was adjourned.

Report by Moji Adeyeye