PQRI Working Group 2: Physical Attributes (beginning with PSA methods)

1. What are the origins of variations in results?

   1. Instruments in use

      • Laser diffraction in slurry mode & dry powder mode was the majority technique around the team
      • Near-IR (?!)
      • ESEM & LM assisted by IA
      • Aerosizer
      • Standard sieve analysis was also recognized although (slipping from view)
      • light obscuration
      • photon correlation spectroscopy for nanoparticles

   2. What instrument approaches?

      • Rank order changing between a lot-series when cf. between techniques

        Example: Given lots A, B, C, D & Instruments 1 & 2
        Results 1: A>B>C>D where 2:C>A>D>B

2. Group issues raised

   1. What is truth?

      For example, does it matter if the absolute PS is determined, or is a trend more important?

      • Specifications?

        • End-use of information

        • What is the meaning of the PSA data?

        • How to set these?

        • PSA-Correlation to IV/IVC

        • Acceptance criteria

      • Context of result

   2. The working group has no generic drug co. represented

   3. What constitutes a suitable data set?

   4. Where will the output of this committee go?

      Eric Duffy (FDA) will discuss this with FDA management in reference to specifications workshop

      • FDA wants a regulatory tool to add to BACPAC II

        • Consider a number of batches

          • What purpose were these batches used for?

            • Clinical: regulatory spec.

            • Manufacturing: in-process spec

      • Qualifying a change in PSA method

   5. Why is PS information important?

      • Where is it important?

        • Stability

        • Injections

          Example: must pass needle

        • Suspensions

        • Dissolution rate control lot-lot

        • Dry powder inhalation

          PSD needs to be controlled enough to get consistent deep lung penetration

        • Powder flow

        • Explosion hazard

      • Where is it NOT important?

   6. Inform practice of PSA based on range distribution Crystallization-controlled

      • Milled
      • "Uncontrolled"
      • Micronized
      • Nanoparticles (>1uM)

3. Housekeeping

   1. List of Group Members

      Frank Etzler, (Boehringer Ingleheim) -- chair (email needs correction to rdg)

   2. Meeting frequency

   3. Means

   4. PQRI literature sources

   5. Literature mentioned at table

      • ISO 13320-1 on Laser diffraction-based PSA (international standard)
      • SUPAC Instrument Addendum is available form FDA
      • Terry Allen's textbook

   6. Assignments: for next meeting

      Each member will...
      • Submit list of in-house instruments; be sure to include software, brands, modes used etc.
      • come with a plan for specific courses of action (action items)

   7. Next meeting dates

      • Informational workshop

        Purpose is for committee to be informed about PSA techniques (TSI, PSS, Malvern, others)
        • How do methods compare?
        • Can methods be standardized?

      • 4/27 teleconf.