Vetting of ICH Q3D Pre-Step 2 Impacts Final Draft; LVP and E&L Issues Could Warrant Further Public Comment

Large volume parenterals (LVPs) and extractables and leachables (E&Ls) from container closure systems were two issues on which the ICH Q3D Expert Working Group (EWG) requested input from stakeholders during the Step 2 drafting process without getting much feedback, and may warrant attention during the draft’s public comment phase that runs through December, EWG members are advising.

In general, the request that the EWG made for outside input (IPQ December 19, 2012) generated a plethora of comments that were used by the working group in refining earlier drafts.  Safety assessments and assessing and controlling risk were among the issues on which input was sought that drew a significant response from those canvassed.

The number of comments that came in substantiated the EWG’s decision to do more extensive vetting than usual before releasing a Step 2 draft for public comment in the three ICH regions in view of the controversial issues involved and the wide-ranging relevance of the guideline across product types, lifecycle phases, and ingredient supply chains.

NSF Health Sciences VP Janeen Skutnik-Wilkinson, who has played a key role with the EWG in the Q3D development process, commented at a PDA Pharmacopeial Interest Group session, held in conjunction with the PDA/FDA annual conference in mid-September in Washington, that the lack of comments regarding LVPs and E&Ls was concerning.

“After many years of working with ICH, when groups are silent, I get nervous” she commented.  “They are either not reading it or do not know how to go through the process of providing feedback.”  She encouraged industry to take a look at the LVP and E&L sections in particular during the public comment process and provide feedback to the EWG.

Heightening the concern regarding LVPs (generally defined as greater than 100 ml in dose) is the metals risk they pose due to their matrix, dose size and the leachables that can be contributed from the primary packaging, about which limited data may be available.  On the other hand, the EWG has been sensitive to the critical need LVPs serve in the hospital setting and does not want to impose standards that would unnecessarily limit patient access to life-saving medications.

Complicating the E&L assessments across different product types is that extractable information may be able to be obtained from suppliers while that on leachables tends to be product-specific.  The relationship to packaging providers in making assessments is also at issue.

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