Regulatory Open Forum

Lisa,

Prior to June 2014 stability was only required for AC and RT conditions, however, for a liquid it was also required for upright and horizontal (or inverted) orientation. The post approval stability protocol that should have been submitted would have only listed the worst case (most likely inverted). As for the RTR, yes, FDA can reject your application each time it's submitted. Keep in mind a different reviewer may review your application upon receipt for filing.

Yes, in my experience, upright and inverted/horizontal have always been required for all three storage conditions.

Has anyone experienced screening comments from FDA regarding a lack of upright and horizontal data for a syringe product?

The ANDA Stability Q&A and ANDA Checklist both seem to suggest they're required. But the scientific rationale for requiring them is lost on me. The solution contacts all components of the syringe irrespective of orientation. And how does one determine whether needle up or needle down is upright for a syringe?

Thanks,

Duncan

Duncan,

Does the product get stored in the upright condition (meaning in a holder)? How is the product sold. None the less upright and horizontal would be needed. You would present your comments explaining why only one orientation post approval is needed.

John

Hi John,

Syringes are typically stored in plastic trays within cartons. The orientation of the tray during storage is largely up to the customer.

Prior to the ANDA Stability Guidance Q&A, and the addition to the ANDA checklist of the requirement for upright and horizontal storage we were typically only providing horizontal data for syringes in the ANDA. FDA didn't seem to have any issue with that approach.

Since the Q&A, and update to the checklist, it seems FDA are looking for both orientations. The low risk approach would be to fall in line with the Q&A, but there's a significant resource implication to adding an additional orientation to the stability program.

I think my bigger question is do FDA really expect both orientations for syringes and why?

The drug product completely fills a syringe and therefore contacts all packaging materials at all times irrespective of orientation. So the additional information that will be obtained as a result of studies in multiple orientations is questionable. A scientific justification for why multiple orientations is unnecessary seems feasible, but FDA may not accept that approach.

If FDA are looking for both orientations do they consider needle up or needle down to be vertical. Or are FDA looking for 3 orientations for syringes: horizontal, needle up and needle down.

Best regards,

Duncan