Particulate Matter in Parenteral Products – Why So Much?

Last week while waiting for my flight home at an airport on the east coast, I decided to look at the recalls listed on the CDER web page.  I realize that I have read about a number of recalls of parenteral products recently and those recalls were for a number of different firms, but what caught my attention was that 12 of 25 recalls listed were for visible particulate matter (including glass particles).

While I am not a manufacturing expert by any stretch of the imagination, I started to wonder why this might be.  There have been many a drug shortage caused by shutdowns (temporary and permanent) of parenteral facilities due to failure to follow cGMP or issues due to aging equipment that have contributed to some of their problems.  Could this be the case here?  Are firms still putting off upgrades at their facilities due to regulatory challenges of gaining approvals for the new upgrades?  Well, one would think not for new drugs since they have a 6-month user fee clock for such supplements.  Could it be lack of FDA resources to conduct the required inspections?  That could be a problem especially now that FDA is gearing up to meet the GDUFA metrics which will drain a lot of the inspectional resources, but still there is a 6-month review clock on those NDA supplements, so I wonder if this is a real issue or one I am dreaming up.

Whatever the reason may be, and, unless I am reading the tea leaves totally wrong, something rather unusual is going on out there in the parenteral world.  Could it be the treatment of the vials, cleaning deficiencies, environmental factors, physical stability of formulations (QBD should help this), the source and control of materials and components, process, filtration technology, the need for improvements in manual/automated inspection, failure of quality systems or temperature stresses posed by longer supply chains?? I just don’t know!  But what I do know is that FDA is looking closely at these issues, but there has been no single common issue that has been identified that has been made public by the Agency.   The issue is indeed complex and FDA and the industry continue to work on this issue.  I don’t even know if there is a thread that links all of these recalls together, but it seems to me that a more holistic look at the seemingly epidemic number of recalls for the same problem might be in order and perhaps this has already been done.  I will discuss this issue with my colleagues in the Compliance Practice Area at Lachman Consultants further, but in the meantime, if anyone has any ideas or thoughts on this issue, please let me know at r.pollock@lachmanconsultants.com. I would be interested in hearing your views and would consider gathering your thoughts into another blog post – blinded of course to commenter and company!  Let’s see what thoughts are out there!