The Enterey Blog

Agency Inspections Are on the Rise

Posted by Tita Tavares on Thu, Jan 19, 2012 @ 11:44 AM

Inspections by the FDA and foreign regulatory agencies have significantly increased since 2003 as manufacturing becomes more global and other countries regulate drug products. Between 2003 and 2005, the number of foreign inspections performed by the FDA ranged between 218 and 252. By 2007, that number had increased to over 450 per year and by 2009, it was up to nearly 550, dropping to 522 in 2010. In 2008, joint inspections began between regulatory agencies. That process continues today:

 Enterey Agency Inspection Rise

With the current leadership at the FDA stressing enforcement (as opposed to repeated warnings) for any violations or irregularities, 2010 saw the following actions:

  • 10 seizures
    (5 CFSAN, 3 CDER and 2 CDRH)

  • 17 injunctions
    (the highest rate since 2006)

  • 673 warning letters
    (171 CDER, 204 CDRH, 15 CBER & 191 CFSAN ).  This was the highest rate in warning letters since 2004.

  • 3,799 recall events
    (1,881 CBER, 258 CDER, 876 CDRH & 738 CFSAN) resulting in 868 different drug products being recalled from the market.

As demonstrated by the data collected by EFPIA, Agency inspections in Europe hit their high point in 2009, then began to level out somewhat. We believe this leveling is due to the major, worldwide regulatory agencies reaching their inspectional resources limits.  The FDA is still conducting the most inspections in Europe followed by the EU, then Brazil, South Korea, Japan and Mexico.  Of concern to us is the ever-growing number of inspectorates conducting “foreign” inspections.  And while China is not represented in the 2010 data, they are anticipated to become a major inspectorate in coming years.


As more and more countries begin implementing GMPs as a requirement for import, inspections of facilities in the US may continue to increase. However, Regulatory Agencies are also realizing that the number of manufacturing sites is growing faster, worldwide, than their resources available to perform inspections. We hope the number of inspections being performed will remain close to current levels.

Several factors make us think this will be true. For example, having the US FDA and other global inspectorates gain entrance to PIC/S will hopefully allow for better information-sharing between agencies, including inspection reports and resource sharing by inspectorates through joint inspections, one example being the recent EMA and FDA joint inspections which should reduce the number of on-site visits by Health Authorities.


At Enterey, in partnership with Mark Tucker, LLC, we can help you meet all your inspection management systems needs. This includes a system to help you self-identify and fully understand your compliance gaps; prioritize work and allocate resources to close those gaps; track gaps, actions taken and assess residual risk; fulfill the compliance requirements of ICH Q10; maintain an inspection-ready posture at all times; and respond to Agency findings systemically and quickly.


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Published by Mark Tucker | Partner of Enterey

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5 Qualities of a Great Project Manager

Tags: Enterey, FDA, Inspection Management, Mark Tucker, ICH Q10, Drug Manufacturers, EU

4 Rules to Facility Start-up. Looking Deeper Into Rule #2

Posted by Tita Tavares on Fri, Jul 01, 2011 @ 02:09 PM

Rule #2: Keep your air in balance

Keep your air in balance” – This rule is part metaphor, part tactical; we’ll start with tactical.

Tactically, air balancing activities are critical to any GMP facility build out.  In fact, you cannot obtain clean room classification by any standard (FDA, EU, or ISO) without performing air balancing.  Room to room pressure cascades, room air changes, particle counts, etc. are all critical to the different clean room classifications and air balancing allows you to prove that your air handling units are capable of maintaining the room classification designation (for more detail on comparisons of the different room classifications, visit: ). 

In order to have a succesful “right first time” air balancing, multiple building systems need to be fully operational and qualified (AHUs, clean utilities, building management system, etc.) and all equipment should be in place.  This means that air balancing should be one of the final activities in a start up schedule.  In fact, I would recommend that air balancing occur just before static and dynamic room PQs for two reasons.

  1. This will ensure all construction activities are complete so that there isn’t an open cavity into wall space that should not be there, that makes air balancing all but impossible (I’ve seen it happen).
  2. Once a room is qualified personnel must be gowned according to the room classification.  This not only requires that you train all personnel entering the room but it also significantly reduces productivity of equipment qualification.  Put simply, gowning slows people down and the room classification may limit the number of personnel that can be in the room at any one time.

Given the two reasons above, it’s best to leave air balancing as one of the final activities that is completed for facility start-up schedule, despite the temptation to do it earlier.  If you follow this rule it will also go a long way to helping you build your start-up schedule.  In short, target when your air balancing work will occur and build backwards from there for the building systems and equipment qualification activities, and build forward from there for all room qualification activities.

Facility Start Up Air In Balance

Metaphorically, “keep your air in balance” is relatively straight forward; air balancing requires just that – balance; and so should your start-up team.  There should be a balance between start-up functions and priorities; meeting schedule deadlines should be important but never “at all costs,” similarly regulatory compliance is of the utmost importance but a risk based approach to decision making should always be employed.  Keeping things in balance at all times will go a long way towards allowing a smooth facility start-up.

Published by: Carlo Odicino, Enterey | Director, Client Services

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Facility Start Up in Biotech

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Tags: FDA, FDA guidelines, Facility Start-up, EU, ISO, GMP Facility Build Out, Construction Activities, Clean Room