Sterility Assurance and Cross Contamination

by Barbara Unger, FDAzilla GMP Quality Expert and Editor-in-Chief of GMP Regulatory Intelligence

Forms 483 Addressing Sterility Assurance and Cross-Contamination 

Along with data integrity, deficiencies in sterility assurance and the potential for product or API contamination identified during FDA inspections often lead to warning letters. Also many product recalls are based on lack of sterility assurance or less frequently on potential cross contamination.  Here we take a look at six forms 483 that include observations associated with sterility assurance and potential cross contamination.  These are certainly not meant to provide an all-inclusive view of the topic, but rather represent recent inspection observations in these areas to demonstrate the broad scope of the topic.  FDA’s flurry of inspections and enforcement actions against compounding pharmacies and outsourcing facilities focuses heavily of requirements associated with expectations regarding aseptic manufacture of sterile drug products. These sites are often also cited for the potential for cross contamination. Lack of sterility assurance and the potential for cross contamination, particularly by high potency compounds or sensitizing agents both have potentially serious consequences for patient safety.   Many compounding pharmacies and outsourcing facilities have recalled large numbers of products due to concerns about sterility assurance.  We include one example of this type of facility in the collection presented below.  Failure to complete adequate cleaning validation for multi-product equipment is often another source of potential cross contamination even when products do not include high potency compounds or sensitizing agents.

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The Story of 3 Consent Decrees

by Barbara Unger, FDAzilla GMP Quality Expert and Editor-in-Chief of GMP Regulatory Intelligence

A consent decree agreement is an agreement filed in the US courts formalizing a voluntary agreement between two parties.  Here we will address consent decree agreements between FDA and several pharmaceutical companies based on repeated failures to adequately address CGMP deficiencies.  It is not an action taken on the basis of a single form 483, or a single warning letter.  Generally, a series of events play out over time when critical inspection observations are not addressed and are identified in subsequent inspections.  Frequently one or more warning letters are involved.  Consent decree agreements often include fines, with the option for additional financial penalties if conditions to which the firm agrees are not met.  Often these firms are required to use a 3rd party consultants to perform lot release.  Firms operating under a consent decree agreement have largely lost their independence in GMP activities.  Unlike Corporate Integrity Agreement which have a defined duration, firms must petition to have the consent decree agreement condition rescinded.

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Haven’t visited us for a while? Get up to speed in 4 minutes

If you haven’t been to FDAzilla.com in a while, then you’ve come to the right place. If any part of your job involves preparing your company for FDA GMP inspections, let me take you on a quick tour of some tools and resources that you might find useful!  Take 4 minutes and check out these 4 things:

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What Does Getting an 483 or Warning Letter Really Cost You?

“Forget about actual warning letters. The cost of us receiving a moderately bad 483 is roughly $250,000.”

I heard this from a reputable Head of Manufacturing of one of the largest biopharma companies in the world.  While most pharma and med device companies seems to learn quickly from everyone else’s mistakes, companies still occasionally get a “moderately bad” 483.  And then what happens after that? Continue reading

EU vs. FDA: My Inspectors are More Rigorous Than Yours

by Barbara Unger, FDAzilla GMP Quality Expert

FDA and the EU have taken serious enforcement actions against several firms in the others geographic jurisdiction in calendar year 2016.  Perhaps this flurry of my-inspectors-are-more-rigorous-than-yours type represents an unofficial test of sorts as these two agencies move to rely more on each other’s inspections.   These inspections may test the limits and validity of the underlying assumption that would permit this mutual recognition.  Also interesting is that the European inspections specifically evaluate investigational product manufacture, something FDA does not generally do except on a for-cause basis.  Below we cover the three EU reports of GMP non-compliance issued regarding sites in the US and three FDA warning letters, one FDA import alert, and one untitled letter issued regarding sites in the EU.

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We Just Added 2,000 EIRs into Our Store

Due to popular demand, we have decided to add EIRs into our store. Establishment Inspection Reports (EIRs) are an important tool in your tool belt of inspection preparation and intelligence. If you aren’t familiar with them, read our recent post on the 5 Things to Look for in an EIR. Continue reading

5 FEATURES TO LOOK FOR IN AN EIR

Benjamin Franklin said, “By failing to prepare, you are preparing to fail.”  Prepare for your FDA inspections with Establish Inspection Reports (EIR).  An EIR is the full report of an FDA inspection written by the investigators.  Among the features identified in the report are:

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