Insanitary Conditions 101: FDA Issues Draft Guidance for Compounding Facilities Based on Prior FDA Inspections: Comments due October 3, 2016

By Karla L. Palmer –

FDA announced last week the availability of a draft guidance document titled, “Insanitary Conditions at Compounding Facilities.”  This draft is FDA’s first attempt to assist compounding facilities and state regulators in identifying “insanitary conditions so they can implement appropriate corrective actions.”  The draft intends to apply to federal facilities, physician’s offices including veterinarian offices (notwithstanding the inapplicability of Sections 503A and B to animal drug compounding), and outsourcing facilities that compound human or animal drugs including radiopharmaceuticals (notwithstanding the applicability of cGMP to these facilities).  The draft comes after FDA has conducted hundreds of compounding pharmacy/facility inspections since late 2012, the substantial majority of which has left at least the traditionally state-regulated pharmacies wondering what inspection standard (if any) applies to their practices.  Note that comments on the draft are due October 3, 2016 (Docket No. FDA-2016-D-2268).

Despite exemptions from certain provisions of the FDCA for lawfully compounded drugs under Sections 503A (e.g., adequate directions for use, new drug, and cGMP provisions) and 503B (e.g., DSCSA, adequate directions for use and new drug provisions), compounders still must comply with the adulteration provisions in Section 501(a)(2)(A): A drug is adulterated "if it has been prepared, packaged, or held under insanitary conditions whereby it may have been contaminated with filth, or whereby it may have been rendered injurious to health." FDA has cited compounders – in Form 483 Observations and Warning Letters – with violations of the Act’s adulteration provision since late 2012.  It typically has stated that, if compounding has occurred under insanitary conditions, other exemptions under Section 503A — such as cGMP — and Section 503B do not apply.

FDA states it published the draft because it is “critical that compounding facilities avoid the presence of insanitary conditions and identify and remediate any insanitary conditions at their facilities before the conditions result in drug contamination and patient injury." The draft provides numerous, non-exhaustive examples of insanitary conditions that FDA investigators have observed in prior compounding facility inspections, including the presence of vermin, visible microbial contamination such as mold and bacteria, and non-microbial contamination such as rust, glass shavings or hair in a production area.  FDA also lists insanitary conditions in aseptic operations (including gowning, procedures, and equipment), cleaning and disinfection.  In addition, it lists procedures for compounders to ensure their facilities are sanitary, and remedial actions when insanitary conditions are found.  The remedial action section reads similar to warning letters issued to compounding facilities where FDA claimed insanitary conditions were present.  Specifically,

In addition to the immediate actions recommended above, if a compounding facility has insanitary conditions, it should undertake a comprehensive assessment of its operations, including, as applicable, facility design, procedures, personnel, processes, materials, and systems, and should consider consulting a third party with relevant drug production expertise to conduct this comprehensive evaluation and to assist in implementing appropriate corrective actions.

FDA notes that facilities should not rely on a passing sterility test as an indication of sterility assurance because “microbial contamination, when present, is not uniformly distributed within a batch and may not be identified by a sterility test.” And, facilities that have insanitary conditions must correct them regardless of whether they pass a sterility test.  Facilities may be subject to federal regulatory actions including warning letters, seizure or injunction proceedings.  FDA also may recommend recalls of adulterated products and institute proceedings against the facility and responsible individuals.  States may also pursue actions under applicable state authority.