JUBILANT HOLLISTERSTIER, LLC RECEIVES WARNING LETTER (11/27/13)

FIRM FAILS TO PERFORM MEDIA FILL PROCESS SIMULATIONS FOLLOWING MAJOR RENOVATION

Jubilant HollisterStier, Spokane, WA was audited by the FDA between April 15 and May 10, 2013.  The FDA reviewed the firm’s response from May 30 and noted that sufficient corrections actions were lacking.  The FDA also received additional correspondence dated July 12 and August 15, but believed that a Warning Letter was required.  Two Observations, both related to microbiology, were subsequently issued.

The first citation cited 21 CFR 211.113(b) which centers itself on “microbiological contamination of drug products purporting to be sterile”.  Observation 1(a)  is very interesting, but basic since the Company, following a major renovation, failed to perform at least one media fill process simulation to demonstrate that the aseptic processing area (APA) are acceptable.

a)   “For example, your firm’s SOP 1608.9, “Quality Control of HollisterStier Facility During and After Shutdown” lacks provisions for adequate impact evaluation of significant maintenance shutdowns and assurance that acceptable conditions are restored to ISO classified areas before restart of operations. In April 2013, your firm shut down filling lines SVP Line 1 and SVP Line 2 used to manufacture aseptically filled injectable drug products. The April 2013 shutdown activities on SVP (b)(4) included removal of the existing (b)(4), rebuilding of the(b)(4) upgrade, and replacement of (b)(4). On SVP (b)(4) the (b)(4) was upgraded on the (b)(4), which included replacement of the (b)(4). Major facility repairs in the April 2013 shutdown included window replacement, floor resurfacing, dead bolt installation, and ceiling painting.

In your response, your firm acknowledges the lack of an adequate, documented evaluation of the effect of major equipment and facility modifications. You also provide a retrospective impact assessment that you performed. Furthermore, you state that SOP 1608.9, “Quality Control of HollisterStier Facility During and After Shutdown” has been revised to include an improved impact assessment process. Your response is inadequate because you do not commit to conducting media fill process simulations to assure the aseptic processing operations are acceptable after major shutdown activities. In addition, your July 12, 2013, response states that SOP 1608.9, “Quality Control of HollisterStier Facility During and After Shutdown” revisions are complete. However, you failed to provide an official procedure”.

Observation 1(b) of Observation 1 discussed the adequate documentation of work orders associated with the shutdown to include Quality Unit oversight.  The Quality Unit failed in 11 instances to place work orders into the “Shutdown Maintenance Work Order Requests List”.  Adequate documentation is a very basic building block within the pharmaceutical industry.

b)    “Your firm also failed to adequately document all work orders associated with the April 2013 shutdown and include appropriate Quality Unit oversight. Your firm’s SOP 1608.9, “Quality Control of HollisterStier Facility During and After Shutdown,” requires Quality Assurance review of work orders “which affect ISO classified areas and/or utilities during shutdown” in the “Shutdown Maintenance Work Order Requests List,” in Attachment 1. In the April 2013 shutdown, 11 of (b)(4) work orders were not documented in Attachment 1. Examples of work orders not documented in Attachment 1 include facility repairs and equipment maintenance at SVP Line 1 and SVP Line 2. Release of the classified production areas after shutdown includes review of Attachment 1.

In your response, you state that SOP 1608.9, “Quality Control of HollisterStier Facility During and After Shutdown” has been revised to include appropriate documentation and Quality Unit approval prior to performing shutdown work.  However, your response is inadequate because you have not provided an official procedure”.