Warning Letter – McGuff Pharmaceuticals – Validation of Aseptic and Sterilization Processes

McGuff Pharmaceuticals Inc 12/28/10

Warning Letter

CGMP Violations

1. “Your firm has not established appropriate written procedures designed to prevent microbiological contamination of drug products purporting to be sterile, including procedures for validation of all aseptic and sterilization processes {21 C.F.R.§211.113(b)}.  For example: 

a.  Your firm has failed to conduct a media fill representative of the different packaging configurations of your drug products for the past two years.  Your firm has been using a volume of (b)(4) for media fills; However, commercial products are available in (b)(4) and (b)(4).  In addition, you have not established maximum aseptic fill duration.

In your response, your firm states that you have amended your Standard Operating Procedure (SOP) (b)(4) to “bracket” the container sizes by utilizing both the (b)(4) and (b)(4) volumes.  Your response, however, is inadequate because you have not provided a risk assessment that examines the effects of differences between product fill sizes (i.e., fill speed, operating methods, container opening size, mass) to determine if bracketing is appropriate.

COMMENTS

Many of the issues covered within this response may be found within the FDA Guidance for Industry. Sterile Drug Products Produced by Aseptic Processing – Current Good Manufacturing Practice. Food and Drug Administration. September 2004.

Representative media fills are to be conducted at six month intervals; volumes for media fills should represent 30-50% of the volume of the product being filled.  Since the volume used is redacted, it can only be assumed that an improper volume was observed in their SOPs and media fill records.

Duration of a fill should also be established based upon number of units, total volume utilized, a time duration, etc.  As noted in the FDA’s next paragraph, the FDA cited the firm for not providing a Risk Assessment that “examines the effects of differences between product fill sizes…” which determines if the bracketing is appropriate.  Items to include fill speed will vary depending upon the size of the containers being filled; “container opening size” can impact the susceptibility of the container to being contaminated by viable airborne microorganisms, e.g, 13mm vs. 20mm neck size.