ANOTHER INDIAN FACILITY RECEIVES WARNING LETTER FOR POOR ASEPTIC PROCESSING

FDA QUESTIONS FIRM’S BASIC UNDERSTANDING AND MICROBIAL CONTROLS CRITICAL FOR THE MANUFACTURE OF STERILE PRODUCTS

Agila Specialties Private Ltd, located at Bommasandra Jigani Link Rd., Bangalore, India was audited by the FDA from June 17 to June 27, 2013.  The audit resulted in the FDA continuing to consider their Import Hold on this facility.  Significant Observations included the following:

1. 1.   Your firm failed to establish and follow appropriate written procedures that are designed to prevent microbiological contamination of drug products purporting to be sterile, and that include validation of all aseptic and sterilization processes (21 CFR 211.113(b).

The most significant examples of this violation include:

1. a.   Non-integral and non-sterile gloves are used for aseptic processing
2. b.   Visible holes and flaking were observed in the (b)(4) gloves purporting to be sterile

Investigators noted that gloves used for processing in the APA (Aseptic Processing Area) as well as gloves remaining from the same vendor lot in the firm’s warehouse possessed similar defects.  The primary glove packaging was also found to be broken, incomplete or missing.  QA had released these gloves for use in production.

Visible holes and flaking were also found within the gloves purporting to be sterile.  Cardboard boxes used to ship and store the gloves were damaged.  Crushed insects were found on one of the glove’s outer package inside a shipping box.  Batches of injectable drug products were made using these defective glove lots.  These defective gloves were of a particular concern because they were used to perform manipulations directly over empty vials.

The firm’s response to FDA’s observation was quite interesting.  They stated: We(FDA) disagree with your rationale for the following reasons:  

“Historical performance data: 

Your response stated that your firm’s examination of incoming glove lots since 2009, using your current sampling procedure, yielded no defects of the samples tested. However, during our inspection, we found that a significant percentage of the gloves already QA-released or being used in production were defective.  We are concerned that your vendor qualification program and incoming material release system are deficient.  You stated that you will discontinue using the current supplier and qualify new glove suppliers.  In your response, please provide the type of tests (methods) and physical examination you conduct to qualify new glove suppliers, the acceptance criteria of the tests/examination of the gloves and primary packaging, criteria for rejection of vendor, and investigation performed, where appropriate.”

COMMENT: 

This entire Warning Letter dwells on very basic issues that were observed within the facility.  One wonders what an Investigator would observe once the investigator got beyond “the lone hanging fruit”.  This is not to denigrate the Investigators’ activities since the FDA Investigators need to begin their investigations somewhere, but what would happen when the Investigators begin to review IQ, OQ, PQ documents for various equipment, examine what validations had been performed, how complete the Batch Records might be and what was the status of their metrology, their water and their Utility systems. 

The fact that the Client was having such basic issues with gloves that receive an Inspection each time an Operator gowns questions the training that is being provided for Gowning.  And, because the Client indicates a lack of release issues also questions their development of SOPs in general and AQLs specifically.