Mylan’s Glove-Integrity Warning Letter Fix Didn’t Extend to Adjacent Site

It’s a constant challenge for pharmaceutical manufacturers to ensure that quality problems identified at one site are fixed globally. In Mylan’s case, a problem with holes in gloves was resolved at one sterile manufacturing facility, but continued at another – even though it was right next door.

Recent FDA inspections of facilities Mylan NV had acquired in India showed once again that, because of their site-specific nature, inspections often trigger improvements that are only site-specific – even though agency officials always say they want responses that are companywide.

FDA officials often tell industry conferences that if an inspection uncovers a problem at one site, the company should check to see if its other sites around the world have the problem too, and fix it there if they do.

In Mylan’s case, a site the company was acquiring fixed a problem FDA emphasized in a warning letter (Also see "Pharma Pursues Generic Injectables Quality Turnaround Opportunities" - Pink Sheet, 27 Mar, 2015.). But the agency discovered that the same problem continued unabated at another site, part of the same acquisition, that was right next door.

In June 2013, FDA investigators could see holes in the gloves workers were using for aseptic processing at Agila Specialties Private Ltd.’s Specialty Formulation Facility in an industrial park on Bommasandra Jigani Link Road in Bangalore, India, the agency said in a September 2013 warning letter.

Gloves in the warehouse waiting to be worn also had holes in them, and employees told investigators they never checked gloves for integrity before putting them on.

FDA learned that Agila had also been using gloves from the same supplier since 2009 at several other facilities. “We are concerned with the lack of sterility assurance of all the aseptically filled drug products you manufactured at these sites,” FDA said in the September 2013 warning letter. “Please provide in your response to this letter the corrective action you intend to implement at all sites that may be affected by similar practices.”

What FDA found when it returned

FDA returned to the Specialty Formulation Facility a year later, after Mylan had completed its acquisition.

The agency described a number of problems at the formulation facility in a warning letter this month, but gloves with holes was not one of them.

The Aug. 6 warning letter also gave findings from inspections at two other facilities Mylan had acquired from Agila. There were problems at both, but it was the one at Plot No. 284-B on Bommasandra Jigani Link Road, the Onco Therapies Limited facility, that still had serious issues with gloves.

Apparently, word hadn’t traveled from the Specialty Formulation Facility at the adjacent Plot No. 284-B/1 on how and why to fix the problem.

The situation at Onco Therapies

When FDA inspected Mylan’s Onco Therapies Limited facility in February, the agency saw lots of problems with gloves.

Inspectors could see that 19 of the gloves workers were using on Feb. 12 had tears and pin holes. One had large cuts in two fingers.

The facility had a procedure for leak testing gloves for integrity. But it enabled the use of bad gloves by substituting good gloves’ test results, the warning letter said.

This occurred even though company officials blamed the gloves for environmental monitoring data excursions in an area designed to meet the International Organization for Standardization 14644 Class 5 cleanroom standard.

FDA explained in the warning letter that because workers at the site were making aseptic connections, clearing jams, purging filling needles and performing other critical interventions, their use of gloves with holes in them “is an unacceptable practice. It is a direct risk to product sterility.”

After watching workers and videos of workers, agency inspectors raised additional concerns about personnel monitoring.

One worker entered a restricted access barrier system, making aseptic connections, purging filling needles and performing interventions on the filling machine without first sanitizing his gloved hands.

Other workers appeared to be sanitizing gloved hands right before sampling them for environmental monitoring checks. That may have produced better looking results, but it undermined the monitoring exercise.

The gloves and the test results weren’t only things full of holes at the Onco Therapies site, FDA said. Sterile gowns, hoods and booties had them too. But more significant was the hole in the company’s response after FDA identified the issue at the site next door.