Smoking hot filters
"When the first lot of product was rejected for a high endotoxin (LAL) result, we were disappointed," notes our GMP Agent-in-Place.
"But our investigation couldn't find a source and we were still looking when the next lot tested hot as well! The laboratory
troubleshooters noted that the LAL response was atypical, so something unusual was happening there. Using in-process test
retention samples, the issue was traced back to a specific lot of filter used.
"At first we thought we had found the smoking gun (pun intended), but the filter contact materials were no different than
what we had used in many other products and processes. Something else was going on, and we couldn't figure it out.
"Working closely with the filter manufacturer, we found the problem was the filter assembly and manufacturing process. This
meant that we would have to test each lot of filters with our product to be sure the same problem didn't continue. What a
pain! And we still had to reject and destroy those two lots."
Out with the old
"The marketing manager thought he could increase sales by keeping an old injectable product viable. He figured we could market
it as a syringe product as well as the current vial format," our GMP Agent-in-Place explains.
"Because it was a small-volume product, the project never had a lot of activity, and the project just perked slowly along
for years. When the marketing manager left the company, the new manager looked at the market and the product and asked, 'Why
are we spending money on this old dog?' And he killed the project."
A diluent by any other name
"An FDA inspector noted that our sterile water-for-injection that was used as a diluent with our freeze-dried product failed
to meet pH specifications during our routine stability studies," says our GMP Agent-in-Place. "We receved a 483 observation
for this failure.
"When I visited the plant to help them fix the problem, I found out that the diluent was filled into Type II glass. I explained
that in that type of system, the water will tend to extract ions from Type II glass, and because it isn't buffered, will
readily change the pH.
"The resolution to the problem was relatively easy: We renamed the diluent as 'Sterile Diluent' rather than 'Sterile WFI,'
and eliminated the pH specification after proving that the pH of the mixture of product and diluent didn't result in product
What does corporate do anyway?
"We were undergoing a regular FDA inspection until the inspector decided to check on follow-up actions we promised because
of our product recall," says our GMP Agent-in-Place. "Recalls are managed out of the corporate office, half-way across the
country where the sales and marketing staff are, but the local FDA district still expects us to have all the details.
"We had committed to send out a second letter to the customers after this particular recall. The corporate quality expert
said he would do it, but he never did. FDA wanted to talk to him directly and called him from my office—no warning, just a
call from an inspector during an inspection! Boy was he surprised. FDA kept him on the line while files were retrieved and
memories searched, still ending with a 483 observation. What does corporate quality do anyway?"
Pharmaceutical Technology's monthly "Agent-in-Place" column distills true-life cautionary tales from the secret files of Control, a senior compliance
officer. If you have a story of clueless operators, oblivious management, inopportune lapses of judgment, or Murphy's Law
in action, please send it to Control at AgentinPlace@advanstar.com
. We won't use any names, but if we do use your tale of disaster, courage, or just plain weirdness, Control will send you
a coveted Pharmaceutical Technology t-shirt.