Pharmaceutical Technology REGULATORY SOURCEBOOK DECEMBER 2019 5
A recent warning letter illustrates how an inad-
equate response to violations can create additional
problems for a drug company. Mylan Laborato-
ries received a warning letter in November 2019
for failing to have adequate written procedures for
the receipt, identification, testing, and handling of
raw materials. Specifically, the citation addressed
the company's failure to identify nitrosamine im-
purities in solvents used to manufacture valsartan
API, which resulted in drug recalls. The company
also was cited for inadequate processes for testing
and handling of these solvents and the subsequent
steps the company took to remedy the problem. In
addition, FDA noted that Mylan's cleaning meth-
ods for non-dedicated equipment were not ad-
equate to prevent contamination or carry-over to
other drugs manufactured on that equipment (3).
Another letter, to Greenbrier International—the
Dollar Tree discount stores—illustrates two points:
quality issues by contractors can result in warning
letters to the drug license holder, and drug license
holders must pay close attention to regulatory en-
forcement activity.
In a January 2019 inspection, FDA noted that
Greenbriar "used contract manufacturers and
suppliers with histories of significant drug CGMP
[current good manufacturing practice] violations."
Some suppliers were placed on import alert, and
Greenbriar was sent copies of the warning letters
when issued.
In addition, FDA noted that Greenbriar required
suppliers to use a testing laboratory, Bureau Veritas
(BVS), to test products it distributes. BVS repre-
sentatives told FDA that BVS's test methods "were
not suitable for drug CGMP purposes and that its
test results were not suitable to make release deci-
sions of drug products for distribution into the US
supply chain."
FDA reminded Greenbrier that the company
was "responsible for ensuring that the drugs you
distribute are not adulterated, including ensuring
that all drug manufacturers supplying Greenbrier
with drugs have had release testing conducted in
accordance with CGMP requirements" (4).
In this issue
The latest installments of the Pharmacopoeia
Compliance Series emphasize the need for drug
companies to establish formal processes to monitor
global and national pharmacopoeia changes to stay
informed, and potentially get involved with defin-
ing changes in compendial guidelines. Likewise,
the quality teams at drug companies and contract
service providers should closely monitor regula-
tory enforcement activity. FDA's online compli-
ance information and Data Dashboard are useful
references. Links to other regulatory sources can
be found in this ebook on pages 38–43.
References
1. FDA, Novel Drug Approvals for 2019, www.fda.gov, accessed
Dec. 11, 2019.
2. FDA, FDA Data Dashboard, accessed Dec. 11, 2019.
3. FDA, Mylan Laboratories Limited-Unit 8, Warning Letter, Nov.
5, 2019.
4. FDA, Greenbrier International, Inc dba Dollar Tree, Warning
Letter, Nov. 6, 2019.
PT
Effective, ongoing
monitoring programs—
for regulatory agency
enforcement actions and
pharmacopoeia updates—
are essential for
bio/pharma compliance.
