After Heparin: - The Pew Charitable Trusts

PHARMACEUTICAL MANUFACTURING: GLOBALIZATION AND QUALITY MANAGEMENT
Ranbaxy is not the only large Indian company to be placed on import alert by the FDA. In June
2010, an intravenous antibiotic product manufactured by Claris Lifesciences Limited, in India, was
discovered to be nonsterile (which can cause infections) and to contain floating white particles,
identified in at least one case as mold. 184 Three intravenous antibiotic products were then recalled
by Claris and by three companies that sold the drugs in the United States under their labels through
licensing agreements: Pfizer Inc., Sagent Pharmaceuticals and West-Ward Pharmaceuticals. 185,186
In November 2010, the FDA placed Claris Lifesciences under import alert, preventing its products
from entering the United States. 187
1.3.2 Drug ingredient quality issues resulting from deceptive practices
In emerging economies, highly competitive markets and lower regulatory enforcement may combine
to encourage deliberate circumvention of costly quality regulations and certifications. Such deceptions
have affected the U.S. drug supply (see case studies 1, 3, 4). The FDA has uncovered falsification of
data several times in recent years. In a January 2010 warning letter, the FDA claimed that employees at
XiAn Libang Pharmaceutical Co., Ltd., in Shaanxi Province, China, were manipulating testing data. 188
The agency informed the API manufacturing plant that it would not consider new marketing applications
until the observed violations were sufficiently addressed. 189 In February 2010, Indian manufacturer
Glochem was found to have falsified batch-manufacturing records for clopidogrel, an antiplatelet
medicine. E.U. inspectors discovered at least 70 batch-manufacturing records in the plant’s waste yard.
All of the records had been re-written, and in some cases original entries had been changed. 190 And as
discussed, in 2008, the FDA cited Indian manufacturer Ranbaxy Laboratories Limited for a number of
U.S. GMP violations, including alleged falsification of stability testing records. 191
Noncompliant drug-ingredient manufacturers may hide uncertified materials or production sites by
physically concealing these factory rooms or warehouses (see figure 10) or through misrepresentations
in documentation and packaging. One auditor in China suggested that some manufacturers claim
regulatory certifications they do not possess. 192 Such deceptions may permit unqualified manufacturers
to gain business inappropriately, and may mislead regulators and industry efforts to assess quality and
safety standards.
Another documented misrepresentation is the relabeling of materials produced at unknown or unapproved
sites (see case studies 3 and 4). Such falsification poses risks to patients because neither the
purchaser nor regulators can ensure a product’s quality without knowing the conditions of its manufacture
(which is why the FDA requires manufacturing sites to be listed in a drug’s marketing application).
While testing may ultimately show some improperly sourced materials to be safe, their untracked and
unvalidated origins could conceal substandard material or poor production.
Economic motivation often drives these behaviors. Drug-ingredient suppliers may bring in additional
material from unreported sources to meet growing product demand, as was the case for Biochimica
After Heparin: PRotecting Consumers from the Risks of Substandard and Counterfeit Drugs 29