A Common Practice No Longer Allowed »
The regulations regarding import of drug supplies (21CFR Parts 312 and 201) into the US has not substantively changed, but the interpretation of
the regulations into practice by industry has evolved. Over the last 20 years, it has been standard practice to allow API/drug product to be imported
in advance of having an effective IND. If the supplies were properly labeled and accompanied by a letter indicating that the material was destined
solely for use in clinical research, then you were usually able to clear customs without a problem. On rare occasions, you might have been asked by
either customs or US Food and Drug Administration (FDA) personnel for the investigational new drug application (IND) number associated with the
supplies. As most sponsors did not obtain an IND number until the IND was actually submitted or until a request was made for a pre-IND meeting,
this request could be satisfied with the number or with an affidavit verifying the intended use of the API. However, not everyone importing API has
been doing so in good faith. According to FDA’s guidance to its field personnel (known as Import Alert 66-66)2:
Import Alert
66-66
“Some persons importing APIs have found that they could obtain entry of these articles if they simply supply an
NDA or IND number at the point of entry. Districts should be alert to the possibility that: 1) the NDA or IND number
provided does not cover the source of the particular API or 2) the persons importing the API have no authorization
to refer to the particular NDA or IND number. In the past, the persons importing an API have referred to legitimate
numbers to get their APIs released, but the APIs were not destined for use in the application referenced.”
In light of these issues and several recent – and troubling
Figure 3. Interpretation
of US Importation Laws
– events (eg, adulterated cancer drugs in 2012, heparin
3
contamination in 2008,4 and the melamine pet food
Present
Past 20 Years
recall in 2007 ), FDA increased its efforts to fight against
5
FDA increased efforts to fight
against counterfeit drug product
and protect supply chain
counterfeit drug product and to protect the supply chain.
The agency maintains a database to improve their ability
to cross reference drug approvals and research permits
(INDs) and ensure that only authorized drug imports
are allowed through customs. This database, called
the Establishment Evaluation System (EES), was first
API/drug product
imported in
advance of having
an effective IND
Supplies properly
labeled and solely for
u
se in Clincal research
usually cleared customs
without problem
IND must be
“in effect” before
important API/drug
product into US
Establishment Evaluation
System (EES) created
by FDA to ensure only
authorized drug imports are
allowed through customs
implemented in a test program in Philadelphia in
1997. Access to the database has expanded to other
FDA districts handling API imports,6 and its use is
becoming standard practice.
clinipace.com
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