Theinvestigator-orientedinspection is initiated
for several reasons. Some include: the investigator
conducted a study that is pivotal to product
approval; representatives of the sponsor have
reported to FDA that they are having difficulty
getting case reports from the investigator or have
some other concern with the investigator’s work; a
study volunteer complains about protocol or sub-
ject rights violations; an investigator has partici-
pated in a large number of studies or has done work
outside his or her specialty areas.
Most inspections are of the study-oriented or
investigator-oriented types. Thebioequivalence
studyinspection is conducted when one study
may be the sole basis for a drug’s marketing
approval.
At the end of the site inspection, the inspector(s)
conducts an exitinterview with the investigator and
appropriate staff. If the inspector uncovered any
significant issues, he or she may issue Form FDA-
483, an ‘inspectional observations’ form docu-
menting deviation from GCP. The investigator
will need to respond to the 483 and take corrective
action.
Following the inspection, the clinical investiga-
tor will receive one of three types of letters:
1.NAI (No Action Indicated):A notice that no
significant deviations from the regulations
were observed. This letter does not require any
response from the clinical investigator.2.VAI (Voluntary Action Indicated):An informa-
tional letter that identifies deviations from reg-
ulations and good investigational practice. This
letter may or may not require a response from
the clinical investigator. If a response is
requested, the letter will describe what is neces-
sary and provide the name of a contact person.3.OAI (Official Action Indicated):Identifies ser-
ious deviations from regulations requiringprompt
correction by the clinical investigator. The letter
will provide the name of a contact person. In this
case, FDA may inform both the study sponsor and
the reviewing IRB of the deficiencies. The agency
may also inform the sponsor if the clinical inves-
tigator’s procedural deficiencies indicate ineffec-
tive monitoring by the sponsor.The vast majority of inspections, some 77%, result
in ‘VAI’. Of the other two categories, 16% result in
‘NAI’ and 7% in ‘OAI’ (Lamberti, 2005).
The number of annual inspections has been
growing steadily, and in 2004, reached a total of
242 for US clinical investigators and 82 for foreign
clinical investigators (2004 Report to Nation). The
top five deficiencies, led by protocol violations,
appear in Figure 11.9.11.4 Final thoughts
The purpose of the investigative site is to produce
clean clinical data by performing a protocol on
study volunteers. Sites that achieve this goal do
so by building an infrastructure that supports the
many functions involved in generating those data.
The infrastructure includes standard business prac-
tices such as quality assurance, writing of SOPs,
regulatory affairs and data management. It must
also include study coordinators and investigators
who are well trained in GCP.
Because the conduct of clinical trials is a
competitive business, sites should document their
performance in terms of quality and timeliness. This- Who did what
- Degree of delegation of authority
- Where specific aspects of the study were
performed - How and where data were recorded
- How test article accountability was
maintained - How monitor communicated with clinical
investigator - How the monitor evaluated the study’s
progress
Figure 11.8 Facts surrounding the conduct of the
study [Source:IRB Information Sheets, 1998]
136 CH11 SITE MANAGEMENT