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DOI: 10.1002/qaj.300
How Do You Do: 1572?
Terry Winchell*
GCP Innovative Dynamics, LLC, 7400 Kansas Ave., Kansas City, Kansas 66111-2639, USA
Summary
Form FDA (US Food and Drug Administration) 1572 completions and revisionsgenerate a lot of paperwork for the pharmaceutical industry. Some of this isnecessary but time can be saved and quality can be enhanced by a carefulexamination of what is actually required by regulation, and by understanding thereal purpose of this form. Copyright # 2005 John Wiley & Sons, Ltd.
Key Words: GCP; quality; Form 1572; FDA; clinical research
The Form 1572 has been a source of confusion
in the clinical research industry for a long time.
Some of the questions that recur are:
(1) Do you have to submit it to the FDA?
(2) Do you have to submit it to the Institutional
Review Board (IRB)?
(3) When do you have to update it?
(4) Who do you list as subinvestigators (SIs)?
(5) What about rotating personnel such as
hospital interns?
(6) Should bioanalytical (plasma) laboratories
be listed or just routine clinical laboratories?
(7) How should it tie in with a clinical site’s
Responsibility/Signature Log?
These and other questions are incidental to
the real purpose of the Form 1572. In reality it is
a statement (commitment) made by the Principal
Investigator (PI) conducting the clinical trial.
Among the commitments made, along with
compliance with other regulations and the
protocol, are for the PI to ‘personally conduct
or supervise’ the trial. This is a very significant
point that the FDA enforces to the fullest extent
possible. It cannot be delegated or contracted
out to a Site Management Organization (SMO)
or Contract Research Organization (CRO).
Whoever signs the Form 1572 is ultimately res-
ponsible for the trial at the investigational site.
Title 21 Code of Federal Regulations (CFR)
also requires that a signed Form 1572 be
obtained from the PI prior to allowing him/her
to participate in the trial [1]. This generally
translates into: don’t ship study drug to a clinical
research site until you have the signed Form
1572 in-house.
Do you need to submit the Form 1572to FDA?
Sponsors are not required by regulation to
submit the Form 1572 to FDA, but many do
because it captures some of the information that
is required to be submitted regarding clinical
investigator information [2]. Updates may also
be submitted with each change to the Form 1572
but submission of the form itself (initial or
updated) to FDA is not required by regulation.
When are you required to update theForm 1572?
Every clinical trial must be well documented as
to its course and changes made. Records
available at each clinical research site must be
adequate to reconstruct the conduct and history
of the trial.
*Correspondence to: Terry Winchell, GCP InnovativeDynamics, LLC, 7400 Kansas Ave., Kansas City, Kansas66111-2639, USA. E-mail: twinchGCP@msn.com
Copyright r 2005 John Wiley & Sons, Ltd. Qual Assur J 2005; 9, 11–13.
A Sponsor must obtain a new signed Form
1572 when a new PI begins or inherits an ongoing
trial, or when a new protocol will be conducted
by an existing PI. Also, if drug will be distributed
from a primary site, where the PI is located, to a
satellite site that is under the immediate direction
of an SI, that SI and location should always be
listed and/or updated on the Form 1572. Study
drug can never be sent to an individual or
location that is not authorized to receive it [3].
Other changes to the Form 1572 such as those
involving IRBs, laboratories, SIs and facilities do
not typically fall within the definition of proto-
col changes that are required to be submitted to
FDA according to 21 CFR 312.30 (b). If these
items change during the course of a clinical
research trial, they do in fact change the
information contained on the original Form
1572 and should therefore be documented in the
study records at the research site and Sponsor
where appropriate. It is industry practice to use
the Form 1572 as a vehicle for this documenta-
tion; however, the requirement to update the
Form 1572 itself is not governed by regulation
except under the circumstances stated above.
Other questionable circumstances surround-
ing the Form 1572 include how it is linked
to Responsibility/Signature Logs as required by
the International Conference on Harmonization
(ICH) Good Clinical Practice (GCP) Guideline
E6 4.1.5 and 8.3.24, when to include rotating
medical interns as SIs, and what to do when an
SI leaves the trial and whether clinical labora-
tory subcontractors be listed. These are also
secondary to the real purpose of the Form 1572,
and as with many issues regarding GCP, the
most precise answers will always be dependent
on individual circumstances. But, the following
can be stated:
(1) Study records should never conflict (e.g., if
someone is listed as a SI on the Form 1572,
they would of necessity need to be included
on the Responsibility/Signature Log and
vice versa).
(2) Rotating interns, if listed on the Form
1572, would necessitate obtaining complete
Financial Disclosure information in com-
pliance with 21 CFR Part 54 (4). If they are
performing regular trial-related duties for a
significant period of time, listing them as SIs
should be given careful consideration.
(3) If an SI leaves the site, keep in mind that
study records should be capable of recon-
structing trial history. It is industry practice
to use the Form 1572 as the vehicle to reflect
trial history; however, this is not required by
regulation.
(4) If a clinical laboratory ‘subcontracts’ work
to other laboratories the question is not so
much should those other laboratories be
listed on the Form 1572, but whether they
are accredited/certified to conduct the pro-
tocol required tests they are being con-
tracted to perform. Generally, if a clinical
laboratory is not certified for the protocol-
required tests, the Sponsor or CRO should
locate a laboratory that is, hiring them
directly. In that manner, ‘subcontracting’
should not become an issue.
(5) Also, the PI should never sign the Form
1572 prior to the date of the finalized
protocol and applicable Investigator’s Bro-
chure. The PI commits to compliance with
the protocol and understanding the Bro-
chure prior to beginning the trial. A ques-
tion of credibility could arise if the PI signs
this commitment prior to the documents
existing in final form.
Do you need to send the Form 1572 toIRBs?
IRBs can place any additional requirement upon
a clinical research trial that they deem necessary.
If they require that the initial Form 1572 and
subsequent updates be sent to the IRB, then this
absolutely becomes a GCP requirement.
Which laboratories must be listed onthe Form 1572?
There are some other ‘gray’ areas beyond what
was mentioned above such as the inclusion on
12 T Winchell
Copyright r 2005 John Wiley & Sons, Ltd. Qual Assur J 2005; 9, 11–13.
the Form 1572 of plasma (bioanalytical) labora-
tories (e.g. laboratories testing for the presence
of study drug or metabolite) in that if these
laboratories do not provide results back to the
clinical investigator (and they usually don’t),
then the purpose of listing them on the Form
1572 (Statement of Investigator) is not grounded
in clarity. Routine clinical laboratories, however,
(either local or central) are clearly required to be
listed.
What is the real message here?
The real purpose of Form FDA 1572 is to ensure
solid PI commitment to conformance with FDA
regulations prior to drug shipment to clinical
research sites. This commitment is very real, and
each PI should carefully read the back of the
1572 prior to signing it. Each Sponsor or
delegated CRO should withhold investigational
product shipment until this commitment has
been satisfied with a signed Form 1572 received
in-house. Also, IRB requirements must be
fulfilled and the evolutionary course of changes
during a clinical trial should always be ade-
quately documented at each research site and
Sponsor where appropriate. Form 1572 is
routinely used as the vehicle of choice to
accomplish some of this documentation.
The use of the Form 1572 is probably
overdone in industry. This single activity gen-
erates a lot of paper and submission work. The
Form 1572 somehow develops a life of its own
with constant updates, signatures, changes, etc.,
and it triggers other activities such as the
obtaining of Financial Disclosure information
[4], and again, prior to investigational product
shipment to the research site [5].
The use of practicality, common sense, and
knowledge of the intended purpose of Forms
1572 will take you a long way towards adequate
compliance. Don’t ever let lesser details obscure
the real heart of GCP in regards to subject care,
valid data and investigational product control.
Keeping the 1572’s real purpose in mind,
knowing what is actually required by the
regulations, and obeying the IRB will help keep
the Form 1572 in perspective and not allow
secondary details to obscure serious concerns.
Not being able to see the forest for the trees can
be very applicable in GCP!
I once worked with a very seasoned compli-
ance director that summarized his GCP strategy
something like this: ‘Don’t ever do anything
that will hurt anyone, goes contrary to common
sense, or that you know is wrong.’ I didn’t
realize how profoundly accurate that statement
was until years later, and how much that
philosophy can guide the many difficult deci-
sions that must be made in the area of clinical
research.
References
1. 21 CFR 312.53 (c) (1). Investigational New Drug
Application; Responsibilities of Sponsors and Investiga-
tors; Selecting Investigators and Monitors; Obtaining
Information from the Investigator. 1 April 2004. http://
www.fda.gov/oc/gcp/regulations.html [5 January 2005].
2. 21 CFR 312.23 (a) (6) (iii) (b). Investigational New
Drug Application; Investigational New Drug Application
(IND); IND Content and Format; Protocols. 1 April 2004.
http://www.fda.gov/oc/gcp/regulations.html [5 January
2005].
3. 21 CFR 312.61. Investigational New Drug Application;
Responsibilities of Sponsors and Investigators; Control
of the Investigational Drug. 1 April 2004. http://
www.fda.gov/oc/gcp/regulations.html [5 January 2005].
4. 21 CFR 54.2 (d) and 54.4. Financial Disclosure by
Clinical Investigators. 1 April 2004. http://www.fda.gov/
oc/gcp/regulations.html [5 January 2005].
5. 21 CFR 312.53 (c) (4). Investigational New Drug
Application; Responsibilities of Sponsors and Investi-
gators; Selecting Investigators and Monitors; Obtain-
ing Information from the Investigator. 1 April 2004.
http://www.fda.gov/oc/gcp/regulations.html [5 January
2005].
How Do You Do: 1572? 13
Copyright r 2005 John Wiley & Sons, Ltd. Qual Assur J 2005; 9, 11–13.
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