How do you do: 1572?

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: [email protected]

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


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


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How do you do: 1572?