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Investigation Operations Manual…
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[Index]
Contents
512 - REPORTS OF OBSERVATIONS
512 - REPORTS OF OBSERVATIONS
The FORM FDA 483 INSPECTIONAL OBSERVATIONS is intended for use in notifying
the inspected establishment's top management in writing of significant
objectionable conditions, relating to products and/or processes, which
were observed during the inspection. The issuance of written inspectional
observations is mandated by law and ORA policy. Only report significant
observations on the FDA 483. Observations of lesser significance should
be discussed with firm management and properly reported in the narrative
report. As of 1997, ORA established a policy of adding "annotations" during
medical device inspections to the FDA 483. See IOM 512.03.
There may be instances where
same day discussion of observations may
not be possible due to the volume of documents collected and document
review reveals observations on a different day than the
documents were collected or in other circumstances.
When these instances occur immediately prior to the conclusion of the
inspection the lack of a daily discussion of observations does not
preclude listing of significant observations which were not previously
discussed on the FDA 483.
With the roll-out of Turbo EIR, an automated FDA 483 and EIR reporting
system, the traditional FDA 483 is created electronically. Turbo EIR
must be used to generate the FDA 483 and write the EIR for any inspection
where applicable cite modules exist. Turbo EIR must not be used to create
a FDA 483 during an inspection of a firm involving multiple commodity
areas and FDA 483 cites do not exist for ALL of the commodity areas for
which observations need to be included on the FDA 483. You must be able
to write the entire FDA 483 using Turbo EIR. You cannot use Turbo to
write the EIR if a FDA 483 was issued to the firm and it was NOT generated
using Turbo EIR. NOTE: Turbo EIR can be used to write the EIR for any
inspection not involving issuance of a FDA 483.
It is not necessary to complete all headings of the FDA 483, when multiple
page 483's are issued. Complete all headings on the first page and,
on subsequent pages, only those necessary to identify the firm and dates
inspected.
Report all significant objectionable conditions noted during the inspection
by issuing a FDA 483, Inspectional Observations. See IOM
Exhibit 510-B. Be alert for specific guidance in assignments or Compliance
Programs which may supplement the following general instructions. FDA
483's should be issued at the conclusion of the inspection and prior
to leaving the premises. However, in preparing some complex FDA 483's,
it may be necessary to leave the premises and return at a later
District Office address and phone number - Legibly print the district
address on copies in advance if desired. Include District Office commercial
telephone number and area code.
Name and Title of individual to whom report is issued - Enter legal
first name, middle initial and last name and full title of the person
to whom the form is issued.
Firm name - Enter full, legal name of the firm, including any abbreviations,
quotation marks, dashes, commas, etc.
Street address, city, state and Zip Code - Enter street address, city,
state and Zip Code. (Not P.O. Box unless P.O. Box is part of the address
such as on a Rural Route).
Date(s) of inspection - Enter actual or inclusive date(s) of inspection.
FEI Number - If the Firm Establishment Number is on the assignment,
enter it here. If not readily available, leave blank.
Type of establishment inspected - Enter the types of the establishment,
such as bakery, cannery, wholesale warehouse, drug repackager, salvage
warehouse, etc.
Employee(s) signature and Employee(s) name & title - Each member
of an inspection team should sign the FDA 483. However, absence of a
team member at the conclusion of an inspection need not prevent issuance
of the FDA 483. See IOM
502.04. If you use an electronically generated FDA 483, assure you
have an exact copy of the original for the District files. An unsigned
photocopy or printed copy is unacceptable.
Signature Policy - You will initial all pages of a multi-page FDA 483
next to the Date of Issue and you will sign the front and final pages.
Ideally, the FDA 483 is signed by all members of an inspection team.
If some members of the inspection team are not available when the FDA
483 is issued, you, as the lead investigator, must sign the FDA 483 as
above, initial the remaining pages of a multi-page FDA 483, and fully
explain in the EIR why the FDA 483 was not signed by all members of the
inspection team. You should follow your district policy in determining
the need for all members to initial each page of the FDA 483. The official
FDA 483 is the printed, pen/ink signed, exact duplicate of the issued
original. This is the copy maintained with the EIR (see IOM
512.05). There are only three possible exact duplicates of any issued
FDA 483, which are to be maintained in the official file:
RETAIN FOR THE OFFICIAL FILE A SIGNED, ISSUED EXACT DUPLICATE OF ALL
FDA 483s ISSUED DURING YOUR INSPECTION.
Date issued - Enter date the form is actually issued to the firm's
management.
"During an inspection of your firm (I) (We) observed" - Enter your reportable
observations succinctly and clearly. Conditions listed should be significant
and must relate to an observed or potential problem with the facility,
equipment, processes, controls, products, employee practices, or records. "Potential
problems" must have a reasonable likelihood of occurring based upon observed
conditions or events. Do not cite deviations from draft Agency policy
statements or directly refer to Agency guidance documents in your written
observations. You should contact your supervisor to discuss and resolve
questionable observations prior to the issuance of the FDA 483. Good
judgment is necessary when deciding whether conditions are objectionable
in view of their relation to other conditions or controls at the given
time and place. When there is continued uncertainty about the significance
of one or more observations, these should not be listed. They should
however be discussed with the firm's management and reported in the
EIR.
If the firm maintains satisfactory controls as intended by the regulations,
but does so by alternate means, it may be possible no adverse condition
will result. See 21
CFR 820.1(e) regarding petitions for exemption or variance from device
GMP's.
To make the FDA 483 observations more concise, avoid unnecessary redundancy.
Items of the same nature should be grouped together. Examples should
be given if a condition with broad or general scope is described. Write
the observations in clear and descriptive terms, including locations,
dates of occurrence, frequency of occurrence, lot numbers, etc., as appropriate.
When reviewing records, the FDA 483 observations should include the number
of records of a given type examined, for example, "Two out of 50 records
examined were * * *."
Required
FDA 483 Language:
The following statement must
be included on each FDA 483:
"This document lists observations
made by the FDA representative(s) during the inspection of your facility.
They are inspectional observations, and do not represent a final Agency
determination regarding your compliance. If you have an objection regarding
an observation, or have implemented, or plan to implement, corrective
action in response to an observation, you may discuss the objection
or action with the FDA representative(s) during the inspection or submit
this information to FDA at the address above. If you have any questions,
please contact FDA at the phone number and address above."
Presently there are three ways
to issue a FDA 483. Use the following guidance as it applies to the
specific type of FDA 483 you are issuing.
Medical Device Quality System
(QSIT) inspections require the following language be inserted on the
FDA 483 in addition to the above statements:
“THE OBSERVATIONS NOTED
IN THIS FORM FDA 483 ARE NOT AN EXHAUSTIVE LISTING OF OBJECTIONABLE
CONDITIONS. UNDER THE LAW, YOUR FIRM IS RESPONSIBLE FOR CONDUCTING
INTERNAL SELF-AUDITS TO IDENTIFY AND CORRECT ANY AND ALL VIOLATIONS
OF THE QUALITY SYSTEM REQUIREMENTS.“
Correction of FDA 483 Errors:
If you discover an error on the FDA 483 at the time of issuance,
correct and initial all copies of the FDA 483. Note: if the FDA 483 was
created in Turbo, all corrections/additions/deletions MUST be made in
Turbo. This procedure does not pertain to adverse conditions noted and
then corrected during the inspection. Observations of this type should
remain on the FDA 483. If a discrepancy is discovered after you leave
the firm, discuss it with your supervisor. If necessary, an additional
FDA 483 will be prepared as an addendum to the original, limiting it
to correction of those discrepancies. This FDA 483 addendum should be
personally delivered to the firm for discussion. If personal delivery
is impossible it should be transmitted by mail including a full explanation
cover letter. A copy of the letter and FDA 483 addendum should be included
with the EIR. In addition, you must call the person to whom the original
FDA 483 was issued, to discuss the change. Document your discussion on
the FDA copies of the FDA 483 and in the EIR. The Inspectional Observations
(FDA 483) is of critical importance to both the Agency and regulated
industry. Individual FDA 483s may become public through publishing in
industry trade press, FOI inquiries, Headquarters postings and other
means.
If an error(s) is found on a signed, issued Turbo FDA 483, you must
follow these instructions. Changes made to correct information in the
text of the observation will show on the face of the final printed FDA
483. Deletions will remain visible but will be crossed out and additions
added, preferably in a different font. If an entire observation is removed,
incidental text will be used to add the statement "An observation concerning
*** was removed based on discussion with management."
512.01 - Reportable Observations
Review Sections 402, 501, 601, & 704 of the FD & C Act [21 U.S.C.
342, 351, 361, & 374]. Include specific factual observations of:
512.02 - Non-Reportable Observations
Do not report opinions, conclusions, or characterize conditions as "violative." The
determination of whether any condition is violative is an agency decision
made after considering all circumstances, facts and evidence. See IOM
516 involving discussions with management at which time opinions
may be discussed.
Do not quote Regulations (e.g., specific CFR sections) when listing
items.
Do not report observations pertaining to:
512.03 - Annotation of the FDA 483
Annotation of the FDA 483 is required for all medical device inspections.
It is left to the district's discretion whether they wish to annotate
the FDA 483s in other program areas. Annotations of FDA 483s for inspections
in other program areas may be done if both the establishment and the
investigator/team believe annotation will facilitate the inspection process.
When a FDA 483 is annotated it must be done in accordance with the guidance
that follows.
When annotating the FDA 483, it is to be done at the time of issuance
to acknowledge an establishment's promised or completed corrective
action. The annotations are succinct comments about the status of the
FDA 483 item. They are added by the Investigator at the time the FDA
483 is issued and are limited to 4 phrases: reported corrected, not verified;
corrected and verified; promised to correct; and, under consideration.
The establishment should review the annotations on this issued FDA 483
to ensure there are no misunderstandings about promised corrective actions.
(BIMO inspections are generally excluded from annotations.)
When annotating the FDA 483, inform the establishment of the annotation
program at some point prior to the final discussion with management.
Determine from management whether they wish to have their FDA 483 observations
annotated. It is voluntary on the part of the establishment. If the establishment
does not want one or more observations annotated, you must honor the
request.
The actual annotation of the FDA 483 must occur during the final discussion
with management. It is not permissible to pre-print or pre-format the
annotations onto the FDA 483 form. The annotations can be made after
each observation, at the end of each page of the FDA 483 or at the bottom
of the last page of the FDA 483 prior to the investigator's signature.
The following details the requirements and procedures for the annotations
of the FDA 483:
- Reported corrected, not verified.
512.04 - Government Wide Quality Assurance Program (GWQAP)
When performing product acceptance examinations under the GWQAP, you
must discuss all deficiencies with management and report these deficiencies
in writing on the FDA 483. This includes all deficiencies related to
the FD&C Act as well as deficiencies in complying with contract requirements,
which result in non-acceptance. There must be a clear differentiation
on the FDA 483 between these two types of deficiencies.
Enter the FD&C type deficiencies (GMP deviations, etc.) first on
the FDA 483. If there are deficiencies in contract provisions, draw a
line across the sheet and add a heading "The Following Additional Contract
Non-Conformances Were Observed." Enter each deficiency, which forms a
basis for non-acceptance, followed by the reference to the applicable
contract requirement or specification.
512.05 - Distribution of the FDA 483
Be sure all copies of the FDA 483 are legible and distribute as follows:
Original - Before leaving the premises at the end of the EI present
the original to the individual who received the FDA 482, Notice of Inspection,
if the person is present
Copies - Submit the two remaining exact copies with your EIR. One of
these copies may be sent to the top management of the firm including
foreign management, unless the individual to whom you gave the original
is the top official of the firm. With Turbo, only the signed, and any
modified/amended copy(ies) should be attached to the EIR package.
If the inspection covered vehicles as described in IOM
511.02, leave an exact copy of the list of observations with the
firm being inspected. The original will be sent by your district to
the firm owning or leasing the vehicle. You must make every effort
to obtain the name and address of the vehicle owner. Usually the firm
name is on the vehicle; however, it may require a trace of the vehicle
license number. Discuss with your supervisor before taking this step.
See IOM
432.02.
513 - RECEIPT - FACTORY SAMPLES
You must issue an FDA 484, Receipt for Samples, if you collect any physical
sample during an inspection. At the end of the EI and prior to leaving
the premises, issue the original FDA 484 to the same individual who received
the FDA 482. (See IOM
412) If this person is not available, give it to someone else who
meets the definition of owner, operator, or agent in charge. Submit an
exact copy with the EIR. Do not comment on type of examination expected
or promise a report of analysis.
513.01 - Items Requiring Receipt
Issue FDA 484 for any item of food, drug, device, or cosmetic actually
removed from the establishment.
NOTE: A receipt must always be issued to anyone from whom you obtain
Rx drugs. This includes individuals as well as firms. See IOM
412.05 and IOM
439.08(23).
The following are examples of exhibit materials also requiring a Receipt
for Samples:
513.02 - Items Not Requiring Receipt
Do not issue a FDA 484 for:
Firm's management may request copies of documents or records you
obtain from their firm. There is no objection to supplying them.
See IOM
527.05 for procedures when a firm requests a receipt for records
copied during an inspection or investigation.
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Regardless of whether an establishment's
FDA 483 is annotated, investigators and analysts should make every
reasonable effort to discuss all observations with the management of
the establishment as they are observed, or on a daily basis, to minimize
surprises, errors, and misunderstandings when the FDA 483 is issued.
This discussion will include those observations, which may be written
on the FDA 483 and those that will only be discussed with management
during the closeout meeting. Industry may use this opportunity to ask
questions about the observations, request clarification, and inform
the inspection team what corrections have been or will be made during
the inspection process. Investigators are encouraged to verify the
establishment's completed corrective actions as long as the verification
does not unreasonably extend the duration of the inspection.