Contents

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.

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.

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 Program Guidance Manuals 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 time to issue and discuss your inspectional observations. In this case, you should advise the firm's management your inspection has not been completed and you will return to issue the FDA 483 and discuss inspectional findings. There must not be unreasonable and unwarranted delays in issuing and discussing the FDA 483. During the inspection, you must not show the firm's management a draft, unsigned copy of the FDA 483 or an electronic copy of the FDA 483 on your computer screen. You must issue only a signed FDA 483 at the closeout discussion with management. It is appropriate for you to discuss potential objectionable conditions with the firm's management on a daily basis or as you observe them. Prepare the FDA 483 as follows:

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:

1. The original, signed FDA 483 issued to the firm,

2. The modified, signed FDA 483 if the original FDA 483 issued contains an error and/or is annotated, and

3. The signed FDA 483 addendum issued after departing the firm.

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 * * *."

You should not identify other individuals or firms by name on the FDA 483 if the identifying information is not related to the establishment being inspected and/or if the information is not relevant to the specific observation. If the FDA 483 observation requires identification of an individual or firm to support the observation, then you should substitute other non-specific identifying information. Document your evidence in your EIR, fully explaining the relationship(s). For example:

• The lot number for a component received from a particular firm.
• The invoice number for a shipment to a particular firm.
• A patient #, record #.
• The study number for a particular CI site.
• Other necessary but non-specific identifying information to show the observation’s relationship to a particular firm and/or individual.

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.

1. Traditional hard copy FDA 483: This language is to be written or typed on the form until additional hardcopy forms are ordered. Note: it is only necessary to write or type this statement on the first page of a multi page FDA 483.
2. Electronic (non-turbo EIR) version of the FDA 483: Use the updated FDA 483 on the official forms web site to replace previous versions of the electronic version of the document in use.
3. Turbo EIR 483: Turbo EIR Field Agent v.2.5 build 220 incorporates this language in the FDA 483.

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. All deletions will remain visible as strike through text and additions added, preferably in a different font.

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:

1. Foods, drugs, devices, or cosmetics consisting in whole or in part of filthy, putrid, or decomposed substances.
2. Undesirable conditions or practices, bearing on filth or decomposition, which may reasonably result in the food, drug, device, or cosmetic becoming contaminated with filth.
3. Insanitary conditions or practices which may reasonably render the food, drug, device, or cosmetic injurious to health.
4. Careless handling of rodenticides or pesticides.
5. Results of field tests (organoleptic examination of fish, crackout of nuts, etc.) if the results revealed adulteration.
6. Observations of faulty manufacturing, processing, packaging, or holding, of food, drug, or device products as related to current good manufacturing practice regulations including inadequate or faulty record keeping.
7. Observations of faulty can closures and/or deviations from recommended processing times and temperatures.
8. Observations indicating non-conformity with commitments made in a New-Drug Application (or NADA) or in an antibiotic certification or certification exemption form.
9. Observations, forming the basis for product non-acceptance under the Government Wide Quality Assurance Program (GWQAP). See IOM 512.04.
10. Deviations from blood and blood products labeling requirements as specified in 21 CFR 606.121 and 21 CFR 640.
11. Deviations from the animal proteins prohibited in ruminant feeds requirements (21 CFR 589.2000), including labeling deviations.
12. Reserved.
13. Observations indicating drug misuse, failure to maintain proper drug use records, and/or poor animal husbandry practices during tissue residue investigations. See the applicable Compliance Program(s) for guidance.
14. Observations indicating non-conformity with the Medical Device Reporting requirements as specified in 21 CFR 803; the Medical Devices Reports of Corrections and Removals requirements as specified in 21 CFR 806; and the Medical Device Tracking requirements as specified in 21 CFR 821.
15. Observations indicating noncompliance with medical device pre-market notification requirements and pre-market approval requirement under FD&C Act sections 510(k) and 515 [21 U.S.C. 360 (k) and 360e] respectively, should only be made with the prior confirmation of CDRH and/or CBER.
16. 21 CFR PART 200.10 does allow reporting observations noted at a contract facility to the contracting facility. Before doing this, check with your supervisor to determine if this is appropriate.
17. Observations indicating non-compliance with LACF/Acidified food registration and failure to file scheduled processes. Before doing this, verify lack of such, as covered in CPGM 7303.803A

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:

1. Label and labeling content, except per IOM 512.01, items 9, 10 & 11 above.
2. Promotional materials.
3. The classification of a cosmetic or device as a drug.
4. The classification of a drug as a new drug.
5. Non-conformance with the New Drug Regulations, 21 CFR 312.1 (New Drugs for Investigational Use in Human Beings: Exemptions from Section 505(a)) unless instructed by the particular program or assignment.
6. The lack of registration required by Section 510 of the FD&C Act.
7. Patient names, donor names, etc. If such identification is necessary, use initials, code numbers, record numbers, etc.
8. Corrective actions. Specific actions taken by the firm in response to observations noted on the FDA 483 or during the inspection are not listed on the FDA 483, but are reported in the EIR. Except as described in IOM 512.03.

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.

See IOM 512 for discussions of FDA 483 observations with management.

The following details the requirements and procedures for the annotations of the FDA 483:

1. During your discussion of the FDA 483 item, ask the establishment if they want the entire FDA 483 or portions annotated using the specific comments as listed in #2 below. If so, place the annotation on the FDA 483 based on the comment of the establishment and your knowledge. The establishment does not initial or sign the FDA 483 or annotations.
   A reportable item will not be deleted from the FDA 483 because the establishment has promised or completed a corrective action. The investigator will continue to have the latitude to delete the observation if the establishment's response to the observation clearly shows the observation is in error or to clarify the observation based on additional information provided.
2. If the establishment has promised and/or completed a corrective action to an FDA 483 observation prior to the completion of the inspection, all copies of the FDA 483 should be annotated (either following each observation or at the end of the FDA 483) with one or more of the following comments, as appropriate:

   - Reported corrected, not verified.
   - Corrected and verified.
   - Promised to correct.
   - Under consideration.
   The term "verified" means "to confirm; to establish the truth or accuracy". In this case, you must do the verification. In some situations, you will not be able to verify the corrective action unless there is further district or Center review or until there is another inspection of the establishment.
   The actual wording of these annotations may be slightly modified as long as the original meaning is not lost. The establishment's stated objections to any given observation or to the FDA 483, as a whole should not be annotated on the FDA 483.

3. If an observation made during a prior inspection has not been corrected or is a reoccurring observation, it is appropriate to note this on the FDA 483. Note: This is not an annotation, it would normally appear as a header to the observation or as part of the current observation itself.
4. All corrective actions taken by the establishment and verified by FDA should be discussed in detail in the Establishment Inspection Report (EIR) and reported using the Compliance Achievement Reporting Systems (CARS).
   Where the investigator and the establishment have "agreed to disagree" about the validity of an observation, you may annotate this observation with "Under consideration" or with no annotation based on the establishment's desire. If they would prefer no annotation, do not annotate it. The EIR should include the establishment's objections to the observation and the fact the establishment declined to have the observation annotated.
   When an establishment has promised corrections and furnishes a date or timeframe (without a specific date) for completion, then you may add "by xxx date" or "within xxxx days or months" in the annotation. The establishment can, and should, follow-up their annotation to the FDA 483 with a written response. If they cannot meet a commitment made in the annotation, they can explain it in the written response. The establishment also has the option to not comment at the time the FDA 483 is presented and leave their commitments to their written response.

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 and qualifies as "most responsible." If the person is not available or is outranked by someone else, present it to the individual who meets the definition of owner, operator, or agent in charge.

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:

1. Air filter pads,
2. Rodent pellets, and
3. Any other physical evidence actually removed from the plant.

513.02 - Items Not Requiring Receipt

Do not issue a FDA 484 for:

1. Items or materials examined during the inspection but not removed from the establishment (report adverse results of analysis of materials on FDA 483 as indicated in IOM 512.01),
2. Labels or promotional material, or
3. Photographs taken during the inspection.
4. Record(s): including production, quality control, shipping and interstate records.

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.