FDA Form 483 and Warning Letter, How do differ from each other?

FDA Form 483 and Warning Letters:

It is very important to know how the Warning Letter and FDA Form 483 are issued by the Food and Drug Administration (FDA) after an inspection of a particular drug manufacturing site.

FDA Form 483 and Warning Letters are often confusing for many pharmaceutical professionals, who cannot properly differentiate between the two. Both communications are issued by the Food and Drug Administration (FDA), usually after a regulatory inspection and never before a regulatory inspection.

FDA Form 483

FDA Form 483:

Form 483 lists observations in order of importance that FDA inspectors record during manufacturing site inspections. Each observation noted on the FDA Form 483 is clear, specific and significant and FDA investigators are specially trained in the matter.

FDA officials communicate their inspection observations on Form 483, and it is usually issued to the manufacturing site after the FDA audit is completed. Observations are not generally made until the investigator’s judgment, conditions or practices observed that any food/drug/device/cosmetic has been adulterated/changed intentionally to its standard practice.

After completion of the Inspection, FDA Form 483s, are discussed with a company’s senior management, regarding the observations of the inspections. To get a full understanding each observation is read and discussed with the company’s senior management so that they get the actual situation regarding inspection observations.

An FDA Form 483, is a report, it does not contain any observations of questionable, or unfamiliar significance at the time of the inspection of a specific firm. It only reports on familiar objectionable conditions. which are observed during the inspection. even if it can’t report other objectionable conditions which didn’t notice during the inspection. The company/Firm is only responsible. to correct the objectionable conditions which are noticed after the completion of the inspection on the due date.

How to handle FDA Form 483?

Upon completion of the FDA inspector’s manufacturing site inspection, the manufacturing site authority should discuss all findings with the FDA inspector and make every effort to resolve negative observations before the inspector leaves the site.

If errors and miscommunications occur, it is best to consult with inspectors.

Try to understand the positive or negative mood of the regulatory body; Their mood can be negative for various reasons or for no reason at all.
Without any hesitation ask any questions to the inspector regarding confusion found during observations.

If you think, you can convince the inspector. Try to convince the inspector/inspectors regarding observations found during inspection with the help of related information. Your convincing power may help to delete some observations from FDA 483.

The purpose of an FDA Form is to notify the company’s senior management regarding objectionable conditions. The FDA Form 483 is presented and discussed with the company’s senior management after the completion of the inspection. Senior management of the Companies is encouraged to respond to the FDA Form 483 with a corrective action plan within the due date.

See Practical Example of

Form 483:

Form 483 for Stryker Craniomaxillofacial Division. Portago, MI.

Form 483 for Teva Parenteral Medicines, Inc. Irvine, CA. Form 483.

Form 483 for Cipla Limited Compliance Record.

Form 483 for Ranbaxy Laboratories Limited.

Form 483 for Lupin Limited.

Warning Letter

Warning Letter for Cipla Limited.

Warning Letter for BioMD Plus LLC.

Warning letter for Walmart inc.

Warning letter for Elements brands inc.

Warning Letter for Alber GmbH.

It is mandatory to respond to the FDA Form 483 within 15 days otherwise regulatory agency will not consider your response regarding the final observation of your company.

FDA Form 483 is not the final decision maker. It just considers along with a written report known as Establishment Inspection Report. All evidence or documentation collected from the manufacturing site, response made by the company/firm. The agency considers all of the information and then they made the final decision for further action.

You may avoid the issuance of a Warning Letter if you respond to FDA Form 483 within due time with appropriate justification.

Form FDA 483 content

Header information

It contains the following information:
[] FDA district office Address and phone number
[] Date(s) of inspection
[] Facility’s FEI [FDA Establishment Identification number].
[] Name and title of the individual to whom the 483 is issued
[] Address of the facility that was inspected and
[] Brief description of the type of facility


This section presents all the listed observations made by FDA investigators [Number of Investigators may be one to three persons or as per FDA policy]. This section contains all of the inspectional observations and this is not the final agency decision. You can consult with the FDA investigator regarding the observations and also can share your plan and implementation regarding observations. If you have any questions you can contact with FDA with the header section and contact number.


During the final discussion, the actual annotation of the 483 occurs with the firm’s management. If the firm management prefers no annotation, then it will not happen. Annotations may be placed at the end of each page or at the last page of the observations where the investigators generally put their signatures. In 1997 FDA introduces an annotation policy for medical device inspections.


For multiple pages, the FDA investigator’s signatures have on the first page and the last page only other pages only initialed. All investigators’ names are printed and signed, & issue date is recorded in this section. FDA investigator’s title may be included there.

Reverse side

This side contains some instructional text regarding Food, Safety, and device cosmetics. And also contains some instructions regarding FDA investigators to their nature of work in the inspected site. All the instructions mention these sections are backed by their specific reference such as

-Pursuant to Section 704(b) of the Federal Food, Drug, and Cosmetic Act
-Section 704(b) of the Federal Food, Drug, and Cosmetic Act

FDA Warning Letter

Warning Letter:

The next step after issuing FDA Form 483 is Warning Letter. FDA may issue a Warning Letter to the manufacturing site which has already been visited and inspected by FDA Inspector. Serious violations of the quality of the product may lead to the issuance of a Warning Letter. Generally, Warning Letter is issued by the higher officials of the FDA after the review of the inspection observations and especially reviewing the product quality matters.

After the issuance of FDA Form 483 and completion of the inspection, a regulatory agency may issue a Warning Letter to the manufacturing site. When any serious issue is found regarding the quality of the product, a Warning Letter is issued by the higher officials of the FDA after the review of the inspection observations. It contains evidence and detailed explanations for the observations. FDA high officials generally concentrate on the quality of the product and do not compromise with it.

A Warning Letter should be replied to within the given time because a delay can lead to an import ban. It may be asked for an extension of the time to justify the things. Most of the Warning Letter issued by FDA high officials has the quality or cGMP issues of the product or facility.

You may easily find both FDA Form 483 and Warning Letters on their website due to these are published immediately publically on and anyone can get it.

Type of warning letter

General FDA Warning Letters
Tobacco Retail Warning Letters
Drug Marketing and Advertising Warning Letters

General FDA Warning Letters

This type of warning letter is issued when FDA found that the manufacturer has significantly violated FDA regulations. Poor manufacturing practices, problems with claims for what a product can do, or incorrect directions for use lead to the issuance of General FDA Warning Letters. The problem mentioned in the warning letter must correct by the company and the action plan to be shared with FDA and subsequent interaction may change the status of the issues mentioned in the letter.

Tobacco Retail Warning Letters

tobacco retailers occur periodically face Compliance check inspections under the Family Smoking Prevention and Tobacco Control Act (Tobacco Control Act) and the Regulations Restricting the Sale and Distribution of Smokeless Tobacco and Cigarettes to Protect Children and Adolescents. Cigarettes and smokeless tobacco also include in compliance check inspections.

Drug Marketing and Advertising Warning Letters

Letters are collected and sorted by month and only cover drug marketing activities. Some of the letters may be edited to remove confidential information. Letters sent electronically may be engaged in illegal activities.

Close-Out of Warning Letter

Warning Letter “close-out letter” issued by FDA. Once the agency completed the evaluation of corrective actions taken by the manufacturing site in response to the Warning Letter and the agency found the corrective action satisfactory then the agency may issue a close-out letter. A ‘close-out letter’ will not be issued depending on some action taken by the firm. The corrective action must be verified by FDA. The agency expects that corrections have been implemented and verified by follow-up inspection.

If any violations exist that can’t be corrected then no “close-out letter” will issue. Future FDA inspection may further assess the violations and enforcement action may be taken without prior notice.

FDA Form 483 and Warning Letter, How do differ from each other? Read More »

Audit Checklist for HR Department in Pharmaceutical Company

Audit Checklist for HR Department: here is the Audit Checklist for HR Department. You can find the best checking point for HR [Human Resources] Department in pharmaceutical Company-

Audit Checklist for HR Department
  1. Career Development Programme
  2. Company business strategy
  3. Company Policy
  4. Control of Entry with illness and open lesion
  5. Cleaning and sanitization records
  6. Departmental Organogram
  7. Dust control and Management Record
  8. Employee list of Organization
  9. Employee Retention Programme
  10. Environment Health and Safety Programme
  11. Entry/Exit Register Management
  12. Final Settlement Procedure
  13. Firefighting System
  14. Fire drill Programme
  15. Human Resources Programme
  16. Handling of laundry procedure
  17. Handling of sewage during production factory
  18. Handling of Accidental hazard and record keeping
  19. Handling of ETP sludge
  20. Identification of Fire Assembly Point
  21. Induction Training Record
  22. In-plant training Management
  23. Job description of Employee
  24. Leave Management Process
  25. Leave Management Process
  26. List of First Aid Item
  27. List of Departmental SOP
  28. Manpower Development Plan
  29. Medical Checkup process for new comer
  30. Previous Audit Report and Incomplete Action Plan List
  31. Pest and Rodent control procedure
  32. Recruitment Process
  33. Short leave/Emergency Leave Register
  34. Training Need Assessment
  35. Yearly Training Calendar
  36. Waste Management Procedure

SOP on

  1. Canteen Facility Management
  2. Charge Hand Over and Take Over of Security Department
  3. Cleaning Procedure for Insects Killer
  4. Company Policy for Visitors
  5. Dress Coding System and Gowning Procedure for Working Personnel and Visitors
  6. Employee Motivation
  7. Entry & exit procedure
  8. Factory gowning management
  9. Factory Gowning Cleaning and Management Procedure
  10. First Aid Kit Management Procedure
  11. House-Keeping and Cleanliness
  12. Induction of the New Employee
  13. Laundry Procedure for Working Dresses
  14. Medical Examination of the Working Personnel
  15. Measures for the Working Personnel at the Plant
  16. Management of Personal Protective Equipment (PPE)
  17. Occupational Health and Safety
  18. Organizational Behavior
  19. Process of Pest and Rodent Control at the Plant Premises
  20. Sanitizing Procedure for Sink and Floor Drain Sanitization
  21. Security Awareness
  22. Selection and Recruitment of Manpower
  23. Training of Employee

This all about the Audit Checklist for HR Department but not limited to.

Audit Checklist for HR Department in Pharmaceutical Company Read More »

Audit Checklist for IT Department in Pharmaceutical Company

Audit Checklist for IT Department: here is the Audit Checklist for IT Department. You can find the best checking point for IT [Information Technology] Department in pharmaceutical Company-

audit checklist for IT Department
  1. CD and Software List
  2. Departmental Organogram
  3. Departmental Objective
  4. Data backup schedule with frequency
  5. Installed Software list for different equipment’s
  6. IT policy and its application
  7. List of technical personnel and their training Certificate
  8. List of Approved Password for user and Administrative Password for System control
  9. List of Password Management for Emailing Account [Including Outlook and Webmail like Zimbra web client]
  10. Personal Computer list with ID
  11. Preventive Maintenance schedule for PC’s and Laptop
  12. Service Record Keeping Logbook
  13. Update Antivirus Software List
  14. Valid Certification for Installed Software

This all about the Checklist for IT Department but not limited to.

Audit Checklist for IT Department in Pharmaceutical Company Read More »

Audit Checklist/Self Inspection Checklist for Quality Control Department

Audit Checklist: Here is the tentative Audit checklist [Internal Audit/Self Inspection Checklist] for Quality Control Department. You may follow the below list at the time of Audit [Internal Audit/Self Inspection] for Quality Control Department-

1. Approved Departmental Organogram.

2. Approved vendor List of Raw and Packaging Materials.

3. Acceptance Record of Raw Material and Packaging Material.

4. Approval or Rejection of Materials and Products.

5. Controlling method of  

  • Purchase
  • Primary Packaging and   
  • Printed Packaging Materials

6. Data Verification based on Logbook and Chromatograms.

7. Document retrieval and achieving Procedure.

8. Collection of retained sample and retrieval system.

9. Certificate of analysis.

  • Primary data
  • Checking of calculations
  • Preservation of primary data

10. Certification of Products for Release.

11. Chemical Reagents consumption records.

12. Calibration Record Keeping for the instruments.

13. Calibration schedule/calendar of instruments.

14. Disinfectant effectiveness testing based on different concentration.

15. Documentation

  • Material receiving report
  • Preservation of original data
  • Final report
  • Communication with related department e.g- Supply chain, Warehouse, Accounts

16. Health checks for all personnel

  • Pre-employment
  • Yearly
  • Record

17. In-process analysis (Specification & method)

  • Currently revised
  • Revision procedure
  • Validation
  • Approval

18. Instruments SOPs of operation, maintenance & calibration

  • Operation Logbook
  • Calibration
  • Servicing
  • Documentation

19. Investigation of Test Failure.

20. Job Responsibilities of all personnel are available.

21. List of Reagents & Solvents.

22. Laboratory Reagents

  • Identified
  • Tested
  • Expiration dated

23. Maintaining of Reference Number for

  • Specification
  • Starting materials (both RM & PM)
  • Finished products
  • Certificate of Analysis

24. Management of HPLC columns.

25. Method for Identification of each starting materials container.

26. Management of Working Standard/Reference Standard.

27. Management of analytical worksheets.

28. Method Validation of Testing Product.

29. Maintain and storage of HPLC Column and column suitability test.

30. Management of Control Sample.

31. Practice and Record keeping of OSS with action plan.

32. Personnel engaged in analytical activity.

  • Personnel Hygiene
  • Lab Coat

33. Prohibited in working area

  • Smoking
  • Chewing tobacco
  • Eating/ Drinking

34. Preparation and record keeping of working standard and volumetric solutions.

35. Record Keeping of

  • Sampling
  • Inspection and
  • Testing procedures

36. Reference Standard

  • Evaluation
  • Maintaining
  • Record Keeping
  • Logbook Entry
  • Storage

37. Receiving Record of

  • Reagents
  • Chemicals
  • Culture Media

38. Retesting procedure

39. Received Material

  • Sampling Plan
  • Sampled Quantity

40. Real Time & On-going Stability Study Calendar/Schedule.

41. Qualification [DQ, IQ, OQ & PQ] records of Oven.

42. Real Time & On-going Stability Study Sample Receiving Record.

43. Real Time & On-going Stability Study Failure Investigation.

44. Real Time & On-going Stability Study Report Evaluation, Recommendations and Conclusion.

45. Safety

  • Fire extinguishers-adequacy
  • First aid-adequacy
  • Possibility of potential electrical hazards

46. SOP on cleaning

  • Glass apparatus
  • General cleaning of department

47. SOP on Material Coding System.

48. SOP on calibration of measurement equipment.

49. SOP on Handling of breakdown of stability chambers.

50. SOP for sampling of

  • Starting Materials
  • Bulk Materials and
  • Finished Products

51. SOP for

  • Label and labeling system
  • Packing Materials handling
  • Handling of the raw material
  • Reanalysis
  • Testing of Market Complaints Sample
  • Testing of Recalled Products
  • Return products

52. Stability study

  • List of products under stability study
  • Stability protocols & reports
  • Temp. % RH monitoring records of the stability chambers

53. Shelf life extension programme based on Real Time Stability Study.

54. Stability Study Record of Primary packaging materials.

55. Standardization of volumetric solution & documentation.

56. SOP for Sampling and Management of Raw Materials, Packaging materials.

57. Sampling of Water System.

58. Specification & Methods

  • Currently revised
  • Revision procedure
  • Validation
  • Approval

59. Standard Lab requirement availability

  • Adequate facilities
  • Trained persons
  • Analyst Validation
  • Approved procedures

60. Standard documented system for

  • Specification
  • Sampling
  • Testing and
  • Release of materials and products

61. Testing

  • Physical
  • Chemical
  • Microbiological/ Biological

62. Tolerance of Electronic balances.

63. Testing of Validation Batch/Scale Up batch Record.

64. Temperature and Relative Humidity Monitoring Record of Oven Humidity chambers.

65. TLC qualifications are document keeping.

66. Validated Excel Sheet for Calculation.

66. Working standards & reference standards.

  • Maintenance
  • Documentation
  • Listing

1. Air Sampling plan of Specific Area .

2. Autoclave validation Record.

3. Autoclave operational Record.

4. Bacterial Endotoxin Test[BET], Sterility Test, Environmental Monitoring Test failure investigation report.

5. Calibration records of equipment’s.

6. Calibration & Recording keeping of Micropipette.

7. Calibration records of measuring devices.

8. Calibration record for heating block for BET.

9. Disposal of microorganism, used culture media, used plates etc.

10. Environmental monitoring records.

11. Growth promotion records of media.

12. Environmental Monitoring and Water Analysis Record.

13. Filter integrity tests record for filters of LAF.

14. Incubators calibration Record.

15. LAF Validation schedule.

16. Microbial culture management.

  • Name of the organisms
  • ATCC/NCTC numbers
  • Sub-culturing of organisms
  • Preservation of microbial culture

17. Master list of SOPs, specifications & methods are updated.

18. Operational Logbooks .

19. Preventive Maintenance schedule for LAF filter cleaning.

20. Record Keeping for Bacterial Endotoxin Test[BET] and Sterility Test.

21. Stock stains available.

22. Testing area.

  • Adequacy of space
  • Adequacy of equipment
  • Cleanliness

23. SOP for

  • Gowning and De-Gowning Procedure Though the Change Room of Microbiology Area
  • Management of Water Sampling and Testing
  • Microbial Disposal of Waste Media
  • Operation of Colony Counter for Microbiology
  • Cleaning and Sanitation of Microbiology Laboratory
  • Operation and Maintenance of Single Door Autoclave
  • Operation, Calibration and Maintenance of Laminar Air Flow Cabinet
  • Operation and Maintenance of Bacterial Incubator
  • Operation and Cleaning Procedure of Oven
  • Preparation and Preservation of Microbiological Media

24. Temperature charts and records of BOD incubators

25. Validation of autoclave machine

26. Validation of LAF

27. Validation Record of BET kit

28. Water monitoring records

This is all about the Audit Checklist [Internal Audit/Self Inspection Checklist] for Quality Control Department [QC & Microbiology Lab] [but not limited to]

Audit Checklist/Self Inspection Checklist for Quality Control Department Read More »

error: Content is protected by !!