Antrix, Inc ANTRIX, Inc
Regulatory Affairs & Quality Assurance Consulting Services for
Medical Device and Medicinal Drugs
O 408 733 1199
F 408 730 5959
 info@antrix.com

Response to FDA Form 483 Observations and Warning Letters

1. Service Description

If your company has received FDA Form 483 with observations we can help you in mitigating them and drafting a response letter to FDA.

There will be productivity increase and cost savings of more than 80% using our service. Your company will save money from several thousand to millions of dollars adding to your bottom line profit. T

he FDA Form 483 is referred to as “Notice of Inspectional Observations.” The 483 is issued by the FDA field investigator after an on-site audit and lists deficiencies of the quality system determined by their inspection. The observations contained in every Form 483 are based on the auditor’s interpretation of the regulations as they relate to operational quality system. The observations are then submitted to the inspector’s superiors for review.

The Form 483 with inspection observations is provided at the closing meeting with management team prior to the inspector's departure. Depending upon the severity of the findings, the company may receive an FDA Warning Letter summarizing the finding of the inspection.  The company has to promptly respond to the FDA giving a detailed answer for each item addressed in their letter, and provide a timeline for correcting the issue. These include analyzing the findings of the FDA 483 and/or Warning Letter and propose “Corrective Actions” to be made to the company’s quality system.

If a firm has repeatedly violated cGMP requirements and have not addressed the FDA 483 Inspection Observations and Warning letters, the FDA may make a legal agreement with the firm to force them to make specific changes; the agreement, the consent decree, is enforced by the federal courts. It is in the firm’s interest to address inspection or warning letter findings and be in compliance. It will be even better if the firm always remains in compliance so they do not have to spend time and money on fixing the deficiencies and is cheaper in the long run.


2. Cost Savings - Return on Investments (ROI)

Amount of money saved by your company on using our service based on the company size is provided in the Table 1.0.

Projected savings is based on

  1. Process efficiency gains (people)
  2. Less personnel requirements (people)
  3. Infrastructure efficiency gains (systems)
  4. Infrastructure validation and maintenance (systems)
  5. Delivering quality products
  6. Avoid regulatory noncompliance cost
  7. Avoid regulatory fines cost

Compared to cost associated with company's inefficient internal manual methods, , systems, tools, software’s, and personnel etc. Detailed Return on Investment (ROI) information is available on request.

Company Size Small Medium Large
$Savings > 80 % > 80 % > 80 %
Annual Sales < $100 million $100 million < Sales < $500 million > $500 million
Number of Submissions <= 2 per year 2 < Sub <= 4 per year > 4 per year

Table 1.0 - Amount of money saved by your company on using our service. Company size is based on annual sales as per FDA classification.


3. Solution Approach

We do complete analysis and help to figure out how the company could have avoided the warning letter. The approach we follow can save you lot of money and time.

  1. First we study the FDA inspection time lines including Form 483 observations,
  2. List areas of deficiencies based on non compliance to the regulation as listed in the warning letter summary and
  3. Summarizing how the company can fix the deficient areas to avoid receiving the warning letters and response to FDA letter.

Some of the sample system inspections areas we focus on are:

  1. Quality System
  2. Facilities and Equipment System
  3. Materials System
  4. Production System
  5. Packaging and Labeling System
  6. Laboratory Control System

4. Definitions

FDA Form 483 and Warning Letters:

The FDA Form 483 is referred to as “Notice of Inspectional Observations.” The 483 is issued by the FDA field investigator after an on-site audit and lists deficiencies of the quality system determined by their inspection. The observations contained in every Form 483 are based on the auditor’s interpretation of the regulations as they relate to operational quality system. The observations are then submitted to the inspector’s superiors for review.   The Form 483 with inspection observations is provided at the closing meeting with management team prior to the inspector's departure.

Depending upon the severity of the findings, the company may receive an FDA Warning Letter summarizing the finding of the inspection.  The company has to promptly respond to the FDA giving a detailed answer for each item addressed in their letter, and provide a timeline for correcting the issue. These include analyzing the findings of the FDA 483 and/or Warning Letter and propose “Corrective Actions” to be made to the company’s quality system. If a firm has repeatedly violated cGMP requirements and have not addressed the FDA 483 Inspection Observations and Warning letters, the FDA may make a legal agreement with the firm to force them to make specific changes; the agreement, the consent decree, is enforced by the federal courts. It is in the firm’s interest to address inspection or warning letter findings and be in compliance. It will be even better if the firm always remains in compliance so they do not have to spend time and money on fixing the deficiencies and is cheaper in the long run.


5. Applicable Laws, Regulations and Standards

  1. Title 21 CFR Part 210 Current Good Manufacturing Practice In Manufacturing, Processing, Packing, Or Holding Of Drugs - General http://www.fda.gov/cder/dmpq/cgmpregs.htm
  2. Title 21 CFR Part 211 Current Good Manufacturing Practice For Finished Pharmaceuticals http://www.fda.gov/cder/dmpq/cgmpregs.htm
  3. Title 21 CFR Part 610 General Biological Products Standards http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfCFR/CFRSearch.cfm?CFRPart=610&showFR=1
  4. ICH Q7A  Good Manufacturing Practice for Active Pharmaceutical Ingredients http://www.emea.eu.int/pdfs/human/ich/410600en.pdf