Most common 483s Observation in USFDA

What is Form 483 :

Form FDA 483 Inspectional observations is a form used by the FDA to document and communicate concerns observed during inspections of the site or firm or organization. It is also reffered to as Form 483.


Most of 483 observations in FDA inspections are repeated frequently in different pharmaceutical companies. The same observation is reported many times in a year but companies or the organizations are not focusing on the elimination of these issues. These common issues/ mistakes could be easily eliminated before any inspection.

1. Absence of Written Procedures :

FDA did not find written procedures 197 times in last one year in different pharmaceutical manufacturing facilities. Companies were not following the thumb rule of pharmaceuticals i.e. “Write what you do, do what is written.” About 50% of these were related to stability studies. Documents like Standard operating Procedure, protocols, Standard Test Procedure and especially for stability studies must available for every procedure and product in the company. Most of the companies have written procedures but people don’t follow those procedures and caught in the inspection. To eliminate this issue proper training of the procedures must be provided to all concerned. Employees must be clearly instructed to refer to Standard Operating procedure and Good Documentation practices before starting any operation.


2. Data Integrity Issues :

Data in computer systems was not found secure 125 times during inspection in last one year. Master production and control records and other documents like Standard operating Procedures, Standard Test Procedures and records must be accessible to authorized personnel only. Digital or physical records must be protected and backed must be taken as per schedule.  Data integrity is a common issue in pharmaceuticals now a days . FDA and WHO recently published their data integrity guidelines. This is a frequent issue but very easy to eliminate and don’t require to work hard.


3. Failure to Investigate the Discrepancies :

This issue was observed 107 times in last one year during FDA inspections. Firms were failed to investigate batch failure or any component of the batch which was not within the specified limits. FDA says to conduct a proper investigation for each and every incidence, Out of specification, Out of Trend,event, deviation or failure that happened in the manufacturing facility and in quality control laboratory. Each failed batch or test must be thoroughly investigated to its actual root cause even though the batch is not released for the distribution.

4. Cleaning, Sanitizing and Maintenance :

Cleaning issues in manufacturing are observed 81 times in a period of last one year. Proper cleaning of equipment and utensils used in manufacturing is essential to manufacture a quality product. It is also required to sanitize equipment before its use to remove any microbial contamination. A study must be conducted to find out the hold time period for cleaned equipment during which period equipment can be used without re-cleaning. A study also required to be conducted to find out the dirty equipment hold time study. Cleaning validation study must be conducted to identify the worst case product by considering different aspects like equipment chain, No of batches manufactured per year,Solubility, Cleanability and therapeutic potency etc.

5. Environmental Monitoring :

Environmental monitoring was not found adequate 76 times in different companies in last one year. Many companies don’t take environmental monitoring seriously especially in oral dosages manufacturing facilities. But FDA takes it seriously too and expects environmental monitoring to be followed in oral dosages forms like sterile facility. A proper environmental monitoring program must be prepared and implemented in all classified  areas of the facility. Environmental monitoring shall be performed with schedule interval and trend shall be prepared and should be monitored .


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