How Warning Letters and Form 483 are issued by the Food and Drug (FDA) after the inspection of a drug manufacturing site

A lot of pharmaceutical professionals have confusion between Form 483 and Warning Letters. Both of these are issued by Food and Drug Administration (FDA) after a regulatory inspection of manufacturing facility and both are the way of communication.

 

Form 483: Form 483 is used by the FDA to communicate the inspection observations. All observations are listed in descending order of their importance. Form 483 is issued at the manufacturing site after the completion of the FDA audit. In other words FDA officials communicate their inspection observations on Form 483.

 

Handling the Form 483:

● At the time of conclusion on inspection, findings should be discussed with the inspector and try to resolve the negative observations before the inspector leaves the site.

● Consult the errors and miscommunications with the inspectors

● Try to understand the message sent by the regulatory agency i.e. their positive or negative mood.

● Ask the questions regarding confusions found in the observations.

● Try to convince the inspector on observation with more related information on the observation. It may help to delete the observation from Form 483.

● Respond the Form 483 within the 15 days otherwise regulatory agency will not consider it during the decision on the company. 

● A good response to the Form 483 may avoid the issuance of a Warning Letter.

 

 

 

Warning Letter: After the issuance of Form 483 and completion of inspection, 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 FDA after the review of the inspection observations. It contains evidences and detailed explanations for the observations.

 

A Warning Letter should be replied within the given time because delay can lead to the import ban. It may be asked for extension of the time to justify the things.

Generally FDA concentrates on the quality of the product and does not compromise with the product quality. Most of the Warning Letter issued by FDA has the quality or cGMP issues.