Highlights on FDA Terminologies

Form 482:

It is also known as a “Notice of inspection” it is an official document that FDA auditor present on his or her arrival to the site that is to be audited.

Form 483:

An FDA 483 observation is formally known as “inspectional observation,” it is a notice sent by the FDA agency to the firm (that was audited by the FDA agency) to highlight any potential regulatory violations found during an inspection i.e. any violation related to facility, equipment, processes, controls, products, employee practices, or records which indicates that any food, drug, device or cosmetic is being prepared, packed, or held under conditions may become adulterated or becomes injurious to health.

At the conclusion of an inspection, the FDA Form 483 is presented and discussed with the company’s senior management and is issued at the end of the inspection when an investigator found any condition or practices which is violation in their judgment from the regulatory act.

When you get FDA 483s, you need to respond and do so within 15 business days.

Form 484:

It is also known as a “Request for Samples”, by showing this form FDA inspectors can collect samples from the site for further investigation but they have to issue a receipt of samples.

Warning letter:

The warning letter will be issued if there is a deficiency or violation in pharmaceutical or medical device operations. These letters tell that FDA-regulated product has a severe violation that requires to take immediate action.

The warning letters are issued publicly so can create a lot of issues for the organization. If organization fails to respond quickly to an FDA warning letter, there can be civil fines, product seizures, product recalls, and more. Occasionally, serious FDA violations that involve irresponsibility, there can even be criminal prosecution.

If one receives an FDA warning letter, organization will have a few weeks to respond it.

When you receive Warning letter, you need to respond and do so within 15 business days.

Establishment Inspection Report (EIR):

EIR is an entire narration of what the FDA investigator / inspector did during the time spent at the establishment (facility), from the stage of introductions till the handover of the inspectional observations (termed as Form FDA 483).?

An EIR provides a wealth of information regarding the site, conduct, and outcome of an inspection.?It is particularly useful for firms to understand what areas the FDA focuses on and how the FDA reviews documents.

Based on the review of EIR by the Competent FDA center, it assigns any of the one category from the following 3 categories to the audited organization.

No Action Indicated (NAI)

It means no objectionable conditions or practices were found during the inspection (or the significance of the documented objectionable conditions found does not justify further action).

The No Action Indicated is the best category a plant can get from the USFDA. This category means it is a green signal for the plant to function as is and the USFDA is satisfied with the state of the plant post the inspection.

An NAI is issued when there are no observations issued to the facility at all during the inspection or are extremely benign.

Voluntary Action Indicated (VAI):

It means objectionable conditions were found and documented but the regulatory agency is not prepared to take or recommend any regulatory action.

This is the second-best category that a plant can get from the USFDA. This classifies that ‘Objectionable conditions or practices were found during the inspection but the agency is not prepared to take or recommend any administrative or regulatory action’.

A VAI is generally issued when a plant receives observations, and responds to them and the regulator believes the response by the company is satisfactory. It is then up to the regulator agency whether they would like to reinspect the facility to assess the remediation.

A VAI recommendation implies that the facility needs re-inspection within 12 months at the earliest, but no later than 24 months.

Official Action Indicated (OAI):

It means objectionable conditions were found and regulatory action should be recommended.

Facility is considered to be in an unacceptable state of compliance with regards to current good manufacturing practice (cGMP).

Facility may be subjected to a cGMP regulatory, or enforcement action based on the inspection, and FDA may withhold approval of any pending applications or supplements in which this facility is listed.

In short this is the strictest regulatory category in which USFDA defines it as regulatory and/or administrative actions that will be recommended on the plant. It means that the regulator issued observations to the plant and was not satisfied with the response provided by the company to the agency.

The regulator can then decide what further action can be taken on the plant, which could be a quicker reinspection, slower approvals as severe as a warning letter or even an import alert.

Plants with OAIs are generally required to be reinspected by the USFDA officials to give it an all-clear.

This article is for those friends & colleagues who have newly joined the pharma industries & this article is just to enlighten the knowledge about the terminologies used by the USFDA regulatory bodies during the inspections.

Thanks for reading.

Regards,

Shailesh Mewada