In your role, you’re likely responsible for vetting potential supplier partners on behalf of your hospital or GPO. You’ve undoubtedly been asked to request each Form 483 and decipher the unnecessarily complex jargon of the FDA. Mosaic by design, it is extremely important that you know how to properly interpret an FDA Form 483.
According to the FDA, the issuance of Form 483 is one of the tools in their enforcement bag. The purpose is to attempt to extract a voluntary correction of objectionable conditions by the agency. Remember, the issuance of a 483 is not the final regulatory action available to the agency. Not everybody that gets pulled over on the road gets a ticket, but it certainly sends a message that the rest of the cars in the area need to exercise caution.
In addition, even if an organization is a Form 483 recipient, at the close of an inspection, does not necessarily translate into a warning letter. Upon conclusion of an inspection, the FDA investigator is tasked with writing the Establishment Inspection Report (EIR). The completed EIR will be reviewed at the local district office; and if the reviewer believes the content and evidence depicted in the EIR points to serious deficiencies in an establishment’s quality system, then a warning letter will be issued.
Additionally, as of April 2009, the agency has adopted a policy of automatically issuing warning letters to establishments failing to respond to a Form 483 within the allotted 15-days.
When it comes to the actual form, you need to carefully review the following:
The first thing that must be understood is the context. This is important because only with a general understanding of the nature of the problem can one figure out the true nature of the letter. This might seem like a simple task but understanding the context can sometimes be a problem.
The reason for this is the 483 does not inform you the true nature of the problem. On the contrary, what they tell you is actually something else:
2.) Severity of the Problem
What you actually get in the 483 is the scale of the problem. The information provided is observations by the FDA in terms of severity or impact. Organizations are given an indication of the severity of the problem, but not the root cause. That is for them to investigate and remedy.
There is a reason why this happens. It has to do with the manner these letters are sent out. The department has fairly industrialized the process to the point where it has reduced the whole process to simple software. The way that this process works is through the selection of a suitable category of problems from a drop down, after which the rest of the letter follows. This can be rather confusing predicated on the nature of the problems. It is essential to review the content after the drop-down menu entries starting with “specifically”. This is where you will find the true comments about the facility being reviewed.
3.) Issue of Extensive Examples
Adding to the vagueness of warning letters is the issue of extensive examples. The FDA often provides a list of different examples pertaining to potential issues that could have triggered the warning letter. The organization must then determine the exact nature of the issue since there can be several different possibilities. In the end, it is possible that none of the examples apply at all.
This is a good indication when it comes to the true nature of the problem in the facility. Short 483s indicate that it could be a trivial issue. Longer ones on the other hand can be more serious in nature. They may range from a single serious issue to several problems existing simultaneously.
5.) Data Integrity Issues
The indication that there could be issues with data integrity is particularly problematic. This is because it is often an indication that there could be potentially multiple problems affecting all systems across an organization.
6.) Mention of Repeat Observations
Another issue is that of repeat observations in a 483. When several observations are repeated as being potential problems, it is much more serious than the first instance of an observation and may likely result in a warning letter.
7.) The Nature of Enforcement
An important thing about the way the US FDA enforces these policies is that they are largely progressive in nature. They seek to enforce compliance in a voluntary manner versus forcibly. Rather than trying to penalize facilities at the first sight of a potential problem, they try to ensure that any necessary changes are carried out voluntarily.
It is only in the case of repeated violations and a general refusal to comply with these requests that the FDA becomes strict. As a whole, the issuance of a 483 is not an indication that something has gone wrong. Almost all 503B organizations have been issued one, and those that haven’t probably have not been inspected yet.
In your evaluation of various facilities, it is important to take all 483’s seriously. Organizations should be open and transparent and provide you with a copy of any letter received (although they are often redacted to remove proprietary information). They should also be able to provide you with a detailed plan on how they are in the process of resolving any outstanding issues, and how they have communicated that information to the FDA.