INSIGHT REPORT
Vol 7#2

2004

INSIGHT REPORT

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Insight Report Vol. 7  No.2

Are you as bad as the FDA483 appears to say you are?

Have you been involved in a FDA audit recently and received a FDA483, List of Observations from the investigator at the conclusion of the inspection? Or, have you been reading the Warning Letters posted on the FDA website (http://www.fda.gov/cdrh/) of other companies that recently had an FDA inspection? If your answers to both questions is “no,” then you may be in for a rude awakening during your next FDA inspection when you see what the FDA thinks of your company if there are any observed deviations from the QSR/cGMP.

The FDA is in the midst of a new policy of trying to make the FDA483s more uniformed from inspection to inspection, district to district and, more importantly, from investigator to investigator. Uniformity of FD483 has been a never ending problem with the FDA: Trying to get every investigator to do their audits the same way and write up their observations in a similar manner has been an almost impossible task. Especially since many investigators have been found to make an error in determining which regulation was actually violated during the inspection, which in turn creates unwanted problems for the agency.

In the effort to make the 483s and Warning Letters more uniformed throughout the FDA, the FDA has come up with a computer program which will provide the headers for the 483. Unfortunately for the company being inspected, the header must be used for a specific observation. This means that though the observation maybe a minor point, the head creates a much different image of the company.

Though 483s are not published on the FDA website like Warning Letters are, they can be requested via FOI from the FDA and these 483’s can be damaging to a company’s reputation. Letting these headers and the actual observations stand as is, should be a great cause for concern in the future.

The following are some actual examples of 483 observations for companies who had recent inspections and had no prior regulatory problems. (We were asked to keep the company’s name confidential).

Example 1. Management Responsibility

483 point stated:

Management with executive responsibility has not ensured that an adequate and effective quality system has been fully implemented and maintained at all levels of the organization.

Specifically:

• Quality Objectives have not been defined, documented and implemented;
•  Personnel have not been adequately trained in the requirements of the Quality Systems regulations;
• Quality Audits did not verify that the Quality System is effective in fulfilling Quality System objectives;
• Deficiencies have been identified in the areas of Design Control procedures, sampling plans, supplier qualification and purchased parts inspection, corrective and preventive action implementation and documentation, Device Master and Device History records, labeling procedures and documentation of labeling acceptance, documentation of employee training, documentation control.

These points alone would lead someone, even a person unfamiliar with FDA regulations, to look at this company and believe they were out of control. A company with this dismal a report could not have had a quality system in place. How could it have had management involved in what was going on, and there should certainly have been defective products with many MDRs and product recalls.

On the contrary, the company was ISO 13485 certified; they had a very strong quality system and had over 10,000 units in the field with no recalls, no injuries or deaths and did not have to file an MDR. Their research and development department took pride in the devices they developed and had followed a strict protocol for design control.

Which leads us to the question: How could an FDA investigator make sure a determination as to what would warrant such an extensive 483 observation for a company that appeared to manufacturing highly regarded and respected products with minimum complaints?

And that is the problem. The FDA investigators are not looking at the forest they are looking at the trees - in this case not even the but the saplings and not the whole picture. If the investigator had taken into account the whole picture and determined what was really important, then the inspection would have provided a true picture of the operations. Instead, the company had to address each issue in their reply to make sure that the next level of review at the FDA had the complete picture of the operations and not just the one that the investigator was painting.

This was ONLY the first observation of a total of over 20 such observations for this company.

A second example of this type of FDA observation hype can be seen in here:

The 483 point stated:

The organization structure is not adequate to assure that quality system requirements are fully met.

Specifically, your organization structure is based on a product-team approach where individuals are responsible for managing certain aspects of the quality system by function, like design, in-process failures, receiving inspection, however, there is not adequate interrelation of all personnel who manage, perform and assess work affecting quality to ensure that the requirements of the quality system are met.

If you were to read this point it would appear that the company did not have a structured organization monitoring the quality system and that things were completely out of specifications. This was contrary to what was actually going on at the company.

The company’s response was as follows:

We are not sure why this point was on the 483. The organizational structure has been used by the company for more than three years and we have successfully manufactured and shipped over 15,000 major instruments in that period of time. We have minimum complaints from the users or the patients on the quality of the devices and we have never had an MDR or recall in that period of time. We do not agree that the quality system requirements are not fully met. There may be areas of improvement and we are continuing to look to improve the operations but our organization structure has proven to work.

As you see, it would appear that the observation did not match the company’s reality. Which was reality and which was a misinterpretation of what was actually occurring? You have to make sure that when you are involved in an FDA inspection that you keep a tight check on the investigator to be certain that if there are problems with inspection and the written 483 points, that you address these points in your response.

It is critical to remember: it is the only time you have to get your voice heard at the next level of review before the issuance on any warning letter or other regulatory follow up.

These two examples are not the only ones you could find when reviewing a company’s 483s or warning letters. This new 483 writing is the cause of great concern to the industry; however, small to medium size companies who are not familiar with what is changing concerning FDA policies are being left in the dark as to what to expect from an FDA inspection and, more importantly, how to react and respond to protect themselves from additional legal problems.

It is paramount to understand that whenever change is made in the name of uniformity, you must be on guard to not be caught in a tidal wave of bureaucratic rhetoric that might affect your company’s image or regulatory history.

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