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Insight Report Vol. 8 No.1

The FDA - “A tale of two inspections”

There is a saying that goes, “the more things that change the more they stay the same”. When it comes to the FDA inspection, this saying holds a lot of truth.

The FDA investigator’s role has not changed. When I was with the FDA way back in the 70’s, we were taught at our orientation classes that we were the “EYES and EARS” of the FDA. It was our job to conduct inspections of manufacturing companies and to determine if that company was in compliance with the required regulations - the GMP (now called the QSR for the medical device industry).

The FDA field investigator is still considered the “EYES and EARS” of the FDA. But after all this time, one would think that the FDA investigators would have been able to become more sophisticated in how they conduct their inspections.

With the advent of Global Harmonization and with the U.S. Congress allowing third party audits of medical device companies; and, with companies meeting the ISO-13485 standards as well as in QSR compliance, one would think that the FDA investigators would have a new perspective in viewing how companies are complying with the regulations.

Yes, we all know and understand that companies are supposed to follow each and every section of the regulation and maintain the required documentation to be able to assure full compliance. The only way the FDA Investigators can determine if a company is in compliance is to inspect the documents. After all, inspections are only supposed to take 4 to 5 days - if they are following the QSIT (quality system inspection technique) approach for conducting inspections.

Unfortunately, for many companies new to the FDA inspection, and there are many companies that still have not been audited by the FDA or had their last audit over 5 years ago, that fall prey to the FDA investigators’ myopic inspection approach.

In the past year we have had two clients who have come across such an experience: In both cases the FDA investigator was professional, treated as such by the companies, and given carte blanch to the documents and facilities. Both companies felt that they had nothing to hide and they were both very proud of their achievements and products. Both were ISO 9000/2000 or ISO 13485 certified.

Yet, both companies were left reeling and licking their wounds after they were issued a lengthy 483 list of observations by the investigator at the conclusion of the inspection.

These two cases were not in the same FDA district nor were they inspected by the same FDA investigator. However, if you look at each of the 483s and take a hard look at the company and their products, it was more than obvious that the FDA investigators did not see the forest, only the trees. We are fully aware of the importance of the complete documentation and of being in compliance with the QSR requirements. But, is there room for the FDA to look at a complete picture before just writing up a long and drawn out 483?

In the first case, the company contacted mdi upon the receipt of the 483 and asked for assistance in responding to the listed observations. There was eleven (11), yes, eleven pages of observations.

In the second case, the company - not familiar with the FDA or its practices - took the FDA investigator’s word that they should just notify the FDA that they will correct the observations. Because the company failed to take the issuance of a 32 point 483 as the start of a possible legal action, it did not make the appropriate response and ended up being issued a Warning Letter. We were called in after the Warning Letter was issued and asked to assist with responding to the FDA.

In both cases, if the 483 was read as a stand alone document, the assumption would have to be that both companies were completely out of control and any possible customer or person would think twice before purchasing or using any of their products.

That is the major fault with the FDA 483. It is a one-sided document that if it is not properly responded to will be accepted as gospel and the FDA will build a case against the company. Remember, FDA investigators are considered the “EYES and EARS” of the agency and it is their observations and documentation that is used for building a case. Unless, and let me repeat, unless you are able to dispute their observations or are able to shed some light on the observation and show that it did not affect the quality or safety of the finished device, you can be certain that the FDA will continue with their required line of regulatory follow-up.

We try to explain to our clients that FDA investigators are just that, investigators. They are taught how to investigator and document regulatory issues for building a case against violators. They are not your friend; they cannot be your friend. As they say at the opening of the Apprentice television show, “It’s nothing personal, it’s just business.” You can apply this same approach to the FDA inspection. But, unlike the Apprentice, where you just get fired for not producing, it is not the same with the FDA. The reality here is that if you don’t know how to defend your company the consequences can be enormously damaging.

In both of the above examples, the FDA investigators were not looking at the whole picture; rather, they looked only at each little point before deciding to make a “Federal Case” out of it. From our experience the FDA investigators are basically not allowed to look at the whole picture in order to make their determinations. The whole picture of your company, unfortunately, is not their job.

Therefore, it is very important for you to look at each observation and determine in what context this observation was made and how did it affect the quality of the production or final product. I can tell you for certain the FDA investigators’ objectives are a lot different from your company’s, although, one would think that they would both put the safety of the public or quality of the product on the top of their list.

Let’s look at the successes of both companies up until the FDA had conducted their inspection.

Both companies were in business for over 40 years. Both had thousands of their products distributed and sold and still in use. In the past 10 years or more, neither company had a product recall or made an MDR (medical device report made to the FDA in the case of a death or serious injury involving their device) report to the FDA.

Based on that information alone, one should be able to conclude that the companies’ operations and products were of the highest quality, with a fully implemented and functioning quality system in place. Unfortunately, common sense and background doesn’t always work out the way you think it would.

It is also very interesting that the management staff of both of these companies had the same questions as to what the FDA was attempting to accomplish with their inspection, “What was the FDA looking for and why were they so difficult to deal with?” One thing is for certain, if you have been involved in both ISO certification and FDA QSR compliance, (and they are both quality systems) the way they are audited against and perceived by the auditor is completely different. Being ISO certified will not in anyway assure that you will pass an FDA audit. On the other hand, being in FDA QSR compliance will put you closer to meeting the ISO standard.

This wasn’t a report on the differences between ISO and the QSR, but you should be aware that they are not the same and not audited to the same level. The ISO audit is for management system and customer satisfaction, while the QSR audit is for product specifications and safety.

Let’s get back to the two cases. In the first case, where the company asked for assistance in preparing a response to the 483, we were able to address each point in a manner that cast a different light onto the observation. It made the compliance officer (the next level of oversight prior to the issuance of a Warning Letter or any other additional action) look more closely at what the investigator was observing as a violation. Be warned, once the investigator concludes the inspection your response to the 483 is the only chance you get to rebut the investigator’s observations put on the 483. Without a well documented and prepared response, the only opinion the FDA compliance officer will see and hear is that of the investigator. This more often than not will put you in a precarious position and end up in additional regulatory action, i.e. Warning Letter (which is usually the next level of regulatory action on a first time violation).

We were able to develop a very comprehensive and appropriate response to each observation, by working closely with the company’s management that participated in the FDA inspection (since we were not present during the inspection). We took each point and determined why the investigator made that particular observation and then looked at how the observation affected the operations and the quality of the finished products.

Where the observation may have been correct, we responded with the appropriate follow up including the corrective action and time frame for completion.

This company, that had called us in to assist with responding to the 483, did not receive a Warning Letter. Remember they had been issued an 11 page 483. Here, the FDA felt that our response was adequate as well as appropriate and that they would review the corrective actions during the next inspection.

In the second case, for the company that received the Warning Letter, this put constructing the response in a much different position. In that the response to the 483 did not provide any contradiction or rebuttal to the observations, the FDA had only one opinion as to the condition of the quality system and the company’s compliance. Similar to constructing the response to the 483 in the first case sited, we had to also work closely with the company’s management staff to determine why each point was made by the investigator; but, in this case, since the FDA proceeded with the next level of regulatory compliance it was hard to counter each observation unless we had strong evidence in the form of proper documentation. This situation required that we respond to each observation and come up with a corrective action that was appropriate. It will be up to the FDA to determine if our response was adequate and if they want additional information. Now we have to continue to work closely with the FDA to assure that the Warning Letter is ultimately rescinded to allow for normal compliance activities to continue.

As you can see, dealing with the agency is not cut and dry. The FDA inspection does not end at the time of the closing meeting with the investigator when he hands you the 483. As a matter of fact, how you respond in writing to the 483 can be more critical to the inspectional outcome and the decision making process by the Agency. Taking a wait and see approach will most definitely be costly in the end.

For comments on this Insight Report, please email us at info@mdiconsultants.com

The next Insight Report will be on the FDA Affidavit.

If you have any comments on these INSIGHTS we hope that you let us hear them. If you have any of your own INSIGHTS that you feel would be of value to other companies, we would be pleased to hear from you and to discuss them with you and if you allow, we would even put them up on this site for others to learn from.
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