You probably know the saying, "the more things change, the more they stay the same." When it comes to FDA inspections, this saying holds a lot of truth.
When I was with FDA way back in the 1970s, we were taught that inspectors were the agency's "eyes and ears." Our job was to conduct inspections of manufacturers and determine if they were in compliance with the required regulations.
The field investigator is still considered the "eyes and ears" of FDA. But after all this time, you would think they would have grown more sophisticated in the conduct of their inspections.
The world has changed—from the advent of global harmonization and third-party audits of medical device companies to companies routinely meeting the ISO 13485 standard and complying with QSR—but not FDA investigators. When it comes to regulatory compliance, they are strict constructionists.
We all appreciate that companies are supposed to follow each and every section of the regulation and maintain required documentation. The only way FDA investigators can determine if a company is in compliance is to inspect the documents. After all, inspections are only supposed to take four to five days . . . if the quality system inspection technique (QSIT) is being followed.Think of the FDA investigator as the agency's camera. He or she determines your compliance prior to the visit by looking at documentation. The investigator monitors your compliance during the audit, but the only way to determine how you will operate in the future is to see how your quality system is constructed and implemented.
Unfortunately, many companies who are new to the FDA inspection process—and there are many companies that still have not been audited by FDA or that have not been audited for more than 5 years— fall prey to FDA investigators' myopic inspection approach. This scenario becomes even more frightening when you consider that FDA is hiring several thousand new investigators. Not only are they unfamiliar with industry, but they are trying to build a reputation for themselves.
In the recent past, my company has dealt with two clients who had the misfortune of being in the crosshairs of an FDA investigator. In both cases, the investigator was professional, treated as such by the companies, and given carte blanche to the documents and facilities. Both companies felt they had nothing to hide and are proud of their achievements and products. Both are certified to ISO 9000/2000 and ISO 13485. Yet, both companies were left reeling and licking their wounds after the investigator issued a lengthy 483 list of observations at the conclusion of the inspection.
These two cases were conducted in different FDA districts by different investigators. A careful examination of the two 483s as well as the companies and their products makes it obvious, however, that the FDA investigators missed the forest for the trees. We are fully aware of the importance of maintaining complete documentation and being in compliance with QSR. But isn't there room for FDA to look at a complete picture before simply writing up a long, drawn-out 483?
In the first case, the company contacted mdi Consultants upon receipt of the 483 asking for assistance in responding to the listed observations. There were 11—yes, 11—pages of observations.
The second company, which was not familiar with FDA or its practices, took the investigator at his word that it should just notify FDA that it would 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 respond appropriately and ended up being issued a warning letter. We were called in after the warning letter had been issued and were asked to assist with responding to FDA.
In both instances, reading the 483 as a stand-alone document would lead one to conclude that both companies are completely out of control and that potential customers should think twice before purchasing or using any of their products.
That is the major fault of the 483. It is a one-sided document, which, if it is not properly answered, will be accepted as gospel and result in FDA building a case against the company. Remember, FDA investigators are the "eyes and ears" of the agency and it is their observations and documentation that are used to build a case. Unless you are able to dispute their observations or can show that the observations did not affect the quality or safety of the finished device, you can be certain that FDA will continue with its required line of regulatory follow-up.
We try to explain to our clients that FDA investigators are just that—investigators. They are taught to investigate and document regulatory lapses that will allow them to build a case against violators. They are not your friends; they cannot be your friends. 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 an FDA inspection. There is one big difference, however. If you fail to produce on the Apprentice, you simply get "fired." With FDA, if you don't know how to defend your company, the consequences can be far-reaching and enormously damaging.
In both cases with which we were involved, the FDA investigators were not looking at the whole picture. On the contrary, they looked only at each little point before deciding to make a federal case out of it. From our experience, FDA investigators are basically not allowed to look at the whole picture in order to make their determinations. Getting a big picture view of your company, unfortunately, is not part of their job.
Consequently, it is very important to look at each observation and determine the context in which it was made and how it affected the quality of the production process or the final product. Let's look at the achievements of these two companies up until the point the FDA came poking around.
Both had been in business for more than 40 years, and had thousands of products in the marketplace and in use. In the past 10 years or more, neither company has had a product recall or issued an MDR for a death or serious injury involving their device to FDA.
Based on that information alone, a reasonable person would conclude that the companies' operations and products were of the highest quality and that they both had a fully implemented and functioning quality system in place. Unfortunately, common sense doesn't always make it to the party.
Both companies' management asked us the same question: "What is FDA looking for, and why is the agency so difficult to deal with?"
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 on the observation. It made the compliance officer (who is the next level of oversight before a warning letter is issued or another action is taken) look more closely at what the investigator observed as a violation. Be warned: once the investigator concludes the inspection, your response to the 483 is your only opportunity to rebut the investigator's observations. Without a well-documented and prepared response, the only opinion the FDA compliance officer will see and hear is that of the investigator. More often than not, this will put you in a precarious position and result in additional regulatory action, such as a warning letter (which is usually the next level of regulatory action on a first-time violation).
Working closely with management, we were able to develop a comprehensive and appropriate response to each specific observation. We determined why the investigator made the observation and then looked at how it affected 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. FDA felt that our response was adequate as well as appropriate, and that they would review the corrective actions during the next inspection.
Constructing a response was a very different exercise for the company that received the warning letter. Its response to the 483 did not contradict or rebut the investigator's observations, leaving FDA with only one opinion as to the condition of the quality system and the company's compliance. Once again, we worked closely with the company's management staff to determine why the investigator made each observation. Since FDA had already issued the warning letter, however, it was more difficult 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 an appropriate corrective action. It will be up to FDA to determine if our response was adequate and if they want additional information. In this case, we have to continue to work closely with FDA to ensure that the warning letter is ultimately rescinded to allow for normal compliance activities to continue.
Clearly, dealing with FDA is not a cut and dry process. The inspection does not end at the closing meeting when the investigator hands you the 483. As a matter of fact, how you respond to the 483 can be more critical to the outcome of the inspection and the way your case is handled by the agency. FDA does not currently have an "industry friendly" policy. Taking a wait and see approach to its oversight will most definitely be costly in the end.
Alan P. Schwartz, mdi Consultants Inc. (Great Neck, NY), has provided strategic planning on FDA regulatory compliance issues since 1978. Prior to joining mdi, Schwartz was a supervisor of field operations for FDA. He has been an invited speaker on FDA policy and issues in the United States and internationally and provides his expertise on FDA to the medical and pharmaceutical industry worldwide. Schwartz has personally participated in more than 400 FDA inspections. His insight and understanding of FDA strategy and his experience preparing replies to FDA 483 and warning letters and acting as a third party certification body under FDA approval has provided companies with novel approaches to dealing with their regulatory problems. mdi Consultants Inc. has been selected by the Chinese Council for the Promotion of International Trade and the Chinese Council for International Standards to assist Chinese companies' interactions with FDA. Schwartz also is an internationally certified lead assessor for ISO 13485, and he is on the editorial advisory board of the Institute of Validation Technology.