Avoid FDA 483 Warnings with Better Documentation

Your company should invest as much time and effort on its paperwork as it does making safe and effective devices.

Larry Elwell

May 1, 2009

8 Min Read
Avoid FDA 483 Warnings with Better Documentation




Elwell

Good documentation is an investment. If you need convincing, all you have to do is glance at FDA 483 warning letters, which cite documentation problems with alarming frequency. The good news is that these problems can be fixed after your company receives a warning letter. The bad news is that, until you fix the problems, they can cost you both time and money. When the FDA investigator shows up, he usually sequesters himself in a room with documents. If documents are the first line of inquiry, shouldn't they also be the first line of defense? The best course of action, therefore, is to avoid 483 warnings altogether by putting in place a logical and comprehensive system of documentation before the FDA inspector comes around.


Considerable Costs
Suppose FDA appears at your door tomorrow, and suppose it finds cause to issue you at least one 483 warning that your company's cGMP documentation is inadequate. How much will that cost you? No one seems to know for sure, not even as an average. This fact is due partly to the variables involved and possibly to hidden intangible expenses. Despite the lack of hard numbers, no one would dispute that the cost is considerable. Just having your corporate inadequacies made a matter of public record throws a lot of dirt on your company name; dirt that may take substantial effort—not to mention time and money—to remove.
First of all, there will be time spent deciding how to respond. Any response is going to involve some sort of corrective action. The corrective action will most likely include changes. The changes could be to facilities, equipment, computer technology, or documents. No matter what the change, there are going to be costs involved. Changes to facilities are generally more expensive than changes to documents, but it's clear that companies should make an effort to avoid 483s whenever possible by ensuring compliance beforehand.
In 2008, FDA issued more than one warning letter per week to 63 different medical device manufacturers in the United States These letters came from nearly every district office. The average for the last 11 years is slightly better at 3 letters every 4 weeks, but that's still too many. By contrast, the pharmaceutical industry has had just 4 letters in the last year and averaged a little more than 1 letter every 2 weeks over the last 11 years. The pharmaceutical industry has had more time to develop documentation systems and has had more audit cycles from the FDA to help the industry determine exactly what the FDA is looking for. Also many device manufacturers are crossing over from other types of manufacturing and are not used to the rigorous FDA requirements. So, are 483s amenable to cost-containment? Is it possible to avoid them? Regardless of how you may feel about the FDA findings or related severity, the simple fact is that warning letters are handed out for cause. And since you can't politely refuse to accept a 483 when FDA comes calling, it would be reasonable to try to figure out the biggest reasons for 483s and how your company can avoid or minimize them. The most cited documentation areas are lack of required procedure or failure to follow the procedures that are in place.

Figure 1. (click to enlarge) Random FDA 483 sampling.

Recently, my company chose at random eight 483 warning letters to device manufacturers. Each letter was addressed to a different manufacturer, and each was issued by a different FDA regional office. As Figure 1 below shows, some aspect of documentation was implicated in a whopping 78% of problems cited in these eight letters (see Figure 1).


Approach Documentation Systematically
Why is documentation such a big problem? There are two main reasons.
One, industries regulated by FDA require vast amounts of documentation. It's understandable that some of it does not get completed accurately. The pressure is usually to get product out the door, not to complete paperwork. If focus is lost at all, some documentation gets pushed to the back burner. The documentation doesn't get left behind because no one thinks it shouldn't be done. Rather, documentation is neglected because companies lack the resources to complete the paperwork. Though companies mean to get back to it, emergencies always seem to pop up that prevent them from doing so.
Most of the time there are no staff members available who are documentation experts. Many companies try to make their engineers, scientists, or production supervisors write documents, but this practice almost always creates problems. For one, engineers, scientists, and supervisors are not writers, and they probably don't want to be; staff who are dedicated to other important tasks may struggle to find time to write documents, and so the documents they do produce may be of lower quality than their usual work.
Most companies do not have technical writers or documentation experts on staff. Therefore, the best approach in these situations is to hire contractors. Not only will outside experts be dedicated to the task of documentation and thus undistracted by other responsibilities, but also their very status as outsiders means they can see processes and procedures with a neutral eye, making it easier to catch problems, missing steps, and lapses of logic.
Though you may balk at hiring contractors, in the long run this approach will likely be the least expensive one, because contractors allow your staffers to focus on their own tasks, require no benefits, and work on a temporary basis.
Two, companies often do not approach documentation systematically. This is important on two levels. First, the various systems of documentation—validation documents and operating procedures, for example—are not properly integrated. At this point relatively high-level management input and decisions are crucial.
Second, manufacturers usually give very little thought to how operating procedures fit together. You may need a procedure for Process A, and so you ask the person who knows the most about that process to write the procedure. Then, when you need a procedure for Process B, you ask the person who knows the most about that to do it, ad infinitum. Because these are self-contained processes, any overlap between them will be documented twice and will probably be inconsistent. Lacking a coherent philosophy of documentation you will get unnecessary duplication.
This duplication and isolation can grow into an unmanageable beast. If workers come across a piece of information they feel needs to be shared, and they can't find it easily in the existing documentation, they'll likely just tack it on to the end of whatever document is handiest, further exacerbating the problem. That is if they think to consult the documentation at all. It's easy to see how, over time, this disjointed approach could make the final documents wholly unusable.
Redundant, inconsistent procedures fight against usefulness. Employees will avoid processes that don't help them complete their tasks. This is such a huge wasted opportunity because good documentation improves processes and, ultimately, the bottom line. Not only that, if employees aren't using documentation, that opens the door for FDA to issue 483 letters, since FDA inspectors seek credible evidence not only that there are adequate written procedures in place but also that these procedures are actually being followed.
In addition, unhelpful documents enormously complicate training. Most companies tie training to procedures in some fashion, but procedures that are inadequate or cumbersome mean that real training is by word of mouth from someone who knows “what's what”—and who may do things differently from someone else who knows “what's what.”
It's easy to see how conducting training this way can contribute to inconsistency. Plus, in cases like this, the time spent with procedures is simply wasted. It's so much better to have trainers who actually use the documentation that exists and require that their trainees use it as well—though, of course, the documents must be usable in the first place.
Follow the Five Cs
Fundamentally, management needs to change its mentality regarding documentation. You spend a lot of time and effort to make sure your product is safe and effective and that it passes regulatory scrutiny. Your documentation needs the same level of attention. If you accept second-class, inferior materials for your product, you will get an inferior, unmarketable result. Likewise, if you accept inferior documentation of your manufacturing processes, you will end up with inadequate paperwork.
So, the argument comes full-circle. Inadequate documentation is a leading cause of 483 warnings that leads to higher costs of doing business.
So, what's an executive to do? Here are three suggestions:
• Resolve to make sure enough resources are available to complete documentation at a high level.• Conduct a thorough analysis of your existing documentation and your needs for new or revised documents. Again, engaging an outside communications company is the best method for doing this, because you'll have actual documentation experts to do the work, rather than your overworked and resistant engineers, scientists, or other staffers. • Provide the resources necessary to create and maintain adequate documentation. Make sure these resources are not simply thrown at the problem, but instead are chosen and managed logically. Coming up with resources is easier said than done, of course, especially in this economy, but you must remember that good documentation is an investment and will very likely save you money in the long run.
Even though documentation problems are a huge cause of 483 warning letters from the FDA, they are avoidable with a plan that is workable, cost-effective, and bulletproof. Think of the ideal documentation plan as fulfilling the five Cs—it must be clear, correct, concise, coherent, and consistent. Nothing less will do.
Larry Elwell is director of engineering services for Prima Communications Inc., a technical communications company with offices in Michigan and Indiana. He can be reached at [email protected].

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