From 'Back' To 'Front': US FDA, Industry Experts Advise Device Manufacturers On Best Inspection 'War Room' Practices

Ever since the first US Food and Drug Administration inspection took place decades ago, medtech manufacturers have relied on so-called "inspectional war rooms" - spaces where subject matter experts and others work to fulfill investigator needs. But such back rooms can cause headaches for medical device firms and stretch out inspections if they select unsuitable workers to staff and manage them.

Larry Kopyta, a quality/regulatory VP for Omnyx, says it's vital for all employees to be adequately trained on FDA inspection activities, but it's even more important to not clog up a rear room with an excessive number of workers, warning that things "can easily become out of control. You need to find a good ringmaster."

A back room isn't the only place where manufacturers should be careful about using the right people. Staff present in the front room – where investigators traditionally work when onsite at a firm – should be helpful and reliable and should facilitate the investigators' requests and answer an array of questions.

Device firms must strike the right balance in the number of subject matter experts and other workers in those back rooms to avoid having too many proverbial cooks in the kitchen. That's because crowding a rear room with an abundance of behind-the-scenes employees could slow down an inspection, agency and industry experts warn. Also, back-room disarray might confound FDA investigators if misleading information or the wrong documents are passed along to them in the so-called front rooms.

"Consider that as you're working and preparing for who's going to speak to us from the back room," said Phil Pontikos, FDA's national device expert and an investigator. "Often the people we typically want to speak to are the ones who actually perform the activity."

Therefore, "when you're trying to designate who an SME [subject matter expert] is, I'm hoping that you also are considering that it is advantageous to bring forth the person who actually, for example, completed a CAPA [corrective and preventive action], or has responsibility for investigations," Pontikos advised.

That's exactly how it's done at Cynosure Inc., a maker of light-based aesthetic and medical treatment systems such as Accolade for removing lesions and Cellulaze for eliminating cellulite, says Connie Hoy, senior VP of regulatory affairs for the firm based in Westford (Massachusetts).

"If the FDA investigator is evaluating, say, a CAPA, then we make available the person who manages the CAPA program," Hoy said. The firm will also bring to the front room the person responsible for working on the particular CAPA being reviewed and questioned by the investigator.

"All of this means you have to prepare your entire organization," Hoy urged. "Inspection readiness applies to everybody in the organization, because the person filling out a CAPA might have been someone on the manufacturing floor, or it might have been a quality engineer or a manufacturing engineer, or someone who's not used to being in front of an investigator."

Truth be told, Hoy is rubbed the wrong way when manufacturers equate the conventional industry term "inspectional war room" to "back room." Although it might seem like simple semantics to some, a "war room" implies chaos and bad blood between firms and FDA investigators, she said, while the phrase "back room" does not.

A rear room is merely "a separate area where you have competent people fulfilling the requests of the investigator in a timely manner. That's the function of the back room. Period," Hoy said. The 25-year-plus device industry veteran wants to make clear what goes on – or at least what should go on – behind closed doors. "Workers aren't in back rooms 'fixing' documents. I want to make sure that is understood."

At Cynosure, there is communication between the back room and the front room via Google Talk. Only one individual on each end is designated and approved to enter information into the online instant-message chat.

Using such technology isn't overwhelming, is user-friendly and minimizes the possibility of error, Hoy said.

Firms that do this won't face "a steady stream of people talking to each other during the entire time of the inspection," she noted. Rather, "there is a dedicated person in the front room talking to a dedicated person in the back room to fulfill document requests and to anticipate what the investigator will ask for next because of how the investigation appears to be flowing."

Meanwhile, small device firm Omnyx LLC uses Skype for Business for two-way inspection room communication.

"You just have to be careful because – and here's a tip – if you're projecting on a screen and you're using Skype, you have to be sure you don't accidentally project an IM [instant message] conversation on the screen for an investigator to see," said Larry Kopyta, VP of QA/RA for the firm. "Also, turn the sound off."

Omnyx is a relatively new firm in Pittsburgh focused on making digital pathology systems. It is part of a joint venture between GE Healthcare and the University of Pittsburgh Medical Center.

Employees in Cynosure's back room include "one person on Google Talk, one person to retrieve documentation, and one person to work on QC [quality control] documentation. And by that I mean, is it the correct document that the investigator wants? And is it a complete document?" Hoy said.

"We also have one person who manages our subject matter experts," she added. Subject matter experts are queued up. "We have a subject matter expert who has a backup, and the backup has a backup. And we have the backup to the backup to the subject matter expert available to us at any given time."

Hoy pointed out that if all of this seems like hard work, it is – especially for smaller manufacturers.

At a small firm, "maybe the backup to your subject matter expert is actually you – and you're the CEO or a senior-level official – but I find that it helps facilitate the flow of the investigation by having you act as an SME [subject matter expert] only when absolutely needed," Hoy said.

And having properly functioning electronic office equipment on hand, tested before the inspection, is a must. Cynosure's back room includes a copier and printer dedicated only to activities that happen within that space. "It saves a lot of time and energy for the people who are managing the inspection and makes things much more efficient," she said.

While it is important for device manufacturers ro identify and position their best and brightest subject matter experts in "war rooms" when FDA comes to inspect, Kopyta says it's even more important to not clog up a rear room with an excessive number of employees.

"One of the things you have to be careful about is having too many people in the back room because it can easily become out of control," Kopyta said. "And there might be multiple people in the front room giving direction too, so things can become confusing.

"So, if nothing else, you need to find a good ringmaster to keep the circus running."

Julie Larsen, director of inspection readiness services at consulting firm BioTeknica, said it should be clear what everyone in the back room is supposed to do.

"There should be a leader in that back room. It's helpful if that's someone who's a little bit more of a senior employee. The person who is in charge of the room is responsible for every request from beginning to end," she said.

Further, "there should be others in the room who are able to pull records readily and who might be the expert on how to extract things from your CAPA system or from your complaint handling system, and all of the various areas where you have data – validation reports, design history files, whatever it might be," said Larsen, who worked in device-maker Abbott's quality and compliance operations for 17 years.

"And somewhere in that process you should have someone who is checking the item that was retrieved for the investigator to ensure that it matches what the investigator asked for," she said.

Although adequately prepping a back room is time consuming, a firm's efforts don't go unnoticed by the FDA.

"I've talked to a few investigators about what they see, and they did say that when everything's working well, they can tell that it's a well-coached team," said William MacFarland, director of the Division of Manufacturing and Quality within the FDA device center's Office of Compliance.

Investigators "can see the requests go out to the back room and things come into the front room through the queue," MacFarland said. "They can sense it. They can hear it. And it really shows that the firm was expecting to be inspected. The company thought about that so investigators can really focus on the documents in front of them."

Comments from Pontikos and Hoy came Nov. 5 at the annual FDA Inspections Summit in Bethesda (Maryland), hosted by FDAnews. Kopyta, Larsen and MacFarland spoke at FDAnews' Twelfth Annual Medical Device Quality Congress, also in Bethesda, in March.

FDA Inspectional 'Program Alignment' And Subject Matter Experts

The industry experts also point out that it's more important than ever to select appropriate subject matter experts because FDA's Office of Regulatory Affairs (ORA), which plans and runs all of the agency's field activities, is ramping up efforts to train investigators on what to look for when it comes to specific types of devices thanks to its new "program alignment" scheme.

The Center for Devices and Radiological Health, along with ORA, is establishing a device inspectorate and a separate mammography quality inspectorate. Its goals are to enhance product quality and make more efficient use of resources. Other agency-regulated commodities – including drugs, biologics, food and tobacco – will each be assigned a dedicated group of investigators.

"Investigators will be more specialized along technical lines – program lines – which means there will be a bit more specialization in certain areas of devices," FDA's MacFarland said.

"But we're still using QSIT. That's not going away, but where investigators are probing in certain areas, you might be asked targeted questions," he said.

Therefore, "you might want to tweak your SME process to know which SMEs to have available given the particular focus of an inspection," MacFarland recommended.

QSIT is FDA's Quality System Inspection Technique. It is designed to ensure that investigators, over the course of about five days, look at the most important compliance issues linked to four major quality system subsystems: management control, CAPA, design control, and production and process control.

Cynosure's Back Room Numbers All Investigator Requests

In its rear inspection room, Cynosure assigns numbers to investigator requests. For example, suppose an investigator's first request is to see the firm's CAPA procedures.

When that first document is asked for by an investigator, it is sent from the back room in a folder labeled "Request No. 1." The second is marked "Request No. 2." And so on.

"That way, when all of the many documents begin to pile up on the table, as they tend to do, you can clearly identify what you have in the room numerically to ensure order," Hoy said.

Further, during an inspection "there is going to be a sampling of complaints, for instance, where the investigator will ask for a certain number of complaints and CAPAs. Don't wait until you have them all accumulated to bring them into the front room," she said.

In other words, "if you are asked for 20 complaint records, don't wait until you have all 20 records and then walk them to the front room," Hoy said. "When you have a couple of records ready, bring them to the front room because then you can keep the inspection flowing and it doesn't look like you're trying to stall the investigator."

Marc Neubauer, an investigator from the agency's Baltimore district office, agreed with Hoy's advice. At the Nov. 5 FDA Inspections Summit he asked attendees: "Do you believe it's fair that investigators expect documentation to come to them quicker if you have a back room?"

But Neubauer didn't wait for an answer from the crowd. "For sure it's fair," he said.

"If documentation is not coming quickly enough, I'll just ask, 'Hey, look. I know you have 10 people in the back room. Why aren't we getting the documentation?'" Neubauer said.

FDA's Pontikos says one of the best ways for firms to try to more swiftly move an investigator through each step of an inspection is by being prepared. That means pulling all relevant records before the audit and not playing hide-and-seek with requested documents.

In fact, Pontikos once inspected a firm that used two back rooms. That particular manufacturer "had a second back room QC'ing [quality controlling] what went to the first back room before it came to the front room where I was," he said.

"That firm's 'back-back' room had attorneys involved; that's what my guess would be. That was really slowing the inspection down and didn't add any value as far as I could see," Pontikos said. "So just be mindful of these things. You likely know probably 75 per cent of what investigators will ask for, so just bring it forward ahead of time."

Use Generalists In The Front Room

A back room isn't the only place manufacturers should be careful about using the right people. Present in the front room should be helpful, reliable facilitators that aid the FDA investigator with requests or to respond to questions, the industry experts say.

"In the front room it's always good to have a person – I call this person a 'generalist' – who is a senior-level individual. Maybe it's the director of operations; maybe it's the director of quality. It should be somebody who's been at that facility for a long time who knows a lot about what's going on and can answer a lot of general questions," BioTeknica's Larsen said.

Ideally, the generalist would stick with the investigator from the beginning of the audit and see it through to the end.

"It's frustrating to an FDA investigator when a company adopts the philosophy of, 'We're talking about CAPA. I must bring in a CAPA person,' or, 'We're talking about such-and-such topic. I must now bring in this person.' That's when the investigator gets the feeling that there isn't anybody in the firm who knows how things work," Larsen said.

"A very good strategy is to have the generalist in the front room be the investigator's tour guide, so to speak, throughout the whole inspection," she advised. "And if you have the luxury to do so, have another person in the room that does nothing but document the investigator's requests."

One thing FDA's MacFarland says he likes about firms that use such an approach is that generalists can make sure that an investigator's question about a particular subject or, say, a specific request, is well understood.

"There's no misinterpretation," he said. "There is nothing as frustrating as making a request as an investigator, having the information come back to you, and realizing that it's not the information you're looking for.

"So that's one thing I like about a generalist – he or she just knows the status of things," MacFarland continued. Generalists "are kept in the loop on the status of investigator requests, because you can imagine that an investigator would become frustrated if it takes a protracted period of time to get documents," – as FDA's Pontikos and Neubauer noted earlier.

"Where the bang-for-the-buck comes in terms of front room efficiency, if you will, is really how long I’m going to spend there," Pontikos said. "Ultimately, we want to make sure that whatever we do is materially accurate, right? I don't think it has an effect on whether you're going to get an FDA-483or not. It has more of an effect of, are we getting to the endpoint in a reasonable, expeditious way?"

When firms are not forthcoming, investigator questions will likely become more difficult. "That can cause undue delays, and the truth is, the longer we're there, there is a probability of finding more problems because we will start looking at more things," he said.

"I can't say definitively that that happens, but I think that's a reasonable statement to make," Pontikos added.

Yet a generalist should be tough enough to push back on some investigator requests. The ability to drill down through an investigator's question or particular need can help the firm provide correct documents and information.

Nevertheless, one individual who probably shouldn't be included in front-room activities is a corporate attorney.

"I was involved in an inspection where there were corporate attorneys in the room. And what that did was it set the tone for the inspection to be extremely defensive, and the investigators were not as transparent as they could have been," Larsen said.

Lawyers make the tone of the meeting "adversarial right out of the box," Omnyx's Kopyta added. "It sends the message to FDA that there's something wrong here and that your attorney has to be there to basically assess everything that's going on."

In fact, any employee who harbors an adversarial streak should be kept far away from the front room and the investigator.

"There's a certain degree of respect that the entity being inspected is entitled to," Kopyta said. "But ultimately the FDA wants the same outcome that you do: safe, effective products. So you can't go into the front room with someone who is going to try to bully the FDA investigator into getting what they want. That doesn't work."

Hire A Front Room Scribe

Investigator Neubauer recommends hiring a scribe for the front room. This is particularly helpful for small mom-and-pop manufacturers who need the additional manpower.

Using a scribe is important, "especially if it's your first inspection or your second inspection. Because sometimes we do find your problems, and sometimes those result in FDA-483s, and sometimes those result in discussion items," Neubauer said.

"Sometimes you're so caught up in the inspection that you're not picking up everything that you should be picking up in the front room," he said. If an important comment or discussion item is overlooked, "then the scribe can write it down and it can be reviewed it at a later time. Having what happens in the front room scribed is a great idea."

Correct Misinformation Quickly

Cynosure's Hoy once dealt with a nightmare front-room scenario when she briefly joined Lumenis Ltd. in 2004 as VP of RA/QA to help the firm clean up quality system troubles discovered by FDA and noted in a warning letter from the agency.

"I was out of the country and we had a for-cause audit, so it was unannounced. I had to fly back to the US from Japan, which obviously takes some time, and the inspection was already underway while I was on the plane," she recounted.

"Eventually I returned to the US and I walked into the front room on day two of the inspection. I sat down and listened to the quality manager lying to the investigator," Hoy said. "I immediately removed her from the room and asked HR [human resources] to ask her to leave the building.

"Then I went back into the front room and told the investigator, "She's lying. Let us now tell you the true story."

Being dishonest earned that quality manager "a one-way ticket out of the company. We didn't keep her as an employee," Hoy said. "Oddly enough, we were trying to clear up a warning letter, and because we were honest and did come clean on the questions the investigator was asking, we were released from the warning letter after that inspection."

A search of FDA's website did not turn up an archived warning letter addressed to Lumenis, however.

"Lucky Lumenis," Hoy quipped with a grin on Nov. 5 when Scrip Regulatory Affairs' sister publication, The Gray Sheet, asked about the letter.

In the end, "it's pretty horrific to hear someone who should be telling the truth to an FDA investigator blatantly lying," she said.

Don't Sequester An Investigator In A Tiny Front Room Because They'll Probably Secretly Hate You For It

Providing an FDA investigator with a sizeable front room to work in is especially important – and surprisingly overlooked by many companies.

"You want to have the right space; you don't want to have a really cramped space," Kopyta said.

When selecting a front room, "it's better for the investigator to be out of the flow of where most of your business takes place. Otherwise employees are going to walk by and peer in. Everybody wants to know what's going on," he said.

Laureen Geniusz, an investigator in FDA's Cincinnati district office, said at May's MedCon medical device conference in Cincinnati that she appreciates a roomy workspace.

"The majority of medical device inspections are essentially a paper review. We do go out to the manufacturing floor and such, but there are a lot of documents that we have to review. So it's nice to have an adequate place to work," she said.

"And a lot of us now bring our own laptops to the inspection, so Wi-Fi connections are very helpful if you can arrange for that," Geniusz added. "Investigators are allowed to take [into the front room] nominal food and drink, things like that; it is law. Everyone always asks about that.

This story has also been published in The Gray Sheet. Scrip Regulatory Affairs brings selected complementary coverage from our sister publications to our subscribers.