Does your FDA inspection plan need to be proactive first?

Maybe you need an FDA inspection plan. Does everyone in your company know what they need to do when FDA inspectors arrive at your facility?

Be proactive and don’t just let FDA inspections happen. You need to have an FDA inspection plan, and that plan needs to cover the roles and responsbilities for everyone. Below we have a list of 15 items that are in our FDA inspection work instruction (WI-009). If you already have a plan, try using the following checklist to assess your readiness for the next next inspection:

1. What will you ask and do when your FDA inspector calls the Friday before the inspection?
2. Who should be contacted by the FDA inspector if you are on vacation?
3. How will you communicate to the rest of your company that an FDA inspection is planned for Monday morning?
4. Who will greet the FDA inspector upon arrival, and what should they do?
5. Which conference room will the FDA inspector spend most of their time in?
6. Who will be in the conference room with you and the FDA inspector?
7. How will you track document and records requests, and how will you communicate that information to others?
8. How will you retrieve documents and records requested by the FDA inspector?
9. Who will conduct a tour of the facility with the FDA inspector and how will the tour be managed?
10. When quality issues are identified, how will you respond?
11. What will you do for lunches during the inspection?
12. Who will attend the closing meeting with the FDA inspector?
13. Should you “promise to correct” 483 inspection observations identified by the FDA?
14. How and when will you repsond to the inspector with corrective action plans?
15. If your company is outside of the USA, what should you do differently to prepare?

What will you ask and do when your FDA inspector calls the Friday before the inspection?

Most people begin their FDA inspection plan with the arrival of the inspector. However, you should consider including earlier events in your plan. Such as closure of previous 483 inspection observations, scheduling of mock-FDA inspections in your annual audit schedule, and details of how to interact with the inspector when they contact you just before an inspection. Most inspections will be conducted by a single inspector, but occasionally inspectors will be training another inspector. In this situation you can count on them following the QSIT manual more carefully, and you are more likely to receive an FDA 483 inspection observation. In the worst-case scenario, the lead inspector will split up from the trainee, and they will “tag-team” your company. This is not proper FDA procedure, but you should be prepared for that possibility. Therefore, make sure you ask the inspector if they are going to be alone or with another inspector when you speak with them on the phone. You should also get their name and phone number. You may even want to consider reviewing FDAZilla Store for details about your FDA inspector’s past inspection 483s and warning letters. Immediately after the call with the inspector, you should reserve a conference room(s) for the inspection and cancel your other meetings for the week. You should also verify that the person that contacted you is really from the FDA. You can do this by looking up their contact information on the Health and Human Services Directory. Your inspector should have a phone number and email you can verify on that directory.

Who should be contacted by the FDA inspector if you are on vacation?

You should always have a back-up designated for speaking with FDA inspectors, handling MDR reporting, and initiating recalls when you are on vacation. These are critical tasks that require timely actions. You can’t expect inspectors, MDRs, or recalls to wait you to get back in the office. It doesn’t matter what the reason is. Weddings, funerals, and ski trips should not be rescheduled. You need a back-up, and often that person is the CEO or President of your company. Make sure you have a strong systems in place (i.e. an FDA inspection plan, an MDR procedure, and a recall procedure). Whomever is your back-up needs to be trained and ready for action. This is also the purpose of conducting a mock-FDA inspection, including examples of MDRs in your medical device reporting procedure, and conducting mock recalls. This ensures you and your back-up are trained effectively. 

How will you communicate to the rest of your company that an FDA inspection is planned for Monday morning?

Most companies have an emergeny call list as part of their business continuity planning, and after the past 18 months of living with a Covid-19 pandemic your firm should certainly have a business continuity plan. Your FDA inspection plan should leverage that process. Contact the same people and notify them of when the FDA inspector is coming. If you are unable to find a conference room available for the inspection (i.e. see below), then ask the manager(s) that reserved the designated room for FDA inspections to relocate to another conference room for the week. Make sure you tell them who the inspector will be, and you might even be able to provide a photo of the inspector (try seraching LinkedIn). Make sure that you remind everyone to smile, and to listen carefully to the question asked. Everyone should be trained to answer only the questions asked, and nobody should run and hide. There should also be no need to stop your operations just because an inspector is visiting. You might even include the name of the inspector on a “Welcome Board” if your company has one at the entryway or in public areas. The more an FDA inspection appears as “routine” the better your outcome will be.

Who will greet the FDA inspector upon arrival, and what should they do?

By the time an FDA inspector(s) actually arrives at your company, all of the managers in your company should already been notified of the inspection and a conference room should be reserved for the inspection. Therefore, when the person that is greeting people in the lobby comes to work on Monday morning, you (or their supervisor) need to communicate with them and make sure that they are prepared for arrival. There are four things that should be communicated:

1. the name of the inspector(s) that are arriving
2. the list of managers that should be notified when the inspector(s) arrives (possibly identical to the buisness continuity call list)
3. the conference room that is reserved for the inspection

If the person greeting the inspector(s) is also going to escort them to the conference room and help them get set-up, then they will need additional instructions. If that escorting inspectors to the conference room and helping them get set-up is delegated to a different person, then the following considerations should be included in that person’s instructions:

1. the location of bathrooms and emergency exit instructions in case of a fire
2. the information for wireless connectivity
3. recommendations for seating in the conference room based upon the expected participants (see below)

It is important that an escort for the inspectors is able to bring the inspector(s) to the conference room as quickly as possible. They should not be expected to wait more than a few minutes for an escort.

Does your FDA inspection plan identify a specific room for the inspector? Is there a back-up?

Some companies have a specific room that is designated for inspections and 3rd party certification audits. If your comapny can do that, it will be very helpful because it reduces the decision making that is required immediatley prior to the inspection. Having a specific room for the inspection also eliminates the need to tell everyone else in the company where the inspector will be. Instead the location of the inspection can be in the work instruction or written FDA inspection plan. You shouldn’t need a back-up plan if there is a specific room designated for an FDA inspection, but our firm has a client that will be hosting three notified body auditors simultaneouly for three days. In that situation, you might need more than one room. 

Does your FDA inspection plan have assigned seating?

You might think that it really doesn’t matter where people sit in a conference room, but you will probably want consider the layout of charging cords and the flow of interviewees requested by the inspector. In your conference room, you will need room for at least the following people:

1. the inspector(s)
2. the management representative (i.e. you)
3. a scribe
4. an interviewee

If there is an inspector and a trainee, you will probably want to seat them together to facilitate them working together. You as the Management Representative also need to be in the room, and it may help for you to sit next to the scribe to facilitate communication between you and to make it easier for them to hand you documents after the scribe logs the documents into their notes. The scribe should probably sit closest to the door, because they will be receiving documents, logs, and records that are brought to the room. You will also need one more seat next to you, and probaby accross from the inspector(s), for interviewees. This person will rotate as different processes are reviewed. I also recommend having a location in the middle of the table for an “in box” where documents, logs, and records for the inspector are placed after being logged in. A second location in the middle of the table can be used for a “discard pile” as you finish using your copy of each document, log, and record. You may refer back to these copies later. The “discard pile” should be 100% copies rather than originals. Originals should never be brought into the room with the inspector.

Who is the scribe in your FDA inspection plan?

The perfect scribe would know the quality system well and they would have the typing skills of a professional stenographer. You might have someone that is an executive assistant in your company or a paralegal that could do this job, but you might also have a document control specialist that fits this requirement. Some companies will even hire a temp for the duration of the inspection that has this type of skill, but a temp is unlikely to know the jargon and quality system requirements well. I have taken on the role of scribe many times for my clients, because I type fast and know their quality system. I also don’t want to interferre with the inspection process. As scribe I can answer questions and offer suggestions when appropriate, but most of my time is spent taking notes and communicating by instant messenger with company members that are outside of the inspection room.

You should seriously consider using an application such as Slack as a tool for communication during the inspection. Then anyone in your company that needs to know the status of the inspection can be provided access to the Slack channel for the inspection. This can also act as your record of requests from the inspector. It’s even possible for people on the Slack channel to share pictures of documents to confirm that they have identified the document being requested. You could even invite someone to speak remotely with the inspector via Slack with Zoom integration. All the scribe needs to do is share the Zoom app with a larger display in the same conference room so the inspector can see it too.

Does your FDA inspection plan include provisions for  document and record retrieval?

The most important part of document and record retrieval during an FDA inspection is to remember that inspectors should never receive the original document. Ideally, a copier would be located immediately outside of the conference room and three copies would be made of every document before it enters the inspection room. The originals can be stored next to the copier until someone has time to return them to the proper storage location. The three copies should all be stamped “uncontrolled documents” to differentiate them from the originals. When the three copies are brought into the room, they should be handed to the scribe. The scribe should log the time the copies were delivered in the Slack channel. Then the copies should be handed to you, the Management Representative. You should skim the document to make sure that the correct document was received. Then one copy would be given to the inspector and another copy would be made available to the interviewee. If only two copies are needed, the extra copy can be placed in the “discard pile.”  Even if your system is 100% electronic, I recommend printing copies for the inspection. The paper copies are easier for inspectors to review, and it eliminates the ability for the inspector to hunt around your electronic document system. In this situation, the scribe may do all of the printing.

Does your FDA inspection plan indicate who will conduct a tour of the facility with the FDA inspector and how will the tour be managed?

I’m surprised by the number of companies that don’t seem to have a map of their facility. Medical device manufacturing facilities should have two kinds of facility maps. One should identify where pest control monitoring stations are located, and the second should indicate your evacuation route to exit the building. All guests should be shown the evacuation route map, probably within the first 30 minutes of arrival. The second map will be requested by the inspector eventually if you conduct manufacturing at your facility. Therefore, it would be helpful to use one or both of these facility maps as a starting point for creating a map of the route that inspectors should be taken on during a tour. I prefer to start with where raw materials enter the facility, and then I follow the process flow of material until we reach finished goods storage and shipping. If you can do this without back-tracking multiple times, then that will probalby be the preferred route. The purpose of planning the route out in advance is to help estimate how long the tour will take, and to make sure there is consistency. If someone starts the tour, and then another person takes over the tour, the new person should be aware of what the next location is and what areas have not been observed yet. There may also be safety reasons for avoiding certain areas during a tour and asking the inspector to observe those areas from a distance. Welding processes, for example, often fall into this safety category.

When quality issues (i.e. FDA 483 inspection observations) are identified, is this covered by your FDA inspection plan?

Third party certificaton body auditors will typically make you aware of nonconformities as they are identified, but FDA inspectors often will hold off on identifying 483 inspection observations until the end of the inspection in a closing meeting. However, you can typically identify several areas that may result in a 483 inspection observation during the inspection. You and the manager of that area may want to consider initiating a draft CAPA plan for each of these quality issues before the closing meeting. This would give you an opportunity to demonstrate making immediate corrections and you might be able to get feedback from the inspector on your root cause analysis and corrective action plan before the closing meeting. Sometimes this will result in an inspector identifying low-risk quality issues verbally instead of writing them out on FDA Form 483. I find the best way to make sure CAPA plans are initiated early is to have a debrief each day after the inspector leaves. All of the managers involved in the inspection should participate, and the debrief can be done virtually or in person. Virtually may be necessary, because often managers need to leave work before the inspector ends for the day. You should consider including this in your FDA inspection plan as well.

Does your FDA inspection plan include plans for daily lunches?

If your facility is located outside the USA, skip this paragraph and go to the section below about companies located outside the USA. If your company is locagted inside the USA, you can be certain that the FDA inspector will not eat lunch at your facility. They will leave for lunch on their own, and then they will return after lunch. Therefore, you may not have control of the timing of a lunch break but you will have time to take one. Most managers use the lunch break as a time to catch-up on emails. However, I think it makes more sense to change your email settings to “out of office.” You can indicate that you are hosting an audit and you will answer questions as a batch that evening or then next morning. You might use the lunch break to take a walk and relax, you might have  short debrief meeting with other managers, and you might spend some time preparing documents, logs, and records that the inspector may have requested before they left. Most inspectors use this strategy of asking for a list of documents and records in advance. This is also a good strategy to learn as an internal auditor or supplier auditor. If you have a back-room team that is supporting you, don’t make them wait for a break. Have someone in your company take their lunch orders or arrange for a catered buffet lunch. This will keep your support team happy, and you should definitely remember to include lunch for the team and changing your email settings to “out of office” in your FDA inspection plan.

Does your FDA inspection plan state who will attend the closing meeting?

Most companies have every manager that was in the opening meeting attend the closing meeting. This is ok, but it is important for anyone that might need to initiate a CAPA to be present in the meeting so that they can ask the inspector for clarification if needed. Scheduling a closing meeting should be part of your FDA inpsection plan. However, the past 18 months of the Covid-19 pandemic has taught us that we can attend this type of meeting remotely via Zoom. Therefore, we recommend letting the managers go home early if they are no longer needed as auditees. Instead, ask them to call in for a Zoom meeting at the time the FDA inspector estimates for review of the 483 inspection observations with the company.

Should you “promise to correct” 483 inspection observations identified by the FDA?

During the closing meeting the FDA inspector will review 483 inspection observations with you and any of the other managers present at the closing meeting. The inspector will ask if you promise to correct the 483 inspection observations that were identified. You should confirm that you will, and the FDA inspector will add this to the Annotations in the Observations section of FDA Form 483 that you will recive at the closing meeting. By stating this, you are agreeing to create a corrective action plan for each of the 483 inspection observations. You could change you mind later, but the better approach is to perform a thorough investigation of the 483 inspection observation first. If you determine that corrective action is not required, you can explain this in your CAPA plan and provide data to support it. The only likely reason for not correcting an observation is that you determined the incorrect information was provided to the inspector. In that case, you may need to do some retraining or organize your records better as a corrective action to prevent recurrence in a future inspection. You might even make modifications to your work instruction for “Conducting an FDA Inspection” (i.e. FDA inspection plan).

How and when will you repsond to the inspector with corrective action plans?

Your FDA inspection plan should include details on how respond to FDA 483 inspection observations and when the response must be submitted by. The FDA inspector will give you instructions for submission of your corrective action plans by email to the applicable email address for your region of the country. This email address and contact information should be added to your work instruction as an update after the first inspection if you are not sure in advance. You should respond with a copy of your CAPAs with 15 business days. Regardless of what the inspector told you, there is always a possibility that the outcome of your inspection could be “Official Action Indicated.” This is because the inspector’s supervisor makes the final decision on whether a Warning Letter will be issued and regarding the approval of the final inspection report. You should also confirm what the 15-day deadline is, because your state’s holidays may be different from the US Federal holidays.

If your company is outside of the USA, what should you do differently to prepare?

The US FDA only has jurisdiction over companies that are located in the USA. Therefore, if your company is registered with the FDA, you can only be inspected if you agree to host the FDA inspector when they contact you. FDA inspectors will contact foreign firms 6-8 weeks in advance, and they will typically give you a couple of weeks to choose from. After you confirm the dates for the inspection, then they will make their travel plans. Therefore, you will know exactly when the FDA inspection is schedulea and you will have more than month to prepare. Therefore, you should do four things differently:

1. You should send the FDA inspector directions from the airport to your facility and provide recommendations for potential hotels to stay at. Ideally the hotels you recommend will provide transportation from the airport and managers that are speak passable English). The hotels should be appropriate for business travel–not royalty. If it is convenient, you may even offer to pick-up the inspector at the hotel each day to ensure they have no problems with local transportation.
2. You should offer to provide lunches for the inspector during the inspection. This should not be considered entertainment. The purpose is make sure the inspector has lunch (i.e. a light meal or snacks) and drinks (i.e. water and coffee) during the inspection so that they do not have to negotiate local traffic, struggle with ordering food in a language they don’t know, and to eliminate delays associate with having lunch off-site. Make sure you remember to ask about food allergies and dietary restrictions. You might even follow-up with a draft menu to obtain confirmation that your proposed menu is appropriate.
3. You should schedule a mock-FDA inspection immediately to verify that everyone is prepared and to identify any CAPAs that need to initiated before the FDA inspector finds the problems.
4. During the first day of the inspection, you may consider asking the inspector if they would like to go out for dinner one of the evenings with a couple of people from your company or if they would like any recommendations for restaurants to eat at. If you are not familiar with US customs and international travel, ask the hotel concierge for advice. When you are out to dinner, the conversation should remain professional and if you normally drink alcohol at dinner you may want to consider the “BOB” compaign in the Netherlands as a role model. 

How are you going to train everyone in your company?

You need an easy way to train everyone in your company. Why not give them a video to watch? Next Monday, July 26, 2021 @ Noon EDT, we are hosting a webinar on how to prepare for an FDA inspection. It is a live webinar where you will be able to ask questions, and we are bundling the webinar with our new work instruction for “Conducting an FDA Inspection” (WI-009). If you register for the webinar, you will receive access to the live webinar, you will receive the native slide deck, and you will receive a copy of the work instruction. You can use the work instruction as an FDA inspection plan template for your company. The webinar will be recorded for anyone that is unable to attend the live session. You will be sent a link to download the recording to watch it as many times as you wish, and we recommend that you use the webinar as training for the rest of your company.

Smile, because you should never be scared of a surprise FDA inspector

If you have a surprise FDA inspector visit, you should never be scared because there is no difference between the best and worst-case outcome.

Why are you scared of an FDA inspector?

There are a number of reasons why you might be scared of an FDA inspector, but if you keep reading you will learn why 95% of your fear is self-induced. A small percentage of device manufacturers evaluate the performance of quality managers based upon the outcome of FDA inspections, but you have no control over whom the FDA Office of Regulatory Affairs (ORA) assigns to perform your inspection. If your company belongs to this 5% minority, you need to change top management’s approach to regulators or you need to find a new employer. For the majority of us, we are scared of embarrassment, failure, or being “shut down.”

There are rare examples of where the FDA has taken action to stop the distribution of medical devices, but this is only done as a last resort. Usually companies cooperate with the FDA with the hope of being able to resolve quality issues and resume distribution after corrective actions are implemented. Not only is this type of action rare, there will be a prior visit to your facility and prior written communication from ORA before you receive a warning letter–let alone removal of your company’s device(s) from the market. You can’t pass or fail an FDA inspection. The FDA inspector is verifying compliance with the FDA Quality System Regulation (i.e. 21 CFR 820) as well as the requirements for medical device reporting (i.e. 21 CFR 803), reports of corrections and removals (i.e. 21 CFR 806), investigational device exemptions (i.e. 21 CFR 812), and unique device identification (UDI). FDA inspectors only have time to sample your records, and with any sampling plan there is always uncertainty. When you do receive an FDA 483 inspection observation you should not consider it to be a condemnation of your company. Likewise, an absence of 483 observations is not a reason to celebrate.

Why you should not be embarrassed when you receive a 483 from an FDA inspector

The most irrational response to an FDA 483 inspection oberservation is embarrassment. Our firm specializes in helping start-up medical device companies get their first product to market. This includes providing training and helping them to implement a quality system. When our clients have their first FDA inspection, it is not uncommon to receive an FDA Form 483 inspection observation. Start-ups have limited resources, limited experience, and most of the employees have never participated in an FDA inspection before. Experience matters, and immature quality systems have only a limited number of records to sample. Any mistakes are easy for an inspector to find.

Instead of feeling embarrassed, acknowledge and embrace your inexperience. For example, during the opening meeting with an FDA inspector you might say, “We are a new company, and this is our first FDA inspection. I am also a first-time quality manager. If you find anything that we are doing incorrectly, please let us know and we will make immediate corrections and start working on our CAPA plan.” You can say this with a smile :), and you can genuinely mean what you said because it’s true.

Anticipation is always worse than reality

Another reason you are scared of an FDA inspection is because you don’t know exactly when the inspection will be. Only Class III PMA devices, and a few Class II De Novo devices with novel manufacturing processes, require a pre-approval inspection. For the rest of the Class II devices, ORA prioritizes inspections based upon risk. There are a few companies prioritized for inspection within the first six months of registration, such as reprocessors of single-use devices and contract sterilizers. For the rest of the Class II device manufacturers, your first inspection should be approximately two years after your company registers with the FDA. If you are located outside the USA (OUS), your first inspection might take three years to schedule. Finally, for Class I device manufacturers and contract manufacturers, you are unlikely to ever be inspected by the FDA. If you didn’t know what the typical timeline was for ORA to schedule your first inspection, you probably just breathed a HUGE sigh of relief when you read this paragraph.

Even if you already knew the approximate timeline and priorities for FDA inspections, it’s normal to feel a little anxiety when the date of your first visit is unknown. Your boss and the rest of top management are probably feeling just as much anxiety as you are, or even more if they have no idea what the timeline and priorities are. You should make sure that everyone in your company understands what they are supposed to do during an FDA inspection, and if you forget to tell them you might cause a lot of unneeded drama when they find out an FDA inspector is in the front lobby. Preparing for an FDA inspection is no different from conducting a firedrill. Everyone should know the procedure, and you should practice (i.e. conduct a mock-FDA inspection). Practice ensures that everyone knows what to do during the first 30 minutes of an FDA inspection, and nobody in your company will panic when an FDA inspector actually arrives.

Let’s define “surprise” visits by an FDA inspector

A surprise visit from an FDA inspector is extremely rare, but in the USA inspectors will call on Friday to confirm that your company will be open the following Monday for an inspection. The FDA has jurisdiction over medical device manufacturers located in the USA, and they are not required to give advanced notice. However, inspectors need time to prepare in advance for their inspection–just like a ISO 13485 auditor. Therefore, before an inspector will arrive on-site for a routine (Level 2) inspection, the inspector will first make a courtesy call to the official correspondent identified in your establishment registration.

What happens when an FDA inspector travels outside the USA

In the case of OUS medical device manufacturers, the FDA inspector does not have jurisdiction. Therefore, they will contact the official correspondent 6-8 weeks in advance to schedule an inspection. Inspectors will typically make contact via email, and you may be given a couple of weeks to choose from for the FDA inspection. The duration off your inspection should be 4.5 days. The inspector will arrive on Sunday, and the inspection will begin on Monday morning. The inspector has four major process areas to cover, and Friday morning will be focused on generating a preliminary report of 483 inspection observations. The reason why you can predict this OUS routine with a degree of certainty is two-fold: 1) these are government workers following a procedure, and 2) the FDA inspector needs time to get to the airport for their flight home.

What is the outcome of a FDA inspection?

FDA inspections have three possible outcomes:

1. No action indicated – there were no FDA 483 inspection observations identified by the FDA inspector
2. Voluntary action indicated – there was at least one FDA 483 inspection observation identified by the FDA inspector, and the FDA inspector requests submission of a CAPA plan to prevent recurrence
3. Official action indicated – there was at least one FDA 483 inspection observation identified by the FDA inspector, and the FDA inspector requires submission of a CAPA plan to prevent recurrence; if a plan is not received in 15 business days, a warning letter will automatically be generated on the 16 day

Even in the rare instances with there is “no action indicated” (i.e. best case scenario), I have always noticed one or more things during and FDA inspection that were overlooked and we needed to be initiate a new corrective action plan(s). In the other two possible scenarios, the FDA inspector identified the need for one or more corrective action plans. Therefore, regardless of whether you FDA inspection results in the best-case scenario or the worst-case, you will always need to initiate a new corrective action plan(s).

If the outcome is always a CAPA, what should you do?

Give your FDA inspector a big smile and say, “We are a new company, and this is our first FDA inspection. I am also a first-time quality manager. If you find anything that we are doing incorrectly, please let us know and we will make immediate corrections and start working on our CAPA plan.” Making sure that you have a genuine smile is just as important as what you say. Smiling will relax you and the anxiety and stress you are feeling will gradually melt away. Smiling will encourage the FDA inspector to trust you. Maybe your smile will even be contagious.

If you need help responding to an FDA 483 inspection observation, or you want to conduct a mock-FDA inspection, please use our calendly app to schedule a call with a member of our team. We are also hosting a live webinar on FDA inspections on July 26, 2021 @ Noon EDT.

About the Author

Robert Packard is a regulatory consultant with 25+ years of experience in the medical device, pharmaceutical, and biotechnology industries. He is a graduate of UConn in Chemical Engineering. Robert was a senior manager at several medical device companies—including the President/CEO of a laparoscopic imaging company. His Quality Management System expertise covers all aspects of developing, training, implementing, and maintaining ISO 13485 and ISO 14971 certification. From 2009-2012, he was a lead auditor and instructor for one of the largest Notified Bodies. Robert’s specialty is regulatory submissions for high-risk medical devices, such as implants and drug/device combination products for CE marking applications, Canadian medical device applications, and 510(k) submissions. The most favorite part of his job is training others. He can be reached via phone 802.258.1881 or email. You can also follow him on Google+, LinkedIn or Twitter.