Presented By: Tiffany Abramsy yChair, ASQ Biomedical

Southern California Discussion Group

Part 1 of 3 – Avoiding The Dreaded 483◦ Focus on being prepared to host an FDA Audit

P t 2 f 3 Oh N Y G t 483 N Part 2 of 3 – Oh No, You Got a 483, Now What?

Part 3 of 3 – Responding to a 483 & Making it Go Awayy

What is it?◦ It is the form on which an FDA inspector issues audit

observations.◦ However, it is not the final document. FDA will issue a

final report; i.e. Establishment Inspection Report (EIR) Why does it matter?◦ It identifies conditions deemed by the FDA inspector toIt identifies conditions deemed by the FDA inspector to

reflect conditions &/or practices at your company that can lead to adulterated products with the potential to cause injury.cause injury.

◦ They are public records. ◦ Your competitors will notice. So will share holders.

Are they a bad thing?N b h d i h k◦ No one wants one, but how you respond is the key.◦ Keep in mind not only do you work in an industry

regulated by the FDA, you are a consumer protected b h FDAby the FDA.

What triggers an FDA audit? What triggers an FDA audit?◦ Most are routine inspections.◦ Some are the result of an application to market a

new productnew product.◦ Others are the results of issues from the

marketplace, such as complaints.

So how do we avoid getting a form 483?Hid ?◦ Hide?◦ Develop the perfect Quality System?

This can not be done & the FDA knows this. They want to see that you have an active Quality System.

Note: There is a little ‘c’ in front of GMP, which stands for current.

So, being active isn’t just for your personal health, itSo, being active isn t just for your personal health, it is also important for the health of your Quality System.

Are you keeping up with the evolving regulations? Are you actively monitoring the guidance documents

either released by the FDA &/or recognized by theeither released by the FDA &/or recognized by the FDA?

h h d k Why is the FDA requiring new device tracking systems?◦ They want to be able to pull together all relevant◦ They want to be able to pull together all relevant

data on your device to understand the full extent of it’s performance.

The notified bodies review your monitoring of evolving regulations and standards. ◦ Did you know the FDA has considered accepting

notified body audits in lieu of an FDA inspection?notified body audits in lieu of an FDA inspection?◦ Think the FDA is watching to see what other

authorities are doing with their laws & regulations?

There is a lot more cross communication with the various regulatory groups. They are even sharing g y g p y gdata.

You have to stay technically strong!S d ff ff i f i i◦ Send your staff off-site for training.◦ Support your staff getting certifications.◦ Find out what is the latest technology & invest in

keeping yours current.◦ Network, become members of relevant industry

organizations.

Remember the FDA is going to everyone’s sites to audit. How do you compare to others in your y p yindustry?

We’re asking the FDA to modernize and speed up the process…..what are you doing at your facility?p y g y y

Review the Code of Federal Regulationsd h bl h C d f d l Read the preamble to the Code of Federal

Regulations.

This seems so obvious, but each time I re-read these documents I find something new.

◦ Please know if you are using the same slide deck year to year to complete your annual GMP training, please stop. It isn’t accomplishing anything. You are just checking a box.

When was the last time you read the law? A guidance document? Visited the FDA website? How do you conduct GMP training?

Why rely on your procedures to cover everything already written in guidanceeverything already written in guidance documents?

What will the FDA look at when they show up?◦ If it is a routine audit, they will follow the Quality

System Inspection Technique (QSIT). This is a readily available document from the FDA.This is a readily available document from the FDA.◦ If it is due to a new product submission, the focus

will be on your project documents for qualification of the productof the product.◦ For cause will focus on complaints and the key area

of concern.

Luck favors the prepared. Do you have a procedure that governs what

to do if the FDA shows up? If th h t i l ?◦ If no, then what is your game plan?

Who owns hosting an FDA audit? ◦ Don’t answer QA what individual(s)? Who is yourDon t answer QA…what individual(s)? Who is your

leader? Define roles & responsibilities Make sure the front desk knows what to do

when the FDA shows up.

Practice!! Set up a backroom & conduct a mock audit.◦ Verify the electronic systems work. ◦ Let folks dry run everything so when a real audit◦ Let folks dry run everything so when a real audit

happens no on panics. Practice a full FDA audit support set up with a

few of your internal audits. Consider sharing the audit process as a

t i i t ltraining tool.

Common roles during an audit.◦ Backroom manager – coordinates all the activities &

is ultimately responsible for all materials & staff entering the audit room.g◦ Scribe – Person seated near the auditor taking notes

& communicating with the backroom.Audit Room Host Coordinates all the activities◦ Audit Room Host – Coordinates all the activities within the audit room.◦ Runner – Runs documents between the backroom &

the audit room.

Backroom manager has the hardest job during an FDA audit.◦ They have to keep things under control & calm.◦ They have to be able to know where everything is◦ They have to be able to know where everything is,

what is needed, & where everyone is throughout the audit.Th d h ‘ l k ’ d h◦ They need to manage the ‘on-lookers’ and the ‘helpers’.◦ They need to be very aware of time.y y◦ They need to manage the gossip.

Identify your subject matter experts (SME) & include backups.◦ Work with your SMEs. Interview them and verify any

presentation materials they intend to presentpresentation materials they intend to present. Everyone should have a top level process flow for their

area, key procedures identified, and ort charts.◦ Make sure the person presenting to the FDA is

capable of speaking appropriately to the area being reviewed, including having the ability to present inreviewed, including having the ability to present in such a way that an auditor can understand. Not everyone is a good presenter.

Stage key documents in the backroom.◦ You do NOT want to keep an auditor waiting on

documents to review.◦ Consider presenting materials electronically◦ Consider presenting materials electronically. ◦ It is becoming very common for the FDA to request

copies to take with them for review. This may mean you will need to box the materials up & handle shipping. This includes your facilities outside the US. Make sure the backroom is ready to handle thisUS. Make sure the backroom is ready to handle this type of request.

How many copies?

Retain audit materials, notes, ext. in the event d i 483 h fyou do receive a 483 so that you can focus on

the auditors concerns. ◦ This maybe needed to prevent CAPA scope creepThis maybe needed to prevent CAPA scope creep.◦ This also helps convince the folks that weren’t there

of what exactly are the issues, if any.

Be sure and visit the FDA website◦ Search Inspection Guides – these provide

information to the inspector on what to review depending on the area being audited. p g g As an example, there are instructions focused on

sterile devices.◦ Use these guides as training tools◦ Use these guides as training tools. Be sure your SME has reviewed the relevant sections of

the inspection guides for the area they are presenting.

The better prepared & cleaner the presentation, the stronger the QS appears to an auditor.

This is an example of the inspection guidance associated with CAPA – 21 CFR 820.100

Y i ti h ld i l d d t il d i ti◦ Your inspection should include detailed inspection of documents maintained under the requirements of 21 CFR 820.100. In particular, you should focus on reliability issues that have not been documented for corrective and preventive actions. The continued distribution of devices with a known problem should be noted on the FDA 483.

Be sure and visit the FDA website◦ Visit the ORA postings, from the ORA FOIA

Electronic Reading Room to review issued 483s. This will provide examples of how 483s are written.p p

Office of Regulatory Affairs (ORA) & Freedom Of Information Act (FOIA)Information Act (FOIA)

Some example 483:◦ Observation 1: Aseptic processing areas are

deficient regarding the system for monitoring environmental conditions. Specifically, your firm’s p y, yprocedures for monitoring the ISO5 hoods are not suitable to ensure the quality of air. For example, (a) during periods of production your firm does not (a) during periods of production, your firm does not

conduct viable air monitoring daily. (b) your firm does not incubate environmental samples

(touch plates & spin air) at 20 25C in order to(touch plates & spin air) at 20-25C in order to maximize the recovery of yeast and mold.

Some example 483:◦ Observation 1: Procedures for conducting quality

audits were not complete. Specifically, the CRM audit procedure 005014 requires an audit plan and p q pchecklist. Review of 2005 CAPA Audit Plan noted a lack of specific details to ensure complete coverage and that all the QSR requirements are met Thereand that all the QSR requirements are met. There was no detailed reference to the auditing of non-conforming data sources or the analysis of those non conforming data sourcesnon-conforming data sources.

There are industry sites designed to keep you up to date on the latest information associated with FDA 483.

◦ There is one site, fda483s.com, with lots of general information.

◦ Fdazilla.com provides data on the number of 483s issued compared to the number of inspectionsissued compared to the number of inspections. Recent data shows roughly 22% rate of 483 compared to inspections.

There are consulting firms offering all kinds of assistance.

Ch k th ti b f d i ff D◦ Check the tires before you drive off. Do your research before selecting a consulting firm. Also, be prepared to go through a few consultants before you find the right one for your situation.

◦ Don’t let them drive. You need to own your QualityDon t let them drive. You need to own your Quality System. You can’t just sit back and hope a consultant will fix all your problems.

Data rich, decision dumb….

Are you reviewing the big picture to identify f ?areas of concern?

◦ Be aware that metrics can drive bad behavior. Are you acting on issues when identified? Are you acting on issues when identified?◦ Are you taking the right level of action?

Do you have a strong audit program that is y g p gfully backed / supported by management?◦ Are actions taken as a result of the audit?

How are you preparing your audit staff?◦ Your internal audits are the best opportunity you

have to improve your quality system. If you aren’t investing in your auditors, you are missing out!g y , y g◦ Are you sending the right auditor out? Can they

cover all the areas to be audited?

Does your facility take audits seriously?◦ This just might be the key to preventing an FDA◦ This just might be the key to preventing an FDA

483.

Use common sense when looking at your data. Statistics is a tool, not the only option.

Y h ld h d id f h t◦ You should have a good idea of what are your problem areas just from the time you have spent reviewing NCR, CAPA, complaints, audit reports….

◦ Issue a field action lately? That would be a prime area to review.area to review.

Make sure it is the right thing to fix.

◦ You validate your product, why not validate your problem? Find a way to confirm it really is a problem.p y y p

◦ Don’t divide the vital resources too much. If every project is the top priority then nothing is a priorityproject is the top priority, then nothing is a priority.

◦ If the data you present to management doesn’t tell them about the issues how do you expect to get the problemabout the issues, how do you expect to get the problem fixed? They have to agree to the time, money, & commitment of resources.

Keep in mind the main focus of the FDA is the safety of each & everyone of us. That should be a key goal for each of us as well. Thus, we are really playing on the same teamare really playing on the same team.

Please feel free to contact me should you havePlease, feel free to contact me should you have questions.

tiffany_abrams@edwards.com