Regulatory Open Forum

Hi All,
Thanks for your previous replies. I learn a lot from your inputs. This time I have a question about the consequences of 483. Say, at the end of the FDA investigation, the company receives 483. What the company representative will do. I think the company representative had to assure the agency inspector that they are going to take remideal actions. However, I want to know whether the company has to quarantine the questionable product in front on the FDA representative to show that they are very serious about taking prompt action.
Thanks in advance.
Keya Bandyopadhyay

Dear Keya,

If your company has received a 483, you need to begin to remedy the issues identified in the 483 so that they are corrected and you need to evaluate why these errors occurred in the first place and put in steps to ensure they do not occur again in the future.  You should take the notice and go through it line by line and address every issue identified.

If you have product that has been deemed misbranded or adulterated because it was not manufactured under GMP or QSR or there is some other reason given, then that lot of product should be reviewed to ensure it meets specifications before it is released, or retained until it can be brought into compliance.

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Michael Tomasovich
Director Business Development
Regulatory Affairs Associates
Inkster MI
United States
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Original Message:
Sent: 08-27-2012 18:15
From: Keya Bandyopadhyay
Subject: 483

Hi All,
Thanks for your previous replies. I learn a lot from your inputs. This time I have a question about the consequences of 483. Say, at the end of the FDA investigation, the company receives 483. What the company representative will do. I think the company representative had to assure the agency inspector that they are going to take remideal actions. However, I want to know whether the company has to quarantine the questionable product in front on the FDA representative to show that they are very serious about taking prompt action.
Thanks in advance.
Keya Bandyopadhyay

Hi Keya,

Although you can't reveal a lot about your 483 observation you are on the correct path on to how to deal with the observation.  "How will the company correct the non-gmp action".  Of course you know that a corrective action response will be sent to FDA to provide a remediation plan to the 483 Observation(s). This will clearly explain how the company will move forward. 

"Quarantine the product": It depends on the 483 Observation.  If you are questioning the validity / quality of the product then I would suggest putting it in quarantine until the proper review / evaluation of the 483 is conducted and concluded with good results.  In my opinion I find it hard to answer since you can't reveal the specific issue.

Although FDA inspections are extremely tense the results are great performance reviews. 

Good luck. 

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Alison Trado
Regulatory Affairs Manager
Hill Dermaceuticals, Inc.
Sanford FL
United States
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Original Message:
Sent: 08-27-2012 18:15
From: Keya Bandyopadhyay
Subject: 483

Hi All,
Thanks for your previous replies. I learn a lot from your inputs. This time I have a question about the consequences of 483. Say, at the end of the FDA investigation, the company receives 483. What the company representative will do. I think the company representative had to assure the agency inspector that they are going to take remideal actions. However, I want to know whether the company has to quarantine the questionable product in front on the FDA representative to show that they are very serious about taking prompt action.
Thanks in advance.
Keya Bandyopadhyay

"However, I want to know whether the company has to quarantine the questionable product in front on the FDA representative to show that they are very serious about taking prompt action."

Absolutely not in front on the FDA representative!!!  It doesn't manifest your seriousness but rather manifests something else regardless of your intent. 

To quarantine the questionable product should be done pursuant to your established procedures (e.g., nonconforming product handling procedures, nonconforming materials report, or whatever).

If no such procedures exist, you must define, document, and implement such procedures.

When you respond to 483s, the response should include the following.  

1. Your remedial action plan (beautiful table, charts, diagrams, etc.).
2. Any procedures revised/updated - attach the copies.
3. Specifically demonstrate your timelines for completing any remedial actions (e.g., correction and/or corrective actions).
4. If correction/corrective actions taken already, demonstrate whether the correction/corrective actions were effective including how the effectiveness has been measured.  
5. Address how you are going to measure your effectiveness of correction/corrective actions to be taken.  
6. Address each and every item shown on the 483.

BTW:  the term "beautiful" is used in a technical sense. 


-------------------------------------------------------
Regulatory Doctor, Coach and Consultant
www.GlobalComplianceSeminar.Com
Riner VA
United States
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Original Message:
Sent: 08-27-2012 18:15
From: Keya Bandyopadhyay
Subject: 483

Hi All,
Thanks for your previous replies. I learn a lot from your inputs. This time I have a question about the consequences of 483. Say, at the end of the FDA investigation, the company receives 483. What the company representative will do. I think the company representative had to assure the agency inspector that they are going to take remideal actions. However, I want to know whether the company has to quarantine the questionable product in front on the FDA representative to show that they are very serious about taking prompt action.
Thanks in advance.
Keya Bandyopadhyay

Hi, Keya. Good question. I'm afraid the best thing to do that day is usually nothing.  Say you'll take these findings seriously, and will answer the findings in writing in the timeframe (FDA should receive the response within 15 days). Your company needs to write the response so someone outside your organization doesn't promise something you can't deliver, but hire a consultant if you need to, at least to review your response.

-------------------------------------------
Andrea Chamblee RAC, FRAPS
Rockville MD
United States
-------------------------------------------




Original Message:
Sent: 08-27-2012 18:15
From: Keya Bandyopadhyay
Subject: 483

Hi All,
Thanks for your previous replies. I learn a lot from your inputs. This time I have a question about the consequences of 483. Say, at the end of the FDA investigation, the company receives 483. What the company representative will do. I think the company representative had to assure the agency inspector that they are going to take remideal actions. However, I want to know whether the company has to quarantine the questionable product in front on the FDA representative to show that they are very serious about taking prompt action.
Thanks in advance.
Keya Bandyopadhyay

A proper response is crucial to avoid a warning letter. Your response should specifically address the observations, both explaining how it was remedy and how it will be prevented from occurring again. This is where your CAPA will kick-in. You don't have to perform those activities while the agent is present, but will need a proper response within 15days.

Be on time and be specific!

-------------------------------------------
Marc Sanchez
Attorney and Regulatory Consultant
Atlanta GA
United States
-------------------------------------------






Original Message:
Sent: 08-27-2012 18:15
From: Keya Bandyopadhyay
Subject: 483

Hi All,
Thanks for your previous replies. I learn a lot from your inputs. This time I have a question about the consequences of 483. Say, at the end of the FDA investigation, the company receives 483. What the company representative will do. I think the company representative had to assure the agency inspector that they are going to take remideal actions. However, I want to know whether the company has to quarantine the questionable product in front on the FDA representative to show that they are very serious about taking prompt action.
Thanks in advance.
Keya Bandyopadhyay

In addition:
a) if you update any procedures to correct the issues, you have to attch the updated procedures and the Change Order/Change Notes that approve/released these documentcomtaining teh date approved and the people who approved it
Updated procedure require re training. The records of the training need to be send to teh FDA.
b) Perform retrospective action according to the updated procedure and send a report with examples to teh FDA.
c) Usually it is impossibel to correct all in time to get it to teh FDA in 15 days but they will accept a detailed plan with date for completion agrred with the FDA inspector.
d) Make sure you keep evidence of the FDA person signing that they recieved your information.


Hope that helps

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Varda Swery
Signostics Ltd
Torrensville
Australia
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Original Message:
Sent: 08-29-2012 08:18
From: Marc Sanchez
Subject: 483

A proper response is crucial to avoid a warning letter. Your response should specifically address the observations, both explaining how it was remedy and how it will be prevented from occurring again. This is where your CAPA will kick-in. You don't have to perform those activities while the agent is present, but will need a proper response within 15days.

Be on time and be specific!

-------------------------------------------
Marc Sanchez
Attorney and Regulatory Consultant
Atlanta GA
United States
-------------------------------------------






Original Message:
Sent: 08-27-2012 18:15
From: Keya Bandyopadhyay
Subject: 483

Hi All,
Thanks for your previous replies. I learn a lot from your inputs. This time I have a question about the consequences of 483. Say, at the end of the FDA investigation, the company receives 483. What the company representative will do. I think the company representative had to assure the agency inspector that they are going to take remideal actions. However, I want to know whether the company has to quarantine the questionable product in front on the FDA representative to show that they are very serious about taking prompt action.
Thanks in advance.
Keya Bandyopadhyay