Regulatory Open Forum

I need to import a drug for animal use. The vials are labeled for investigational use as per 21 CFR 312.6. For a couple of different reasons, this product is no longer suitable for use in humans.

I could easily have the supplier put the vials in boxes that are labeled as per 21 CFR 312.160 ("CAUTION: Contains a biological product for investigational in vitro diagnostic tests only.")

The supplier is resistant to the idea of overlabeling the vials.

I need to determine whether labeling of the box will be adequate. 21 CFR 312.160 does not specifically require that the caution statement be printed on the primary packaging. On the other hand, I am concerned that the product labeling could be considered misleading, since the vials themselves will still appear as if they were appropriate for use in humans under an IND.

We will have full chain of custody documentation and tight control of the drug, so there is no actual risk that the product will be administered to humans. 

Does anyone have any experience with this issue?

Any help is appreciated. Thank you!

-------------------------------------------
Michael Hellerstein
GeoVax, Inc.
Smyrna GA
United States
-------------------------------------------

CORRECTION - I had a copy-paste error in the original post. Please ignore it and read this one. Thank you!

I need to import a drug for animal use. The vials are labeled for investigational use as per 21 CFR 312.6. For a couple of different reasons, this product is no longer suitable for use in humans.

I could easily have the supplier put the vials in boxes that are labeled as per 21 CFR 312.160 ("CAUTION: Contains a new drug for investigational use only in laboratory research animals, or for tests in vitro. Not for use in humans.")

The supplier is resistant to the idea of overlabeling the vials.

I need to determine whether labeling of the box will be adequate. 21 CFR 312.160 does not specifically require that the caution statement be printed on the primary packaging. On the other hand, I am concerned that the product labeling could be considered misleading, since the vials themselves will still appear as if they were appropriate for use in humans under an IND.

We will have full chain of custody documentation and tight control of the drug, so there is no actual risk that the product will be administered to humans. 

Does anyone have any experience with this issue?

Any help is appreciated. Thank you!

-------------------------------------------
Michael Hellerstein
GeoVax, Inc.
Smyrna GA
United States
-------------------------------------------




-------------------------------------------
Michael Hellerstein
GeoVax, Inc.
Smyrna GA
United States
-------------------------------------------


Original Message:
Sent: 10-16-2014 08:11
From: Michael Hellerstein
Subject: Interpretation of 21 CFR 312.160

I need to import a drug for animal use. The vials are labeled for investigational use as per 21 CFR 312.6. For a couple of different reasons, this product is no longer suitable for use in humans.

I could easily have the supplier put the vials in boxes that are labeled as per 21 CFR 312.160 ("CAUTION: Contains a biological product for investigational in vitro diagnostic tests only.")

The supplier is resistant to the idea of overlabeling the vials.

I need to determine whether labeling of the box will be adequate. 21 CFR 312.160 does not specifically require that the caution statement be printed on the primary packaging. On the other hand, I am concerned that the product labeling could be considered misleading, since the vials themselves will still appear as if they were appropriate for use in humans under an IND.

We will have full chain of custody documentation and tight control of the drug, so there is no actual risk that the product will be administered to humans. 

Does anyone have any experience with this issue?

Any help is appreciated. Thank you!

-------------------------------------------
Michael Hellerstein
GeoVax, Inc.
Smyrna GA
United States
-------------------------------------------

Michael,

21 CFR 312.6 (a) states the following:

(a) The immediate package of an investigational new drug intended for human use shall bear a label with the statement "Caution: New Drug--Limited by Federal (or United States) law to investigational use."

(b) The label or labeling of an investigational new drug shall not bear any statement that is false or misleading in any particular and shall not represent that the investigational new drug is safe or effective for the purposes for which it is being investigated.

The immediate package is the vial and needs to have the caution statement regardless if it is for human use or for research and not for human use. This statement is also typically included in any secondary packaging. 

You are correct that by not over labeling the vials with the new caution statement, which should cover the old caution statement only, will be misleading in the context of 21CFR 314.6 (b). 

The full chain of custody and tight control of the drug is appropriate, but the regulations are clear and these are codified. Think about what happens when the vials are taken out of the box and circulated, etc. Your instincts are correct, follow them and have the supplier over label in compliance with the codified regulations on this topic. 

Good luck,

Dar
-------------------------------------------
Darlene Rosario RAC
Principal Consultant RA, Quality and Compliance
Velocity Consulting
Ventura CA
United States
-------------------------------------------


Original Message:
Sent: 10-16-2014 08:14
From: Michael Hellerstein
Subject: Interpretation of 21 CFR 312.160

CORRECTION - I had a copy-paste error in the original post. Please ignore it and read this one. Thank you!

I need to import a drug for animal use. The vials are labeled for investigational use as per 21 CFR 312.6. For a couple of different reasons, this product is no longer suitable for use in humans.

I could easily have the supplier put the vials in boxes that are labeled as per 21 CFR 312.160 ("CAUTION: Contains a new drug for investigational use only in laboratory research animals, or for tests in vitro. Not for use in humans.")

The supplier is resistant to the idea of overlabeling the vials.

I need to determine whether labeling of the box will be adequate. 21 CFR 312.160 does not specifically require that the caution statement be printed on the primary packaging. On the other hand, I am concerned that the product labeling could be considered misleading, since the vials themselves will still appear as if they were appropriate for use in humans under an IND.

We will have full chain of custody documentation and tight control of the drug, so there is no actual risk that the product will be administered to humans. 

Does anyone have any experience with this issue?

Any help is appreciated. Thank you!

-------------------------------------------
Michael Hellerstein
GeoVax, Inc.
Smyrna GA
United States
-------------------------------------------




-------------------------------------------
Michael Hellerstein
GeoVax, Inc.
Smyrna GA
United States
-------------------------------------------


Original Message:
Sent: 10-16-2014 08:11
From: Michael Hellerstein
Subject: Interpretation of 21 CFR 312.160

I need to import a drug for animal use. The vials are labeled for investigational use as per 21 CFR 312.6. For a couple of different reasons, this product is no longer suitable for use in humans.

I could easily have the supplier put the vials in boxes that are labeled as per 21 CFR 312.160 ("CAUTION: Contains a biological product for investigational in vitro diagnostic tests only.")

The supplier is resistant to the idea of overlabeling the vials.

I need to determine whether labeling of the box will be adequate. 21 CFR 312.160 does not specifically require that the caution statement be printed on the primary packaging. On the other hand, I am concerned that the product labeling could be considered misleading, since the vials themselves will still appear as if they were appropriate for use in humans under an IND.

We will have full chain of custody documentation and tight control of the drug, so there is no actual risk that the product will be administered to humans. 

Does anyone have any experience with this issue?

Any help is appreciated. Thank you!

-------------------------------------------
Michael Hellerstein
GeoVax, Inc.
Smyrna GA
United States
-------------------------------------------

Dar:

Thanks a million! I really appreciate the help.

- Mike

-------------------------------------------
Michael Hellerstein
GeoVax, Inc.
Smyrna GA
United States
-------------------------------------------


Original Message:
Sent: 10-16-2014 13:57
From: Darlene Rosario
Subject: Interpretation of 21 CFR 312.160

Michael,

21 CFR 312.6 (a) states the following:

(a) The immediate package of an investigational new drug intended for human use shall bear a label with the statement "Caution: New Drug--Limited by Federal (or United States) law to investigational use."

(b) The label or labeling of an investigational new drug shall not bear any statement that is false or misleading in any particular and shall not represent that the investigational new drug is safe or effective for the purposes for which it is being investigated.

The immediate package is the vial and needs to have the caution statement regardless if it is for human use or for research and not for human use. This statement is also typically included in any secondary packaging. 

You are correct that by not over labeling the vials with the new caution statement, which should cover the old caution statement only, will be misleading in the context of 21CFR 314.6 (b). 

The full chain of custody and tight control of the drug is appropriate, but the regulations are clear and these are codified. Think about what happens when the vials are taken out of the box and circulated, etc. Your instincts are correct, follow them and have the supplier over label in compliance with the codified regulations on this topic. 

Good luck,

Dar
-------------------------------------------
Darlene Rosario RAC
Principal Consultant RA, Quality and Compliance
Velocity Consulting
Ventura CA
United States
-------------------------------------------


Original Message:
Sent: 10-16-2014 08:14
From: Michael Hellerstein
Subject: Interpretation of 21 CFR 312.160

CORRECTION - I had a copy-paste error in the original post. Please ignore it and read this one. Thank you!

I need to import a drug for animal use. The vials are labeled for investigational use as per 21 CFR 312.6. For a couple of different reasons, this product is no longer suitable for use in humans.

I could easily have the supplier put the vials in boxes that are labeled as per 21 CFR 312.160 ("CAUTION: Contains a new drug for investigational use only in laboratory research animals, or for tests in vitro. Not for use in humans.")

The supplier is resistant to the idea of overlabeling the vials.

I need to determine whether labeling of the box will be adequate. 21 CFR 312.160 does not specifically require that the caution statement be printed on the primary packaging. On the other hand, I am concerned that the product labeling could be considered misleading, since the vials themselves will still appear as if they were appropriate for use in humans under an IND.

We will have full chain of custody documentation and tight control of the drug, so there is no actual risk that the product will be administered to humans. 

Does anyone have any experience with this issue?

Any help is appreciated. Thank you!

-------------------------------------------
Michael Hellerstein
GeoVax, Inc.
Smyrna GA
United States
-------------------------------------------




-------------------------------------------
Michael Hellerstein
GeoVax, Inc.
Smyrna GA
United States
-------------------------------------------


Original Message:
Sent: 10-16-2014 08:11
From: Michael Hellerstein
Subject: Interpretation of 21 CFR 312.160

I need to import a drug for animal use. The vials are labeled for investigational use as per 21 CFR 312.6. For a couple of different reasons, this product is no longer suitable for use in humans.

I could easily have the supplier put the vials in boxes that are labeled as per 21 CFR 312.160 ("CAUTION: Contains a biological product for investigational in vitro diagnostic tests only.")

The supplier is resistant to the idea of overlabeling the vials.

I need to determine whether labeling of the box will be adequate. 21 CFR 312.160 does not specifically require that the caution statement be printed on the primary packaging. On the other hand, I am concerned that the product labeling could be considered misleading, since the vials themselves will still appear as if they were appropriate for use in humans under an IND.

We will have full chain of custody documentation and tight control of the drug, so there is no actual risk that the product will be administered to humans. 

Does anyone have any experience with this issue?

Any help is appreciated. Thank you!

-------------------------------------------
Michael Hellerstein
GeoVax, Inc.
Smyrna GA
United States
-------------------------------------------

Based on your description, I suggest you please review the following:

http://wp.me/P33LGu-3Ak

In particular, 21 CFR Part 511 in comparison with 21 CFR 312.160

Please note: over-labeling is not prohibited but is strongly discouraged due to a potential risk as it may become detached.

____________________________________________________________
Dr. David Lim, Ph.D., RAC, ASQ-CQA 


Original Message:
Sent: 10-16-2014 08:11
From: Michael Hellerstein
Subject: Interpretation of 21 CFR 312.160

I need to import a drug for animal use. The vials are labeled for investigational use as per 21 CFR 312.6. For a couple of different reasons, this product is no longer suitable for use in humans.

I could easily have the supplier put the vials in boxes that are labeled as per 21 CFR 312.160 ("CAUTION: Contains a biological product for investigational in vitro diagnostic tests only.")

The supplier is resistant to the idea of overlabeling the vials.

I need to determine whether labeling of the box will be adequate. 21 CFR 312.160 does not specifically require that the caution statement be printed on the primary packaging. On the other hand, I am concerned that the product labeling could be considered misleading, since the vials themselves will still appear as if they were appropriate for use in humans under an IND.

We will have full chain of custody documentation and tight control of the drug, so there is no actual risk that the product will be administered to humans. 

Does anyone have any experience with this issue?

Any help is appreciated. Thank you!

-------------------------------------------
Michael Hellerstein
GeoVax, Inc.
Smyrna GA
United States
-------------------------------------------

David:

Thank you! I appreciate the advice.

- Mike

-------------------------------------------
Michael Hellerstein
GeoVax, Inc.
Smyrna GA
United States
-------------------------------------------


Original Message:
Sent: 10-17-2014 10:13
From: David Lim
Subject: Interpretation of 21 CFR 312.160


Based on your description, I suggest you please review the following:

http://wp.me/P33LGu-3Ak

In particular, 21 CFR Part 511 in comparison with 21 CFR 312.160

Please note: over-labeling is not prohibited but is strongly discouraged due to a potential risk as it may become detached.

____________________________________________________________
Dr. David Lim, Ph.D., RAC, ASQ-CQA 

President and CEO | REGULATORY DOCTOR
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Original Message:
Sent: 10-16-2014 08:11
From: Michael Hellerstein
Subject: Interpretation of 21 CFR 312.160

I need to import a drug for animal use. The vials are labeled for investigational use as per 21 CFR 312.6. For a couple of different reasons, this product is no longer suitable for use in humans.

I could easily have the supplier put the vials in boxes that are labeled as per 21 CFR 312.160 ("CAUTION: Contains a biological product for investigational in vitro diagnostic tests only.")

The supplier is resistant to the idea of overlabeling the vials.

I need to determine whether labeling of the box will be adequate. 21 CFR 312.160 does not specifically require that the caution statement be printed on the primary packaging. On the other hand, I am concerned that the product labeling could be considered misleading, since the vials themselves will still appear as if they were appropriate for use in humans under an IND.

We will have full chain of custody documentation and tight control of the drug, so there is no actual risk that the product will be administered to humans. 

Does anyone have any experience with this issue?

Any help is appreciated. Thank you!

-------------------------------------------
Michael Hellerstein
GeoVax, Inc.
Smyrna GA
United States
-------------------------------------------

One quick point of clarification. I realized that I was not adequately clear in my description of the intended use of the product.

By "animal use" I meant nonclinical studies in animals. There is no intention to develop this product for the veterinary market.
Thanks to all for your help.

Hi Michael,

My advise was based on an assumption of nonclinical evaluation and not veterinary medicine. It goes without saying that the "over labeling" should adhere to Good Documentation Practices for labeling and be well-controlled.  While not a good practice routinely, sometimes it is necessary and as long as overseen by Quality can be appropriate. Removing labels and relabeling is more complicated and harder to manage from a Quality perspective as all labels that are removed need to be accounted for as do the labels that are applied. I would still advocate over labeling the caution statement and not obscuring the original label information. 

Thanks for clarifying nonetheless,

Good luck,

Dar


-------------------------------------------
Darlene Rosario RAC
Principal Consultant RA, Quality and Compliance
Velocity Consulting
Ventura CA
United States
-------------------------------------------


Original Message:
Sent: 10-19-2014 18:15
From: Michael Hellerstein
Subject: Interpretation of 21 CFR 312.160

One quick point of clarification. I realized that I was not adequately clear in my description of the intended use of the product.

By "animal use" I meant nonclinical studies in animals. There is no intention to develop this product for the veterinary market.

Thanks to all for your help.

Understood, and I appreciate the advice. My last comment was in response to the messages that I received referring to part 511. Thanks again!

-------------------------------------------
Michael Hellerstein
GeoVax, Inc.
Smyrna GA
United States
-------------------------------------------



Original Message:
Sent: 10/20/2014 6:47:35 PM
From: runher6@yahoo.com
Subject: RE: Interpretation of 21 CFR 312.160

Hi Michael, My advise was based on an assumption of nonclinical evaluation and not veterinary medicine. It goes without saying that the "over labeling" should adhere to Good Documentation Practices for labeling and be well-controlled.  While not a good practice routinely, sometimes it is necessary and as long as overseen by Quality can be appropriate. Removing labels and relabeling is more complicated and harder to manage from a Quality perspective as all labels that are removed need to be accounted for as do the labels that are applied. I would still advocate over labeling the caution statement and not obscuring the original label information.  Thanks for clarifying nonetheless, Good luck, Dar ------------------------------------------- Darlene Rosario RAC Principal Consultant RA, Quality and Compliance Velocity Consulting Ventura CA United States -------------------------------------------
Original Message: Sent: 10-19-2014 18:15 From: Michael Hellerstein Subject: Interpretation of 21 CFR 312.160 One quick point of clarification. I realized that I was not adequately clear in my description of the intended use of the product.

By "animal use" I meant nonclinical studies in animals. There is no intention to develop this product for the veterinary market.

Thanks to all for your help.