Regulatory Open Forum

Hello,

I have a question regarding compliance to USP 467.  If the supplier tests the API for USP <467> and results conform to USP <467>. Is the DP manufacturer required to test for residual solvents when residual solvent levels in the ingredients used to produce the drug product are below the levels listed in the USP <467>?

Thanks in advance.

Olga

------------------------------
Olga Figueroa Brito
Santa Ana CA
United States
------------------------------

Hi Olga.

As with any issue you have the responsibility as the manufacturer of the drug product to ensure that your product meets any specifications that have been agreed to by FDA and the manufacturer.  There is the opportunity to "qualify" a supplier through complete specification testing of 3 separate supplier lots and if your results meet the requirements and match up to the data that the supplier has provided on their certificate of analysis you could theoretically then consider the supplier as qualified regarding the solvents in the future and thereby only need to perform a test that would ensure that what they sold you and what they sent you are what you expected.  This can be as simple as an IR scan of the material or could be more complex.  You would still be expected to provide evidence of continuing qualification of the supplier by typically testing the material to full specification annually for 1 lot but this is the best option in general to minimize testing if you plan to use the supplier and the material for the long term.

------------------------------
Victor Mencarelli
Global Director Regulatory Affairs
MelvilleNY
United States
------------------------------

Original Message:
Sent: 07-Feb-2021 23:35
From: Olga Figueroa Brito
Subject: USP 467 Residual Solvents question

Hello,

I have a question regarding compliance to USP 467.  If the supplier tests the API for USP <467> and results conform to USP <467>. Is the DP manufacturer required to test for residual solvents when residual solvent levels in the ingredients used to produce the drug product are below the levels listed in the USP <467>?

Thanks in advance.

Olga

------------------------------
Olga Figueroa Brito
Santa Ana CA
United States
------------------------------

Victor's suggestion is spot on, but I'll add to a comment made by anonymous.  If you document the supplier does not use the solvents in the manufacturing process, you don't need to test for it.

------------------------------
Christopher Smith, CQE, RAC
Coastal Pharmaceutical Consultants, Inc.
7950 Old River Road
Burgaw, NC 28425, USA
910.789.1232 (mobile)
chrissmith@coastalpharmaconsultants.com
------------------------------

Original Message:
Sent: 08-Feb-2021 12:08
From: Victor Mencarelli
Subject: USP 467 Residual Solvents question

Hi Olga.

As with any issue you have the responsibility as the manufacturer of the drug product to ensure that your product meets any specifications that have been agreed to by FDA and the manufacturer.  There is the opportunity to "qualify" a supplier through complete specification testing of 3 separate supplier lots and if your results meet the requirements and match up to the data that the supplier has provided on their certificate of analysis you could theoretically then consider the supplier as qualified regarding the solvents in the future and thereby only need to perform a test that would ensure that what they sold you and what they sent you are what you expected.  This can be as simple as an IR scan of the material or could be more complex.  You would still be expected to provide evidence of continuing qualification of the supplier by typically testing the material to full specification annually for 1 lot but this is the best option in general to minimize testing if you plan to use the supplier and the material for the long term.

------------------------------
Victor Mencarelli
Global Director Regulatory Affairs
MelvilleNY
United States

Original Message:
Sent: 07-Feb-2021 23:35
From: Olga Figueroa Brito
Subject: USP 467 Residual Solvents question

Hello,

I have a question regarding compliance to USP 467.  If the supplier tests the API for USP <467> and results conform to USP <467>. Is the DP manufacturer required to test for residual solvents when residual solvent levels in the ingredients used to produce the drug product are below the levels listed in the USP <467>?

Thanks in advance.

Olga

------------------------------
Olga Figueroa Brito
Santa Ana CA
United States
------------------------------

This message was posted by a user wishing to remain anonymous

To Chris: Sorry, Isn't that obvious? The question from Olga clearly indicates that API process does use certain residual solvents so the test was performed by the supplier and it complied with the USP 467 criteria.
Original Message:
Sent: 09-Feb-2021 06:31
From: Christopher Smith
Subject: USP 467 Residual Solvents question

Victor's suggestion is spot on, but I'll add to a comment made by anonymous.  If you document the supplier does not use the solvents in the manufacturing process, you don't need to test for it.

------------------------------
Christopher Smith, CQE, RAC
Coastal Pharmaceutical Consultants, Inc.
7950 Old River Road
Burgaw, NC 28425, USA
910.789.1232 (mobile)
chrissmith@coastalpharmaconsultants.com

Original Message:
Sent: 08-Feb-2021 12:08
From: Victor Mencarelli
Subject: USP 467 Residual Solvents question

Hi Olga.

As with any issue you have the responsibility as the manufacturer of the drug product to ensure that your product meets any specifications that have been agreed to by FDA and the manufacturer.  There is the opportunity to "qualify" a supplier through complete specification testing of 3 separate supplier lots and if your results meet the requirements and match up to the data that the supplier has provided on their certificate of analysis you could theoretically then consider the supplier as qualified regarding the solvents in the future and thereby only need to perform a test that would ensure that what they sold you and what they sent you are what you expected.  This can be as simple as an IR scan of the material or could be more complex.  You would still be expected to provide evidence of continuing qualification of the supplier by typically testing the material to full specification annually for 1 lot but this is the best option in general to minimize testing if you plan to use the supplier and the material for the long term.

------------------------------
Victor Mencarelli
Global Director Regulatory Affairs
MelvilleNY
United States

Original Message:
Sent: 07-Feb-2021 23:35
From: Olga Figueroa Brito
Subject: USP 467 Residual Solvents question

Hello,

I have a question regarding compliance to USP 467.  If the supplier tests the API for USP <467> and results conform to USP <467>. Is the DP manufacturer required to test for residual solvents when residual solvent levels in the ingredients used to produce the drug product are below the levels listed in the USP <467>?

Thanks in advance.

Olga

------------------------------
Olga Figueroa Brito
Santa Ana CA
United States
------------------------------

Hello Christopher,

Thank you for your feedback. I want to add the following to my original question. The supplier is qualified and do we need to test only the API for residual solvents to confirm what the supplier provided on COA? No solvents are used in the DP. 

Thanks in advance,
Olga

------------------------------
Olga Figueroa Brito
Santa Ana CA
United States
------------------------------

Original Message:
Sent: 09-Feb-2021 06:31
From: Christopher Smith
Subject: USP 467 Residual Solvents question

Victor's suggestion is spot on, but I'll add to a comment made by anonymous.  If you document the supplier does not use the solvents in the manufacturing process, you don't need to test for it.

------------------------------
Christopher Smith, CQE, RAC
Coastal Pharmaceutical Consultants, Inc.
7950 Old River Road
Burgaw, NC 28425, USA
910.789.1232 (mobile)
chrissmith@coastalpharmaconsultants.com

Original Message:
Sent: 08-Feb-2021 12:08
From: Victor Mencarelli
Subject: USP 467 Residual Solvents question

Hi Olga.

As with any issue you have the responsibility as the manufacturer of the drug product to ensure that your product meets any specifications that have been agreed to by FDA and the manufacturer.  There is the opportunity to "qualify" a supplier through complete specification testing of 3 separate supplier lots and if your results meet the requirements and match up to the data that the supplier has provided on their certificate of analysis you could theoretically then consider the supplier as qualified regarding the solvents in the future and thereby only need to perform a test that would ensure that what they sold you and what they sent you are what you expected.  This can be as simple as an IR scan of the material or could be more complex.  You would still be expected to provide evidence of continuing qualification of the supplier by typically testing the material to full specification annually for 1 lot but this is the best option in general to minimize testing if you plan to use the supplier and the material for the long term.

------------------------------
Victor Mencarelli
Global Director Regulatory Affairs
MelvilleNY
United States

Original Message:
Sent: 07-Feb-2021 23:35
From: Olga Figueroa Brito
Subject: USP 467 Residual Solvents question

Hello,

I have a question regarding compliance to USP 467.  If the supplier tests the API for USP <467> and results conform to USP <467>. Is the DP manufacturer required to test for residual solvents when residual solvent levels in the ingredients used to produce the drug product are below the levels listed in the USP <467>?

Thanks in advance.

Olga

------------------------------
Olga Figueroa Brito
Santa Ana CA
United States
------------------------------

Hello Victor, 

Thank you for your feedback. I want to add the following to my original question. The supplier is qualified and do we need to test only the API for residual solvents to confirm what the supplier provided on COA? No solvents are used in the DP. 

Thanks in advance,
Olga

------------------------------
Olga Figueroa Brito
Santa Ana CA
United States
------------------------------

Original Message:
Sent: 08-Feb-2021 12:08
From: Victor Mencarelli
Subject: USP 467 Residual Solvents question

Hi Olga.

As with any issue you have the responsibility as the manufacturer of the drug product to ensure that your product meets any specifications that have been agreed to by FDA and the manufacturer.  There is the opportunity to "qualify" a supplier through complete specification testing of 3 separate supplier lots and if your results meet the requirements and match up to the data that the supplier has provided on their certificate of analysis you could theoretically then consider the supplier as qualified regarding the solvents in the future and thereby only need to perform a test that would ensure that what they sold you and what they sent you are what you expected.  This can be as simple as an IR scan of the material or could be more complex.  You would still be expected to provide evidence of continuing qualification of the supplier by typically testing the material to full specification annually for 1 lot but this is the best option in general to minimize testing if you plan to use the supplier and the material for the long term.

------------------------------
Victor Mencarelli
Global Director Regulatory Affairs
MelvilleNY
United States

Original Message:
Sent: 07-Feb-2021 23:35
From: Olga Figueroa Brito
Subject: USP 467 Residual Solvents question

Hello,

I have a question regarding compliance to USP 467.  If the supplier tests the API for USP <467> and results conform to USP <467>. Is the DP manufacturer required to test for residual solvents when residual solvent levels in the ingredients used to produce the drug product are below the levels listed in the USP <467>?

Thanks in advance.

Olga

------------------------------
Olga Figueroa Brito
Santa Ana CA
United States
------------------------------

Hi Olga,

Prepare a risk assessment report. If your product meets USP <467> Option 1 or 2 and that you are not adding solvents to your product, the test is not required.

Best Regards,

------------------------------
Tyng-Yi (Tina) Lee MS RAC
Consultant
North Brunswick NJ
United States of America
------------------------------

Original Message:
Sent: 07-Feb-2021 23:35
From: Olga Figueroa Brito
Subject: USP 467 Residual Solvents question

Hello,

I have a question regarding compliance to USP 467.  If the supplier tests the API for USP <467> and results conform to USP <467>. Is the DP manufacturer required to test for residual solvents when residual solvent levels in the ingredients used to produce the drug product are below the levels listed in the USP <467>?

Thanks in advance.

Olga

------------------------------
Olga Figueroa Brito
Santa Ana CA
United States
------------------------------

Hello Tina,

Thank you for your feedback. I want to add the following to my original question. The supplier is qualified and do we need to test only the API for residual solvents to confirm what the supplier provided on COA? No solvents are used in the DP.

Thanks in advance,
Olga

------------------------------
Olga Figueroa Brito
Santa Ana CA
United States
------------------------------

Original Message:
Sent: 08-Feb-2021 16:39
From: Tyng-Yi (Tina) Lee
Subject: USP 467 Residual Solvents question

Hi Olga,

Prepare a risk assessment report. If your product meets USP <467> Option 1 or 2 and that you are not adding solvents to your product, the test is not required.

Best Regards,

------------------------------
Tyng-Yi (Tina) Lee MS RAC
Consultant
North Brunswick NJ
United States of America

Original Message:
Sent: 07-Feb-2021 23:35
From: Olga Figueroa Brito
Subject: USP 467 Residual Solvents question

Hello,

I have a question regarding compliance to USP 467.  If the supplier tests the API for USP <467> and results conform to USP <467>. Is the DP manufacturer required to test for residual solvents when residual solvent levels in the ingredients used to produce the drug product are below the levels listed in the USP <467>?

Thanks in advance.

Olga

------------------------------
Olga Figueroa Brito
Santa Ana CA
United States
------------------------------

This message was posted by a user wishing to remain anonymous

Your question is very specific to residual solvents testing of a drug product. Specifically if your API is already complied with RS spec per USP do you additionally test for drug product if all other ingredients also complies with USP RS. I am repeating your question not because your question is not specific enough but for others who respond nonspecifically to your question. I am sorry to say as to why people dont specifically answer to your querstion.

The answer is " NO" unless listed solvents are used in the manufacturing process of the drug product!

Hope this helps!
Original Message:
Sent: 07-Feb-2021 23:35
From: Olga Figueroa Brito
Subject: USP 467 Residual Solvents question

Hello,

I have a question regarding compliance to USP 467.  If the supplier tests the API for USP <467> and results conform to USP <467>. Is the DP manufacturer required to test for residual solvents when residual solvent levels in the ingredients used to produce the drug product are below the levels listed in the USP <467>?

Thanks in advance.

Olga

------------------------------
Olga Figueroa Brito
Santa Ana CA
United States
------------------------------

You hit nail on the head Anonymous! Agree 100% with your response and also with your comment on specificity of the response!

------------------------------
GRSAOnline
------------------------------

Original Message:
Sent: 08-Feb-2021 12:20
From: Anonymous Member
Subject: USP 467 Residual Solvents question

This message was posted by a user wishing to remain anonymous

Your question is very specific to residual solvents testing of a drug product. Specifically if your API is already complied with RS spec per USP do you additionally test for drug product if all other ingredients also complies with USP RS. I am repeating your question not because your question is not specific enough but for others who respond nonspecifically to your question. I am sorry to say as to why people dont specifically answer to your querstion.

The answer is " NO" unless listed solvents are used in the manufacturing process of the drug product!

Hope this helps!
Original Message:
Sent: 07-Feb-2021 23:35
From: Olga Figueroa Brito
Subject: USP 467 Residual Solvents question

Hello,

I have a question regarding compliance to USP 467.  If the supplier tests the API for USP <467> and results conform to USP <467>. Is the DP manufacturer required to test for residual solvents when residual solvent levels in the ingredients used to produce the drug product are below the levels listed in the USP <467>?

Thanks in advance.

Olga

------------------------------
Olga Figueroa Brito
Santa Ana CA
United States
------------------------------