Regulatory Open Forum

Dear Experts,

I would like to know about post approval ANDA filling category (PAS, CBE-30, CBE-0, AR) for reduction of API testing frequency. 

Reduced testing strategy:-

• For every lot, some test parameters (Appearance, ID, Assay etc) will be performed by us and result of rest of the test parameter to be captured from Vendor CoA. 
• Full tests to be performed at our end after every 10/20 lots
• Risk assessment has been performed to identify potential impact and action taken accordingly. 

Your insight, experience or guidance reference is highly appreciated. 

Good day, Sujan.

You list seems comprehensive with one exception: you did not mention what has been done to qualify the vendor in terms of audits or amount of time / number of batches your company has with that vendor.  It is my personal opinion that full testing every 10 - 20 batches may be too infrequent, depending on how quickly you go through those 10 - 20 batches. I would suggest that you perform full testing once every quarter, as things can change at a vendor site without your knowledge.

I hope this is helpful.

Dear Experts,

I would like to know about post approval ANDA filling category (PAS, CBE-30, CBE-0, AR) for reduction of API testing frequency. 

Reduced testing strategy:-

• For every lot, some test parameters (Appearance, ID, Assay etc) will be performed by us and result of rest of the test parameter to be captured from Vendor CoA. 
• Full tests to be performed at our end after every 10/20 lots
• Risk assessment has been performed to identify potential impact and action taken accordingly. 

Your insight, experience or guidance reference is highly appreciated. 

Hello Madam Arvilla,

Hope you are having good time.

Thank you for your valuable insight regarding this matter. I want to inform you that we have also system in place for vendor qualification with onsite inspection and review of the vendor's data. I forgot to include that in my earlier post. Sorry for that.  

I want to know that what kind of filling mechanism should I follow to notify FDA regarding reduced testing of API ? Can you please comment on that.

Looking forward to hear from you soon.

With thanks,

Good day, Sujan.

You list seems comprehensive with one exception: you did not mention what has been done to qualify the vendor in terms of audits or amount of time / number of batches your company has with that vendor.  It is my personal opinion that full testing every 10 - 20 batches may be too infrequent, depending on how quickly you go through those 10 - 20 batches. I would suggest that you perform full testing once every quarter, as things can change at a vendor site without your knowledge.

I hope this is helpful.

Dear Experts,

I would like to know about post approval ANDA filling category (PAS, CBE-30, CBE-0, AR) for reduction of API testing frequency. 

Reduced testing strategy:-

• For every lot, some test parameters (Appearance, ID, Assay etc) will be performed by us and result of rest of the test parameter to be captured from Vendor CoA. 
• Full tests to be performed at our end after every 10/20 lots
• Risk assessment has been performed to identify potential impact and action taken accordingly. 

Your insight, experience or guidance reference is highly appreciated. 

Hello Sujan.  None of the previous replies make reference that reduced testing is clearly described in the drug GMP regulations in 21 CFR 211, Subpart E, 122.80 - Control of Components and Drug Product Containers and Closures, specifically 211.84(d)(2) as follows: 

"(2) Each component shall be tested for conformity with all appropriate written specifications for purity, strength, and quality. In lieu of such testing by the manufacturer, a report of analysis may be accepted from the supplier of a component, provided that at least one specific identity test is conducted on such component by the manufacturer, and provided that the manufacturer establishes the reliability of the supplier's analyses through appropriate validation of the supplier's test results at appropriate intervals."

Reduced testing likely has nothing to do with the NDA/ANDA filing, unless something is specifically written.

Hello Madam Arvilla,

Hope you are having good time.

Thank you for your valuable insight regarding this matter. I want to inform you that we have also system in place for vendor qualification with onsite inspection and review of the vendor's data. I forgot to include that in my earlier post. Sorry for that.  

I want to know that what kind of filling mechanism should I follow to notify FDA regarding reduced testing of API ? Can you please comment on that.

Looking forward to hear from you soon.

With thanks,

Good day, Sujan.

You list seems comprehensive with one exception: you did not mention what has been done to qualify the vendor in terms of audits or amount of time / number of batches your company has with that vendor.  It is my personal opinion that full testing every 10 - 20 batches may be too infrequent, depending on how quickly you go through those 10 - 20 batches. I would suggest that you perform full testing once every quarter, as things can change at a vendor site without your knowledge.

I hope this is helpful.

Dear Experts,

I would like to know about post approval ANDA filling category (PAS, CBE-30, CBE-0, AR) for reduction of API testing frequency. 

Reduced testing strategy:-

• For every lot, some test parameters (Appearance, ID, Assay etc) will be performed by us and result of rest of the test parameter to be captured from Vendor CoA. 
• Full tests to be performed at our end after every 10/20 lots
• Risk assessment has been performed to identify potential impact and action taken accordingly. 

Your insight, experience or guidance reference is highly appreciated. 

Hello Sujan.  None of the previous replies make reference that reduced testing is clearly described in the drug GMP regulations in 21 CFR 211, Subpart E, 122.80 - Control of Components and Drug Product Containers and Closures, specifically 211.84(d)(2) as follows: 

"(2) Each component shall be tested for conformity with all appropriate written specifications for purity, strength, and quality. In lieu of such testing by the manufacturer, a report of analysis may be accepted from the supplier of a component, provided that at least one specific identity test is conducted on such component by the manufacturer, and provided that the manufacturer establishes the reliability of the supplier's analyses through appropriate validation of the supplier's test results at appropriate intervals."

Reduced testing likely has nothing to do with the NDA/ANDA filing, unless something is specifically written.

Hello Madam Arvilla,

Hope you are having good time.

Thank you for your valuable insight regarding this matter. I want to inform you that we have also system in place for vendor qualification with onsite inspection and review of the vendor's data. I forgot to include that in my earlier post. Sorry for that.  

I want to know that what kind of filling mechanism should I follow to notify FDA regarding reduced testing of API ? Can you please comment on that.

Looking forward to hear from you soon.

With thanks,

Good day, Sujan.

You list seems comprehensive with one exception: you did not mention what has been done to qualify the vendor in terms of audits or amount of time / number of batches your company has with that vendor.  It is my personal opinion that full testing every 10 - 20 batches may be too infrequent, depending on how quickly you go through those 10 - 20 batches. I would suggest that you perform full testing once every quarter, as things can change at a vendor site without your knowledge.

I hope this is helpful.

Dear Experts,

I would like to know about post approval ANDA filling category (PAS, CBE-30, CBE-0, AR) for reduction of API testing frequency. 

Reduced testing strategy:-

• For every lot, some test parameters (Appearance, ID, Assay etc) will be performed by us and result of rest of the test parameter to be captured from Vendor CoA. 
• Full tests to be performed at our end after every 10/20 lots
• Risk assessment has been performed to identify potential impact and action taken accordingly. 

Your insight, experience or guidance reference is highly appreciated. 

Dear Sir,

Thank you for your valuable input. If you please clarify "unless something is specifically written" .

After adopting reduced testing, we want mention below statement in the approved API specification "All test parameters will be done as intermittent testing (after every 10th batch), appearance and Identification by IR will be tested routinely."

Do we need to submitted revised API specification after that? If yes, how we should address?

Looking to hear from you.

Hello Sujan.  None of the previous replies make reference that reduced testing is clearly described in the drug GMP regulations in 21 CFR 211, Subpart E, 122.80 - Control of Components and Drug Product Containers and Closures, specifically 211.84(d)(2) as follows: 

"(2) Each component shall be tested for conformity with all appropriate written specifications for purity, strength, and quality. In lieu of such testing by the manufacturer, a report of analysis may be accepted from the supplier of a component, provided that at least one specific identity test is conducted on such component by the manufacturer, and provided that the manufacturer establishes the reliability of the supplier's analyses through appropriate validation of the supplier's test results at appropriate intervals."

Reduced testing likely has nothing to do with the NDA/ANDA filing, unless something is specifically written.

Hello Madam Arvilla,

Hope you are having good time.

Thank you for your valuable insight regarding this matter. I want to inform you that we have also system in place for vendor qualification with onsite inspection and review of the vendor's data. I forgot to include that in my earlier post. Sorry for that.  

I want to know that what kind of filling mechanism should I follow to notify FDA regarding reduced testing of API ? Can you please comment on that.

Looking forward to hear from you soon.

With thanks,

Good day, Sujan.

You list seems comprehensive with one exception: you did not mention what has been done to qualify the vendor in terms of audits or amount of time / number of batches your company has with that vendor.  It is my personal opinion that full testing every 10 - 20 batches may be too infrequent, depending on how quickly you go through those 10 - 20 batches. I would suggest that you perform full testing once every quarter, as things can change at a vendor site without your knowledge.

I hope this is helpful.

Dear Experts,

I would like to know about post approval ANDA filling category (PAS, CBE-30, CBE-0, AR) for reduction of API testing frequency. 

Reduced testing strategy:-

• For every lot, some test parameters (Appearance, ID, Assay etc) will be performed by us and result of rest of the test parameter to be captured from Vendor CoA. 
• Full tests to be performed at our end after every 10/20 lots
• Risk assessment has been performed to identify potential impact and action taken accordingly. 

Your insight, experience or guidance reference is highly appreciated. 

Sujan,

Your specifications should not change, only your testing schedule. If your API has a specific SOP for all of its testing, that may need revision, depending on how it is worded. If you do not already have a written reduced testing procedure, you will need one.

Please note that if your specifications do change, you will need to resume full testing of the API to qualify it for reduced testing again. 

Best of luck!

Dear Sir,

Thank you for your valuable input. If you please clarify "unless something is specifically written" .

After adopting reduced testing, we want mention below statement in the approved API specification "All test parameters will be done as intermittent testing (after every 10th batch), appearance and Identification by IR will be tested routinely."

Do we need to submitted revised API specification after that? If yes, how we should address?

Looking to hear from you.

Hello Sujan.  None of the previous replies make reference that reduced testing is clearly described in the drug GMP regulations in 21 CFR 211, Subpart E, 122.80 - Control of Components and Drug Product Containers and Closures, specifically 211.84(d)(2) as follows: 

"(2) Each component shall be tested for conformity with all appropriate written specifications for purity, strength, and quality. In lieu of such testing by the manufacturer, a report of analysis may be accepted from the supplier of a component, provided that at least one specific identity test is conducted on such component by the manufacturer, and provided that the manufacturer establishes the reliability of the supplier's analyses through appropriate validation of the supplier's test results at appropriate intervals."

Reduced testing likely has nothing to do with the NDA/ANDA filing, unless something is specifically written.

Hello Madam Arvilla,

Hope you are having good time.

Thank you for your valuable insight regarding this matter. I want to inform you that we have also system in place for vendor qualification with onsite inspection and review of the vendor's data. I forgot to include that in my earlier post. Sorry for that.  

I want to know that what kind of filling mechanism should I follow to notify FDA regarding reduced testing of API ? Can you please comment on that.

Looking forward to hear from you soon.

With thanks,

Good day, Sujan.

You list seems comprehensive with one exception: you did not mention what has been done to qualify the vendor in terms of audits or amount of time / number of batches your company has with that vendor.  It is my personal opinion that full testing every 10 - 20 batches may be too infrequent, depending on how quickly you go through those 10 - 20 batches. I would suggest that you perform full testing once every quarter, as things can change at a vendor site without your knowledge.

I hope this is helpful.

Dear Experts,

I would like to know about post approval ANDA filling category (PAS, CBE-30, CBE-0, AR) for reduction of API testing frequency. 

Reduced testing strategy:-

• For every lot, some test parameters (Appearance, ID, Assay etc) will be performed by us and result of rest of the test parameter to be captured from Vendor CoA. 
• Full tests to be performed at our end after every 10/20 lots
• Risk assessment has been performed to identify potential impact and action taken accordingly. 

Your insight, experience or guidance reference is highly appreciated. 

Dear Sir,

Thank you for your valuable input. If you please clarify "unless something is specifically written" .

After adopting reduced testing, we want mention below statement in the approved API specification "All test parameters will be done as intermittent testing (after every 10th batch), appearance and Identification by IR will be tested routinely."

Do we need to submitted revised API specification after that? If yes, how we should address?

Looking to hear from you.

Hello Sujan.  None of the previous replies make reference that reduced testing is clearly described in the drug GMP regulations in 21 CFR 211, Subpart E, 122.80 - Control of Components and Drug Product Containers and Closures, specifically 211.84(d)(2) as follows: 

"(2) Each component shall be tested for conformity with all appropriate written specifications for purity, strength, and quality. In lieu of such testing by the manufacturer, a report of analysis may be accepted from the supplier of a component, provided that at least one specific identity test is conducted on such component by the manufacturer, and provided that the manufacturer establishes the reliability of the supplier's analyses through appropriate validation of the supplier's test results at appropriate intervals."

Reduced testing likely has nothing to do with the NDA/ANDA filing, unless something is specifically written.

Hello Madam Arvilla,

Hope you are having good time.

Thank you for your valuable insight regarding this matter. I want to inform you that we have also system in place for vendor qualification with onsite inspection and review of the vendor's data. I forgot to include that in my earlier post. Sorry for that.  

I want to know that what kind of filling mechanism should I follow to notify FDA regarding reduced testing of API ? Can you please comment on that.

Looking forward to hear from you soon.

With thanks,

------------------------------
SUJAN BOSE
M.Pharm

Original Message:
Sent: 28-Aug-2023 07:45
From: Arvilla Trag
Subject: Reduced testing of API

Good day, Sujan.

You list seems comprehensive with one exception: you did not mention what has been done to qualify the vendor in terms of audits or amount of time / number of batches your company has with that vendor.  It is my personal opinion that full testing every 10 - 20 batches may be too infrequent, depending on how quickly you go through those 10 - 20 batches. I would suggest that you perform full testing once every quarter, as things can change at a vendor site without your knowledge.

I hope this is helpful.

Dear Experts,

I would like to know about post approval ANDA filling category (PAS, CBE-30, CBE-0, AR) for reduction of API testing frequency. 

Reduced testing strategy:-

• For every lot, some test parameters (Appearance, ID, Assay etc) will be performed by us and result of rest of the test parameter to be captured from Vendor CoA. 
• Full tests to be performed at our end after every 10/20 lots
• Risk assessment has been performed to identify potential impact and action taken accordingly. 

Your insight, experience or guidance reference is highly appreciated. 

Dear Experts,

I would like to know about post approval ANDA filling category (PAS, CBE-30, CBE-0, AR) for reduction of API testing frequency. 

Reduced testing strategy:-

• For every lot, some test parameters (Appearance, ID, Assay etc) will be performed by us and result of rest of the test parameter to be captured from Vendor CoA. 
• Full tests to be performed at our end after every 10/20 lots
• Risk assessment has been performed to identify potential impact and action taken accordingly. 

Your insight, experience or guidance reference is highly appreciated. 

Your proposal seems adequate but I think your question is whether it is CBE, PAS etc filing mechanism! This depends on your approved ANDA and what it originally contained! Was accepting of API testing schedule included in your original ANDA? If not then it should simply go through your Change Control process and make it your SOP for incoming testing schedule for APIs and other excipients. If this schedule was included and approved as part your ANDA, then I'd propose CBE-30. Usually in my experience with NDAs, this incoming acceptance testing schedule is not included, only acceptance tests are included. 

Dear Experts,

I would like to know about post approval ANDA filling category (PAS, CBE-30, CBE-0, AR) for reduction of API testing frequency. 

Reduced testing strategy:-

• For every lot, some test parameters (Appearance, ID, Assay etc) will be performed by us and result of rest of the test parameter to be captured from Vendor CoA. 
• Full tests to be performed at our end after every 10/20 lots
• Risk assessment has been performed to identify potential impact and action taken accordingly. 

Your insight, experience or guidance reference is highly appreciated. 

Dear anonymous.

Good day. 

You are right, our original ANDA does not contain any API testing schedule, it covers in our internal procedure.

We are planning to include reduced testing for one of our API used in ANDA application and we have followed all the procedures described in the procedure.

Are you  suggesting to notify Agency in Annual report regarding this reduce testing? Any FDA guidance/real life experience insight is highly appreciated.

Thank you for your valuable time. Looking forward to hear back from you soon.

------------------------------
SUJAN BOSE
M.Pharm

Original Message:
Sent: 28-Aug-2023 09:46
From: Anonymous Member
Subject: Reduced testing of API

This message was posted by a user wishing to remain anonymous

Your proposal seems adequate but I think your question is whether it is CBE, PAS etc filing mechanism! This depends on your approved ANDA and what it originally contained! Was accepting of API testing schedule included in your original ANDA? If not then it should simply go through your Change Control process and make it your SOP for incoming testing schedule for APIs and other excipients. If this schedule was included and approved as part your ANDA, then I'd propose CBE-30. Usually in my experience with NDAs, this incoming acceptance testing schedule is not included, only acceptance tests are included. 

Dear Experts,

I would like to know about post approval ANDA filling category (PAS, CBE-30, CBE-0, AR) for reduction of API testing frequency. 

Reduced testing strategy:-

• For every lot, some test parameters (Appearance, ID, Assay etc) will be performed by us and result of rest of the test parameter to be captured from Vendor CoA. 
• Full tests to be performed at our end after every 10/20 lots
• Risk assessment has been performed to identify potential impact and action taken accordingly. 

Your insight, experience or guidance reference is highly appreciated. 

If it is nor included in the original ANDA, then there is no regulatory impact! Only your internal change control process need to be followed and get it approved! You don't need to submit this to your ANDA! Hope this helps! As I said before, in my experience the incoming acceptance testing schedule for any materials is not included in NDAs!

Dear anonymous.

Good day. 

You are right, our original ANDA does not contain any API testing schedule, it covers in our internal procedure.

We are planning to include reduced testing for one of our API used in ANDA application and we have followed all the procedures described in the procedure.

Are you  suggesting to notify Agency in Annual report regarding this reduce testing? Any FDA guidance/real life experience insight is highly appreciated.

Thank you for your valuable time. Looking forward to hear back from you soon.

------------------------------
SUJAN BOSE
M.Pharm

Original Message:
Sent: 28-Aug-2023 09:46
From: Anonymous Member
Subject: Reduced testing of API

This message was posted by a user wishing to remain anonymous

Your proposal seems adequate but I think your question is whether it is CBE, PAS etc filing mechanism! This depends on your approved ANDA and what it originally contained! Was accepting of API testing schedule included in your original ANDA? If not then it should simply go through your Change Control process and make it your SOP for incoming testing schedule for APIs and other excipients. If this schedule was included and approved as part your ANDA, then I'd propose CBE-30. Usually in my experience with NDAs, this incoming acceptance testing schedule is not included, only acceptance tests are included. 

Dear Experts,

I would like to know about post approval ANDA filling category (PAS, CBE-30, CBE-0, AR) for reduction of API testing frequency. 

Reduced testing strategy:-

• For every lot, some test parameters (Appearance, ID, Assay etc) will be performed by us and result of rest of the test parameter to be captured from Vendor CoA. 
• Full tests to be performed at our end after every 10/20 lots
• Risk assessment has been performed to identify potential impact and action taken accordingly. 

Your insight, experience or guidance reference is highly appreciated.