Regulatory Open Forum

Hello,

I am looking for some advice on this confusing subject.

Although not specifically outlined by guidelines (FDA/EMA/WHO), it is generally accepted that a minimum of 3 batches are used for process validation of a chemical product - I get this idea.

I am wondering, should 3 (or more) finished product batches used for process validation, be manufactured using 3 different API batches?

To clarify, the details of the situation are as follows;
Our company (manufacturer of both the API and the FPP) is planning to perform Process Validation on 3 consecutive batches of the finished product. Since the batch size of our FPP is very small, it is sufficient to product 3 batches of FPP using only 1 batch of API. In our case, is it acceptable to carry out
Process Validation using these 3 batches of FPP which are manufactured from 1 identical API batch?

If this is not possible and each FPP batches for PV should be manufactured using different API batches, is there any guideline(s) that specifies this requirement?


Any input of yours would be greatly appreciated!
Thank you.
-------------------------------------------
Dahuin Lee
Global Regulatory Affairs Associate
Seoul
Korea, Republic of
-------------------------------------------

http://www.fda.gov/downloads/Drugs/Guidances/UCM070336.pdf

Dahuin,

I have attached a link for FDA guidance on Process Validation. FDA does not require multiple API lots for process validation.


John

-------------------------------------------
John Lay
Director, Regulatory and Quality
Vistapharm Inc.
Largo FL
United States
-------------------------------------------


Original Message:
Sent: 03-09-2015 05:55
From: Dahuin Lee
Subject: 1 API batch to produce 1 Finished Product Batch for Proess Validation?

Hello,

I am looking for some advice on this confusing subject.

Although not specifically outlined by guidelines (FDA/EMA/WHO), it is generally accepted that a minimum of 3 batches are used for process validation of a chemical product - I get this idea.

I am wondering, should 3 (or more) finished product batches used for process validation, be manufactured using 3 different API batches?

To clarify, the details of the situation are as follows;
Our company (manufacturer of both the API and the FPP) is planning to perform Process Validation on 3 consecutive batches of the finished product. Since the batch size of our FPP is very small, it is sufficient to product 3 batches of FPP using only 1 batch of API. In our case, is it acceptable to carry out
Process Validation using these 3 batches of FPP which are manufactured from 1 identical API batch?

If this is not possible and each FPP batches for PV should be manufactured using different API batches, is there any guideline(s) that specifies this requirement?


Any input of yours would be greatly appreciated!
Thank you.
-------------------------------------------
Dahuin Lee
Global Regulatory Affairs Associate
Seoul
Korea, Republic of
-------------------------------------------

If you do use a different (registered) API in future you will then need to concurrently validate your drug product process for that API. Despite identical specifications for the APIs you may encounter processing differences
Siegfried

-------------------------------------------
Siegfried Schmitt
Principal Consultant
PAREXEL
Braintree, Essex
United Kingdom
-------------------------------------------


Original Message:
Sent: 03-09-2015 05:55
From: Dahuin Lee
Subject: 1 API batch to produce 1 Finished Product Batch for Proess Validation?

Hello,

I am looking for some advice on this confusing subject.

Although not specifically outlined by guidelines (FDA/EMA/WHO), it is generally accepted that a minimum of 3 batches are used for process validation of a chemical product - I get this idea.

I am wondering, should 3 (or more) finished product batches used for process validation, be manufactured using 3 different API batches?

To clarify, the details of the situation are as follows;
Our company (manufacturer of both the API and the FPP) is planning to perform Process Validation on 3 consecutive batches of the finished product. Since the batch size of our FPP is very small, it is sufficient to product 3 batches of FPP using only 1 batch of API. In our case, is it acceptable to carry out
Process Validation using these 3 batches of FPP which are manufactured from 1 identical API batch?

If this is not possible and each FPP batches for PV should be manufactured using different API batches, is there any guideline(s) that specifies this requirement?


Any input of yours would be greatly appreciated!
Thank you.
-------------------------------------------
Dahuin Lee
Global Regulatory Affairs Associate
Seoul
Korea, Republic of
-------------------------------------------

Dear Dahuin,

I think you are asking about the requirement for using different batches/lots of API from the same supplier - not asking about using a different API supplier. Our policy is to use a different lot of API for each of the 3 process validation drug product batches.

ICH Q1A (R2) guidanec on Stability Testing of Drug Substances and Drug Products states...

Data from stability studies should be provided on at least three primary batches of the drug

product. The primary batches should be of the same formulation and packaged in the same

container closure system as proposed for marketing. The manufacturing process used for

primary batches should simulate that to be applied to production batches and should provide

product of the same quality and meeting the same specification as that intended for marketing.

Two of the three batches should be at least pilot scale batches, and the third one can be smaller if

justified. Where possible, batches of the drug product should be manufactured by using different

batches of the drug substance.

Hope this is helpful.

-------------------------------------------
Tom Stothoff
Director, Regulatory Affairs
Lundbeck LLC
Deerfield IL
United States
-------------------------------------------


Original Message:
Sent: 03-10-2015 03:21
From: Siegfried Schmitt
Subject: 1 API batch to produce 1 Finished Product Batch for Proess Validation?

If you do use a different (registered) API in future you will then need to concurrently validate your drug product process for that API. Despite identical specifications for the APIs you may encounter processing differences
Siegfried

-------------------------------------------
Siegfried Schmitt
Principal Consultant
PAREXEL
Braintree, Essex
United Kingdom
-------------------------------------------


Original Message:
Sent: 03-09-2015 05:55
From: Dahuin Lee
Subject: 1 API batch to produce 1 Finished Product Batch for Proess Validation?

Hello,

I am looking for some advice on this confusing subject.

Although not specifically outlined by guidelines (FDA/EMA/WHO), it is generally accepted that a minimum of 3 batches are used for process validation of a chemical product - I get this idea.

I am wondering, should 3 (or more) finished product batches used for process validation, be manufactured using 3 different API batches?

To clarify, the details of the situation are as follows;
Our company (manufacturer of both the API and the FPP) is planning to perform Process Validation on 3 consecutive batches of the finished product. Since the batch size of our FPP is very small, it is sufficient to product 3 batches of FPP using only 1 batch of API. In our case, is it acceptable to carry out
Process Validation using these 3 batches of FPP which are manufactured from 1 identical API batch?

If this is not possible and each FPP batches for PV should be manufactured using different API batches, is there any guideline(s) that specifies this requirement?


Any input of yours would be greatly appreciated!
Thank you.
-------------------------------------------
Dahuin Lee
Global Regulatory Affairs Associate
Seoul
Korea, Republic of
-------------------------------------------

Hello Dahuin

ICH Q1A(R2) ​​​​​recommends that where possible, batches of the drug product should be manufactured by using different batches of the drug substance.

It may also be noted that in the Q&A for ANDAs: Stability Testing of Drug Substances and Produt, FDA recommends that a minimum of two lots of the drug substance should be used to prepare the three primary batches of drug product. For nasal aerosols and nasal sprays, three different lots of the drug substance should be used. ​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​ 

Best Regards

Navneet


Original Message:
Sent: 03-09-2015 05:55
From: Dahuin Lee
Subject: 1 API batch to produce 1 Finished Product Batch for Proess Validation?

Hello,

I am looking for some advice on this confusing subject.

Although not specifically outlined by guidelines (FDA/EMA/WHO), it is generally accepted that a minimum of 3 batches are used for process validation of a chemical product - I get this idea.

I am wondering, should 3 (or more) finished product batches used for process validation, be manufactured using 3 different API batches?

To clarify, the details of the situation are as follows;
Our company (manufacturer of both the API and the FPP) is planning to perform Process Validation on 3 consecutive batches of the finished product. Since the batch size of our FPP is very small, it is sufficient to product 3 batches of FPP using only 1 batch of API. In our case, is it acceptable to carry out
Process Validation using these 3 batches of FPP which are manufactured from 1 identical API batch?

If this is not possible and each FPP batches for PV should be manufactured using different API batches, is there any guideline(s) that specifies this requirement?


Any input of yours would be greatly appreciated!
Thank you.
-------------------------------------------
Dahuin Lee
Global Regulatory Affairs Associate
Seoul
Korea, Republic of
-------------------------------------------

Dear Tom and Nanveet, and all the others who have responded to my question,
thank you very much for your help!

Tom and Nanveet - this is exactly the information I was looking for, as I was referring to using different BATCHES of API and not different sources of API.

Again, thank you for all of your input.

Best Wishes
-------------------------------------------
Dahuin Lee
Seoul
Korea, Republic of
-------------------------------------------


Original Message:
Sent: 03-11-2015 03:05
From: Navneet Ubhi
Subject: 1 API batch to produce 1 Finished Product Batch for Proess Validation?

Hello Dahuin

ICH Q1A(R2) ​​​​​recommends that where possible, batches of the drug product should be manufactured by using different batches of the drug substance.

It may also be noted that in the Q&A for ANDAs: Stability Testing of Drug Substances and Produt, FDA recommends that a minimum of two lots of the drug substance should be used to prepare the three primary batches of drug product. For nasal aerosols and nasal sprays, three different lots of the drug substance should be used. ​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​ 

Best Regards

Navneet


Original Message:
Sent: 03-09-2015 05:55
From: Dahuin Lee
Subject: 1 API batch to produce 1 Finished Product Batch for Proess Validation?

Hello,

I am looking for some advice on this confusing subject.

Although not specifically outlined by guidelines (FDA/EMA/WHO), it is generally accepted that a minimum of 3 batches are used for process validation of a chemical product - I get this idea.

I am wondering, should 3 (or more) finished product batches used for process validation, be manufactured using 3 different API batches?

To clarify, the details of the situation are as follows;
Our company (manufacturer of both the API and the FPP) is planning to perform Process Validation on 3 consecutive batches of the finished product. Since the batch size of our FPP is very small, it is sufficient to product 3 batches of FPP using only 1 batch of API. In our case, is it acceptable to carry out
Process Validation using these 3 batches of FPP which are manufactured from 1 identical API batch?

If this is not possible and each FPP batches for PV should be manufactured using different API batches, is there any guideline(s) that specifies this requirement?


Any input of yours would be greatly appreciated!
Thank you.
-------------------------------------------
Dahuin Lee
Global Regulatory Affairs Associate
Seoul
Korea, Republic of
-------------------------------------------

People, the question is related to process validation and not related to stability or different API producers. Process validation does NOT REQUIRE 3 different batches of API. While your company may have a lot of money and does process validation on three separate lots of API it is not required by FDA.  

-------------------------------------------
John Lay
Director, Regulatory and Quality
Vistapharm Inc.
Largo FL
United States
-------------------------------------------


Original Message:
Sent: 03-12-2015 06:15
From: Dahuin Lee
Subject: 1 API batch to produce 1 Finished Product Batch for Proess Validation?

Dear Tom and Nanveet, and all the others who have responded to my question,
thank you very much for your help!

Tom and Nanveet - this is exactly the information I was looking for, as I was referring to using different BATCHES of API and not different sources of API.

Again, thank you for all of your input.

Best Wishes
-------------------------------------------
Dahuin Lee
Seoul
Korea, Republic of
-------------------------------------------


Original Message:
Sent: 03-11-2015 03:05
From: Navneet Ubhi
Subject: 1 API batch to produce 1 Finished Product Batch for Proess Validation?

Hello Dahuin

ICH Q1A(R2) ​​​​​recommends that where possible, batches of the drug product should be manufactured by using different batches of the drug substance.

It may also be noted that in the Q&A for ANDAs: Stability Testing of Drug Substances and Produt, FDA recommends that a minimum of two lots of the drug substance should be used to prepare the three primary batches of drug product. For nasal aerosols and nasal sprays, three different lots of the drug substance should be used. ​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​ 

Best Regards

Navneet


Original Message:
Sent: 03-09-2015 05:55
From: Dahuin Lee
Subject: 1 API batch to produce 1 Finished Product Batch for Proess Validation?

Hello,

I am looking for some advice on this confusing subject.

Although not specifically outlined by guidelines (FDA/EMA/WHO), it is generally accepted that a minimum of 3 batches are used for process validation of a chemical product - I get this idea.

I am wondering, should 3 (or more) finished product batches used for process validation, be manufactured using 3 different API batches?

To clarify, the details of the situation are as follows;
Our company (manufacturer of both the API and the FPP) is planning to perform Process Validation on 3 consecutive batches of the finished product. Since the batch size of our FPP is very small, it is sufficient to product 3 batches of FPP using only 1 batch of API. In our case, is it acceptable to carry out
Process Validation using these 3 batches of FPP which are manufactured from 1 identical API batch?

If this is not possible and each FPP batches for PV should be manufactured using different API batches, is there any guideline(s) that specifies this requirement?


Any input of yours would be greatly appreciated!
Thank you.
-------------------------------------------
Dahuin Lee
Global Regulatory Affairs Associate
Seoul
Korea, Republic of
-------------------------------------------