Comments on: Defining a Batch in Continuous Manufacturing http://blog.pharmtech.com/2012/07/09/defining-a-batch-in-continuous-manufacturing/ The blog of Pharmaceutical Technology magazine Thu, 09 May 2013 23:30:55 -0400 http://wordpress.org/?v=2.8.4 hourly 1 By: Griet Van Vaerenbergh http://blog.pharmtech.com/2012/07/09/defining-a-batch-in-continuous-manufacturing/comment-page-1/#comment-47952 Griet Van Vaerenbergh Tue, 07 Aug 2012 12:39:37 +0000 http://blog.pharmtech.com/?p=5689#comment-47952 This posts asks many questions at the same time. Some answers are below. 1. Definition of a batch. FDA is very clear on the definition of a batch or lot, both in a batch manufacturing system as in a continuous manufacturing system: • 21 CFR 210.3 (b)(2):□ Batch means a specific quantity of a drug or other material that is intended to have uniform character and quality, within specified limits, and is produced according to a single manufacturing order during the same cycle of manufacture. • 21 CFR 210.3 (b)(10): □ Lot means a batch, or a specific identified portion of a batch, having uniform character and quality within specified limits; or, in the case of a drug product produced by continuous process, it is a specific identified amount produced in a unit of time or quantity in a manner that assures its having uniform character and quality within specified limits. 2. Start-up losses. Currently, there are continuous production systems on the market that take only about 4 secs (approx. 30g) to come to stable conditions. The amount of out of spec material produced in this time frame is neglectable with respect to the total sub batch or batch size and nothing has to be rejected. 3. Quality testing Continuous systems are ideal to implement on-line quality measurement systems. All critical quality attributes can be measured on-line and if there is a drift from the steady-state, corrective actions can be taken to avoid producing out-of-spec material. In fact, because of the continuous on-line quality measurements, a product produced in a continuous way is much better controlled than a product produced in a batch manner, as in the last case, one relies on small samples taken at certain intervals of the process, while in a continuous system, all the product is monitored continuously. The current data management systems are powerful enough to gather and process the data coming from both the production system and the on-line measurement tools. If you want more information, please contact GEA Pharma Systems (www.gea-ps.com) Griet Van Vaerenbergh GEA Pharma Systems Wommelgem, Belgium This posts asks many questions at the same time.
Some answers are below.
1. Definition of a batch.
FDA is very clear on the definition of a batch or lot, both in a batch manufacturing system as in a continuous manufacturing system:
• 21 CFR 210.3 (b)(2):□ Batch means a specific quantity of a drug or other material that is intended to have uniform character and quality, within specified limits, and is produced according to a single manufacturing order during the same cycle of manufacture.
• 21 CFR 210.3 (b)(10): □ Lot means a batch, or a specific identified portion of a batch, having uniform character and quality within specified limits; or, in the case of a drug product produced by continuous process, it is a specific identified amount produced in a unit of time or quantity in a manner that assures its having uniform character and quality within specified limits.

2. Start-up losses.
Currently, there are continuous production systems on the market that take only about 4 secs (approx. 30g) to come to stable conditions. The amount of out of spec material produced in this time frame is neglectable with respect to the total sub batch or batch size and nothing has to be rejected.

3. Quality testing
Continuous systems are ideal to implement on-line quality measurement systems. All critical quality attributes can be measured on-line and if there is a drift from the steady-state, corrective actions can be taken to avoid producing out-of-spec material.
In fact, because of the continuous on-line quality measurements, a product produced in a continuous way is much better controlled than a product produced in a batch manner, as in the last case, one relies on small samples taken at certain intervals of the process, while in a continuous system, all the product is monitored continuously.
The current data management systems are powerful enough to gather and process the data coming from both the production system and the on-line measurement tools.

If you want more information, please contact GEA Pharma Systems (www.gea-ps.com)
Griet Van Vaerenbergh
GEA Pharma Systems
Wommelgem, Belgium

]]> By: Durga Prasad http://blog.pharmtech.com/2012/07/09/defining-a-batch-in-continuous-manufacturing/comment-page-1/#comment-47749 Durga Prasad Tue, 10 Jul 2012 12:41:42 +0000 http://blog.pharmtech.com/?p=5689#comment-47749 We faced tough challenges during the documentation procedures when some one manufactures on a continuous scale. Pharmaceutical Quality is at a defined and higher level than foods and cosmetics. When we have a problem with Out of specification the problem remains Where to Stop, Who to stop, What to reprocess or Retest and what documents to be given for batch record and investigation purpose. Incase the batch stops in a continuous line, the problem remains how and well this batch is treated and how the non-confirmaces are being treated in relation to out put time and Quality of product. We faced a lot of problems in issued another set of extended batch records to the Manufacturing floor. The question remains from QA why such documents should be issued again? If given -- what extra controls and specifications that should be incorporated in such an extended Batch Manufacturing record. At the end of the batch it will undergo a reggerous scrutiny and review. Well at the end of the day documenting all the processes and quality along with signatures are extremely important on an electronic batch record. In case of real time review the problem comes and will remain at the descrition of QA to proceed further or not as the batch went OOS or at times we have Non-Confirmances due to utility factors or sampling errors. This issue must be taken by Pundits of Pharma manufacturing and lay a set of Guidelines, Sampling Plans, How to treat OOS and Non-Confirmances and how to document such issues in records when the process is continuous. Regards Durga Prasad GMP Specialist Kneat Solutions Ltd Copenhagen,Denmark We faced tough challenges during the documentation procedures when some one manufactures on a continuous scale.
Pharmaceutical Quality is at a defined and higher level than foods and cosmetics.
When we have a problem with Out of specification the problem remains Where to Stop, Who to stop, What to reprocess or Retest and what documents to be given for batch record and investigation purpose.
Incase the batch stops in a continuous line, the problem remains how and well this batch is treated and how the non-confirmaces are being treated in relation to out put time and Quality of product.
We faced a lot of problems in issued another set of extended batch records to the Manufacturing floor.
The question remains from QA why such documents should be issued again? If given — what extra controls and specifications that should be incorporated in such an extended Batch Manufacturing record.
At the end of the batch it will undergo a reggerous scrutiny and review.
Well at the end of the day documenting all the processes and quality along with signatures are extremely important on an electronic batch record.
In case of real time review the problem comes and will remain at the descrition of QA to proceed further or not as the batch went OOS or at times we have Non-Confirmances due to utility factors or sampling errors.
This issue must be taken by Pundits of Pharma manufacturing and lay a set of Guidelines, Sampling Plans, How to treat OOS and Non-Confirmances and how to document such issues in records when the process is continuous.
Regards
Durga Prasad
GMP Specialist
Kneat Solutions Ltd
Copenhagen,Denmark

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