Regulatory Open Forum

Hello all,

I have a question regarding aliquot validation (not sure if it is needed) for the raw materials.

We purchased raw materials from qualified vendors such as sterile water, media, PBS.... and obtained certificate of analysis with endotoxin, sterility and sometimes mycoplasma. Since we need to aliquot these materials to use in manufacturing, do we need to retest those aliquots with endotoxin, sterility and mycoplasma?

Or will the SOP of aliquoting process is sufficient to show that the whole process is sterile? Or should we validate the aliquot process? Any recommendation on how to validate aliquoting process? 

Thank you!


------------------------------
An Dao
Regulatory Affairs Manager
Houston, TX
------------------------------

​Hi An.

As a microbiologist in a prior life, I would suggest the following would be prudent:

1. Validate the aliquot process such that there is data sufficient to show that the process works and is able to control the potential for contamination if performed according to process.
2. Validate the supplier's COA for the material testing that is important to you (you mentioned things like sterility, mycoplasma, endotoxin).
3. Once validation of the process and the COA are completed, you can reasonably move to a "monitoring" process where you might test once a quarter or even once per year or if there were to be a question about the process or the materials.  However, until you truly can present data to the FDA during inspection that your process and your raw materials (in this case media, PBS, water, etc.) are acceptable you really can put yourself into a difficult position defending the company's use of these materials.

Let's be realistic.  While a material might well leave the production site completely acceptable, lots of things can happen in the process of transport between the production facility and your company.  Some things might be obvious like broken caps or cracks.  Others might not be so obvious like loss of seal integrity.  So if your product requires sterile, endotoxin negative and mycoplasma negative material to be safe and effective you really need to know what is happening and not just rely solely on your "process" and the COA from the vendors.

I am sure others will have views on this as well but this is just someone who spent almost a decade dealing with these exact issues on my side.

------------------------------
Victor Mencarelli
Director - Regulatory Affairs
Hain Celestial Group
United States
------------------------------

Original Message:
Sent: 17-Aug-2017 13:36
From: An Dao
Subject: Validation of aliquots for raw materials

Hello all,

I have a question regarding aliquot validation (not sure if it is needed) for the raw materials.

We purchased raw materials from qualified vendors such as sterile water, media, PBS.... and obtained certificate of analysis with endotoxin, sterility and sometimes mycoplasma. Since we need to aliquot these materials to use in manufacturing, do we need to retest those aliquots with endotoxin, sterility and mycoplasma?

Or will the SOP of aliquoting process is sufficient to show that the whole process is sterile? Or should we validate the aliquot process? Any recommendation on how to validate aliquoting process?

Thank you!


------------------------------
An Dao
Regulatory Affairs Manager
Houston, TX
------------------------------

​Overall, I agree with Victor's approach but offer the following commentary.  Generally one does not "Validate" a supplier's COA.  The requirement is to " Qualify" the supplier and to verify the accuracy of supplier's test results as reported in the COA.  This is done by conducting full testing per the material's specification and to compare your results to those reported on the COA.  Minimally, three separate lots of material from the supplier are selected for qualification, however additional lots may be needed if there are significant variances in test results.  Qualification of the supplier, includes an evaluation of the supplier's quality system including its SOPs, training programs and outcome of onsite audit especially for raw materials considered critical to the overall quality of your finished product.  Since you noted that the raw materials under consideration are labeled as sterile, any processes involving aliquots of sterile raw materials should also be validated to demonstrate that such theses activities are not introducing contamination during the manufacturing process.

------------------------------
Michael Trapani
Senior Consultant
Biologics Consulting Group, Inc.
Monroe Township NJ
United States
------------------------------

Original Message:
Sent: 18-Aug-2017 08:27
From: Victor Mencarelli
Subject: Validation of aliquots for raw materials

​Hi An.

As a microbiologist in a prior life, I would suggest the following would be prudent:

1. Validate the aliquot process such that there is data sufficient to show that the process works and is able to control the potential for contamination if performed according to process.
2. Validate the supplier's COA for the material testing that is important to you (you mentioned things like sterility, mycoplasma, endotoxin).
3. Once validation of the process and the COA are completed, you can reasonably move to a "monitoring" process where you might test once a quarter or even once per year or if there were to be a question about the process or the materials.  However, until you truly can present data to the FDA during inspection that your process and your raw materials (in this case media, PBS, water, etc.) are acceptable you really can put yourself into a difficult position defending the company's use of these materials.

Let's be realistic.  While a material might well leave the production site completely acceptable, lots of things can happen in the process of transport between the production facility and your company.  Some things might be obvious like broken caps or cracks.  Others might not be so obvious like loss of seal integrity.  So if your product requires sterile, endotoxin negative and mycoplasma negative material to be safe and effective you really need to know what is happening and not just rely solely on your "process" and the COA from the vendors.

I am sure others will have views on this as well but this is just someone who spent almost a decade dealing with these exact issues on my side.

------------------------------
Victor Mencarelli
Director - Regulatory Affairs
Hain Celestial Group
United States

Original Message:
Sent: 17-Aug-2017 13:36
From: An Dao
Subject: Validation of aliquots for raw materials

Hello all,

I have a question regarding aliquot validation (not sure if it is needed) for the raw materials.

We purchased raw materials from qualified vendors such as sterile water, media, PBS.... and obtained certificate of analysis with endotoxin, sterility and sometimes mycoplasma. Since we need to aliquot these materials to use in manufacturing, do we need to retest those aliquots with endotoxin, sterility and mycoplasma?

Or will the SOP of aliquoting process is sufficient to show that the whole process is sterile? Or should we validate the aliquot process? Any recommendation on how to validate aliquoting process?

Thank you!


------------------------------
An Dao
Regulatory Affairs Manager
Houston, TX
------------------------------

Thank you Victor and Michael for the advice. Sorry that I was not able to reply earlier due to the flooding. All is good now, the water receded and then I have a clear plan for validation of the aliquot and qualification of the vendor once I'm back in office :).

------------------------------
An Dao
Regulatory Affairs Manager
Houston, TX
------------------------------

Original Message:
Sent: 18-Aug-2017 10:31
From: Michael Trapani
Subject: Validation of aliquots for raw materials

​Overall, I agree with Victor's approach but offer the following commentary.  Generally one does not "Validate" a supplier's COA.  The requirement is to " Qualify" the supplier and to verify the accuracy of supplier's test results as reported in the COA.  This is done by conducting full testing per the material's specification and to compare your results to those reported on the COA.  Minimally, three separate lots of material from the supplier are selected for qualification, however additional lots may be needed if there are significant variances in test results.  Qualification of the supplier, includes an evaluation of the supplier's quality system including its SOPs, training programs and outcome of onsite audit especially for raw materials considered critical to the overall quality of your finished product.  Since you noted that the raw materials under consideration are labeled as sterile, any processes involving aliquots of sterile raw materials should also be validated to demonstrate that such theses activities are not introducing contamination during the manufacturing process.

------------------------------
Michael Trapani
Senior Consultant
Biologics Consulting Group, Inc.
Monroe Township NJ
United States

Original Message:
Sent: 18-Aug-2017 08:27
From: Victor Mencarelli
Subject: Validation of aliquots for raw materials

​Hi An.

As a microbiologist in a prior life, I would suggest the following would be prudent:

1. Validate the aliquot process such that there is data sufficient to show that the process works and is able to control the potential for contamination if performed according to process.
2. Validate the supplier's COA for the material testing that is important to you (you mentioned things like sterility, mycoplasma, endotoxin).
3. Once validation of the process and the COA are completed, you can reasonably move to a "monitoring" process where you might test once a quarter or even once per year or if there were to be a question about the process or the materials.  However, until you truly can present data to the FDA during inspection that your process and your raw materials (in this case media, PBS, water, etc.) are acceptable you really can put yourself into a difficult position defending the company's use of these materials.

Let's be realistic.  While a material might well leave the production site completely acceptable, lots of things can happen in the process of transport between the production facility and your company.  Some things might be obvious like broken caps or cracks.  Others might not be so obvious like loss of seal integrity.  So if your product requires sterile, endotoxin negative and mycoplasma negative material to be safe and effective you really need to know what is happening and not just rely solely on your "process" and the COA from the vendors.

I am sure others will have views on this as well but this is just someone who spent almost a decade dealing with these exact issues on my side.

------------------------------
Victor Mencarelli
Director - Regulatory Affairs
Hain Celestial Group
United States

Original Message:
Sent: 17-Aug-2017 13:36
From: An Dao
Subject: Validation of aliquots for raw materials

Hello all,

I have a question regarding aliquot validation (not sure if it is needed) for the raw materials.

We purchased raw materials from qualified vendors such as sterile water, media, PBS.... and obtained certificate of analysis with endotoxin, sterility and sometimes mycoplasma. Since we need to aliquot these materials to use in manufacturing, do we need to retest those aliquots with endotoxin, sterility and mycoplasma?

Or will the SOP of aliquoting process is sufficient to show that the whole process is sterile? Or should we validate the aliquot process? Any recommendation on how to validate aliquoting process?

Thank you!


------------------------------
An Dao
Regulatory Affairs Manager
Houston, TX
------------------------------