Regulatory Open Forum

Regarding US FDA submission:

The Guidance for Industry, "Changes to an Approved NDA or ANDA" States the following regarding changes to the Container Closure System:

"The following are examples of changes considered to have a substantial potential to have 
an adverse effect on the identity, strength, quality, purity, or potency of a drug product as 
these factors may relate to the safety or effectiveness of the drug product.

4. For sterile drug products, any change that may affect drug product sterility 
assurance, such as: 
• A change from a glass ampule to a glass vial with an elastomeric closure. 
• A change to a flexible container system (bag) from another container 
system. 
•A change to a prefilled syringe dosage form from another container system. 
• A change from a single unit dose container to a multiple dose container 
system. 
• Changes that add or delete silicone treatments to container closure systems 
(such as elastomeric closures or syringe barrels). 
• Changes in the size and/or shape of a container for a sterile drug product."


If the size/shape of a container is changed, but sterility is not affected; justifiable by media fill testing and container/closure integrity testing that show sterility- Can this information be enough to justify that sterility is not affected therefore suitable for submission as a CBE-30 instead of a PAS?

Any comments or considerations are helpful.

Thank You,


-------------------------------------------
Sherry Condie
Regulatory Affairs Specialist
United States
-------------------------------------------

This is one of those topics that I would error on the side of caution and file a PAS with appropriate data to demonstrate sterility of the process and CCI of the packaging configuration over time with more than one lot if possible. You could try the CBE-30 approach and be ready for the request for a PAS. Alternatively you might want to run this change pass the chemistry reviewer, Good luck, Dar ------------------------------------------- Darlene Rosario Vice President RA and Quality Biothera Eagan MN United States -------------------------------------------
Original Message: Sent: 11-15-2013 10:58 From: Sherry Condie Subject: Container Closure System Change Regarding US FDA submission: The Guidance for Industry, "Changes to an Approved NDA or ANDA" States the following regarding changes to the Container Closure System: "The following are examples of changes considered to have a substantial potential to have an adverse effect on the identity, strength, quality, purity, or potency of a drug product as these factors may relate to the safety or effectiveness of the drug product. 4. For sterile drug products, any change that may affect drug product sterility assurance, such as: • A change from a glass ampule to a glass vial with an elastomeric closure. • A change to a flexible container system (bag) from another container system. •A change to a prefilled syringe dosage form from another container system. • A change from a single unit dose container to a multiple dose container system. • Changes that add or delete silicone treatments to container closure systems (such as elastomeric closures or syringe barrels). • Changes in the size and/or shape of a container for a sterile drug product." If the size/shape of a container is changed, but sterility is not affected; justifiable by media fill testing and container/closure integrity testing that show sterility- Can this information be enough to justify that sterility is not affected therefore suitable for submission as a CBE-30 instead of a PAS? Any comments or considerations are helpful. Thank You, ------------------------------------------- Sherry Condie Regulatory Affairs Specialist United States -------------------------------------------

This is a prior approval change.  FDA will want to agree that there is no issue to the sterility before you go forward with the change.  Providing your media fill data will prove your point.  You don't mention what the change is, but if there is a change in the opening size of your container, the sterility could be affected.

-------------------------------------------
Janet DeLeon RAC
CEO
DeLeon Pharmaceutical Consulting
Leawood KS
United States
-------------------------------------------





Original Message:
Sent: 11-15-2013 10:58
From: Sherry Condie
Subject: Container Closure System Change

Regarding US FDA submission:

The Guidance for Industry, "Changes to an Approved NDA or ANDA" States the following regarding changes to the Container Closure System:

"The following are examples of changes considered to have a substantial potential to have 
an adverse effect on the identity, strength, quality, purity, or potency of a drug product as 
these factors may relate to the safety or effectiveness of the drug product.

4. For sterile drug products, any change that may affect drug product sterility 
assurance, such as: 
• A change from a glass ampule to a glass vial with an elastomeric closure. 
• A change to a flexible container system (bag) from another container 
system. 
•A change to a prefilled syringe dosage form from another container system. 
• A change from a single unit dose container to a multiple dose container 
system. 
• Changes that add or delete silicone treatments to container closure systems 
(such as elastomeric closures or syringe barrels). 
• Changes in the size and/or shape of a container for a sterile drug product."


If the size/shape of a container is changed, but sterility is not affected; justifiable by media fill testing and container/closure integrity testing that show sterility- Can this information be enough to justify that sterility is not affected therefore suitable for submission as a CBE-30 instead of a PAS?

Any comments or considerations are helpful.

Thank You,


-------------------------------------------
Sherry Condie
Regulatory Affairs Specialist
United States
-------------------------------------------

Agree with Janet.   Also, if you're changing the closure material you will need to perform extractables / leachables testing as well.

-------------------------------------------
Donald Kruppa
Azaya Therapeutics, Inc.
San Antonio TX
United States
-------------------------------------------






Original Message:
Sent: 11-17-2013 22:41
From: Janet DeLeon
Subject: Container Closure System Change

This is a prior approval change.  FDA will want to agree that there is no issue to the sterility before you go forward with the change.  Providing your media fill data will prove your point.  You don't mention what the change is, but if there is a change in the opening size of your container, the sterility could be affected.

-------------------------------------------
Janet DeLeon RAC
CEO
DeLeon Pharmaceutical Consulting
Leawood KS
United States
-------------------------------------------





Original Message:
Sent: 11-15-2013 10:58
From: Sherry Condie
Subject: Container Closure System Change

Regarding US FDA submission:

The Guidance for Industry, "Changes to an Approved NDA or ANDA" States the following regarding changes to the Container Closure System:

"The following are examples of changes considered to have a substantial potential to have 
an adverse effect on the identity, strength, quality, purity, or potency of a drug product as 
these factors may relate to the safety or effectiveness of the drug product.

4. For sterile drug products, any change that may affect drug product sterility 
assurance, such as: 
• A change from a glass ampule to a glass vial with an elastomeric closure. 
• A change to a flexible container system (bag) from another container 
system. 
•A change to a prefilled syringe dosage form from another container system. 
• A change from a single unit dose container to a multiple dose container 
system. 
• Changes that add or delete silicone treatments to container closure systems 
(such as elastomeric closures or syringe barrels). 
• Changes in the size and/or shape of a container for a sterile drug product."


If the size/shape of a container is changed, but sterility is not affected; justifiable by media fill testing and container/closure integrity testing that show sterility- Can this information be enough to justify that sterility is not affected therefore suitable for submission as a CBE-30 instead of a PAS?

Any comments or considerations are helpful.

Thank You,


-------------------------------------------
Sherry Condie
Regulatory Affairs Specialist
United States
-------------------------------------------