Confuse between CBE-0, CBE-30 and PAS Submission in ANDA?
Let understand this in a simplest way with an example:
Imagine a pharmaceutical company that has received FDA approval for an ANDA to produce a generic version of a certain medication. The approved ANDA specifies the manufacturing processes, the composition of the product, labeling, and other critical details.
Let's say the pharmaceutical company wants to make some changes to the product after it has received FDA approval. Here's how each type of submission might apply:
𝐂𝐁𝐄-0 (𝐂𝐡𝐚𝐧𝐠𝐞𝐬 𝐁𝐞𝐢𝐧𝐠 𝐄𝐟𝐟𝐞𝐜𝐭𝐞𝐝 - 𝐋𝐞𝐯𝐞𝐥 0):
The company decides to change the color of the tablets to improve patient identification. Since this change is minor and does not impact the safety, effectiveness, or quality of the drug, they can submit a CBE-0 notification to the FDA. The company can implement the change immediately after the notification is submitted, without waiting for FDA approval.
𝐂𝐁𝐄-30 (𝐂𝐡𝐚𝐧𝐠𝐞𝐬 𝐁𝐞𝐢𝐧𝐠 𝐄𝐟𝐟𝐞𝐜𝐭𝐞𝐝 - 𝐋𝐞𝐯𝐞𝐥 30):
Now, let's say the company wants to change the packaging of the drug by updating the design of the outer carton. While this change is more significant than a color change, it is still not expected to affect the safety, effectiveness, or quality of the drug. The company can submit a CBE-30 notification to the FDA, informing them of the change at least 30 days before distributing the product with the new packaging. If the FDA does not raise any objections within those 30 days, the company can proceed with the updated packaging.
𝐏𝐀𝐒 (𝐏𝐫𝐢𝐨𝐫 𝐀𝐩𝐩𝐫𝐨𝐯𝐚𝐥 𝐒𝐮𝐩𝐩𝐥𝐞𝐦𝐞𝐧𝐭):
Finally, suppose the pharmaceutical company wants to change the formulation of the drug by substituting a different inactive ingredient that might impact the dissolution profile of the tablet. This change could potentially affect the bioavailability and therapeutic efficacy of the drug. Since this change is more significant and has the potential to impact the quality and effectiveness of the product, the company would need to submit a Prior Approval Supplement to the FDA. The FDA would need to review the proposed change and grant approval before the company can implement the new formulation.
𝑪𝑩𝑬-0 𝒂𝒏𝒅 𝑪𝑩𝑬-30 𝒔𝒖𝒃𝒎𝒊𝒔𝒔𝒊𝒐𝒏𝒔 𝒂𝒓𝒆 𝒖𝒔𝒆𝒅 𝒇𝒐𝒓 𝒎𝒊𝒏𝒐𝒓 𝒄𝒉𝒂𝒏𝒈𝒆𝒔 𝒕𝒉𝒂𝒕 𝒉𝒂𝒗𝒆 𝒎𝒊𝒏𝒊𝒎𝒂𝒍 𝒊𝒎𝒑𝒂𝒄𝒕 𝒐𝒏 𝒕𝒉𝒆 𝒅𝒓𝒖𝒈 𝒑𝒓𝒐𝒅𝒖𝒄𝒕, 𝒘𝒉𝒊𝒍𝒆 𝒂 𝑷𝑨𝑺 𝒔𝒖𝒃𝒎𝒊𝒔𝒔𝒊𝒐𝒏 𝒊𝒔 𝒓𝒆𝒒𝒖𝒊𝒓𝒆𝒅 𝒇𝒐𝒓 𝒎𝒂𝒋𝒐𝒓 𝒄𝒉𝒂𝒏𝒈𝒆𝒔 𝒕𝒉𝒂𝒕 𝒄𝒐𝒖𝒍𝒅 𝒂𝒇𝒇𝒆𝒄𝒕 𝒕𝒉𝒆 𝒔𝒂𝒇𝒆𝒕𝒚, 𝒆𝒇𝒇𝒊𝒄𝒂𝒄𝒚, 𝒐𝒓 𝒒𝒖𝒂𝒍𝒊𝒕𝒚 𝒐𝒇 𝒕𝒉𝒆 𝒅𝒓𝒖𝒈. 𝑻𝒉𝒆 𝒓𝒆𝒈𝒖𝒍𝒂𝒕𝒐𝒓𝒚 𝒓𝒆𝒒𝒖𝒊𝒓𝒆𝒎𝒆𝒏𝒕𝒔 𝒆𝒏𝒔𝒖𝒓𝒆 𝒕𝒉𝒂𝒕 𝒂𝒏𝒚 𝒎𝒐𝒅𝒊𝒇𝒊𝒄𝒂𝒕𝒊𝒐𝒏𝒔 𝒎𝒂𝒅𝒆 𝒕𝒐 𝒂𝒏 𝒂𝒑𝒑𝒓𝒐𝒗𝒆𝒅 𝑨𝑵𝑫𝑨 𝒂𝒓𝒆 𝒕𝒉𝒐𝒓𝒐𝒖𝒈𝒉𝒍𝒚 𝒆𝒗𝒂𝒍𝒖𝒂𝒕𝒆𝒅 𝒕𝒐 𝒎𝒂𝒊𝒏𝒕𝒂𝒊𝒏 𝒕𝒉𝒆 𝒊𝒏𝒕𝒆𝒈𝒓𝒊𝒕𝒚 𝒐𝒇 𝒕𝒉𝒆 𝒅𝒓𝒖𝒈'𝒔 𝒑𝒆𝒓𝒇𝒐𝒓𝒎𝒂𝒏𝒄𝒆 𝒂𝒏𝒅 𝒑𝒂𝒕𝒊𝒆𝒏𝒕 𝒔𝒂𝒇𝒆𝒕𝒚.
Read also:
- List of Stringent Regulatory Authorities
- FDA Field Alert Report
- Difference Between (NDA) 505(b)(1) and (NDA) 505(b)(2)
Resource Person: Amit Singh (Regulatory Affairs Specialist)
