RE:RE:RE:RE:IBRX Crashes as FDA issues CRL
ScienceFirst wrote: Theralase's molecule is considered a NDA, unlike IMMUNITYBIO that is a BLA and much more complicated to receive approval.
Ferring's approval for its gene therapy that was was finally approved in Nov. 2022 was also delayed by 2y in 2020 as it was also a BLA.
So, a much less stringent approval process when it comes to evaluating the manufacturing process of TLD1433 (Ruvidar).
Key Differences Between BLAs & NDAs
While BLAs and NDAs serve the same purpose of gaining approval to market a drug in the United States, they differ slightly in terms of their application content and submission requirements. Regarding approval criteria, NDAs must fulfill three conditions:
- The drug is safe and effective for the proposed use and that the benefits outweigh the risks
- The labeling is appropriate and contains all necessary information about the drug
- Manufacturing methods preserve the drug’s identity, strength, quality, and purity
Similarly, contents of a BLA should establish that the biological product is safe and potent; however, because biological products are processed from living material, BLA content must also demonstrate purity specifically in terms of showing that the final product does not contain extraneous material. Due to the complexities of manufacturing biological products, a pre-license inspection of the facility is generally required before a BLA is approved. Pre-approval inspections sometimes also take place during an NDA review, but are typically conducted based on risk assessment by the Agency. Once a BLA is approved, the Sponsor is granted a license for the biological product, which permits its introduction into interstate commerce per Section 351 of the PHS Act. This licensing process is not a part of the NDA, as drugs that are approved by NDA are regulated only by the FD&C Act, and not the PHS Act. Until very recently, certain biological products could be approved under an NDA rather than a BLA. However, according to the Biologics Price Competition and Innovation Act (further discussed below) this is no longer the case, and all biological product approvals now occur through a BLA.
Any Big Pharma wanting to partner with us will love the fact that an NDA and manufacturing for our drug is vastly more advantageous than a biological drug. Ease of production and much lower risk for approval IMHO.
"Manufacturing of Biological Products is Inherently Riskier than Production of Drugs.
The manufacturing processes for biological products are different than processes for pharmaceuticals. Traditional drug products are typically manufactured using pure chemical substances that are sterile, and the end products can be relatively easily analyzed. On the other hand, biological products are made from living organisms and are much more complex in nature — making product analysis very difficult. Indeed, most biological products are defined by the manufacturing processes used for production. The manufacturing process and manufacturing facilities are so crucial to biologics that “purity” is part of the agency’s requirements for licensing.
The FDA strictly controls changes to the manufacturing processes that evolve during the development of the biologic, as well as after licensing. Biologics are much more sensitive to process changes than are drugs – even a small change in the manufacturing process can result in an adverse change in the biological product. This is why biological products are regulated under the PHS Act. Initial manufacturing procedures are detailed in the IND application and then modified as needed throughout the IND phase of clinical evaluation and through the final BLA submission.
Modification to manufacturing may be needed to scale up from pilot to full-scale production or to improve efficiency; this can include any changes in equipment, facilities, handling, or storage and testing of cell substrates that may be required.
Changes to the biologic’s manufacturing process, equipment, facilities, or handling have the potential to affect the products identity, safety, purity, and potency. Therefore, any changes to production must be brought to the attention of the regulatory authorities, and the FDA will use its “comparability” ruler to determine if additional studies are required to support the license application. "