Investigational New Drugs/New Drug Applications (INDs/NDAs) filed as 505(b)(2) products represent a “hybrid,” faster process for FDA approval of new drugs, that in terms of complexity and innovation are somewhere between drug products that are the same as products already on the market and the “full” process of a 505(b)(1), which involves fully sponsor-funded study applications for what are often totally new substances.
These products are often altered versions of existing FDA-approved drugs. 505(b)(2) drugs can include drugs with new indications, or combinations of preexisting drugs, or other options like drug-device combinations. This section specifically allows for the use of studies not provided by the sponsor to prove the efficacy of a drug’s active ingredients, which is one of the most appealing parts of a 505(b)(2) application. A well-structured 505(b)(2) application can eliminate the need for most nonclinical studies, which is a huge expense.
Defining the detail and scope of the information that needs to be included in an application is one major area of difficulty for these INDs. Drawing on multiple sources of information, and cross-referencing them when dealing with new combination drugs as a 505(b)(2) application, is a tricky job. It is vital to understand exactly which safety protocols must be included from each of the cross-referenced materials.
What is Chemistry, Manufacturing and Controls (CMC)?
However, actually putting a 505(b)(2) application together can be quite a challenge, because of the varying sources of information. Some parts of the 505(b)(2) application may come from a reference product, and some may come from the new additions to the product. One of the most important sections specifically for 505(b)(2) IND/NDAs is the Chemistry, Manufacturing, and Controls (CMC) section. The CMC section is the part involving the actual assembly and hazard control of the drug. This involves establishing its physicochemical properties, its format in terms of capsules, tablets, IV formulations etc., as well as its manufacturing process. Considering that many 505(b)(2) products are already proven in terms of medical efficacy or medical need, the CMC portion of the application is often the single most important step, as it determines whether or not the new drug product is safe and worth the effort of development.
What is a Drug Master File (DMF)?
What is a Drug Master File (DMF)? How do they work? A DMF is a file you submit to the FDA including confidential, detailed information on facilities/processes/materials used in the manufacture of the drug you’re submitting an application for. DMF types include DMFs for the manufacturing site or process, the materials, packaging, colorant or flavor, and miscellaneous reference information. Whether or not to submit a DMF, which are often labor-intensive to compile, or refer to a preexisting one is another major question for the CMC section of a 505(b)(2) IND/NDA.
Regulatory affairs professionals, clinical trial specialists, and FDA-project investors should be very careful about how they assemble a 505(b)(2) application, as these applications make up 50% of FDA’s total applications. And considering that information in a 505(b)(2) application may come from multiple sources, expert advice on how to collate those sources can be invaluable. An upcoming webinar on February 4th will showcase exactly how to manage these sources, what should and should not be included, as well as common errors in the CMC section.