By Sharon Turner-Rinehardt, Associate Director, PAREXEL® Consulting
Are you ready for the NDA to BLA conversion? March 23, 2020 is fast approaching. FDA has issued a Guidance for Industry: Implementation of the “Deemed to be a License” Provision of the Biologics Price Competition and Innovation Act of 2009 regarding the BPCI Act that requires all “protein based products” convert from an NDA to a BLA/Biosimilar. All products must be approved by March 23, 2020. Although, all approved NDA applications for these products will convert automatically, applications with pending or tentative approval status by the deadline must be resubmitted as a BLA/Biosimilar. Are you ready?
The types of “protein based products” that are impacted are non-chemically synthesized peptides >40AA residues and naturally derived or recombinant proteins such as insulin/insulin analogs, hyaluronidase, thyrotropind, HCG).
For NDA applications for these products under 505(b)(2) development, consideration should be given to submit applications as a BLA or under section 351(k) of PHS Act (biosimilar). These applications are typically for products that contain complete reports of data for safety and effectiveness where you own the product or have right of reference to the data. Modifications to your development program for these protein products should be considered to meet the requirements for a BLA/Biosimilar. The option for a biosimilar relies upon whether there is a licensed product under 351 approved that could be used as a referenced product. How will you know the availability of this reference product?
Consideration should be given to the development and management of INDs for these products. These INDs will be no longer follow the development guidelines considered for NDA applications but rather BLA/Biosimilars. Are there any differences at the IND stage that you should be concerned about? The INDs will follow the BLA or 351 filing process. Ongoing INDs will transfer at milestones. Do you know the milestones and when they will occur?
Some of the key factors for consideration for this conversion are the readiness for inspections, understanding the BLA/Biosimilar licensure process, managing type II DMF changes, data needed if there are changes to an approved application such as stability, number of lots, etc. as well as a determination if a biosimilar can be developed for your product, i.e. is there a “referenced product”. Additionally, converting the NDA to BLA does not provide for periods of exclusivity; although, orphan drug designation will transfer. Considering that all PMR/PMC approved under the NDA will transfer to the BLA, understanding any new differences caused by this conversion may require clarification discussion with FDA. Understanding the impact of different product types and what this conversion means regarding development and maintenance of the application such as pancrelipase products based on the guidance “Exocrine Pancreatic Insufficiency Drug Product-Submitting NDAs” must be taken into consideration.
Understanding BLA/Biosimilars is key to a successful transition. Engaging with FDA as soon as possible is key. PAREXEL can help you navigate through the complexity of these changes and provide you with key strategies to assist with conversations with FDA as they begin the conversion process for NDA to BLA. Please contact us to discuss your options and development to assist in minimizing the anxiety of making this conversion.