by Brenda Rascon
Preparing an initial marketing authorization application (MAA) for a biologic is both a journey and an elephant (more on that in a bit) that requires what is perhaps the greatest resource in any organization: people. There are necessary tools to make an initial MAA a success. However, given that regulatory approval procedures for biologics alone can take a year-and-a-half, the MAA preparation involves a great deal of commitment. Therefore, without a committed group of individuals or a sense of ownership, the MAA can be a daunting and nearly impossible endeavor.
So, we have established that committed people are a necessity to make this work. But back to the point about the elephant. The MAA product dossier can range anywhere between 30,000 to 100,000 pages in size; therefore, the elephant is large. Once, upon embarking on a MAA for a biological product, a thoughtful boss asked me, “How do you eat an elephant?” He was referencing the Desmond Tutu quote, which says you must do it one bite at a time. Both he and Mr. Tutu were right. You need people who know how to eat the elephant working in concert with one another.
Planning with purpose
When confronted with “the elephant” for a biological product, you first need to create a MAA content plan and identify which sections of the eCTD can be started first and which may need to wait for receipt of incoming data. This is important because all programs have gaps to fill and are rarely in possession of all required data for a regulatory filing of this degree. As a result, the schedule of arrival of data—be that CMC, non-clinical, or clinical—will inform the content plan and will drive the creation of mitigation plans for late incoming data. This approach lends itself naturally to an efficient staggering of the writing, review, editing and finalization, and publishing of individual documents, ensuring there are no additional (there will always be unforeseen challenges) bottlenecks at the end.
For the creation of a content plan, it is essential to assign an owner to each document and to track all stages of the MAA preparation process: writing, review, editing and finalization, and publishing dispatch dates. Without ownership, there will be nothing to manage, track, or finalize.
Once the content plan is in place, it should be used to evaluate internal resources and to inform decisions about whether outsourcing is needed for the initial MAA submission or future regulatory work, e.g., response preparation, labeling, and launch materials. If external vendors are needed, it is important to evaluate several early on prior to the start of MAA preparation.
Project management and coordination
Eating the elephant requires people of diverse expertise. Therefore, cross-functional teams are a necessity. Of equal importance is to assign an empowered leader who has oversight of the project and providers, and who can coordinate tasks across functions and keep team members engaged in the entire process. This will create cohesion, an awareness of project needs, and will ensure team members are available to provide input during submission finalization and during agency requests for information.
A meeting to “kick-off” the MAA preparation is a pre-requisite for the dual purpose of team engagement and to ensure there is basic understanding of the regulatory procedure and the submission preparation process. In addition, there should be tools in place, e.g., submission tracker per module, to give all team members an overview of the project progress and its status.
Clear writing and messaging
One of the most undervalued skills in MAA preparation is clear, succinct writing that is purpose-driven. Another is how to present data. As scientists, many of us think our data speak for themselves. We often also forget our audience because we have grappled with our data for so long, we end up believing that our audience is able to see what we can. In the case of a MAA, the audience is the regulatory agency. And while the people in charge of the scientific assessment at the regulatory agency are also scientists, we should not forget that they evaluate many product-related documents and may not see the hidden message in our data straightaway. Therefore, when faced with “the elephant”, it is of utmost importance to get down to basics and do what our teachers and professors taught us:
Develop a clear, convincing strategy and a coherent message that is supported by data
Create a clear outline for each section that needs to be written
Use the old principle of “one topic per sentence”. This is particularly key when writing about complex topics or ideas
Use topic sentences to frame your paragraphs and tell the reader about the intent or point of the text
Keep in mind that length is not necessarily a determinant of substance or depth
Use data with purpose. Data should serve and support your overall message
Remember: a dossier is not a collection of all project data ever generated. It is a collection of required data needed to establish the purity, safety, and efficacy of the proposed medicinal product. Therefore, the dossier is an opportunity to showcase program data in a deliberate manner to support the overall goal: gaining product approval.
And lastly, ensure writing tools, e.g., eCTD writing templates, a style guide, standardized naming and versioning of documents, a secure transmission or safe sharing tool for documents, are available. This will guarantee consistency and harmonization across the entire writing process.
Expertise and commitment
It is no secret that expertise is required for the preparation of the MAA. People who have already eaten the elephant are an invaluable resource to an organization intent on gaining regulatory approval of a biologic. Expertise in the following areas is vital:
Development of biologics. Hands-on experience in this key area and proficiency in the interpretation and implementation of relevant guidelines for biologics.
Agency feedback. Experience obtaining, evaluating, and complying with Agency feedback.
Knowledge of the eCTD. Understanding the contents of the eCTD—which is required by the regulatory agencies in countries and regions with strict requirements—is essential.
Expert reviewing skills. A small team or a point person with regulatory expertise is invaluable for harmonizing the message across numerous, seemingly disparate, sections of the eCTD, ensuring the file speaks the same story throughout.
Regulatory expertise. Proficiency in the management of regulatory approval procedures and familiarity communicating with regulatory agencies is critical, given that this knowledge will provide a framework for and guide the expectations of the cross-functional team. In addition, this knowledge will enable organizations to make strategic decisions about licensure scenarios and ultimately, product launch.
Hands-on experience in these areas can safeguard companies from making mistakes, which can be costly in terms of money and time. At Biopharma Excellence, we have hands-on experience and welcome the opportunity to help bring your product across the finish line. Should you wish to learn more about our services in this area, please contact us.