Between September/2019 and February/2020, we published a series of articles regarding the discussions on the regulatory framework for incremental innovation where we intend to implement the registration pathway system. In a quick assessment, the new system seems quite positive, as it will bring flexibility in proving safety and effectiveness, but are companies prepared for this paradigm shift?
The registration route system significantly changes the way companies develop an innovation, as there will no longer be a list of studies that must be carried out to prove safety and effectiveness, which provided a certain regulatory comfort.
The big window of opportunity for pharmaceutical companies is the mixed route where it will be allowed to use part of the data from drugs already known as the basis for preparing the dossier for registering the innovative drug.
The companies that are starting their developments should already do so considering the registration routes and the CTD format, since these requirements will most likely be mandatory when submitting it. Based on these premises, companies need a multidisciplinary team to think about product development in an integrated way, starting with a real understanding of what the drug is intended for, what innovation and benefits the product will deliver, what medical need it will meet and what product rationality.
The intense bibliographic research raising robust data about the disease, the molecule, and the existing products that use it, sets the basis for all development planning. The collection of information should consider that the data needs to be robust enough to adequately complete all modules of the CTD, including those of 2.4, 2.6 and 4 on non-clinical studies. In-depth product knowledge is the cornerstone from which product development planning will be built, as from this stage the outline of the others begins:
Based on the physicochemical properties of the molecule (s) and the delivery target of the API (s), analytical and pharmacotechnical development is planned.
From the collected non-clinical data, it is assessed whether they are sufficient to support the clinical development, or if any complementation is needed.
From the knowledge of the disease, previous clinical studies and the mechanism of action of the active principle, the clinical development is designed to determine which clinical studies will be necessary: relative bioavailability; pharmacokinetic interaction; phase I, II and III; phase I and III; only phase III, or even, only product performance studies for specific cases where it is possible to substantiate efficacy and safety without the need for clinical tests.
Development planning must involve the whole team, so that in the end, it is clear what I usually call “WDWW”, who does it, what and when. That is, the responsibilities, deadlines and delivery sequence must be clear to be monitored.
Choosing what to outsource and with which company is also an important step, as an inappropriate choice can ruin a project, so before hiring, research the suitability of the partner, clearly define what is expected of the job and what tasks should be executed and the delivery schedule.
It is important to note that all stages must be recorded in a systematic way from the planning, way of execution, data collection, explanation of the choices made along the analytical, pharmacotechnical, non-clinical and clinical development; always contemplating good manufacturing, laboratory and clinical practices. The objective is to generate consistent data for the preparation of the registration dossier in CTD format.
Special care should be taken with recording problems and deviations that arise during development and how they have been overcome, including the discussion of assessing the impact on product performance. The aim should be to clarify and explain, not to hide the negative facts that may arise. ANVISA and companies must have the maturity and experience to discuss these issues in a transparent manner.
Speaking of ANVISA, a fundamental point in the entire innovation development project carried out in Brazil is to develop a coherent strategy to present, discuss, and previously approve the clinical development rationale with the Agency; so that at the end, once the results of the studies be positive, they achieve the objective of demonstrating the safety and efficacy of the product for the purpose of registering the drug in Brazil.
I highlight this last sentence because it is important to focus on the registration of the drug, as nothing would be more frustrating than having a successful clinical study with interesting scientific data, but whose design does not achieve the primary objective of demonstrating safety and efficacy for health authorities be able to grant the registration of the medicine. Therefore, alignment with ANVISA, although not mandatory, is highly advisable, avoiding wasted time and money.
Everything mentioned above will only be successful if there is an efficient project management that privileges the work of a finely tuned team, with teams that support and prioritize the solution instead of problems and hunting the guilty; and with well-selected and broached third parties so that project deliveries take place as agreed.
Finally, there must be a continuous concern with communication so that the members of the team can fully understand the progress, successes and problems that are happening, and an interesting way is to conduct constructive discussions with the objective of making the project feasible and overcoming the obstacles that arise during development.
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