Question: Project Orbis model may be more applicable to most pediatric submission reviews due to the small volume of most pediatric submissions (supplementals). ACCESS model could apply to NDAs for pediatric use but may not be applicable to most supplementals because of the small package of those submissions and there is no need of worksharing.
Answer: Thank you, Helen for your comment. Your experience with the ACCESS model would be very helpful to share with the group.
Question: Do the Common Commentaries have any kind of legal or other weight in Regulatory Authority deliberations, or are they free to ignore them?
Answer: The regulatory authorities are not bound to follow the common commentary.
Question: Please explain Beysian model as if you were explaining to a 10 year old
Answer: You take what you already know (the prior) and draw a conclusion (the posterior) based on what you learn through new experience (the likelihood).
Question: Would another way to frame: helps determine the posterior probability of a condition? and in the state of uncertainty?
Answer: Yes. Knowledge is based on probability. The amount of borrowing can be framed in the context of uncertainty.
Question: I think only safety events that are PK driven could be extrapolated. Still tolerability can change and depend on the patient population. E.g. children may tolerate vomiting less well.
Answer: This may be limited to formulation changes. In IV and SC, the formulation may be exactly the same. In adolescents, the dose is usually the same.
Question: when you are doing clinical trials with pediatric stakeholders, let’s say a for orphan drugs/rare diseases– who decides who would be eligible for these clinical trials- ie parents who think their children could be helped by these drugs? — and isn’t it more risky for a new drug to test on such little ones? hope that question is clear enough…
Answer: Legally the parents need to provide consent. Where possible children should be asked to assent to the study – this requires expertise in communication with children. Often this type of study needs to engage with the most suitable patient advocacy groups to make sure that the study is truly in the best interest of patients. There is a session on patient engagement in clinical research tomorrow where it would be interesting to raise this question
Question: when you said that the orphan exemption for pediatric studies has been eliminated, is that just in oncology or across the board for all orphan diseases?
Answer: Only oncology, through the RACE Act.
Answer 2: Indeed, only for pediatric oncology medicines, knowing that this exemption doesn’t apply to Europe.
Question: The idea of prioritization is interesting, but not feasible per FDA regulations (outside of oncology) by my understanding. From an FDA perspective, is there a path forward in other TAs? You have used the IBD c4c example, but the FDA representative to that meeting did not feel that prioritization (and by implication waivers for de-prioritized medications) was feasible.
Answer: “FDA does not “prioritize”. However the FDA have granted waivers for pediatric assessments of multiple same in class products.
Question: At the peadiatric cluster meetings, how much modelling and simulations is discussed here?
Answer: For discussions of oncology products modeling and simulation for pediatric dosing considerations are discussed when proposed by sponsors in their respective PIs and iPSPs. On occasion, recommendations to consider modeling approaches when there is sufficient adult data to do so and in situations where extremely small patient numbers are expected.
Question: what is PIP?
Answer: Pediatric Investigation Plan which is the required tool to be submitted to EMA that outlines the approach to pediatric development
Question: kindly share acronyms: TGA, MPDA, and the last one in that particular slide if you recall?
Answer: TGA is Therapeutics Goods Administration which is equal to FDA in Australia and PMDA which is Pharmaceuticals and Medical Device Agency in Japan
Question: Pediatric Clusters provide a platform for regulatory exchange focusing on pediatric plans. What is the EMA and FDA thought on regulatory colleboration on the reviews of pediatric applications?
Answer: Regulatory reviews of oncology products are discussed at the Oncology Cluster meetings among regulators. To date, products for which pediatric approval is being sought have not figured prominently on the agenda generally because they have been discussed at the Pediatric Cluster. The only real regulatory collaboration is Project Orbis in which the EMA is not currently participating.
Question: May I have a comment on the AYA related presentations, pl. 1. I wonder whether the PIP should include a section about the involvement of adolescents as well. If we speak about a population as young as 12 year old children then this may be overlapping with PIP. 2.Also I wonder whether a waiver system could be introduced for AYA in general? For some tumours ( e.g. haematology) it could be a default approach whilst for tumours that are very rare in AYA ( e.g. Lung cancer) a waiver could be issued. 3. Finally, could the current FDA MOA list for paediatric development be extended for AYA?
“1. I wonder whether the PIP should include a section about the involvement of adolescents as well. If we speak about a population as young as 12 year old children then this may be overlapping with PIP.
The PIP needs(as well as the iPSP) to address the entire paediatric age group from birth up to 18 years of age so the PIP will in fact describe planned studies in adults that include adolescent that would be included as part of the Key Elements Form with specific details regarding the contribution of the adolescent population
2.Also I wonder whether a waiver system could be introduced for AYA in general? For some tumours ( e.g. haematology) it could be a default approach whilst for tumours that are very rare in AYA ( e.g. Lung cancer) a waiver could be issued.
For purposes of pediatric labeling and the age range to be addressed in the iPSP, FDA defines pediatrics from birth to 16 years (Although pediatric trials typically will include participants up to 18 years). The FDA has published a list of Adult-Related Conditions that qualify for a waiver because they rarely or never occur in pediatrics* https://www.fda.gov/media/101440/download. Specifically this list includes a waiver for treatment of lung cancer (small and non-small cell) as well as other adult cancers. This approach is applicable for pediatric plans that are subject to PREA but not FDARA as waiver is based on age in relation to the relevant to a molecular target and not to a specific condition.
3. Finally, could the current FDA MOA list for paediatric development be extended for AYA?
The FDA target list addresses targets relevant to pediatric cancers include children and adolescents/young adults. The regulatory requirement for a sponsor to study the pediatric population is from 0 to 16 years of age”
Question: My question/wondering: whenever I am in these kinds of seminars, etc. I pose the question about how these communities engage with ‘alternative medicines’/practices approach… and often, there is no answer/response…. As someone who blends both and finds both useful, are there groups in these clusters that takes this on? would be great if someone could/would take this on/addresses this? I realize there can be tensions between these paradigms… but I feel can be useful…
Answer: The Cluster would not address alternative medicines as that is not under the jurisdiction of the FDA or EMA