Preparing and Submitting Robust Paediatric Investigation Plans

Pharma IQ

Pharma IQ held a Q&A session with Karl-Heinz Huemer, PDCO Member and Clinical Assessor, Austrian Medicines Agency  to gain a few insights into preparing and submitting robust PIPs...

The paediatric clinical development landscape has changed. How do you feel the industry is responding to these changes?

The industry is responding to new regulations in paediatric clinical development very heterogeneously. This ranges from drug developers who are eagerly over-compliant, setting up trials to be in accordance with guidelines but which are infeasible to others who are in complete opposition and would rather consult lawyers than propose a paediatric investigation plan (PIP). In terms of the standard of PIP proposals being submitted to the PDCO for approval, to date they have ranged from investigational plans which have clearly taken minimal effort and lack any clear concept to highly professional, elaborate development programmes. The quality of proposals often depends on both the scientific and regulatory expertise of the drug development company, particularly in terms of how much the company is aware of the requirements and how much it is willing to invest in resources.

How do you feel the role of PDCO has evolved?

For the PDCO, my immediate observation would be that the increase in regulation of paediatric clinical development has of course meant a shift from a high workload to even higher workload! As an organisation, we have become increasingly aware of companies having – based on rumour – an extremely biased view of what to expect from the new procedures. However, we are finding that the regulatory premise – that the problem of developing better medicine for children has to be addressed – is slowly getting through to stakeholders. On our own side, there is a steep learning curve for PDCO in terms of how to tackle specific issues which are coming up over and over again. In response to these challenges, we have intensified our interaction with other working parties and committees to enhance economic assessment and to improve the process going forwards.

What are the factors crucial to the development of a robust PIP?

There are a number of key factors to be taken account of in developing a strong PIP. The drug developer must make a clear effort to propose solutions where possible and to present evidence for arguments used – be it for study parameters or reasons for deferrals or waivers. It is also important to draw up a proposal in terms of timing, which should ideally be integrative with the adult drug development schedule. Another vital step in ensuring a robust PIP is to go through the issues outlined in the summary reports and to generate concepts for all points that are applicable to the respective development.

What would be your three top tips for companies on how to avoid delaying marketing authorisation?

As companies are still getting to grips with what is being asked of them by the new regulations, delayed marketing authorisation happens in some cases. However, if I were to give three top tips on guarding against delayed authorisation, firstly I would encourage drug developers to ensure that the PIP proposal comes in on time (i.e. after Phase I). Secondly, companies should ensure that the proposal submitted is as clear as possible – outlining exactly what is considered feasible and how it can be achieved. Finally, it is important that the proposal talks about science, therapeutic needs and feasibility – rather than mainly about legal or regulatory aspects, and arguing against performing a paediatric trial simply because of rarity of a disease among children is not sufficient.

What opportunities do you think there are for paediatric clinical development in the next five years?

There is a wealth of opportunities for paediatric clinical development over the next few years. Increased networking is to be expected among stakeholders in the field including industry, societies, academia, and I also anticipate the introduction of specialised centres and contract research organisations for paediatric aspects. Over time, I would expect PIPs to become perceived as an integral part of a development programmes and dossiers, rather than being seen as an additional burden. As we move forwards, harmonisation of summaries of product characteristics of currently licensed drugs can also be expected. This will help in two ways – firstly to provide clear information for paediatricians to prescribe efficient and safe drugs and secondly, to communicate to insurance companies that child-appropriate formulations – even if more expensive – are not ‘luxury’ but required to ensure best practice.

Interview conducted by Helen Winsor