Dr Parvinder Punia, senior regulatory affairs manager, ELC Group, discusses the use of guidelines in drug development
As costs of development escalate and guidelines grow, the need for scientific advice from regulators becomes an essential part of any drug development timeline. As guidelines are open to interpretation, the basis of the scientific reasoning should be open for debate. In this way, many guidelines have gone through evolutions.
The pharma industry is not developing in isolated, single regions. The needs of global development must be accounted for. So, which NCA to ask advice from and how to navigate differences of opinion? The logical way is to approach agencies where clear-cut guidelines do not exist. This can alleviate ambiguities. Advice can be tailored to suit the needs of the other regions without compromising the requirements of each agency at each stage.
Another approach would be to use precedents set by other companies, leveraging decisions made earlier to turn opinion in your favour. However, this is a double-edged sword and the opinion previously given may not be favourable to your development plan. It can happen, where a company has sought advice and has developed a product at the high standard that regulators previously thought would be the only route. However, as experience grew, it was noted that maybe some parts of development could enjoy abridgement (this is particularly a problem for biosimilars). However, since the bar was already set, it was not possible for regulators to lower it, without backlash from competitors in industry. One territory did move forward and applied minimised development plans in the advice given but another territory has refused to align. In these cases, either the global plan must become more localised, or the development itself terminated.
With some regions applying strict timetables to how an advice is applied for and finalises the minutes, utilising timings of committee meetings and experts availability, a company could spend years seeking scientific opinion. In the EU, for example, the EMA advice is strictly timetabled. In the US, a preliminary meeting request needs to be completed to begin the countdown of days to the allotment of the audience with the regulators. Since there is no way to challenge the timelines, the company must plan in advance – in some cases, years – in order to allot the needed time. In the EU, the problem can be eased by the use of the local NCA for opinion. In any case, a large development of innovation should first be “checked” at the local level. The regulators sitting on panels at the EMA are primarily made up of personnel at the local authorities and therefore, pinpointing expertise around the EU and approaching those agencies is beneficial. Ultimately, the EMA opinion should be sought, but the final advice package could be tailored around the general opinion gathered.
The purpose of the meetings is to steer a regulator towards your opinions using scientific facts and regulations/guidelines to assist understanding. Asking a closed question is beneficial. The meeting is the opportunity to create challenges. Ask thought-provoking questions and challenge opinions. Choosing key personnel within the applicant's team who can do this is an integral part of planning the scientific advice meeting more efficiently. Ask if the regulator agrees/disagrees with general consensus and guidelines.
However, one can only cite the usual phrase given to any advice: That this document is not legally binding and cannot be taken as indicative of any future agreed position.