Since clinical trials are often designed as multi-centre studies, potentially involving different Member States, on March 2006 the European Medicines Agency (EMA) introduced the Guideline on the requirements to the chemical and pharmaceutical quality documentation concerning investigational medicinal products in clinical trials to define harmonized requirements for the documentation to be submitted throughout the European Union for approval prior to beginning a clinical trial in humans.

On July 1^st, a new Draft of the Guideline, which will replace the earlier version issued in 2017, has been published for public consultation. Comments on the Draft of Revision 2 of the Guideline should be provided using the appropriate template provided by the EMA and sent to QWP@ema.europa.eu by 31^st of August 2021.

The section on the changes to the Investigational Medicinal Products (IMP) has been implemented aligning it with the Clinical Trial Regulation (CTR) in order to help the Sponsor in management of the amendments which can be classified as:

• Substantial modification (art 2.2.13)
• Change relevant to the supervision of the trial (art 81.9)
• Non-Substantial modification (changes outside the scope of substantial modifications and changes irrelevant to the supervision of the trial)

In particular, in the Revision 2 of the Guideline, the concept of non-substantial changes relevant to the supervision of the trial (Art 81.9 change) has been introduced: these have the purpose of updating certain, specified information in the CTIS without the need for an substantial modification application, when this information is necessary for oversight but does not have a substantial impact on patients safety and rights and/or data robustness.

RPN is available to offer companies support for the assessment on the classification of IMP amendments, as well as to provide full support for the management of IMPD documentation in compliance with the European requirements.

The use of the research product identifier (RPI) is used to make EMA processes more efficient by creating a single identifier for all pre-authorisation activities and it is already required for procedures such as the Scientific Advice request or the application of Orphan Drug Designation.

Starting from 10 October 2021, the RPI number is also necessary to carry out new Paediatric Procedures. In particular, the RPI number is a mandatory field in the updated electronic application form for paediatric investigation plans (PIPs), modifications of agreed PIPs, and requests for waivers, which is availableon the EMA website.

Applicants that approach EMA for the first time with a new medicinal product and do not have a previously assigned RPI, will need to request a new RPI via the IRIS platform after verifying that the Active Substance in the product is registered and appear as “authorised” on the official EMA list of all substances (SMS).

Regulatory Pharma Net (RPN) has successfully supported companies in the early dialogue procedures with EMA, including the Paediatric procedure (PIP).

RPN is already registered on IRIS and can offer support to companies that need to request the RPI to fulfill the EMA requirements.

On 3^rd March 2022 the European Medicines Agency (EMA) released the 5-years report for its PRIME (PRIority MEdicines) scheme, that provides a detailed analysis and review of the Agency's experience with the scheme in its first 5 years of application.

Launched in March 2016, the PRIME scheme supports the development of medicines that may offer a major therapeutic advantage over existing treatments, or benefit patients without treatment options.

Through PRIME, the Agency offers early dialogue, interaction and proactive support to medicine developers to optimize the generation of robust data on a medicine’s benefits and risks and so to speed up evaluation and availability for the patients of therapies that may significantly improve their quality of life.

Key benefits for applicants are:

• early appointment of Rapporteur from the Committee for Medicinal Products for Human Use (CHMP) or from the Committee on Advanced Therapies (CAT) in the case of an advanced therapy;
• kick-off meeting with the CHMP/CAT Rapporteur and a multidisciplinary group of experts;
• assignment of a dedicated EMA contact point;
• scientific advice at key development milestones, involving additional stakeholders such as health-technology-assessment (HTA) bodies;
• confirm potential for accelerated assessment at the time of an application for marketing authorization.

In order to be eligible and accepted for PRIME scheme, a medicine has to show its potential to benefit patients with unmet medical needs, based on early clinical data.

The 5-years report outlines the positive impact the EMA’s PRIME scheme has had on drug development for unmet medical need over the last five years: this positive trend is more pronounced for SMEs and ATMPs. The analysis also showed that supporting PRIME products during development resulted in a reduction in the time required by the applicant to answer EMA questions during the evaluation (clock-stop) leading to faster reviews and faster access to patients to PRIME products.

In particular, the report reveals that:

• a total of 95 requests for PRIME eligibility were granted.
• the orphan designation appears to increase the probability to be granted PRIME (the 56% of PRIME products are orphan-designated even if the orphan designated products account for ~42% of PRIME eligibility requests)
• a total of 18 medicines that had PRIME support were approved in the European Union (EU), 10 of which received a conditional marketing authorisation (CMA).

Regulatory Pharma Net provides support to companies in targeting the proper regulatory milestones to facilitate faster access for patients to new medicines in EU, including assistance in the eligibility request for PRIME.

Do not hesitate to contact us at info@regulatorypharmanet.com

The Paediatric Investigation Plan (PIP), introduced by Regulation (EC) No 1901/2006, is a research and development programme aimed at ensuring that the necessary data are generated determining the conditions in which a medicinal product may be authorised to treat the paediatric population.

In principle, the PIP shall be submitted early in the product development, no later than upon completion of the human pharmacokinetic studies in adults.

However, there are exceptional cases where there is a lack of crucial information needed to define the PIP in this early phase of the development, such as in the case of:

• a first medicine for a disease (e.g. very rare disease only recently identified in children),
• a medicine whose mechanism of action has not been fully characterized yet and which may have implications for ontogeny related changes,
• a medicine with multiple development options to address significant unmet paediatric need in several paediatric indications where adult data are lacking.

Therefore, EMA is proposing to test through a pilot the concept of the ‘stepwise PIP’ (sPIP) consisting of only a partial development program, conditional on the development of a full PIP once the crucial information has become available. It would rely on predefined steps agreed with the EMA's Paediatric Committee (PDCO), such as applicants being able to hold discussions with the PDCO once they obtain more data.

Regulatory Pharma Net (RPN) has successfully supported companies in the early dialogue procedures with EMA, including the PIP, and is available to support companies in the preliminary interaction with the Paediatric Medicines (PME) Office to explore the possibility to join to the sPIP pilot program.

The public consultation on the revised ICH Q1 Guideline, “Stability Testing of Drug Substances and Drug Products,” officially closed on 30 July 2025, marking an important milestone in the evolution of this essential regulatory framework. Initiated on 11 April 2025 with Step 2b of the ICH process, the draft was made available for stakeholder input by the EMA at the end of April.

This comprehensive revision unifies and replaces the former Q1A–F and Q5C guidelines. Crucially, it extends its applicability to both synthetic and biological entities, including advanced therapies such as vaccines, gene therapies, and combination products. One of the most significant advancements is the introduction of lifecycle stability management, aligning with principles set forth in ICH Q12.

Among the most impactful updates are the inclusion of all climatic zones for global harmonization, clear guidance for stability in clinical settings, and dedicated sections for Advanced Therapy Medicinal Products (ATMPs). The emphasis on Quality by Design and risk-based methodologies reflects a strong alignment with ICH Q8–Q11 and the emerging Q14, underscoring a more strategic integration of stability into the broader drug development process.

As the ICH process moves forward, stakeholders across R&D and regulatory functions should prepare for changes that may affect dossier strategies, development timelines, and global submissions.

RPN will provide any further update and is available to provide full support for drug development and regulatory strategy activities.

Paediatric Investigation Plans (PIPs), introduced by Regulation (EC) No 1901/2006, play a crucial role in the development of medicines intended for use in children. A PIP is a comprehensive plan developed by pharmaceutical companies in collaboration with the European Medicines Agency (EMA) to ensure that data on the use of medicines in children is generated. This is particularly important for treatments initially developed for adult populations, where the safety and efficacy for children must be specifically evaluated due to their unique physiological characteristics.

The requirement for a PIP aims to guarantee that medicines undergoing development include appropriate paediatric studies, ensuring that children have access to safe and effective treatments. The plan includes details on study design, dosing regimens, and the timing of clinical trials.

As part of the ongoing effort to improve the submission and review process, starting from 04 June 2024, the EMA transitioned to the IRIS portal for paediatric-related submissions, including initial PIPs, modifications, product-specific waivers, and more. The IRIS platform significantly enhances the transparency and efficiency of the paediatric application process by enabling real-time tracking, better integration of data, and faster interactions with the EMA.

RPN multidisciplinary team has the expertise to provide PIP strategic guidance, to define a tailored PIP and support companies in interacting with EMA, including the use of the IRIS portal.