Regulatory Affairs is key in the pharmaceutical industry, from drug development to commercialisation. Learn more about the roles and functions that RA teams can provide in the lifecycle management of your pharmaceutical product.
Regulatory Affairs is essential in the pharmaceutical industry. Especially during drug development: a lengthy, complex, and highly costly but necessary process.
Regulatory Affairs experts are involved in all development phases, even after drug approval and commercialisation. They possess unique scientific and management skills to achieve a commercially important goal within a drug development organisation.
The Regulatory Affairs department provides strategic and technical advice at the highest level in such companies. In this way, they make a significant contribution, both commercially and scientifically, to the success of a development program and the company.
Many pharmaceutical companies seek external RA team members with specific expertise to ensure that products are developed, manufactured, and controlled at all expected quality, safety, and efficacy levels. Experienced consultants to ensure all filing and submission goals are met, with high quality and within expected timelines.
Sounds familiar? This post will give you a better understanding of the role of Regulatory Affairs in the pharmaceutical industry and the functions that Regulatory Affairs teams can provide in the lifecycle management of your pharmaceutical product.
Lifecycle management: keeping your pharmaceutical product alive and kicking
Within the pharmaceutical industry, a strong lifecycle management strategy is important to ensure the successful and lasting commercialisation of the pharmaceutical product. Lifecycle management will start early at the beginning of the discovery and R&D phase and will continue after the patent expiry of a product.
The Regulatory Affairs team plays a key role throughout the product lifecycle to demonstrate the product’s quality, control, conformity, safety, and efficacy in the documentation submitted to the competent authorities for review and approval.
The role of Regulatory Affairs in Pharma throughout the lifecycle of a medicinal product
Once the drug discovery phase, during which potentially interesting compounds are tested for their non-clinical characteristics, the clinical phases (early to late phase) are initiated further to test the safety and efficacy of the drug candidate. After successful clinical trials, marketing approval for a medicinal product must be sought by submitting a marketing authorisation.
When the competent authorities grant the marketing authorisation, commercialisation of the medicinal product can begin. Still, through variation, post-approval amendments will continue to be submitted by the regulatory affairs team to ensure the dossier being approved by regulators is constantly updated.
In the next section, we will take a closer look at the different phases of the lifecycle of a drug and the role Regulatory Affairs plays throughout the pharmaceutical industry.
R&D – Clinical phase: Setting up the right Clinical Development Strategy
Early in the development process, at the research stage, it is critical to involve regulatory affairs to ensure the development of an appropriate Clinical Development Strategy . This approach involves a careful sequence of clinical studies, including Phase I human testing through proof-of-concept Phase II trials and critical Phase III trials in pursuit of approval from regulatory agencies. This means that the regulatory affairs team is part of such a strategy to ensure that such an approach meets the regulation requirement, and it is also designed to generate the type of data needed for a successful registration. Clinical trials require extensive finances and usually take years to complete, and the results cannot be predictable about this drug candidate’s demonstration of effectiveness. Suppose a pharmaceutical company delays completing or discontinuing a clinical trial of its drug candidates. In that case, the commercial prospects of the drug candidates will be harmed, and the ability to generate revenue from any of these will be delayed. The Clinical Trial Application (CTA), the Investigational Medicinal Product Dossier (IMPD), which contains Chemical Manufacturing and Control (CMC) data, is an essential part of the CTA.
The regulatory affairs teams will develop the quality sections of the IMPD (CTD Modules 2.3 and 3) with a phase-appropriate level of detail. Although the EMA provides guidance to the industry on the expected content for an IMPD for chemical-based products, biological products, or ATMPs (Advanced Therapy Medicinal Products), an experienced CMC writer will need to provide the appropriate level of detail in the IMPD for the clinical phase in which the investigational product is currently at.
In the case of complex developments or innovative technologies, Regulatory Affairs experts will seek scientific advice from national competent authorities or EMA through a specific procedure to ensure that the development and future registration of the dossier proceed according to the agreed expectations of the regulators.
For some products for pediatric use, for the treatment of rare diseases (the prevalence of the condition in the EU should not exceed 5 in 10,000), or for products that may be designated as Advanced Therapy Medicinal Products (ATMPs), the regulatory team will ensure that the necessary applications are submitted to the competent authorities for either a pediatric investigation plan, an orphan designation or an ATMP classification.
Marketing Authorisation Application
After a successful clinical phase, a company wants to obtain regulatory approval for the medicinal product. Still, the regulatory approval processes of the competent authorities are lengthy, time-consuming, and inherently unpredictable.
Consequently, the role of an experienced regulatory affairs team in the approval process will be important to maintain the goal of timely product commercialisation.
Knowing that a medicinal product may be marketed in the EU only when a Marketing Authorization has been issued by:
- the European Commission via Centralized Procedure (CP) or
- The competent authority of member states via National Procedure (NP), Mutual Recognition Procedure (MRP) or Decentralised Procedure (DCP)
When applying for the Marketing Authorization application, pharmaceutical companies have to decide on the submission strategy of the marketing authorisation dossier.
The applicant must carefully consider all logistical and regulatory issues before submission. A key source for input and implementation throughout the decision-making process will be the regulatory affairs team, which will need to estimate
- the approval time based on the existing registration routes,
- the specific registration dossier requirements for each country,
- the mandatory registration route for certain products (Annex Medical Products to be Authorised by the Community),
- Moreover, the costs incurred in reimbursing the authorities for dossier evaluation and marketing authorisation in the countries of interest.
For the registration dossier, the CMC experts, the (non-)clinical experts together with the regulatory affairs offices ensure the compilation of a compliant CTD dossier, which is submitted through the Common European Submission Portal (CESP) on behalf of the pharmaceutical company in eCTD in any of the EU countries through the most appropriate registration procedure.
Commercialisation
The pharmaceutical company can commercialise the product after the competent authority grants marketing authorisation.
Even after the competent authority grants marketing authorisation, the work of the regulatory team continues. Post-approval changes, such as variations or amendments, will trigger the need for additional regulatory affairs work. This includes updating the dossier to reflect any changes, ensuring compliance with regulatory standards, and maintaining communication with the competent authorities.
Variations to keep the marketing authorisation up to date
Variations are all the changes made in the dossier of an authorised product after its initial registration. They may concern administrative, quality, safety/Efficiency, or vigilance changes.
The regulators foresee four types of variations: type IA, type IB, type II, and extensions of marketing authorisations (line extensions). Type IA variations are minor changes that have only minimal or no impact on the medicinal product’s quality, safety, and efficacy.
Regulatory updates triggered by referrals
Due to continuous improvements at the manufacturing plant and changes in the pharmaceutical product supply chain, changes must be made to the approved registration dossier by compiling and submitting variation packages.
With more than 150,000 marketing authorisations in the EU listed in the EMA’s Article 57 database, the risk assessment process and subsequent reporting of the results significantly burden all regulatory affairs teams, especially those with larger portfolios.
With the support of external RA service providers, who provide the relevant expertise for risk assessment and reporting activities, most pharmaceutical companies could meet the reporting deadline of March 31, 2021, for chemical-based medicines and July 1, 2021, for biological medicines. A great example of the key role of Regulatory Affairs in the pharmaceutical industry.
Companies that need to make changes in the manufacturing process to reduce or prevent the number of nitrosamines in the finished product must make the appropriate changes in the registration dossier.
In this case, the quality sections in Module 3 may need to be updated, and the changes should be submitted to the competent authorities by September 26, 2022, for chemical medicines and by July 1, 2023, for biological drugs. Meeting these deadlines will continue to put pressure and workload on pharmaceutical companies’ regulatory affairs teams in the coming months.
New filings of existing dossiers
For already granted and approved dossiers in certain countries, new markets of interest may be identified by the pharmaceutical company, additional strengths may be added at a later stage, or new indications after successful additional clinical trials may lead to the submission of new marketing authorisation applications by the regulatory affairs team.
Product classification switch
In some cases, a switch from a prescription drug (Rx) to an over-the-counter drug (OTC) may be possible after the product has been marketed without safety and efficacy concerns. This product reclassification requires an understanding of the regulations and an application to the competent authorities to change the classification for the medicinal product supply.
Renewal or withdrawal of marketing authorisation
When a product has been on the market for 5 years, a renewal must be prepared and submitted to the competent authorities.
At some point, the pharmaceutical company may stop commercialising a particular product. At that point, the regulatory teams must apply to withdraw the product from the market officially.
Conclusion: Involve RA in
your drug development As you can see, the role of Regulatory Affairs in the pharmaceutical industry is substantial. To ensure the successful development and commercialisation of a medicinal product, it is essential to involve the regulatory experts in all stages of development, from the early phase of the clinical trial to post-approval changes during the commercialisation of the product.
