Documentation is an essential component of the drug development process throughout the journey to regulatory approval. Regulatory documentation serves as the primary means of communication with health authorities regarding the safety, efficacy, and quality of medicinal products. Compiling and directing that communication is, consequently, of paramount importance, and companies depend on skilled regulatory writers, who are responsible for preparing all the necessary documentation and managing the requirements in a complex, detailed and ever-changing landscape.
According to the European Medical Writers Association, regulatory writers produce regulatory documents that must “adhere to the relevant guidance and be fit for purpose”, which means conveying information in a way that is accurate, transparent and clear to its intended audience, typically regulatory authorities[1]. The American Medical Writers Association describes regulatory medical writers as key to the process of providing clear documentation to the authorities through their ability to analyze, coordinate and distill complex scientific information[2].
The regulatory documents involved
Depending on the product specificities and the chosen regulatory strategy, the required documentation may include:
- Briefing documents: Also known as briefing packs, briefing packages, and briefing books, these documents are prepared by a pharmaceutical company during drug development to support interactions with health authorities (e.g., pre-submission meetings, requests for scientific advice/agency meetings, and protocol assistance) in order to receive guidance and direction from the European Medicines Agency (EMA), US Food and Drug Administration (FDA) or other national competent authorities on the best methods and study designs to generate robust information[3],[4]. Such documents are expected to be clear, thorough and proactive at addressing potential regulatory concerns to facilitate smooth and productive meetings with health authorities.
- Orphan drug application: The scientific part of the application provides the necessary information to apply for an orphan designation for a drug intended to treat a rare disease or condition[5]. Developing ODDs involves persuasively demonstrating the unmet medical need and the potential benefit of the drug, while navigating stringent criteria and limited data availability due to the rarity of the condition.
- Pediatric investigation/study plans: The scientific documents needed to support marketing authorization of medicines for pediatric use are expected to include the strategy for investigating the safety and efficacy of a medicinal product in the pediatric population. The format and content must adhere to strict guidelines by region, covering all subsets of the pediatric population and including all relevant information, whether favorable or not.
- Common Technical Document (CTD) modules: This is a standardized set of documents required by regulatory authorities for the registration of medicines. In most major markets, the requirement is now for an electronic CTD (eCTD)[6]. Regulatory submission dossiers are critical documents encapsulating the entirety of research and development efforts and requiring meticulous preparation to align with specific regulatory guidelines.
All these documents constitute strategic assets that significantly shape the development of a medicinal product and critically impact timelines and outcome of drug approval. They should contain high-quality scientific and technical information accurately reflecting the comprehensive data supporting the proposed therapeutic indication according to regional regulatory requirements. Conversely, our experience finds that inaccurate, inconsistent, incomplete or non-compliant documents can hinder review by regulatory agencies, resulting in avoidable questions and responses, potentially prolonging development, increasing costs, and delaying approval.
An evolving regulatory landscape
While it is important that companies develop robust and strategic approaches to managing documentation, the evolving regulatory landscape presents challenges. Regulatory bodies such as the FDA and EMA regularly update submission requirements, setting new standards that significantly impact document preparation[7],[8].
This puts pressure on pharmaceutical companies and regulatory writers to anticipate and stay abreast of new regulations by monitoring guidelines and directives, understanding the implications of these new legislations on the documentation, and mastering how these changes should be applied and interpreted in practice.
Regulatory submissions should follow a legal basis under which the dossiers will be submitted. In the EU, these documents must adhere to the legal framework outlined in European Directive 2001/83/EC as amended.[9]
In the US, the drug approval pathways fall under Section 505 of the Federal Food, Drug and Cosmetic Act[10] and under Section 351 of the Public Health Service Act[11]
Each legal basis is associated with specific data requirements that must be fulfilled during the development process and addressed in the content and structure of the documentation. For each of these applications, specific guidelines should be strictly followed.
Geographical differences
Regulatory trends can vary significantly from one region to another, despite efforts to standardize worldwide.
For example, although there is substantial overlap in sections of the FDA’s initial Pediatric Study Plan (iPSP)[12] and the EMA’s Paediatric Investigation Plan (PIP)[13], a single template would not serve the regulatory needs of both agencies.
The reviewing requirements of the different agencies may also shape the expected contents of the different modules of the CTDs. In our experience, the FDA tends to conduct a bottom-up review based on the raw data, while the EMA performs a top-down review highlighting the overview of the data.
In addition, mandatory module sections required for registration in the US CTD dossier might not be required within the MAA dossier in the EU. This is, for example, the case of the integrated summary of safety (ISS) and the integrated summary of efficacy (ISE) within Module 5[14] .
All these differences may represent a further challenge when adapting US dossiers to comply with the specific requirements of the EMA to approve and launch a product in the EU market. It becomes even more complex when a geographical rollout is planned globally.
A team effort
The development of regulatory documents typically involves a multidisciplinary team, with the primary responsibility falling on professional scientific regulatory writers. These experts in scientific communication and regulatory requirements of different document types act as primary author, project leader and document manager, and play a pivotal role in ensuring documents are prepared to the highest regulatory and scientific standards and finalized in a timely manner. Writers interpret complex scientific and statistical data and work closely with regulatory affairs teams to produce crafted documents that meet the stringent standards of global regulatory agencies.
Documents must not only meet regulatory standards but also support seamless review by regulatory bodies. As such, regulatory writers need a deep understanding of regulatory expectations and a skillful approach to document preparation. Writers should anticipate and address potential questions and concerns of regulatory reviewers within the documents.
A good writer should, therefore, have the skills to draft highly technical documents and a comprehensive understanding of global regulatory requirements, ensuring adherence to guidelines while accommodating the unique needs and preferences of scientific, medical, and regulatory teams. Additionally, a good writer should be able to pull teams together and keep stakeholders focused on messaging, timelines, and collaborative work ethics.
In summary, scientific regulatory writing is a critical component in the drug development, maintenance and approval process, serving as the foundation for communication with regulatory authorities. Effective documentation significantly influences the success of pharmaceutical products in the market.
What challenges have you faced with regulatory writing – whether from the perspective of scientific and clinical expertise, understanding of the legal framework, communication skills, or oversight of development activities? We would like to hear about your experience with scientific regulatory writers and efforts to streamline document development.
About the author:
Dr. Emna El Hammi is a Senior Manager within the scientific writing team at PharmaLex. Emna has broad experience in drug development and provides her writing expertise, supported by her scientific and medical communication background and her knowledge of the regulatory landscape.
[1] Medical writing, regulatory writing basics. https://journal.emwa.org/regulatory-writing-basics/regulatory-writing-basics/
[2] Medical Communicators’ Guide to Regulatory Writing, American Medical Writers Association. https://info.amwa.org/a-medical-communicators-guide-to-regulatory-writing#what_is_regulatory_writing
[3] European Medicines Agency Guidance for Applicants seeking scientific advice and protocol assistance, EMA, Oct 2022. chrome-extension://efaidnbmnnnibpcajpcglclefindmkaj/https://www.ema.europa.eu/en/documents/regulatory-procedural-guideline/european-medicines-agency-guidance-applicants-seeking-scientific-advice-and-protocol-assistance_en.pdf
[4] Formal Meetings Between the FDA and Sponsors or Applicants of PDUFA Products, Guidance for Industry, FDA, Sept 2023. chrome-extension://efaidnbmnnnibpcajpcglclefindmkaj/https://www.fda.gov/media/172311/download
[5] Orphan drug designation in Europe: A booster for the research and development of drugs in rare diseases, Therapies, April 2020. https://www.sciencedirect.com/science/article/abs/pii/S0040595720300081
[6] Electronic Common Technical Document (eCTD), FDA. https://www.fda.gov/drugs/electronic-regulatory-submission-and-review/electronic-common-technical-document-ectd
[7] European Commission. Reform of the EU pharmaceutical legislation. https://health.ec.europa.eu/medicinal-products/pharmaceutical-strategy-europe/reform-eu-pharmaceutical-legislation_en
[8] US FDA. Laws, Regulations, Policies and Procedures for Drug Applications. https://www.fda.gov/drugs/development-approval-process-drugs/laws-regulations-policies-and-procedures-drug-applications
[9] Directive 2001/83/EC of the European Parliament and of the Council of 6 November 2001 on the Community code relating to medicinal products for human use. https://eur-lex.europa.eu/legal-content/EN/ALL/?uri=CELEX:32001L0083
[10] Federal Food, Drug and Cosmetic Act. Chapter V: Drugs and Devices. https://www.fda.gov/regulatory-information/federal-food-drug-and-cosmetic-act-fdc-act/fdc-act-chapter-v-drugs-and-devices#Part_A
[11] Biological Products Regulated Under Section 351 of the Public Health Service Act; Implementation of Biologics License; Elimination of Establishment License and Product License. October 20, 1999. https://www.federalregister.gov/documents/1999/10/20/99-27159/biological-products-regulated-under-section-351-of-the-public-health-service-act-implementation-of
[12] Pediatric Study Plans: Content of and Process for Submitting Initial Pediatric Study Plans and Amended Initial Pediatric Study Plans. Guidance for Industry. July 2020. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/pediatric-study-plans-content-and-process-submitting-initial-pediatric-study-plans-and-amended
[13] Paediatric investigation plans: Templates and forms. European Medicines Agency (EMA). https://www.ema.europa.eu/en/human-regulatory-overview/research-development/paediatric-medicines-research-development/paediatric-investigation-plans/paediatric-investigation-plans-templates-forms
[14] Integrated Summaries of Effectiveness and Safety: Location Within the Common Technical Document. Guidance for Industry. April 2009. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/integrated-summaries-effectiveness-and-safety-location-within-common-technical-document
