SOW Rare Disease Regulatory Operations Support.pdf

Statement of Work

Title: Rare Disease Regulatory Operations Support for the Development of Therapeutic Biotechnology Products

The National Institute of Neurological Disorders and Stroke (NINDS) Extramural and Intramural programs has a need for international Orphan Drug Designation (ODD) Sponsor/Representation, European Medicines Agency (EMA) and international regulatory consultants, and FDA regulatory affairs consultants for rare diseases through subject matter expert (SME) to provide technical recommendations and advice that will support the translational development of novel therapeutics for NIH drug discovery and development extramural and intramural programs. The support included in this contract will cover regulatory support.

Scope of Work

General Requirements:

Independently and not as an agent of the Government, the Contractor shall furnish all the necessary ser vices, qualified personnel, material, equipment, and facilities not otherwise provided by the Governmen t that are needed to support NIH extramural and intramural rare disease programs.

The contractors will provide US-based FDA regulatory support, EU and international regulatory support, and, if necessary, hold an EU Orphan Drug Designation. This support will be provided on an ad hoc basis or while serving on intramural and extramural meetings for Rare Disease programs, as well as HEAL Lead Development Teams (LDTs) and URGENT Multi-Disciplinary Project Teams (MPTs), which include both SME consultants and NIH staff. These teams will develop a clear regulatory strategy with defined milestones aligned with the FDA regulatory requirements and EMA’s orphan drug designation requirements, respectively. This includes navigating the various stages of drug development (preclinical, clinical, and post-approval), handling submissions, maintaining orphan drug status, and ensuring compliance with FDA and EMA criteria for international and EU-specific regulations. Additionally, the teams will establish a comprehensive product development and clinical evaluation research strategy, complete with milestones, while overseeing manufacturing and nonclinical study services provided by Contract Manufacturing Organizations (CMOs) and Contract Research Organizations (CROs).

SME consultants will be expected to provide feedback and guidance on project milestones, development strategy, study design, and data interpretation through in-person meetings, conference calls, and email. Specific consulting responsibilities will depend on the expertise of the individual consultant and the needs of individual biologics projects and programs.

Consultants may be involved in multiple projects.

Specific Requirements:

The contractor shall provide consulting services in the following Performance Area.

Performance Area 1: Regulatory Affairs

Subject Matter Experts in drug discovery and development for rare diseases focusing on FDA, EU and international regulatory affairs when needed. Consultants will be expected to provide senior-level expertise and contribute to feedback and guidance on regulatory aspects of projects to the NIH extramural and intramural programs and to LDT/MPT members through conference calls and by email.

1. Knowledge of FDA and EMA drug discovery and development process.

• Develop policies, program directions, and procedures surrounding the administration of drug research programs ensuring compliance with FDA.

• Develop regulatory strategies that align with the latest international and EMA guidelines for advanced therapeutic medicinal products (ATMPs), rare disease therapies.

• Ensure milestone-driven project management and provided quantitative and qualitative assessments of project progress, adjusting regulatory strategies to expedite product development while ensuring compliance with FDA, EU and international regulations.

• Evaluate regulatory milestones, provided guidance for Investigational New Drug (IND)-equivalent filings such as the Clinical Trial Regulation (CTR) under the EU regulatory framework.

• Monitor the progress of drug development programs, making critical recommendations regarding project continuation based on regulatory reviews and feedback from FDA and EMA consultations.

• Manage milestone-driven research and development projects in the area of rare disease-based therapeutics, which require well-defined goals and objectives achieved with greatest efficiency. Develop and implement quantitative and qualitative reviews of milestones to determine if they appropriately translated into accelerated progress of therapeutic candidates toward Investigational New Drug (IND) applications to the FDA, EMA and/or international regulatory agencies and provided clear indicators of a project's continued success or emergent difficulties.

• In concert with medical writing SMEs, provide comprehensive regulatory strategy and assistance with the preparation of critical designations such as Investigational New Drug (IND)/Clinical Trial application (CTA) applications, and expedited paths like Fast Track and Breakthrough Therapy Designations. Ensure that clients navigate the FDA's complex regulatory framework by leading interactions through Type A, B, C and INTERACT meetings, managing engagements with the Office of Orphan Products Development (OOPD), and handling submissions for rare diseases. Manage the submission of annual reports and facilitate priority review vouchers for medical countermeasures, ensuring all regulatory documents are fully compliant with FDA guidelines, accelerating time to approval.

• Streamline regulatory processes by offering end-to-end support for Orphan Drug Designations, Priority Medicines (P.R.I.M.E.), and Advanced Therapy Medicinal Products (ATMP) classifications. Assist clients through critical early interactions, including pre-submission meetings, scientific advice, and protocol assistance at every stage of development. Facilitate smooth engagement with the FDA, EMA, and other international regulatory bodies. Leverage key meetings with the Innovation Task Force (ITF) and managing post-PRIME interactions. Ensure seamless representation and timely submissions through required portals, enhancing the chances of expedited approvals and regulatory success.

• For Orphan Drug Designation support:

i. Collaborate with internal and external stakeholders, including nonclinical, clinical, and CMC teams, to ensure cross-functional alignment with ODD regulatory requirements.

ii. Ensure regulatory strategies are integrated with broader drug development plans, including fast-tracking and priority designation requests where applicable.

iii. Leverage multi-disciplinary expertise to advise on the overall orphan drug strategy, including opportunities for accelerated approvals (e.g., PRIME designation) and other expedited programs.

iv. Provide expert regulatory advice on ODD application feasibility, guiding clients through strategic planning, evaluation of orphan criteria, and submission readiness.

v. Lead early interactions with EMA, including pre-submission meetings and protocol assistance to facilitate efficient regulatory approvals.

vi. Develop comprehensive regulatory strategies that align with EMA’s orphan drug regulations, ensuring that all development milestones support the eventual marketing authorization.

vii. Actively engaged with EMA’s Innovation Task Force (ITF) and provide support for scientific advice meetings at all stages of development.

viii. Prepared clients for meetings with EU regulatory bodies, including the development of briefing documents, presentation materials, and strategy reviews.

2. Ability to analyze and evaluate milestones to manage a drug development program.

• Develop project plans and associated communications documents. Manage the day-to-day activities of assigned Programs and Projects; direct and manage project development from beginning to end; and estimate the resources needed to achieve Program and Project goals. Manage key relationships internal and external to an organization.

• Review, analyze, and evaluate pre-clinical drug development data.

• Provide an in-depth review, analysis, evaluation, and recommendation of milestones at the beginning of a funding year or funding cycle (depending on the Program or Project) to support a determination as to whether a project should be continued. This in-depth review included assessment and recommendations to ensure that individual projects were competitively evaluated against the broader research landscape.

3. Skill in applying Project Management tools to manage drug discovery and development programs.

• Ensure that projects are managed and executed in line with the rules and governance of an organization and cognizant regulating bodies.

• Prepare a variety of routine and special reports as requested by senior management. Research and prepared reports, briefing materials, and other compilations of Program and Project activities and policies for use in policy development, program planning, evaluation and implementation, and presentation to senior advisors. Research and wrote scientific review presentations, position papers, talking point papers, and briefing materials for senior staff as requested.

• Define project objectives; plan, execute, and finalize projects according to strict deadlines and within budget; oversaw quality control, assemble data, and managed program budgets.

4. Ability to communicate clearly, logically and persuasively on complex scientific issues.

• Develop and deliver progress reports, proposals, requirements documentation, and presentations.

• Build and develop relationships vital to the success of a Program or Project to establish worldwide collaborative relationships among government, academia, and industry that are focused on the search for therapeutic interventions and treatments for neurological disorders.

• Work in a virtual, cross-functional team environment and manage competing priorities.

• Participate actively in project team discussions.

Performance Area 2: Medical Writing

Medical Writing consultants shall be responsible for the preparation and submission of high quality regulatory and other supporting documents for NIH projects. The consultants shall coordinate with project teams to prepare, edit, review, and submit documents to regulatory agencies (e.g., FDA and EMA) within project timelines. Documents may include but are not limited to clinical protocols, Investigational New Drug applications (INDs), Investigator Brochures (IBs), IND Amendments, Drug Master Files, and Statement of Investigators (Form FDA 1572), drug dossiers, Clinical Trial Applications, Fast Track and Breakthrough Therapy Designations, Orphan Drug Designations, meeting packages (Types A, B, C,D and INTERACT).

The role of the Medical Writing consultant may include but is not limited to the following responsibilities and tasks:

• 1. Work independently or as part of a team to gather, compile, write, and edit regulatory documents for submission to regulatory agencies.

2. Ensure that submissions meet format and content requirements applicable to FDA requirements in compliance with ICH guidelines.

3. Manage timelines for regulatory submissions.

4. Work independently to complete assigned projects.

5. Maintain familiarity with current best industry practices and regulatory requirements that affect medical writing.

6. Review and perform quality control (QC) on other documents as part of the overall clinical research process.

7. Manage timelines for dossier submissions.

8. Work independently to complete assigned projects.

9. Maintain familiarity with current best industry practices and regulatory requirements that affect drug dossier development.

10. Write, review, and provided feedback on the preparation of critical designations such as

Investigational New Drug (IND)/Clinical Trial application (CTA) applications, and expedited paths like Fast Track and Breakthrough Therapy Designations. Ensure that clients navigate the FDA's complex regulatory framework by leading interactions through Type A, B, C, D and INTERACT meetings, managing engagements with the Office of Orphan Products Development (OOPD), and handling submissions for rare diseases. Manage the submission of annual reports and facilitate priority review vouchers for medical countermeasures, ensuring all regulatory documents are fully compliant with FDA guidelines, accelerating time to approval.

11. Provide all of the above for documents, meetings and designations for international regulatory bodies, such as the EMA.

12. For Orphan Drug Designations requiring writing: Author and review all regulatory documents related to the ODD process, including but not limited to the ODD applications, IMPD, and associated regulatory submissions. Ensure that all submissions are prepared in accordance with EMA's regulatory guidelines and delivered through appropriate portals (e.g., IRIS, eCTD).

Manage lifecycle maintenance of the orphan designation, including document updates, submissions of amendments, and responses to queries from regulatory agencies.

Performance Area 3: Orphan Drug Designation (ODD) Sponsor/ Representation

The contractor shall serve as an EU and international Orphan Drug Designation (ODD) sponsor and provide representation services for clients seeking ODD status. The following tasks and responsibilities outline the contractor's role in ensuring effective management and interaction with EU and international regulatory bodies, particularly the European Medicines Agency (EMA), to secure and maintain ODD status for drug candidates. It is anticipated that up to 5 ODDs will be held by the contractor each year during the POP.

1. EU Orphan Drug Designation Management and Compliance

• Serve as the designated EU sponsor for Orphan Drug Designation (ODD) applications on behalf of the client.

• Advise on clinical trial applications (CTAs), provided scientific advice procedures, and helped in obtaining regulatory feedback from EU health authorities.

• Lead regulatory projects from initiation through to EMA submissions, ensuring adherence to timelines, budgets, and the EU’s complex regulatory framework.

• Coordinated post-designation requirements, such as Orphan Drug Annual Reports (ODAR), to be submitted via EMA’s IRIS system.

• Monitor regulatory timelines and provide strategic advice to ensure compliance with ongoing obligations related to orphan designation, including annual updates and renewals.

• Ensure the sponsor's responsibilities are upheld until the ODD status is transferred to a new legal entity or sponsor, if applicable.

2. Communication and Regulatory Interaction

• Act as the primary regulatory contact for EMA on behalf of the client for all ODD-related matters.

• Provide clear and concise regulatory communication to clients regarding the status of ODD applications, EMA feedback, and ongoing obligations.

• Ensure all interactions with health authorities are properly documented, with copies of all final correspondence shared with the client for transparency.

• Ensure annual reporting on the development status of orphan-designated medicines is submitted on time and accurately reflects the progress in line with EMA expectations.

• Continuously monitor regulatory developments and update the client on any new requirements or opportunities that may impact their orphan drug designation.

SME Requirements

Performance Area 1: General Requirements (Regulatory Expert):

Required Experience and Expertise:

a. A MS, PhD, or MD in a relevant scientific discipline is preferred. If a BS or MS, PhD-level experience in biopharmaceutical industry is required.

b. Must have at least 10 years of relevant professional experience

c. Must have at least 10 years demonstrated experience in biologics product development

d. At least 10 years of experience in managing or being a senior leader in regulatory strategy.

e. At least 5 years of experience in supporting rare and/or ultra-rare biologics product development programs

f. Experience interacting with the FDA and international regulatory authorities

g. Demonstrated senior-level oversight of research and development efforts for therapeutic products of both the US, EU and international regulatory process for rare disease therapy products, including both early-stage and late-stage development.

h. Managed a portfolio of preclinical drug discovery and development projects (e.g., cooperative agreements) in the area of rare disease-based therapeutics (including but not limited to e.g.

peptides, proteins, antibodies, oligonucleotides, gene and cell therapies) with responsibility for all aspects of administration (i.e., organizing and managing). Secured and implemented scientific advice from senior leaders and colleagues and applied drug discovery and development expertise.

i. Have managed a portfolio of comprehensive, milestone-driven pre-clinical drug development rare disease-based therapeutics projects; planned, organized and directed inter-disciplinary drug research or development team efforts in line with US, EU and international regulatory standards.

j. Experience in team leadership, consulting, or service on strategic and advisory boards

k. Broad experience across the entire rare disease discovery and development process within the context of US, EU and international regulations processes especially desired.

l. Must have experience working with multi-disciplinary teams at a senior level preferably in the biopharmaceutical industry, especially teams with members from outside organizations and members at various management levels.

Preferred Experience and Expertise:

m. Expertise in Pediatric Investigation Plans (PIP), IMPD submissions, and clinical trial applications.

n. Has experience in team leadership, consulting, or service on strategic and advisory boards.

o. A significant track-record of scientific accomplishment as evidenced by publications and/or contributions to the development of marketed products.

p. Experience with biologics development for nervous system conditions is preferred but not required

q. At least 10 years of experience in supporting rare and/or ultra-rare biologics product development programs

Performance Area 2: General Requirements (Medical Writer Expert)

Required Experience and Expertise

• Proven experience in writing for scientific journals, regulatory submissions, clinical study reports (CSRs), or other medical documents.

• At least 5 years’ experience writing documents such as clinical trial protocols, investigator brochures, informed consent forms, clinical study reports, and regulatory submissions (e.g., IND, NDA, BLA for FDA or EMA submissions) is crucial for regulatory medical writers.

• Familiarity with medical terminology, drug development processes, and guidelines for medical writing such as ICH-GCP (International Council for Harmonisation – Good Clinical Practice) guidelines.

• Organizational skills to handle multiple writing projects simultaneously, often under tight deadlines.

• Understanding regulatory guidelines (FDA, EMA, ICH) and other compliance requirements in medical writing, such as handling sensitive data (HIPAA compliance) or adhering to ethical guidelines for publication (e.g., avoiding plagiarism or ghostwriting).

• Familiarity with country-specific drug approval processes and regulatory requirements for clinical trials and product marketing.

• Familiarity with software like Microsoft Word, EndNote, and citation management tools, as well as specialized medical writing platforms.

• Excellent interpersonal, written, and verbal communication skills including the ability to effectively communicate with project teams and to lead virtual meetings to discuss documents.

• Familiarity with Electronic Common Technical Document (eCTD) format and other formats expected by international regulatory bodies

Preferred Experience and Expertise

• Additional Certification (Optional): Certifications such as those from the American Medical Writers Association (AMWA), European Medical Writers Association (EMWA), or the Regulatory Affairs Certification (RAC)

• Prior experience in medical communications, pharmaceutical companies, or CROs

• Experience with peer-reviewed articles, white papers, abstracts, or scientific posters

Performance Area 3: General requirements (ODD sponsor/representation)

Required Experience and Expertise

1. Be legally established in the European Economic Area (EEA) to hold the Orphan Drug Designation. If the applicant is located outside of the EEA, they must appoint a legal representative within the EU to act on their behalf for regulatory purposes.

2. Have a comprehensive understanding of EU/EMA and international regulatory processes, particularly concerning orphan drugs, including knowledge of the Orphan Regulation (EC) No 141/2000. This includes familiarity with EMA requirements, submission of Orphan Drug Designation (ODD) applications, and navigating processes such as scientific advice and protocol assistance.

3. Must be able to compile and submit the orphan drug designation application and be equipped to handle post-designation obligations, such as submitting annual reports on the status of development and complying with any requests from the EMA during the marketing authorization process.

4. Must possess scientific knowledge in the area of orphan drug development, including the ability to provide strategic advice on regulatory submissions, clinical development, and the generation of required documentation (e.g., Investigational Medicinal Product Dossier (IMPD).

5. Facilitate ongoing communication with the EMA and relevant EU Member State health authorities, including participation in meetings such as scientific advice sessions, protocol assistance meetings, and pre-submission interactions.

6. At least 5 years’ experience managing technical submissions via the EMA’s IRIS system, ensuring proper documentation and data management protocols are followed for orphan drug applications and related regulatory procedures.

7. At least 5 years’ experience preparing and submitting documentation for Orphan Drug Designation (ODD), Investigational Medicinal Product Dossiers (IMPD), and Marketing Authorization Applications (MAA) to the EMA on behalf of another entity.

Period of Performance:

The NIH anticipates needing one vendor during this time.

The period of performance (POP) for this contract will total 3 years as follows:

Base Period: Tentative Start Date – 21 September 2026 – September 2027

Option Period 1: September 2027 – September 2028

Option Period 2: September 2028 – September 2029

Place of Performance:

The primary place of performance will be the Contractor site. Conference calls and email will be the primary mode of communication; however, the Contractor may be required to work at Government facilities or the facilities of selected principal investigators on an as needed basis.