Manufacturing and Nonclinical Studies Support for the Development of Therapeutic Biotechnology Products (Biologics) for Neurological-related Disorders
THIS IS NOT A REQUEST FOR PROPOSALS (RFP). THIS IS A PRE-SOLICITATION ANNOUNCEMENT ONLY. A REQUEST FOR PROPOSALS (RFP) NUMBER 75N95022R00013, ENTITLED: “Manufacturing and Nonclinical Studies Support for the Development of Therapeutic Biotechnology Products (Biologics) for Neurological-related Disorders" WILL BE ISSUED VIA SAM ON OR ABOUT January 03, 2023. The National Institutes of Neurological Disorders and Stroke (NINDS) has a need for current Good Manufacturing Practices (cGMP) manufacturing and Good Laboratory Practice (GLP) nonclinical (preclinical) support services to support translational development of therapeutic biotechnology products (Biologics) for National Institutes of Health (NIH) drug discovery and development programs. To that end, several NIH programs are being implemented or expanded to provide support for academic and industry investigators developing medical interventions for neurological disorders. This requirement supports the NIH biologics development projects for the NIH Blueprint Neurotherapeutics Network Biologics (BPN-Biologics) program, the NINDS Ultra-Rare Gene Therapy (URGenT) program, the Helping to End Addiction Long-term Pain Therapeutics Development Program (HEAL-PTDP), as well as other extramural or intramural NIH drug discovery and development programs. The Contractor shall provide support for both Biologics current good manufacturing practices (cGMP) manufacturing and GLP nonclinical services, including execution of the studies and completing study reports and documentation that will enable regulatory filing and evaluation of biological therapeutics in clinical trials for NIH drug development programs. These services may be provided tough a combination of internally executed studies and subcontracted work. Toughout the contract ordering period and awarded task order (TO) periods of performance, the Contractor must maintain the technical capabilities, subcontractor network, minimum resources and organizational compliances with which to successfully perform the range of activities under both Task Area 1: Manufacturing and Task Area 2: Nonclinical Studies. Additionally, unless otherwise requested, any assigned research must be performed in compliance with all current Food and Drug Administration (FDA), and International Committee on Harmonization (ICH) policies, practices, procedures, guidelines and regulations specific to GLP and cGMP, as may be applicable. Data and documentation shall be prepared in a form acceptable to the FDA for inclusion in a Drug Master File (DMF), Investigational New Drug (IND) application, or New Drug Application (NDA). In its own facilities and/or tough its subcontractors, the Contractor shall conduct and/or oversee all manufacturing activities and nonclinical therapeutics evaluation and characterization in appropriate in vitro, in vivo, and/or ex vivo models, including cGMP manufacturing and preclinical IND-enabling and related studies. Nonclinical activities may include, but not are limited to, bioassay development, and/or efficacy studies, and/or absorption, distribution, metabolism, and elimination (ADME) studies, and/or pharmacokinetic (PK) and/or pharmacodynamic (PD) characterization, and/or GLP toxicology studies or other preclinical IND-enabling studies in support of requirements for IND applications. The Contractor shall provide Chemistry, manufacturing, and controls (CMC) and nonclinical study documentation to enable regulatory interactions, IND filing and evaluation of biological therapeutics in clinical trials for NIH drug development programs. The Contractor shall effectively and efficiently manage cost, schedule, and performance under any resultant contract/TOs by using integrated program management processes across all aspects of performance and in a manner that yields cost savings and/or performance efficiencies toughout the execution of all TOs issued to the Contractor. The Contractor shall provide project management for its own core team to ensure project planning, execution, delivery of reports, and accurate and timely communication with the NIH Contracting Officer (CO), Contracting Officer’s Representative (COR), and other stakeholders. The Contractor shall have a designated head Program Manager as the point of contact for the contract. The Contractor shall also provide a project management plan for how subcontracted work will be executed, including, but not limited to, how qualified subcontractors will be identified, how studies will be scheduled to meet NIH timelines, and how subcontractor work will be managed and overseen. The Contractor shall provide project management support for the overall administration of the contract; and development, tracking and management of all TOs issued under the contract. The Contractor’s project management support staff shall work in coordination with designated federal staff and will be responsible for performing all the non-inherently governmental activities associated with administration of the contract. Independently and not as an agent of the Government, the contract awardee(s) shall furnish all the necessary services, qualified personnel, materials, equipment, and facilities, not otherwise provided by the Government as needed to perform the actions outlined in each of the following Task Areas: Task Area 1: Manufacturing - Manufacturing of biological therapeutic modalities required to support BPN-Biologics, URGenT, HEAL PTDP, or other biologics programs includes, but is not limited, to the following categories of biologics: Oligonucleotides, such as antisense oligonucleotide (ASOs), small interfering RNAs (siRNAs), and/or other nucleic acids such as plasmid DNAs for generating viral gene vectors, etc. Viral gene delivery vectors, such as adenovirus-associated viruses (AAV), lentiviruses, retroviruses, herpesviruses, adenoviruses, etc. Purified proteins, including purification of polypeptides from a variety of expression systems including, prokaryotic, mammalian, avian, yeast, insect or plant, and may include protein modifications such as bioconjugation, or other protein modifications Peptides, including those with modified amino acids, structures, or conjugations Antibody-based Biologics, including antibody–drug conjugates (ADCs), bi- and multi-specific antibodies, peptibodies, nanobodies, antibody fragments, etc. Cell-based therapeutics such as iPSC cell line generation, stem cell, mesenchymal stromal cell therapies, ex vivo cellular therapies, chimeric antigen receptor T-cell (CAR-T) modalities, cell banks for bioassays and/or for manufacturing viral vectors, etc. Novel genome-editing modalities, such as clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9, etc. Formulations of biological therapeutics, including common formulations for biologics, and/or liposomes, micelles, polymers, or solid metallic nanoparticle formulations Manufacturing services for the Biologics listed above may include, but are not limited to, the following subtasks: Technology-transfer of an R&D laboratory scale process from a research facility to the Contractor Biological therapeutics manufacturing process development Analytical Methods Development CMC development Small-scale manufacture, scale-up, engineering runs and/or manufacturing under cGMP Formulation and Dosage Form Manufacture and Validation Fill-finish, release testing, stability testing, validation and other associated tasks Task Area 2: Nonclinical Studies – Nonclinical services include conduct of in vitro, in vivo and/or ex vivo studies, as well as the completion of associated nonclinical study reports and documentation that will enable regulatory filing and evaluation of biological therapeutics in clinical trials for NIH drug development programs. Nonclinical studies may include but are not limited to: GLP or non-GLP efficacy testing in in vitro, in vivo or ex vivo models, including modeling neurological disease using patient derived pluripotent stem cells, or in animal models of disease, or in naïve animals, or in ex vivo tissue or small explant cultures GLP or non-GLP ADME studies; PK and PD characterization; toxicology studies including, but not limited to single-dose and/or repeat dose toxicology studies, and/or reproductive toxicology and/or carcinogenicity studies, and/or neonatal and juvenile toxicology studies in small animal, large animal, and/or non-human primate (NHP) models, and Bioassay development and/or assay qualification or validation to support nonclinical or clinical studies. All nonclinical work (GLP and non-GLP) should be conducted in facilities that are GLP capable and compliant, unless a written waiver is given by the COR for work to be conducted in a non-GLP capable facility. The Contractor shall perform in vivo, in vitro and/or ex vivo characterization studies, including, but not limited to, the following: The Contractor and/or subcontractors shall perform efforts associated with planning, conducting, and reporting on approved in vitro and/or ex vivo characterization studies and/or in vivo animal studies (non-GLP and/or GLP), as directed by each individual TO and in accordance with approved protocols. Efficacy testing may include studies with in vitro, in vivo or ex vivo models, including, but not limited to, modeling neurological disease using patient derived pluripotent stem cells, and/or in ex vivo tissue or small explant cultures. The Contractor and/or subcontractors shall assist with a broad range of animal efficacy studies to support preclinical research involving species such as NHP, rodent and/or other small or large mammalian animal models. Support may include acquisition, housing and care of animals; health monitoring and surveillance; procedures in high containment areas; imaging; laboratory animal medicine; sample collection; model development; and immunogenicity, safety and efficacy testing, generate positron emission tomography (PET) and/or other radiolabeled ligands for distribution studies, etc. The Contractor shall perform, as directed by a TO and according to approved protocols, all types of PK and toxicology studies required for advancing an agent into clinical testing. In vivo general toxicology, safety pharmacology and efficacy studies (via oral, intramuscular (IM), intravenous (IV), subcutaneous (SC), intrathecal (IT), ocular, intraperitoneal (IP), or other routes of administration) for IND/Biologics License Applications (BLA)-enabling nonclinical packages) may include, but are not limited to: Non-GLP range finding studies in rodent and non-rodent species Dose ranging and/or maximum tolerable dose (MTD) studies to define the highest dose of a biologic therapeutic that does not cause unacceptable side effects or toxicity. GLP studies in rodent and non-rodent species Single-dose and/or repeat-dose safety pharmacology studies (pulmonary, cardiovascular or other) in relevant species, including the assessment of effects on vital functions, such as cardiovascular, central nervous, renal, gastrointestinal, hepatic, and respiratory systems. These evaluations may be conducted as part of an existing study or in a separate study and must comply with ICH Guidelines. Reproductive toxicology studies Carcinogenesis studies in rodent and non-rodent models Non-GLP and/or GLP efficacy studies in appropriate animal models of neurological diseases Develop (or adapt) and validate appropriate analytical methodology which is sufficiently sensitive, specific, and reproducible to allow measurement and quantitation of assigned test agents and metabolites in body fluids and/or tissues of animals at therapeutic and/or toxic concentrations. Conduct PK studies in animals (e.g. rodent and non-rodent) using various routes of administration (e.g., intravenous, oral, intraperitoneal, subcutaneous, continuous infusion, etc.). Studies will include collection of multiple blood samples by suitable methods to obtain plasma or serum and, in some studies, collection of urine, feces, and tissue samples, including brain. Studies may be for administration of a single compound or for administration of multiple compounds in a cassette dosing format. Use modern modeling software to fit concentration versus time data (for plasma, brain and possibly tissues) to appropriate PK models and calculate relevant PK parameters (e.g., half-life, volume of distribution, area under the curve, clearance, brain to plasma ratio, etc.) for a given agent and route of administration. Calculate systemic bioavailability for various routes (e.g., oral, ip, sc) and determine if bioavailability is dose dependent. Bioassay development and/or assay qualification or validation to support nonclinical or clinical studies may include but is not limited to: Neutralizing antibody assays, including assays to measure neutralizing antibodies to viral vectors such as AAVs or other viral vector modalities used in gene-therapy studies. Enzyme-linked immunosorbent assays (ELISA). Relative potency assays to support release testing of manufactured biologics. Assays that measure the biological activity of a bioactive molecule, including ligand-receptor binding, or signal transduction processes, etc. Human or animal tissue bioassays. Suitable analytical methods to determine concentrations of test agents in biological samples (e.g., plasma, urine, bile, saliva, brain and other tissues). The NINDS anticipates awarding multiple Indefinite Delivery Indefinite Quantity (IDIQ) type contracts to support these programs with an eight-year ordering period to allow for the issuance of fixed-price and cost reimbursement type TOs. It is also anticipated that the IDIQ award will be made in the third quarter of Fiscal Year 2022. Offerors are required to be registered in the System for Award Management (SAM) when submitting an offer or quotation, and shall continue to be registered until time of award, during performance, and tough final payment of any contract, basic agreement, basic ordering agreement, or blanket purchasing agreement resulting from a solicitation. Processing time should be taken into consideration when registering. Offerors who are not registered in SAM should consider applying for registration immediately upon receipt of this pre-solicitation. See FAR 52.204-7 System for Award Management (Oct 2018) and https://www.sam.gov for information on registration. THIS IS NOT A REQUEST FOR PROPOSALS (RFP). RFP No. 75N95022R00013 will be available electronically and may be accessed tough SAM (URL: https://www.sam.gov) 15 or more calendar days after the issuance of this synopsis. THIS SOLICITATION WILL BE AVAILABLE ELECTRONICALLY ONLY. OFFERORS ARE RESPONSIBLE FOR ROUTINELY CHECKING THE SAM WEBSITE FOR ANY POSSIBLE SOLICITATION AMENDMENTS THAT MAY BE ISSUED. NO INDIVIDUAL NOTIFICATION OF ANY AMENDMENTS WILL BE PROVIDED. All responsible sources may submit a proposal, which shall be considered by the agency.
75N95022R00013 Department of Health and Human Services National Institutes of Health National Institute on Drug Abuse
12/2/21, 9:30 AM