Chemistry, Manufacturing and Controls and Related Services for Development of Drug Products

Chemistry, Manufacturing and Controls and Related Services for Development of Drug Products Classification Code/Title: AN12 - Health R&D Services; Health care services; Applied Research NAICS Code/Title: 325412 – Pharmaceutical Preparation Manufacturing Related Notice: Presolicitation Notice ID PS75N95023R00037, Chemistry Manufacturing and Controls and Related Services for Drug Products, published May 30, 2023. Purpose of Notice: This is a Research and Development (R&D) Small Business Sources Sought notice. This is NOT a solicitation for proposals, proposal abstracts, or quotations. The purpose of this notice is to obtain information regarding the availability and capability of Small Business sources to perform a potential R & D requirement. The purpose of this notice is to obtain information regarding: (1) the availability and capability of qualified small business sources; (2) whether they are small businesses; HUBZone small businesses; service-disabled, veteran-owned small businesses; 8(a) small businesses; veteran-owned small businesses; woman-owned small businesses; or small disadvantaged businesses; and (3) their size classification relative to the North American Industry Classification System (NAICS) code for the proposed acquisition. Your responses to the information requested will assist the Government in determining the appropriate acquisition method, including whether a set-aside is possible. An organization that is not considered a small business under the applicable NAICS code should not submit a response to this notice. This notice is issued to help determine the availability of qualified companies technically capable of meeting the Government requirement and to determine the method of acquisition. It is not to be construed as a commitment by the Government to issue a solicitation or ultimately award a contract. Responses will not be considered as proposals or quotes. No award will be made as a result of this notice. The Government will NOT be responsible for any costs incurred by the respondents to this notice. This notice is strictly for research and information purposes only. The Government will not entertain questions regarding the results of this market research. Background: The Therapeutic Development Branch (TDB) within the Division of Preclinical Innovation (DPI) at the National Center for Advancing Translational Sciences (NCATS) within the National Institutes of Health (NIH) conducts translational research to support therapeutic development by moving small molecule and biologic drug candidates forward in the drug development pipeline. Upon reaching predetermined milestones, TDB hands off clinical candidates to external partners to bring these novel therapies to patients. In addition to developing new candidate drugs, TDB seeks to advance the entire field of drug discovery and development by encouraging scientific and technological innovations aimed at improving success rates in the crucial preclinical stage of drug development. The TDB model is to operate as a comprehensive small molecule and biologics drug development organization, moving therapeutic candidates through each phase of the preclinical development process until an Investigational New Drug (IND) application is filed with the US Food and Drug Administration (FDA). For certain drug development campaigns, TDB will support studies up to human Phase IIb. TDB conducts drug development through collaborations, with therapeutic candidates originating from academia, industry, non-profit foundations, or internally from NCATS and other NIH institutes. TDB's operational strategy is to combine the capabilities of in-house staff and collaborative partners with complementary support from contract research organizations (CROs). Each development program operates in a multi-disciplinary matrix team environment, with NCATS responsible for overall planning and execution. The scope of this requirement is Chemistry, Manufacturing, and Controls and Related Services for Development of Drug Products. The objective of these support services is to ensure receipt of Drug Products (DP) of sufficient quality and quantity to support preclinical, IND-enabling and clinical studies. The NCATS has an existing multiple-award IDIQ contract for Drug Product Development and Manufacture. This potential procurement would be a re-competition (ramp-on) of this existing contract. Purpose and Objectives: The purpose of this Small Business Sources Sought is to obtain information about Small Business capabilities to support the DPI drug development programs by providing Chemistry, Manufacturing, and Controls (CMC) services; provide support for a broad range of preclinical services required for the design, development, manufacture, and release of DP as Clinical Trial Material (CTM), including precursors, preliminary states, Reference Standards (RS) and all required testing. Ancillary products (e.g., placebos, diluents, adjuvants, master cell banks, testing standards, reference materials) and other materials manufactured or purchased to support clinical trials or CMC activities may also be required. All activities preliminary to manufacturing in accordance with current Good Manufacturing Practice (cGMP) may be required (e.g., development or engineering lots, formulation studies), even without an associated cGMP manufacturing task. All activities required to maintain material in a usable state, including storage, shipping, testing (in process, release, stability, and quality actions), and preparation of documents to support regulatory submissions may also be required. Product formats may include small molecules, short oligomeric compounds, biological (large) molecules, quaternary molecular assemblies (homogenous or heterogenous), vectors for gene therapy, nanoparticles, and any of the above modified genetically, biologically, or chemically. Novel formats identified after this draft might also be needed. Formats could also include Devices or Combination Products. Project Requirements: The potential acquisition is anticipated to be a multiple-award Indefinite Delivery / Indefinite Quantity (IDIQ) contract for Chemistry, Manufacturing, and Controls and Related Services for Development of Drug Products. The current IDIQ contract(s) has three separate technical areas: Technical Area 1: Formulation Development, Manufacture and Analysis of Small Molecule Drug Products; Technical Area 2: Formulation Development, Manufacture and Analysis of Synthetic Peptides, Oligonucleotides, and Related Substances; and Technical Area 3: Formulation Development, Manufacture and Analysis of Biopharmaceutical and Gene Therapy Drug Products. The anticipated IDIQ contract(s) may be awarded under one or more technical areas. The contractor shall be compliant with applicable domestic or international regulations. These may include, but are not limited to, one or more of the following: US FDA current Good Manufacturing Practice (cGMP), Good Laboratory Practice (GLP) and Good Clinical Practice (GCP) regulations, and/or International Council for Harmonisation (ICH) and International Organization for Standardization (ISO) regulations. The contractor shall provide biohazard, environmental and occupational health safety, emergency management/preparedness, security, transportation and logistics services. All work with hazardous biological materials shall comply with all applicable regulations. Anticipated period of performance: The IDIQ contract(s) currently have a seven-year ordering period. Task orders issued under the IDIQ contract(s) will have a shorter period of performance. It is estimated that the remaining ordering period will be approximately six years. Information Requested: Vendors should provide a capability statement that addresses their capability and experience in one or more of the below technical areas. Vendors may provide a capability statement in one area, two areas, or all three areas. Vendors with prior, similar experience should clearly demonstrate that experience and include information on the size and scope of that experience. If prior experience was gained with the Government as a prime or subcontractor, describe the size and scope of the work and provide the contract number. Capability statements should address each point listed under the applicable technical area(s). Capability statements must address the specific technical area(s) and points in this Notice; general capability statements will not be reviewed. Vendors seeking to respond to this Notice as part of a teaming arrangement should include the requested information from each vendor in the proposed team. Technical Area 1: Formulation Development, Manufacture and Analysis of Small Molecule Drug Products I. The Contractor shall perform activities related to the formulation development, manufacture and analysis of small molecule drug products. II. Anticipated activities related to the formulation development and manufacture of small molecule drug product include, but are not limited to, the following: a. Perform technology transfer from the Government or its collaborators, and route familiarization. b. Perform formulation development studies and define final formulation. c. Perform pre-formulation studies based on the targeted dosage form. d. Conduct formulation development studies based on the targeted dosage form. e. Determine critical/key process parameters and optimize final formulation using Design of Experiments (DoE) f. Perform process demonstration runs. g. Perform cost analysis. h. Manufacture non-GMP DP of sufficient quality and in quantities necessary to meet the needs of preclinical studies, typically 500 to 5,000 units. i. Manufacture DP under cGMP, of sufficient quality and in quantities to support clinical studies, typically 1,000 to 10,000 units. III. Anticipated activities related to the analysis of small molecule drug products include, but are not limited to, the following: a. Develop necessary in process control (IPC) methods for manufacture of DP. b. Validate analytical and stability-indicating, dosage-specific analytical methods (e.g., dissolution method for capsule dosage form). c. Identify, isolate, and characterize impurities and degradation products. d. Develop release specifications. e. Perform all tests necessary to release DP for clinical use, including issuing a certificate of analysis (COA). f. Establish stability protocols with proper specifications for DP and perform stability studies up to 24 months (minimum) per guidelines published by the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH). g. Perform clinical simulation studies of the intended administration of DP to humans. IV. Anticipated activities considered ancillary to the formulation development, manufacture and analysis of small molecule drug products include, but are not limited to, the following: a. Deliver study reports, including but not limited to weekly status update reports, summary development reports, analytical methods development and qualification/validation protocols and reports, Master Batch report, GMP campaign report, and CMC report in the common technical document (CTD) format utilized for regulatory submissions to the FDA. b. Conduct bi-weekly or weekly (as required) project update teleconferences. c. Perform technology transfer from/to a third party when required. d. Store non-GMP and GMP lots of Reference Standard (RS), Drug Substance (DS) and DP. e. Ensure compliance with cGMP. f. Maintain quality systems to support cGMP activities. g. Provide quarterly cost schedule and performance reports. Technical Area 2: Formulation Development, Manufacture and Analysis of Synthetic Peptides, Oligonucleotides, and Related Drug Products I. The Contractor shall perform activities related to the formulation development, manufacture and analysis of synthetic peptides, oligonucleotides, and related drug products. II. Anticipated activities related to the formulation development and manufacture of synthetic peptides, oligonucleotides, and related substances include, but are not limited to, the following: a. Perform technology transfer from the Government or its collaborators, and route familiarization. b. Perform pre-formulation studies based on the targeted dosage form. c. Conduct formulation development studies based on the targeted dosage form. d. Perform formulation development studies and define final formulation. e. Determine critical/key process parameters and optimize final formulation using Design of Experiments (DoE) f. Perform process demonstration runs. g. Perform cost analysis. h. Manufacture non-GMP DP of sufficient quality and in quantities necessary to meet the needs of preclinical studies, typically 500 to 5,000 units. i. Manufacture DP under cGMP, of sufficient quality and in quantities to support clinical studies, typically 1,000 to 10,000 units. III. Anticipated activities related to the analysis of synthetic peptides, oligonucleotides, and related substances include, but are not limited to, the following: a. Validate analytical and stability-indicating methods. b. Perform forced degradation studies. c. Identify, isolate, and characterize impurities and degradation products. d. Develop release specifications. e. Perform all tests necessary to release DP for clinical use, including issuing a COA. f. Establish stability protocols with proper specifications for DP and perform stability studies up to 24 months (minimum) per ICH guidelines. g. Perform clinical simulation studies of the intended administration of DP to humans. IV. Anticipated activities considered ancillary to the manufacture and analysis of synthetic peptides, oligonucleotides, and related substances include, but are not limited to, the following: a. Deliver study reports, including but not limited to weekly status update reports, summary development reports, analytical methods development and qualification/validation protocols and reports, forced degradation study protocols and reports, Master Batch reports, GMP campaign reports, and CMC report in CTD format. b. Conduct bi-weekly or weekly (as required) project update teleconferences. c. Perform technology transfer from/to a third party when required. d. Store non-GMP and GMP lots of RS, DS and DP. e. Ensure compliance with cGMP. f. Maintain quality systems to support cGMP activities. Technical Area 3: Formulation Development, Manufacture and Analysis of Biopharmaceutical and Gene Therapy Drug Products I. The Contractor shall perform activities related to the formulation development, manufacture and analysis of biopharmaceutical and gene therapy drug products. II. Anticipated activities related to the manufacture and analysis of biopharmaceuticals and gene therapies include, but are not limited to, the following: a. Analytical method development: o Develop, qualify and/or validate analytical methods, per ICH guidelines. o Perform characterization of Drug Substance (DS) and Drug Product (DP) for identity, content, purity, potency and safety. o Develop release specifications. b. Formulation development studies: o Perform excipient screening, optimize, and develop final formulation buffer for liquid formulation and lyophilization protocol for lyophilized DP. o Perform accelerated stability studies. o Define container closure and fill finish strategy. c. Manufacturing under current Good Manufacturing Practices (cGMP): o Manufacture Master Cell Banks and perform cryo-storage (expected to be not less than 300 vials per candidate). o Conduct viral clearance validation studies. o Manufacture cGMP lots of DP (including fill finish, in amounts determined per TO) to support clinical studies, typically 1,000 to 10,000 units. o Perform all tests necessary to release DP for clinical use, including issuing a COA. o Perform stability evaluation of DP, per ICH guidelines. III. Anticipated activities considered ancillary to the manufacture and analysis of biopharmaceuticals and gene therapies include, but are not limited to, the following: a. Deliver study reports, including but not limited to weekly status update reports, summary development reports, analytical methods development and qualification/validation reports, executed cGMP batch records, a CMC report in CTD format. b. Conduct bi-weekly or weekly (as required) project update teleconferences. c. Perform technology transfer from/to a third party when required. d. Store non-GMP and GMP lots of RS, DS and DP. e. Ensure compliance with cGMP. f. Maintain quality systems to support cGMP activities. Response Instructions: Responses are required no later than 10:00am Eastern Time on July 21, 2024. Responses must be submitted via email to [email protected] and should include the following: a. Capability statement that addresses one or more technical areas AND the overall technical requirements as applied to each technical area in the capability statement. b. Cover Page that includes the following: • DUNS • Company Name • Company Address • Company Point of Contact, Phone, and Email address • NAICS code under which the company conducts business as a small business • Company Size / Socio Economic status (e.g., small business, 8(a), woman owned, veteran, etc.) - validated via SAM • State whether your organization uses any proprietary technology for any of the activities described for Technical Areas 1, 2, or 3. If so, clarify whether NCATS and NCATS’ collaborators will have freedom to use the technology at a third-party facility in the event the project is later transferred to a third party. • State whether there are any classes of scheduled compounds or hazardous reagents / reactions your organization is unable to handle due to regulation or safety limitations. • Acknowledgment of compliance with FAR Clause 52.219-14. As noted below, FAR Clause 52.219-14 will apply to any portion of the acquisition that is set aside for Small Business. Respondents must acknowledge they will comply with this clause if they are awarded an IDIQ contract under a set-aside. Respondents who fail to acknowledge this will be deemed not capable for the purposes of this Small Business Sources Sought. Disclaimer and Important Notes: This notice does not obligate the Government to award a contract or otherwise pay for the information provided in response. The Government reserves the right to use information provided by respondents for any purpose deemed necessary and legally appropriate. Any organization responding to this notice should ensure that its response is complete and sufficiently detailed to allow the Government to determine the organization’s qualifications to perform the work. Respondents are advised that the Government is under no obligation to acknowledge receipt of the information received or provide feedback to respondents with respect to any information submitted. After a review of the responses received, a pre-solicitation synopsis and solicitation may be published in SAM. However, responses to this notice will not be considered adequate responses to a solicitation. If any portion of the potential acquisition is set aside for Small Business, FAR Clause 52.219-14, Limitations on Subcontracting, will apply to the portion that is set aside. This clause states the prime Small Business contractor cannot subcontract more than 50% of the work to a non-similarly situated entity. The full text of the clause is available at https://www.acquisition.gov/far/part-52#FAR_52_219_14. To enable Contributors to retain control of the intellectual property for compounds created under the anticipated IDIQ contracts, the Government has an executed Declaration of Exceptional Circumstances (DEC) to the Federal Acquisition Regulations (FAR) for this program. Confidentiality: No proprietary, classified, confidential, or sensitive information should be included in your response. The Government reserves the right to use any non-proprietary technical information in any resultant solicitation(s).