SOURCES SOUGHT
A -- CRO Support for NCATS Drug Product Development and Manufacture
- Notice Date
- 1/22/2016
- Notice Type
- Sources Sought
- NAICS
- 325412
— Pharmaceutical Preparation Manufacturing
- Contracting Office
- Department of Health and Human Services, National Institutes of Health, National Institute on Drug Abuse, 6001 Executive Boulevard, Room 4211 - MSC 9559, Bethesda, Maryland, 20892, United States
- ZIP Code
- 20892
- Solicitation Number
- HHS-NIH-NCATS-SBSS-16-003
- Archive Date
- 3/2/2016
- Point of Contact
- Jeffrey Schmidt, Phone: (301) 402-1488, Lisa V. Bielen, Phone: 301.451.7167
- E-Mail Address
-
schmidtjr@mail.nih.gov, lisa.bielen@nih.gov
(schmidtjr@mail.nih.gov, lisa.bielen@nih.gov)
- Small Business Set-Aside
- N/A
- Description
- This is a 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: (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. Please note that to qualify as an eligible small business for purposes of a small business set-aside, at least 50% of the cost of contract performance incurred for personnel must be expended for employees of the small business awardee (see FAR 52.219-14 Limitations on Subcontracting). Background Researchers nationwide and across the globe face common barriers in translational research that can delay the development of new interventions for patients in need. The National Center for Advancing Translational Sciences (NCATS) at the National Institutes of Health (NIH) studies translation on a system-wide level as a scientific and operational problem to accelerate the development of treatments and preventive strategies for a wide range of diseases. Within NCATS, the Division of Pre-Clinical Innovation (DPI) plans, conducts and uses both internal and contract resources to advance collaborative research projects across the pre-clinical phases of the translational science spectrum. Contract research organizations (CROs) provide manufacturing, pharmacology, toxicology, regulatory and clinical operations services to DPI to assist with probe and assay development, lead selection and optimization, and Investigational New Drug (IND)-directed studies. Purpose and Objectives The objective of the Translational Research Chemistry, Manufacturing, and Control (TRCMC) Program is to ensure the delivery of active pharmaceutical ingredients (API) and formulated drug product (DP) of identity, strength, and quality suitable for testing in preclinical and clinical studies in support principally of the Treatment of Rare and Neglected Diseases (TRND) Program and the Bridging Interventional Gaps Program (BrIDGs). Note: no human subject testing is to be performed under this contract. Project Requirements Written capability statements should demonstrate your organization's ability and related experience in one or more of the following separate Technical Areas: (1) Development, Manufacturing and Stability studies of non-sterile dosage forms; and (2) Development, Manufacturing and Stability studies of sterile dosage forms. If your organization has capabilities in both of the listed Technical Areas, your response must separately describe the organization's ability and related experience for each separate Technical Area. Technical Area (1) Development, Manufacturing and stability studies of non-sterile dosage forms Written capability statements should demonstrate your organization's ability and related experience in the formulation, analytical, and other tasks listed below. Note: Synthesis of the small molecule active pharmaceutical ingredient (API), synthesis of peptides and oligonucleotide APIs, or preparation of the Biopharmaceutical API are not part of this Task Area. Also, polymorph screening and selection of appropriate solid state form as well as salt screening and selection of appropriate salt form are also not part of this Task Area. Formulation: - Transferring, qualifying and modifying, if necessary, the stability indicating method for the API to determine drug content and impurities in the drug product. - Carrying out excipient compatibility studies with the AP. - Development of a suitable dissolution test for the drug substance in the drug product. - Performance of solubility studies of the API if requested in water miscible organic solvents, surfactant solutions and with complexing agents, etc. - Using data acquired from excipient compatibility studies and the developed dissolution method as well as any other data provided from NCATS, select appropriate drug formulas, and develop manufacturing processes for solid oral dosage forms (e.g. capsules or tablets) and other non-sterile formulations: oral solutions, oral suspensions, topical solutions, creams, and ointments. - Carrying out short term stability studies of formulations manufactured on pilot scale over 3-6 months; monitoring the dosage form(s) for drug content, degradation products, and appearance. Solid oral dosage forms will also be monitored for impact on dissolution on stability. - Development of a placebo formulation of the drug product that is similar in appearance to the formulation containing active drug substance. - Micronization of the drug substance may be infrequently required. Should this capability be needed, describe how micronization will be carried out and impact on quality and performance assessed. - Control of impurity profile in the drug product. - Cost analysis in the selection of appropriate formulation. - Development of Self Emulsifying Drug Delivery systems (SEDDS) is anticipated with selected projects. - Distribution of SEDDS formulations into hard gelatin or hydroxypropyl methylcellulose capsules. - Preparation of master batch production records for active and for placebo. - Manufacture of drug products for Phase I/II clinical trials. Batch sizes are expected to be 3,000-10,000 units/batch of solid oral or SEDDS formulations, 15-50 L of oral liquid or suspension formulations, and 3-10 kg of topical formulations packaged in units of 5-15 g. Analytical: - Development and validation of analytical methods. Modifying the analytical method for drug substance and impurities in the presence of excipients to demonstrate recovery of the API from the excipient mixture in non-sterile formulations. Note: methods are to be suitable for assay of active ingredient and impurities/degradants in drug products over a concentration range of active ingredient of at least 8 fold. - Identification of impurities and degradation products in drug formulations - Development of specifications for drug product(s) and placebo - Preparation of certificates of analysis for active and placebo drug products - Evaluation of drug product(s) and placebo stability per ICH guidelines - Release testing of drug substance, excipients, packaging components and labels, - In process and final product testing of pilot scale and clinical supplies of drug products (assay, impurities, appearance and dissolution) and placebo formulations (absence of active). - Carry out studies to demonstrate effective cleaning of equipment used in manufacture of drug products. Other: - Packaging and labeling of drug products and placebo. Active and placebo formulations will be labeled as to content. Randomization will be done at the clinical site pharmacy. - Coded labeling at the drug product manufacturing site is not anticipated. - Delivery of study reports, including CMC report in CTD format - Technology transfer (when required) - Storage of non-GMP and GMP lots of API and Drug product for ≥6 mo.is anticipated. - Low temperature storage of API and drug products is anticipated. - Compliance with cGMP - Maintaining Quality systems to support cGMP activities Technical Area (2) Development manufacturing and stability studies of sterile dosage forms Written capability statements should demonstrate your organization's ability and related experience in the formulation, analytical, and other tasks listed below. All formulations are anticipated to be sterilized by 0.2 μm filtration. Some projects could involve non-aqueous solutions. Note: Synthesis of the small molecule active pharmaceutical ingredient (API), synthesis of peptides and oligonucleotide APIs or preparation of the Biopharmaceutical API are not part of this Technical Area. Also, polymorph screening and selection of appropriate solid state form as well as salt screening and selection of appropriate salt form are not part of this Technical Area. Formulation: - Transferring, qualifying and adapting, if necessary, the stability indicating method for the drug substance to determine content of drug substance and impurities in the drug product. - Determining the pH vs. stability behavior of the drug substance over a range of pH. - Determining the pH vs. solubility behavior of the drug substance over a range of pH. - Examining approaches to increase the solubility of the drug substance in vehicle systems suitable for the intended route of administration: intravenous, intramuscular, subcutaneous, inhalation or ophthalmic. - Development and manufacture sterile liquid and sterile freeze dried formulations. - Optimization of the formula by including excipients to yield a formulation with acceptable solubility, osmolality, pH and stability for the intended route of administration. - If drug candidate's properties do not permit a liquid formulation, development of a suitable freeze dried formulation and cycle to yield rapid reconstitution, acceptable product appearance and low moisture. - Determining compatibility of the drug formulation with product contact materials (filters, vessels, mixers, tubing, filling equipment) and packaging equipment both during drug manufacturing and under simulated use conditions: syringes, infusion fluids and tubing, etc., and nebulizers used for inhalation of sterile solution drug products. - Carrying out studies to evaluate the antimicrobial properties of the drug product: method suitability test for sterility (USP <71>), enhancement inhibition tests of the bacterial endotoxin test (USP <85>) and the USP antimicrobial effectiveness test (<51> for multidose formulations. - Filtering integrity test (bubble point determination) is carried out on all manufactured batches. - Using the results from the studies listed above, to develop a manufacturing process for the drug product and demonstrate its suitability by assessing its stability short term using stress conditions (e.g. heat, humidity). - Developing a placebo formulation of the drug substance and demonstrate its acceptability for manufacture. Batch size is expected to be between 1000-3000 vials (2-50 L) of sterile liquid or lyophilized dosage forms. Analytical: - Development and validation of analytical methods. Note: methods are to be suitable for assay of active ingredient and impurities/degradants in drug products over a concentration of active ingredient of at least 8 fold. - Identification of impurities and degradation products in drug formulations. - Development of specifications for drug product(s) and placebo. - Preparation of certificates of analysis for active and placebo drug products. - Evaluation of drug product(s) and placebo stability per ICH guidelines. - Release testing of drug substance, excipients, packaging components and labels. - In process and final product testing of pilot scale and clinical supplies of drug products (assay, impurities, appearance, moisture (freeze dried products) and placebo formulations (absence of active). - Carry out studies to demonstrate effective cleaning of equipment used in manufacture of drug products. - Development and validation of stability-indicating methods. - Identification of impurities and degradation products in drug products. Other: - Delivery of study reports, including CMC report in CTD format. - Packaging and labeling of drug products and placebo. Active and placebo formulations will be labeled as to content. Randomization will be done at the clinical site pharmacy. Coded labeling at the drug product manufacturing site is not anticipated. Storage of non-GMP and GMP lots of drug product for ≥ 6 mo. after manufacture. - Low temperature storage of API and drug products is anticipated. - Compliance with cGMP. - Maintaining Quality systems to support cGMP activities. Additional Information Specify whether your organization uses any proprietary technology for any of the activities described for Technical Areas 1 and 2. If so, clarify whether NCATS and NCATS collaborators will have freedom to use the technology at a third party facility in case the project is later transferred to a third party. In addition, your organization's capability statement should: - Indicate how many staff members the small business would be able to dedicate to the program, and which of those would be available in-house; - Identify which requirements would be performed in-house versus those that would be performed outside your organization; and - Describe your organization's ability to rapidly scale staff capacity up or down to support the anticipated workload. Anticipated Period of Performance The Government anticipates making multiple Indefinite Delivery/Indefinite Quantity (ID/IQ) type contract awards under the future solicitation-each with a five year ordering period. The Government anticipates awards will be made in the fourth quarter of FY2017. Other Important Considerations Work performed under this program must be conducted in accordance with Current Good Manufacturing Practices regulations (cGMPs) and, as appropriate, Good Laboratory Practice regulations. In addition, data and documentation generated under this program must be prepared in a form acceptable to the FDA for inclusion in a Drug Master File (DMF), IND application, or New Drug Application (NDA). To enable Collaborators to retain control of the intellectual property for compounds created through the TRCMC program, the Government has sought a Declaration of Exceptional Circumstances (DEC) to the Federal Acquisition Regulations (FAR) for this program. Required Information All capability statements must provide the following: (1) DUNS number; (2) organization name; (3) organization address; (4) point of contact; (5) point of contact title, address, telephone, and email address; and (6) size and type of business (e.g., 8(a), HUBZone, etc.) pursuant the applicable NAICS code. Submission Instructions and Due Date Written capability statements must be SUBMITTED NO LATER THAN TUESDAY, FEBRUARY 16, 2016 to the below Contracting Office Address, Attn: Jeffrey Schmidt. Electronic capability statements will be accepted by the primary point of contact. 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 Federal Business Opportunities. However, responses to this notice will not be considered adequate responses to a solicitation. 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). Contracting Office Address NINDS R&D Contracts Management Branch NCATS Section 6001 Executive Boulevard Suite 3287, MSC 9531 Bethesda, Maryland 20892-9531* *Use Rockville, MD 20852 for Fed-Ex/USPS/Courier/Hand-Delivery
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