SOURCES SOUGHT
65 -- Dosage Form Assay Transfer, Forced Degradation Study, and Stability Studies of R-VK4-116
- Notice Date
- 3/1/2024 3:32:10 PM
- Notice Type
- Sources Sought
- NAICS
- 325412
— Pharmaceutical Preparation Manufacturing
- Contracting Office
- NATIONAL INSTITUTES OF HEALTH NIDA Bethesda MD 20892 USA
- ZIP Code
- 20892
- Solicitation Number
- 75N95024Q00188
- Response Due
- 3/18/2024 1:30:00 PM
- Archive Date
- 04/02/2024
- Point of Contact
- Michelle Cecilia, Phone: 3018277199
- E-Mail Address
-
michelle.cecilia@nih.gov
(michelle.cecilia@nih.gov)
- Description
- Background Opioid use disorder (OUD) is a major public health concern. According to the CDC, overdose deaths from methamphetamine more than doubled from 2005 to 2015 and deaths from cocaine have nearly tripled since 2014.� All drugs of abuse share the ability to elevate dopamine in the shell nucleus accumbens, a key component of the reward system. The D3 receptor (D3R) expressed in the ventral forebrain mesolimbic dopamine system is thought to influence reward, emotion, and motivation and, by extension, drug seeking and relapse (Sokoloff 1990). Animal data show an upregulation of D3R expression following exposure to cocaine, nicotine, and alcohol (Newman 2012; Keck 2014, 2015). D3R-selective antagonists decrease craving for drugs of abuse and drug-seeking behaviors in animal models of abuse (Heidbreder and Newman et al, 2010, Sokoloff 2017). A highly selective D3R antagonist has been selected as the lead candidate for this new molecular entity stage program (VK4-116). VK4-116 has been characterized in a comprehensive package of in vitro and in vivo studies demonstrating its selectivity for D3R and showing efficacy in several animal models of abuse. There is promising pre-clinical evidence that VK4-116 will be effective in the treatment of multiple forms of substance use disorders. Plan is to continue on preclinical development of VK4-116, with the aim of filing an IND and initiating human studies in 1-2 years. CMC development of (R)-VK4-116 dihydrochloride salt with oral dosage form as capsule will support the Phase 1 clinical studies. During the synthesis of R-VK-116, it's possible for an S enantiomer to be produced as an unintended byproduct. To ensure that only the R enantiomer is isolated, specific measures are taken. Consequently, it becomes necessary to conduct a chiral forced degradation study to evaluate the chiral purity of the final R enantiomer. 2.�� �Scope of Work and Specific Requirements The scope of this contract is to provide the forced degradation study by using chiral impurity, transfer assay methods, and long term stability study of the GMP clinical materials.� Molecular structure of (R)-VK4-116 dihydrochloride salt is shown below.� R-VK4-116 drug product (as a HCl salt form) was manufactured in the GMP condition and released. There are 4 GMP drugs products manufactured, 50mg and 100mg active drugs, and two matching placebo drugs. Due to the service interruption, the long term stability has to be performed by the different company. Currently the formulation contains gelucire 44/14, labrasole and polysorbate 80 in 50mg and 50 capsule drug products.� The Offeror will be provided with the certificate of analysis, an HPLC (High Performance Liquid Chromatography) method, dissolution method developed and validated by the manufacturer of R-VK4-116 salt drug product, validation report on that HPLC assay and related substance method, and material safety data sheet. The contractor will be responsible for providing all other consumable supplies, facilities and equipment to perform the stability study.� Upon award of a TO, the Contractor shall perform the following tasks:� 1)�� �Forced degradation study� A forced degradation study will be performed to confirm the stability indicating assay method. The offeror will include a chiral method in the forced degradation study to ensure that S-isomer is not produced in the stability study. Chiral HPLC: ChiralPac OJ 4.6x250 mm, MeOH/DEA = 100:0.1, 1 mL/min., 85 bar, 30 C, 15 min. 2)�� �Assay methods transfer The contractor will transfer and qualify the HPLC method for R-VK4-116 by using the validated report. Dissolution validation of the capsule dosage form will occur at specific time points following USP guidance. The validated methods on assay and dissolution test will be provided. 3)�� � Stability studies of R-VK4-116 capsules and placebo capsule Stability of each batch of R-VK4-116 and placebo will be monitored for assay, impurities, appearance, dissolution and yearly bioburden at labeled storage condition (2-8C) for three years (3, 6, 9, 12, 18, 24 and 36 month timepoints), at intermediate condition (room temperature) for 12 months (3, 6, 9 and 12 month timepoints) and at accelerated condition (40C, 75%RH) for 6 months (3, and 6 month timepoints). The placebo batches will be monitored under the same conditions, and at the same time intervals. The final product release data will also serve as the zero time stabili �
- Web Link
-
SAM.gov Permalink
(https://sam.gov/opp/050654961dc74d398b6c0326b95fcc57/view)
- Place of Performance
- Address: Bethesda, MD 20892, USA
- Zip Code: 20892
- Country: USA
- Zip Code: 20892
- Record
- SN06983712-F 20240303/240301230053 (samdaily.us)
- Source
-
SAM.gov Link to This Notice
(may not be valid after Archive Date)
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