Pomalidomide is an immunomodulatory active pharmaceutical ingredient (API) belonging to the thalidomide analogue class. It is chemically identified as 4-amino-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione and has the molecular formula C13H11N3O4 with a molecular weight of 273.24 g/mol. The CAS Number of Pomalidomide is 19171-19-8. FDA substance records identify Pomalidomide as a racemic chemical substance with one defined stereocenter and optical activity of (+/−).
Pomalidomide is an important oncology API used in the development and manufacture of pharmaceutical formulations for specific hematological and oncological indications. The FDA-approved product POMALYST contains pomalidomide and is indicated, in combination with dexamethasone, for certain adult patients with multiple myeloma following prior therapies. Pomalidomide is also approved in the United States for adult patients with AIDS-related Kaposi sarcoma after failure of highly active antiretroviral therapy and for HIV-negative adult patients with Kaposi sarcoma.
From a chemical and pharmaceutical perspective, Pomalidomide is a pale yellow to yellow powder according to the proposed Indian Pharmacopoeia monograph. The compound has limited aqueous solubility, while it is soluble in dimethyl sulfoxide (DMSO). FDA product information similarly describes Pomalidomide as a yellow solid powder with low solubility in water and across different pH conditions.
Pomalidomide is structurally related to thalidomide and contains an amino-substituted isoindolinone/dioxopiperidine framework. Its pharmaceutical significance is associated with immunomodulatory and antineoplastic activity. It is classified as an immunomodulatory agent and is used in oncology-focused pharmaceutical development.
The exact identity of the API is particularly important because Pomalidomide has stereochemical characteristics and may be associated with process-related and degradation-related impurities. FDA GSRS identifies CAS 19171-19-8, UNII D2UX06XLB5, molecular formula C13H11N3O4, and molecular weight 273.24 for the racemic substance.
Pomalidomide API is primarily relevant to oncology formulations and pharmaceutical research involving:
The current FDA labeling specifies Pomalidomide in combination with dexamethasone for certain adult patients with multiple myeloma who have received at least two prior therapies, including lenalidomide and a proteasome inhibitor. It also includes approved indications for adult Kaposi sarcoma patients.
Quality control of Pomalidomide API requires identity testing, chromatographic assay, related-substance testing, water determination and inorganic residue testing. The publicly available Indian Pharmacopoeia draft monograph specifies infrared identification together with chromatographic identity confirmation. It proposes liquid chromatography for both related substances and assay.
The proposed IP specification establishes an assay range of 98.0–102.0%, calculated on the anhydrous basis. Related substances include specifically identified Pomalidomide impurities A, B and C, each controlled at NMT 0.15%, while any other secondary impurity is controlled at NMT 0.10% and total secondary impurities at NMT 1.0%. The reporting/disregard threshold specified in the draft is 0.05%.
The same proposed monograph specifies sulfated ash NMT 0.1% and water NMT 1.0%. These are more appropriate CMS specification fields than substituting unrelated tests such as residue on ignition or loss on drying.
A Pomalidomide API manufacturer in India should maintain stringent controls over synthesis, purification, impurity removal and analytical testing because Pomalidomide is a cytotoxic oncology compound. The proposed Indian Pharmacopoeia monograph specifically cautions that Pomalidomide is cytotoxic and requires precautions to prevent inhalation of particles and skin exposure.
API manufacturing programs should therefore incorporate appropriate containment, validated analytical methods, controlled handling procedures and complete batch documentation. Typical quality documentation can include Certificate of Analysis (CoA), Safety Data Sheet (SDS), analytical method information, residual-solvent information, impurity profile and manufacturing-related documentation, according to the applicable customer and regulatory requirements.
Pomalidomide should be protected from light and moisture. The proposed IP monograph specifies storage at a temperature not exceeding 30°C.
For commercial API packaging, suitable tightly closed pharmaceutical-grade containers with appropriate secondary protection can be used to minimize exposure to moisture, light and contamination. Actual packaging configuration should be based on validated stability and transport requirements.
Pomalidomide API documentation can include:
Pomalidomide is an oncology API for which analytical traceability and controlled documentation are particularly important.
Pomalidomide is a strategically important immunomodulatory oncology API with established pharmaceutical applications in multiple myeloma and Kaposi sarcoma. Its defined chemical identity, recognized CAS Number 19171-19-8, established analytical methodology and proposed Indian Pharmacopoeia quality parameters make it suitable for controlled pharmaceutical API manufacturing programs.
For manufacturers and pharmaceutical development organizations seeking Pomalidomide API from India, emphasis should be placed on consistent purity, controlled related substances, validated analytical testing, appropriate cytotoxic handling and comprehensive documentation.
| Parameter | Specification |
|---|---|
| Appearance | white to off-white crystalline powder |
| Identification | IR & HPLC compliant |
| Assay (HPLC) | 98.0% – 102.0% |
| Loss on Drying | NMT 0.5% |
| Residue on Ignition | NMT 0.10% |
| Individual Impurity | NMT 0.10% |
| Total Impurities | NMT 1.0% |
| Water Content | NMT 1.0% |