NOMENCLATURE Pregna-1,4-diene-3,20-dione, 9-fluoro-11,17,21-trihydroxy-16-methyl, (11β,16α)- 9-Fluoro-11β,17,21-trihydroxy-16α-methylpregna-1,4-diene-3,20-dione DESCRIPTION Dexamethasone from Pfizer is a white to practically white, odorless crystalline powder. It is stable in air and melts at about 250°C, with some decomposition. It is practically insoluble in water; sparingly soluble
in acetone, in alcohol, in dioxane, and in methanol; slightly soluble in chloroform; very slightly soluble in
USP SPECIFICATIONS Specification USP SPECIFICATIONS (continued) Specification Dexamethasone USP Micronized In addition to the US Registration Specifications, the following apply to Dexamethasone from Pfizer labeled “EP”. CHARACTERS Dexamethasone from Pfizer is a white or almost white, crystalline powder. It is practically insoluble in
water; sparingly soluble in ethanol, slightly soluble in methylene chloride.
EP SPECIFICATIONS Specification Additional Tests & Particle Size for Micronized Grades Parameter Regulatory Filings: Organic Volatile Impurities
Of the solvents targeted in USP 26 General Chapter <467>, only methylene chloride may appear in bulk
pharmaceutical products manufactured by Pfizer at the Kalamazoo plant. For those products where OVI
testing is required, our material will meet the compendial limits for methylene chloride and other solvents
that may be added to the target list in the future. Dexamethasone from Pfizer meets the requirements of USP 26 General Chapter <467>.
ICH Residual Solvents
As of 01 July 2000, Pfizer’s laboratories began to internally report all solvents that are present above the
assay detection limit. During the review of the batch data, it is verified that no solvents are present above
Dexamethasone USP Micronized
the ICH limits. Therefore, all lots of Dexamethasone released after 01 July 2000 will meet the ICH
Pfizer Specification * ICH Class and Specification
* Pfizer does not have Registered Specifications for residual solvents, only quality control Targets.
ICH Residual Metals
Pfizer is currently developing a strategy to assess the detection and quantitation of ICH residual metals in
Pfizer’s active pharmaceutical ingredients. Currently, no residual metals are known to be present in
Chemical Certificate of Suitability
Certificate No. R0-CEP 2000-261-Rev 00 was granted to Pfizer by the European Directorate for the
Quality of Medicines on 18 June 2002 for five years, for the product Dexamethasone. A copy of the
TSE Certificate of Suitability
Certificate No. R0-CEP 2000-260-Rev 00 was granted to Pfizer by the European Directorate for the
Quality of Medicines on 24 October 2001 for five years, for the product Dexamethasone. A copy of the
Viral Safety Statement for Active Pharmaceutical Ingredients
Pfizer has reviewed the viral safety risks of its manufacturing practices for production of non-biological
active pharmaceutical ingredients (APIs). The API Dexamethasone presents no viral safety concerns.
Pfizer APIs produced by bacterial or fungal fermentation and/or bioconversion processes are not
considered to present viral safety risks. The raw materials used in the stages of production are sterilized
prior to inoculation with a monoculture of the desired microorganisms. Only Pfizer’s bioconversion
reactions that employ purified enzymes (e.g. introduction of a double bond at the 1,2-position of the
steroid ring system) use animal-derived materials that are not sterilized prior to introduction to the
process. To support the safety of these enzymes, suppliers are required to provide documentation to
Pfizer that these materials are in compliance with the CPMP and CVMP guidances on minimization of
Dexamethasone USP Micronized
the risk of transmitting animal spongiform encephalopathy (TSE) agents via medicinal or veterinary
products. Pfizer requires suppliers to provide similar certification for all TSE-risk animal-derived
Based upon the nature of our manufacturing processes and the control of animal-derived materials used in
the manufacture of APIs, Pfizer is in compliance with applicable regulatory requirements for viral safety.
Statement Regarding Genetically Modified Materials in the Production of Active Pharmaceutical Ingredients (APIs)
The organism(s) currently used in the fermentation/bioconversion of plant sterols to produce
intermediates that are chemically transformed into Dexamethasone are not genetically
engineered. However, Pfizer does not make any commitment that would preclude using
genetically modified (recombinant) strains at some future date.
There are a number of ingredients used in the fermentation/bioconversion process that are derived from
plants that are major agricultural products in the United States. It is well known that the U.S. agriculture
industry has a growing reliance upon genetically modified (recombinant) plants such as corn and
soybeans. Although some grain handlers and processors have contacted farmers about needing to
segregate genetically modified seeds from non-genetically modified seeds, this concept has only recently
been introduced and lacks effective enforcement and monitoring components. Pfizer has not evaluated
the sources of ingredients for fermentation/bioconversion-derived intermediates and APIs relative to
ingredients having been derived in part from genetically engineered varieties of plants or other organisms.
Vegetable Origin of Raw Materials
Pfizer produces steroid active pharmaceutical ingredients (APIs) by what is best described as a semi-
synthetic process using a crude mixture of vegetable sterols that are isolated from various oilseeds as the
starting material. These vegetable sterols, stigmasterol and sitosterol, are processed through several
fermentation and chemical steps to yield Dexamethasone.
The raw materials used in the manufacture of Dexamethasone are not derived from the gluten-containing
grains wheat, rye, barley, or oats. Therefore, although Pfizer does not specifically assay for the presence
of gluten, it is unlikely that any gluten proteins are present.
Polymorphism
Evaluation of infrared (IR) spectra indicates that Dexamethasone from Pfizer has only one crystal
structure (or crystal form). An IR assay has been implemented to assure detection of any occurrence of
Dexamethasone USP Micronized Chirality
Dexamethasone has eight chiral carbons: C8, C9, C10, C11, C13, C14, C16, and C17. Pfizer’s
manufacturing process can modify the chirality of four of them: C9, C11, C16, and C17.
Stereoisomer Content
Please note that one of the known impurities of Dexamethasone, Betamethasone, is a stereoisomer of
Dexamethasone. However, Betamethasone is an impurity which is not typically present in
Dexamethasone from Pfizer. Therefore, the stereoisomer content is LT 0.1%.
Name______________________________________________ Doctor’s Name_______________________City______________State_______ Date of Last Physical Exam____________________________________ Blood Test or Blood Work-Up________________________________ Are You Presently Taking Any Medications, Drugs, YES NO YES NO Pills, Over-the-Counter Medications, or Having Do You Have High or Low Blood Pressure? ___
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