A raw material specification is defined as a list of tests, references to analytical procedures, and appropriate acceptance criteria which are numerical limits, ranges, or other criteria for the tests described.
When a specification is first proposed, justification should be presented for each procedure and each acceptance criterion included. The justification should refer to relevant development data, pharmacopoeial standards, test data for drug substances and drug products used in toxicology and clinical studies, and results from accelerated and long term stability studies, as appropriate.
Universal Tests/Criteria for Raw Material
The following tests and acceptance criteria are considered generally applicable to all new drug substances.
a) Description: a qualitative statement about the state (e.g. solid, liquid) and color of the new drug substance.
b) Identification: identification testing should optimally be able to discriminate between compounds of closely related structure which are likely to be present. Identification tests should be specific for the new drug substance, e.g., infrared spectroscopy.
c) Assay: A specific, stability-indicating procedure should be included to determine the content of the new drug substance.
d) Impurities: Organic and inorganic impurities and residual solvents are included in this category.
Specific Tests/Criteria for Raw Material
a) Physicochemical properties: These are properties such as pH of an aqueous solution, melting point / range, and refractive index.
b) Particle size: For some new drug substances intended for use in solid or suspension drug products, particle size can have a significant effect on dissolution rates, bioavailability, and / or stability.
c) Polymorphic forms: Some new drug substances exist in different crystalline forms which differ in their physical properties. Polymorphism may also include solvation or hydration products (also known as pseudo-polymorphs) and amorphous forms.
d) Water content: This test is important in cases where the new drug substance is known to be hygroscopic or degraded by moisture or when the drug substance is known to be a stoichiometric hydrate.
e) Inorganic impurities: The need for inclusion of tests and acceptance criteria for inorganic impurities (e.g., catalysts) should be studied during development and based on knowledge of the manufacturing process.
g) Microbial limits: There may be a need to specify the total count of aerobic microorganisms, the total count of yeasts and molds, and the absence of specific objectionable bacteria (e.g., Staphylococcus aureus, Escherichia coli, Salmonella, Pseudomonas aeruginosa).
Pharmaceutical Raw Material Specification Template
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