Follow
Specification & STP of Raw Materials (Drug substances & Excipients):
Specification & STP of Drug Substances (API) shall mainly be prepared based onPharmacopoeia, if the material is monographed in the Pharmacopoeia, otherwise (forINN materials) the specification & STP of the material manufacturer shall be followed.
The following tests are considered as universal test criteria and must be listed in the specifications of an active substance:
– Description/Appearance
– Identification
– Assay
– Impurities
i) Organic Impurities (Related substances)
ii) Inorganic Impurities (e.g. Heavy metals, Sulphated ash)
iii) Residual Solvents
– Moisture content (Water/LOD)
The specification of an active substance should cover all the related substances mentioned in the relevant Pharmacopoeia plus the process related & degradable impurities listed by the API manufacturer.
The test procedure for related substances should be prepared following the test procedure of the material manufacturer. However, if there is no additional process related /degradable impurities other than the Pharmacopoeial impurities, the Pharmacopoeial method can be followed.
For residual solvents, the specification and STP should be prepared following the specification and test procedure of the respective API manufacturer; however, the limits of the components of residual solvents must be within the limits mentioned in the Pharmacopoeia. In case there is more than one supplier of a single API with different specifications of residual solvents (different component, different limits), specifications & methods for each of the supplier shall be prepared.
Appropriate method for moisture content (Water by KF or Loss on Drying) should be written which should preferably be based on pharmacopoeia.
Specifications for other tests like bulk density (tapped/untapped), particle size distribution etc should be fixed based on the requirement of Research & Development department which they set during the development of the product formulation or it can be set as per the supplier’s specification. However, the test procedures for these tests should be same as that followed by the API manufacturer.
In case of the specifications & STPs of excipients, pharmacopoeial monograph should be followed. However, if an excipients is not available in the pharmacopoeia, the manufacturer’s specification as well as test procedure should be followed.
For the excipients (specially the key excipients) whose functionality related tests (e.g. particle size, bulk density etc.) are important, specifications for the tests should be set based on the requirement of Research & development department.
Specifications & methods of microbiological limit tests should be set for both API and excipients based on the requirement of individual monograph (where applicable) or general monograph of pharmacopoeia.
In all cases, the tighter requirement should be included in the specification, i.e. if the
Specification followed by the material manufacturer is tighter than that mentioned in the relevant pharmacopoeia, the specification of the material manufacturer to be followed.
