Starting Materials

Starting Materials for Drug Products:

Analysis of 108 FDA Form 483’s issued to Compounding pharmacies in 2018 was performed. A textual analysis for the term non-pharmaceutical identified approximately 11% of the facilities (12) received an observation associated with the use of non-pharmaceutical products as an ingredient (starting materials) and 1 case where a non-pharmaceutical cleaning solution was used for washing glassware. Examples include but are not limited to:

  • Situations where the compounding pharmacy used non-pharma grade starting materials (i.e.,  components, or non-pharma grade water), in the formulation of a drug product. In many cases these non-pharma grade materials lacked microbial and/or chemical analysis to demonstrate compliance with USP standards.
  • In one case the compounding pharmacy ran out of the pharmaceutical grade component used in the compounding of Progesterone 100MG capsules and purchased food grade material as a substitute from the grocery store to continue production of the Progesterone 100MG capsules.
  • In one case the compounding pharmacy used non-pharmaceutical household grade dishwashing detergent when cleaning processing equipment (stir bars, glass beakers and glass graduated cylinders) prior to sterilization and/or depyrogenation.

Do you need to use the appropriate grade of starting materials to make a finished drug product? YES

This includes components, Active ingredients, including water, and Inactive ingredients. No you cannot use something different just because it is cheaper, convenient, or the required material is not available.

Components, active ingredients, and inactive ingredients are defined in 21 CFR 210:

21 CFR 210.3(b)(3) – Component means any ingredient intended for use in the manufacture of a drug product, including those that may not appear in such drug product.

21 CFR 210.3(b)(7)- Active ingredient means any component that is intended to furnish pharmacological activity or other direct effect in the diagnosis, cure, mitigation, treatment, or prevention of disease, or to affect the structure or any function of the body of man or other animals. The term includes those components that may undergo chemical change in the manufacture of the drug product and be present in the drug product in a modified form intended to furnish the specified activity or effect.

21 CFR 210.3(b)(8) Inactive ingredient (Excipient) means any component other than an active ingredient.

Management of this material is addressed in 21 CFR 211.80 and the sub-clauses of this subpart.  General requirements are addressed in (211.80), Receipt and storage of untested material (quarantine prior to use (21 CFR 211.82), testing, approval and rejection (21 CFR 211.84), inventory control (21 CFR 211.86), retesting (21 CFR 211.87), and rejected materials (21 CFR 211.89).

The requirement to use the appropriate grades of starting materials is also addressed in the USP General Notices section.

In pharma manufacturing and compounding by either a 503A/B the correct starting materials must be used.  Have a question please sent it to our  Contact Us page and we will respond shortly.