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Regulatory Guidelines for Pharmaceutical Excipients

An excipient is any ingredient or substance that intentionally added to a drug that is not part of the active substance. FDA reviews an excipient as a component of a finished drug product in a new drug application or a generic drug application.

As per FDA guideline, 

There is no regulatory status and may not be sold for use in food or approved drugs unless it can be qualified through one or more of the three U.S. Food and Drug Administration (USFDA) approval mechanisms that are available for components used in food and/or drug product.

FDA maintains a database of excipients that is posted on their website as the Inactive Ingredient Database (IID). In this database each excipient which has been allowed as a consequence of its presence in an approved innovator drug product.

But in Europe, there is no comprehensive European Union list of excipients that have been approved in drug products. Therefore, in order to establish precedence of use, it is necessary to review the drug catalogues such as the “Dictionnaire Vidal” (France), “Die Rote Liste” (Germany), or “The Electronic Medicines Compendium (EMC)” (UK).

As per IPEC guideline,

There are three phases of the excipient qualification process:

  • Phase One: The Excipient supplier’s Process shows the steps a chemical manufacturer may take to evaluate the market and regulatory requirements for the proposed excipient and the steps leading up to the market launch,
  • Phase Two: The User’s Process illustrates the path a pharmaceutical company ordinarily follows in evaluating the excipient and its manufacturer for use in a formulation, and
  • Phase Three: The Negotiation Process shows the process by which the supplier and user interact to reach a mutual agreement on quality requirements.

There are several safety related issues that should be assessed by the potential excipient manufacturer as part of their decision to introduce an excipient to the pharmaceutical market.Excipient suppliers should control over the following aspects of excipient quality since they may also have implications for end user safety:

  • Origin of raw materials (TSE & BSE)
  • Viral safety information
  • Degradation products of the excipient
  • Presence of catalyst residue (Heavy metals)
  • Inclusion of additives and processing aids (anti-oxidants, stabilizers etc.)

Excipient Master Files

An excipient Drug Master File (DMF) is a compilation of technical details related to the manufacture of the excipient and is formatted so that it is aligned with the ICH Common Technical Document (CTD) format for easy future application. The DMF typically includes specifications and test methods for raw materials, in-process testing, and the finished excipient product, a complete description of the manufacturing process, safety data, packaging details, and label content.

Submission of an excipient Drug Master File (DMF) to the FDA is not required by law or FDA regulations. But in Europe relevant excipient data must be provided directly to the pharmaceutical company for inclusion in their drug product dossier. It is recommended that it be provided under a suitable confidentiality agreement.

Excipient suppliers should familiarize themselves with the following two documents as pharmaceutical customers will expect to see compliance to these guidelines.

  • ICH Q3A: Impurities in New Drug Substances
  • ICH Q3C: Impurities: Guideline for Residual Solvents

Where appropriate, consideration should be given to establishing specification limits for certain other components. It is suggested that a composition profile is to be developed.

Few Reference Guide for Excipients

  • FDA Inactive Ingredient database,
  • U.S. Pharmacopeia (USP-NF),
  • European Pharmacopoeia (Ph. Eur.), 
  • Japanese Pharmacopoeia (JP), 
  • Handbook of Pharmaceutical Excipients o
  • Fiedler: Lexikon der HilfsstoffefürPharmazie, Kosmetik und angrenzendeGebiete

Terms and Definition

  • Novel Excipients: An excipient used for the first time in a drug product or by a new route of administration is classified as a Novel Excipient. (According to the ICH Guideline)
  • TSE: Transmissible spongiform encephalopathies
  • BSE: Bovine Spongiform Encephalopathy

So it is important that the excipient is produced using a manufacturing process that is in a state of control, often referred to as a capable process. Whether the process is by batch or continuous, there should be a written set of manufacturing instructions listing the raw materials, operating equipment, operating conditions, in-process controls, sampling plan, packaging operations, packaging components, and labeling materials with their content. While dedicated manufacturing equipment is preferred, multi-use equipment is acceptable provided there is no incidental carryover of contaminants from the manufacture of another chemical.


  • IPEC-PQG Excipient GMP Guide to all excipients
  • ICH
  • EMA

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