Excipients are pharmacologically inactive materials from different origins (biological or biotech products, minerals, chemical synthesis-based, etc.) Excipients are used in most drug products, and their quality, manufacturing processes and test methods are vital to the production of safe and effective therapies.

How are pharmaceutical excipients classified?

They are classified by the functions they perform in a pharmaceutical dosage form. Principal excipient classifications (functions) are the following:
• Binders
• Disintegrants
• Fillers (diluents)
• Lubricants
• Glidants (flow enhancers)
• Compression aids
• Colors
• Sweeteners
• Pharmaceutical Water
• Preservatives
• Propellant
• Suspending/dispersing agents
• Film formers/coatings
• Flavors
• Suspending or viscosity agent
• Printing inks
• pH Modifier
• Antioxidants

Why is it introduced/or Produced in the sample?

Excipients add properties to the formulation that allow the API to be made into a drug product, and the performance of these excipients may be related to the manufacturability, stability and performance of the drug product during and after its administration. In addition, excipient variability can also contribute to product variability.

Excipients have a physiological role to transport the active drug to the site in the body where the drug is intended to exert its action, some excipients are used simply to make the product taste and look better. Pharmaceutical excipients are critical and essential components of a modern drug product. In many products, excipients make up the bulk of the total dosage form.

Why do we need to test for the analyte?

The most important function of any excipient is to ensure the safety and efficacy of the medicine throughout the formulation, the storage period, and during and after its administration. Excipients are no longer considered inert substances because they can interact with the API, lowering their titer. They also can generate undesirable impurities or alter the absorption, distribution, metabolism and excretion (ADME) that ultimately, reduce the bioavailability of the API. They are assessed as functional and essential substances added to a modern pharmaceutical formulation. These problems may be overcome by adopting and carefully adhering to good manufacturing practices (GMPs) and quality control similar to those for active principles.

What is the regulatory requirement?

• All excipient manufacturer sites and products require approval . A licence is required to manufacture/stock and sell or distribute the excipient.
• As per Indian regulatory agencies the application for drug approval needs to list the excipients used in the drug preparations.
• Manufacturer is required to comply with IP, if a compendial monograph exists. In case of No IP claim by manufacturer then it is the user’s responsibility to ensure the excipient compliance to IP monograph.
• In absence of an IP monograph compliance to another international Compendia such as USP/EP/BP/JP etc. is acceptable, if the excipient is listed as such in the drug approval application.
• For exports, in-house specification and validated test methods are acceptable, if the excipient is listed as such with inclusion of the specification & test method, in the drug approval application.
• For new IP monograph insertion, if the manufacturer or regulator to include in IP, IP commission review the testing details, validation, etc. testing is conducted in IP laboratory to verify tests.
• Change in any excipient or levels of an excipient in a finished products formulation may simply be notified to your agency with justification for the change.

What is the global/importing country requirement?

Global regulatory agencies require Excipient Testing to verify identity and to confirm appropriate purity, strength, and quality.

USA

Under U.S. law, an excipient, unlike an active drug substance, has 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 (FDA) approval mechanisms that are available for components used in food and/or finished new drug dosage forms.

These Machanism are:

Determination by FDA that the substance is “generally recognized as safe” (GRAS) pursuant to Title 21, U.S. CFR, Parts 182, 184 or 186

Approval of a food additive petition as set forth in 21 CFR 171.

The excipient is referenced in, and part of, an approved new drug application (NDA) for a particular function in that specific drug product.

Excipients contained in over-the-counter (OTC) drug products subject to FDA monographs referenced in 21 CFR Parts 331-358 must comply with the requirements in 21 CFR 330.1(e).

European market & regulation EC2015/C95/02

The EU has formalised risk assessment for ascertaining the appropriate good manufacturing practice for excipients of medicinal products for human use. Manufacturing authorisation holders should have the risk assessment/management documentation for appropriate GMP for excipients available on site for review by GMP inspectors. Consideration should be given to sharing relevant information from the risk assessment with the excipient manufacturer to facilitate continuous improvement.

Excipients described in the European Pharmacopoeia

When the monograph covers a group of related materials, the particular specification chosen for the excipient, should be submitted, together with the rationale for its selection.

If tests other than those mentioned in the pharmacopoeia are used, proof should be supplied that the test methods are at least equivalent to those described in the pharmacopoeia. Where an excipient is not described in the European Pharmacopoeia, compliance with the monograph of a third country pharmacopoeia (e.g. USP/JP) can be accepted.

Excipients not described in any pharmacopoeia

An appropriate specification for the excipient should be established

Physical characteristics

Identification tests

Purity tests, (limits for total and individual impurities, physical, chemical, biological and, if appropriate, immunological) Assay or limit tests.

Harmonisation of Excipient monographs (PDG)

Pharmacopoeial Discussion Group (PDG), which comprises the European Pharmacopoeia (Ph. Eur.), Japanese pharmacopoeia (JP), and United States Pharmacopeia (USP). PDG met under the International Conference on Harmonization (ICH) intended to remove some of these differences that are mirrored by similar discussions between the corresponding pharmacopoeial authorities. Moves towards harmonized requirements in pharmacopoeial monographs depend on a consensus view of the purpose and scope of their contents. Aspects of the construction of the four main elements (identification, characterization, control of impurities and assay) of a monograph for an excipient are considered. The choice of analytical methods is influenced by their availability, the level of control required and their transfer reproducibility between laboratories.

The harmonized compendial standards are an important achievement and reflect the long-term commitment by the PDG partners to establish consistent standards for use in these three major regions of the world.

The relevant regulations of these regulatory bodies are designed to ensure that excipient manufacture and use complies with the overall drug specification according to the appropriate pharmacopoeia monograph.

How will it help the business?

Testing of excipients with some frequency prior to formulation is necessary to confirm final drug product safety and efficacy. This testing is not only reasonable from a business sense, but also a regulatory requirement. The regulatory agencies around the world require testing to verify the excipients identity as well as confirmation that the ingredient conforms to appropriate written specifications for purity, strength, and quality.

How will it help the consumer/customer?

Regulatory authorities have called for more secure supply lines and clearly defined quality measures for excipients and increasingly using risk management principles to better protect patients; this renewed focus on safety and efficacy of drugs for end users.