FAQ Reference Standards

USP Reference Standards are highly characterized physical samples used by the pharmaceutical industry and related institutions for testing to ensure the identity, strength, quality and purity of the active ingredients and constituents contained in drug products. These are the highest purity chemical substances and biological preparations.

USP Reference Standards are based directly on the official monographs of the USP National Formulary (USP-NF), whose requirements are enforced in the United States by the U.S. Food and Drug Administration (FDA).

The USP Reference Standards are developed through a collaborative process between USP, the pharmaceutical industry and expert committees, and are reviewed and approved through a thorough, rigorous and open review process with experienced industry, academic, healthcare and regulatory authorities. This gives users peace of mind 

This gives users the assurance that they are purchasing an official USP reference standard that comes from a trusted organization that supports the achievement of high drug quality in more than 140 countries. Widespread recognition of official USP monographs and Reference Standards makes it easier for drug manufacturers to gain market access in these countries.

The EDQM Reference Standards (chemical substances, biological preparations, herbs and herbal extracts) are intended exclusively for use in accordance with the monographs of the European Pharmacopoeia, Ph. Eur. for short.

Any use deviating from a monograph is at the user's/buyer's own risk and expense.

Each user is responsible for ensuring that the Reference Standards used originate from an officially valid batch/lot before commencing work.

Like all Reference Standards, the EDQM Reference Standards are not approved for use on humans or animals.

Official Reference Standards from an officially recognized source should preferably be used as primary standards, as the official Reference Standards are generally considered to be compendial Reference Standards, with a few exceptions. They are therefore considered to be the most accurate and traceable Reference Standards. Exceptions are some of the biological Reference Standards, which are classified as secondary compendial standards due to their calibration and testing against international standards of the World Health Organization (WHO).

Answer: Only if a USP reference standard meets all the requirements specified in the relevant monograph, the applicable General Chapters and the General Notes does it comply with the official USP-NF standards. 

The official standards apply continuously from the date of manufacture until the expiry date is reached. Each official reference standard tested in accordance with the instructions in the relevant monograph must meet the defined standards to demonstrate compliance. The frequency of testing and sampling is left to the manufacturers, purchasers or regulatory authorities performing the compliance testing.

Any use deviating from a monograph is at the risk and expense of the user/buyer.

Each user is responsible for ensuring that the Reference Standards used originate from an officially valid batch/lot before starting work.

The tests and trials described in the European Pharmacopoeia (European Pharmacopoeia, Ph. Eur. for short) are the officially approved analytical methods on which the Ph. Eur. standards are based. Only if an EDQM reference standard fulfills all the requirements stated in the corresponding monograph is it compliant with the official Ph. Eur. standards.

The use of an alternative analytical method for control purposes is possible, provided that a clear decision can be made as to whether the standards of the monograph would also be met if the official methods were used (cross-validation). This requires the express approval of the competent authority in advance. In case of doubt, only the official analytical methods of Ph. Eur. apply.

In addition to the pharmacologically active pharmaceutical ingredients (API), medicinal products also contain excipients that have an influence on shelf life, stability, shaping, weight, consistency, taste, appearance, the promotion of drug release, absorption and bioavailability, the adjustment of pH and osmolarity (number of osmotically active particles per liter of test material), for the manufacturing process and generally as protection. Considering excipients as inactive is considered outdated as they can influence pharmacokinetics, contain unexpected impurities and cause adverse effects (e.g. allergic reactions).

Exemplary selection of excipient groups for the manufacture of medicinal products:

• Antioxidants
• Flavorings
• Bases
• Binding agents
• Emulsifiers
• Colorants
• Film formers
• Fillers
• Gelling agents
• Flavoring agents
• Complexing agents
• Preservatives
• Solvents
• Solubilizers
• Buffers
• Ointment bases
• Acidifiers
• Acid regulators
• Acids
• Lubricants
• Sweeteners
• Coating agents
• Thickening agents
• Disintegrants

Impurities in medicinal products are undesirable chemicals that can adversely affect the efficacy and safety of the pharmaceutical product. They can occur naturally, be added to the active ingredient or excipient in the production process intentionally, accidentally, unavoidably or incidentally and can arise during the storage of the medicinal product. The maximum permissible content of known impurities is defined in the official monographs.

The USP divides impurities in drug substances into three categories:

1) Organic impurities (manufacturing process and/or storage of the drug product; Are usually identified or also not yet identified, volatile or non-volatile;):

a) Starting materials

b) By-products

c) Intermediate products

d) Degradation products

e) Reagents, ligands and catalysts

f) Residual solvents

2) Inorganic impurities (manufacturing process; are usually known and identified):

a) Reagents, ligands and catalysts

b) Heavy metals or other residual metals

c) Inorganic salts

d) Other materials (e.g. filter aids, charcoal) 

3) Residual solvents.

With the help of corresponding official Reference Standards, impurities can be identified and documented in an active ingredient and excipient as well as in a finished medicinal product.

In addition, the numerous pharmaceutical analytical impurities of the USP can be used for the early identification of impurities. They are not (yet) monographed, but offer a wide range of applications:

• Research and development - R&D
• Method development
• Manufacturing
• Quality control
• Stability testing
• Monitoring after market launch

The Reference Standards offered by Eurofins PHAST GmbH comply with the classifications of the UNSPSC - United Nations Standard Products and Services Code:

• UNSPSC Code 41116107: Chemistry quality controls or calibrators or standards
• UNSPSC Code 41116135: Molecular biology quality controls or calibrators or standards