Reference Standards

Click the below sections to reveal Frequently Asked Questions about Reference Standards

Miscellaneous

  1. What information do I need when ordering from outside of the United States?

    Special instructions for orders from outside of the United States can be found on our Purchasing/Customer Support page.

  2. Why has USP changed the lot number format of USP Reference Standards and Certified Reference Materials?

    The new lot numbering format allows for many more lot numbers of a given item, while maintaining the same number of characters (7) as the previous numbering format.

  3. Why is USP not requiring annual recertification of the USP Near IR System Suitability Reference Standard (Catalog No. 1457844)?

    The USP Near IR System Suitability Reference Standard does not require recertification because of a combination of the component material, a proprietary housing and seal, and USP's commitment to a Continued Suitability for Use Program.  For more details, please view our official statement.

  4. How do I reliably remove powdered material from the vial?

    Please see Tips for Effective Retrieval of Powder from Vials .

  5. Why is the catalog number on my Reference Standard different than others, and will that affect its compendial use?

    USP changed the numbering system for all USP Reference Standard catalog numbers.  A “1” was added as the first digit to the existing catalog number.  If there was punctuation in the previous number, such as a hyphen, it was removed.  All catalog numbers are now 7 digits in length.  There are still lots that were labeled prior to this change in distribution, so the catalog number on the label will be the previous number.  Whether the catalog number printed on the USP RS label is from the old or new numbering system, it has no bearing on the potency, stability, or suitability for use of the USP RS.  USP monitors items in our inventory on a regular basis in the Continued Suitability for Use Program.  The following chart shows the new numbering system. 

    ItemOld Item No.New Item No.
    Acetaminophen (400 mg)00300-91003009
    Brompheniramine Maleate (125 mg)

    07800-8

    1078008
  6. How do USP Units convert to International Units?

    USP Endotoxin Units are identical to International Units.  Please click here to read USP’s statement on the Heparin Potency Unit Assignment and Harmonization with the International Standard for Unfractionated Heparin.  Relationships for other USP units must be determined on a case–by–case basis.  Please refer to the USP compendial monograph of a specific material for further information.

Technical Data Sheets

  1. Does USP issue Certificates of Analysis (COAs) for USP Reference Standards?

USP does not provide COAs.  USP does provide USP Certificates for most USP Reference Standards (RS).  USP Certificates do not completely describe the test results obtained during evaluation.  Rather, they are issued to provide customers with information such as a hard copy of the USP RS label text, molecular information, typical chromatograms (limited cases), and additional use/handling information that may not be contained on the RS label.  USP Certificates for current & previous lots, when available, can be viewed on our web site by clicking on the catalog number for an item in our online USP Catalog or by clicking on the Product name in the A to Z Reference Standards Index.  If there is not a link to view the USP Certificate for a specific lot number, then a USP Certificate is not available for that lot.  Read USP's policy statement on USP Certificates.

  1. Where can I find the Safety Data Sheet (SDS) for a USP Reference Standard?

    SDSs are available online for all USP Reference Standards at www.usp.org/sds.  They can also be viewed on our Web site by clicking on the catalog number for an item in our online USP Catalog or by clicking on the Product name in the A to Z Reference Standards Index.

  2. Are Safety Data Sheets (SDSs) available in different formats and languages?

    SDSs are not available in additional formats and languages.  It is the responsibility of the importer to provide SDSs in the required format, if different.

  1. Is the Safety Data Sheet (SDS) available on the website the most up-to-date version?

    The SDS's posted on our web site are the most recently updated versions.  The U.S. OSHA Hazard Communication Standard does not specify a specific time frame beyond which SDS information is to be considered unacceptable.  [See, 29 Code of Federal Regulations § 1910.1200(g)(5)]

  2. Why does the Safety Data Sheet (SDS) of a particular USP Reference Standard not meet the U.S. Occupational Health and Safety Administration (OSHA) standard (HazCom2012) requirements that went into effect on May 25, 2012?

    OSHA published the HazCom2012 requirements to bring U.S. SDSs in line with the Globally Harmonized System of Classification and Labeling of Chemicals (GHS).  USP is currently revising its SDSs to comply with these new OSHA regulations.  The regulatory deadline for implementation is June 1, 2015.

  3. Is the information on the Safety Data Sheet (SDS) of a USP Reference Standard obtained in USP laboratories?

    Testing is not required for a safety evaluation or an SDS by the U.S. Occupational Health and Safety Administration (OSHA).  USP relies on published and supplier data in conformance with OSHA regulations.  USP Reference Standards are intended only for use in their associated USP compendial applications.  Any use beyond these applications is the responsibility of the user.  USP Reference Standards are not intended for human and animal use.

  1. Does USP provide chromatograms and IR spectra for USP Reference Standards?

    There are a limited number of USP Reference Standards that have an available Typical Chromatogram.  If provided, the Typical Chromatogram is included in the USP Certificate.  Details that are not included on the chromatogram are confidential and not available.  IR spectra are not available for USP Reference Standards.

  2. Where can I find specific test results for a USP Reference Standard?

All information required for official uses of a USP Reference Standard may be found on the label and, when available, in the USP Certificate.  Monographs or other USP standards that have specified particular USP Reference Standards to be suitable for use may also provide additional information or directions for use.  Due to legal and scientific reasons, test results and data that are not included in these sources cannot be shared.  (Read our Document Disclosure Policy)

Labeled Value (Purity/Potency)

  1. Where can I find the purity/potency value of a USP Reference Standard?

In most cases, the assigned value can be found on the label of a USP Reference Standard.  If a value is not provided on the label or accompanying documentation and the Reference Standard has a quantitative USP compendial application, a value of 100.0% is used.  This applies only to USP Reference Standards intended for quantitative use in USP compendial procedures.  The purity value is not applicable for qualitative uses.  Please refer to a USP Reference Standard’s USP compendial application(s) to determine if the RS is used qualitatively and/or quantitatively.  The USP Catalog also contains the labeled values for the current lot of most quantitative USP Reference Standards.

  1. How is the labeled value of a USP Reference Standard calculated?

The method of choice in computing the assigned value of a USP Reference Standard is a mass balance analysis using independently determined components such as moisture, solvent residues, inorganic residues, chromatographic impurities and ion content.  The mass balance equation used is confidential and cannot be shared due to legal and scientific reasons.  The assay results against a previous lot or against another validated standard and the results of the functional group analysis are for confirmatory purposes only.

USP uses the mass balance approach as this provides a more precise determination of the assigned value than assaying versus a previous lot.  The assaying versus a previous lot approach inherently causes greater variability and less precision due to the variability of the previous lot being incorporated into the overall variability of the lot under evaluation.  The mass balance approach also results in higher accuracy.

Exceptions to the mass balance approach include many biological Reference Standards, especially those which define the Unit of Activity.  A label value is not assigned to Reference Standards having only qualitative USP compendial uses.

  1. Why has the basis of the labeled value changed from one lot to another?

Labeled values, including their basis, are lot specific and may change from one lot to another.  For the convenience of our customer, USP is labeling a USP Reference Standard "as is" whenever possible.  It is the preferred option and is selected whenever valid data indicates that the volatiles content is constant over time.  The change to "as is" will not affect the USP compendial use of a USP Reference Standard.

Labels

  1. Do USP Reference Standard labels meet the requirements put into law by the U.S. Occupational Health and Safety Administration (OSHA) HazCom2012 standards?

USP is currently transitioning to revised label formats to meet the labeling requirements of the HazCom2012 standard.  The required label elements are signal words, hazard statements, precautionary statements & pictograms, product identifier, and supplier identification.  All elements except the precautionary statements will be visible on the outside label of a USP Reference Standard vial.  The precautionary statements can be found under the wrap label.  During this transition, you may receive units in both the old label format and the new label format.  The regulatory deadline for implementation is June 1, 2015.  By this date, all USP Reference Standards will be shipped using the new label format only.

  1. Why is a USP Reference Standard over-labeled?

Select USP Reference Standards have a wrap label with all label elements required by HazCom2012 placed over the original labels.  The updated wrap label includes the same information as the label in the old format with the addition of precautionary statements & pictograms, and the updated language for signal words and hazard statements.  These items will include a statement on the label indicating that they are intentionally over-labeled.  Please refer to FAQ #18 for more details about the new label format.

  1. What does “AS” stand for on the label of a USP Reference Standard?

AS stands for Authentic Substance.  Authentic Substances were developed by USP as a service primarily to analytical, clinical, pharmaceutical, and research laboratories.  Such substances may be used for identification, method development, evaluation of method performance, or other applications as found suitable and validated by the user.  AS Reference Standards do not have USP applications in monographs or other compendial standards.  All available information can be found on the label of the AS Reference Standard.  No additional data is publicly available.

Uses and Applications

  1. Are USP Reference Standards suitable for use as drugs, medical devices or diagnostic purposes?

USP Reference Standards are intended for test and assay use only as directed by USP compendia; they are not intended for use in humans or animals as drugs or medical devices.  View USP's policy statement on the storage and usage of Reference Standards.

  1. Are USP Reference Standards suitable for applications not specified in the USP-NF publication and other USP compendia?

USP Reference Standards are intended only for use in analytical or laboratory applications as specified in USP compendia.  It may be possible to use a USP Reference Standard in other compendial or quality assessment applications however it is the responsibility of the user to determine the suitability of the USP Reference Standard for other non-specified purposes.

  1. Do USP Reference Standards require any special preparation before use?

Any specific instructions for use may be provided in the compendial monograph, the label of the USP Reference Standard and/or on its USP Certificate, if available.   Some lots can be used as–is but others may require drying before use or a correction with a concurrent moisture or Loss on Drying determination.  Additional information on special preparation requirements for USP Reference Standards may be found in General Chapter <11> USP Reference Standards and the USP Reference Standard’s associated USP compendial methods.  See Use and Storage for more details.

Shipping and Storage

  1. What is the storage condition for a USP Reference Standard?

The storage condition for an unopened USP Reference Standard can typically be found on the container label.  Storage conditions are no longer provided in the Safety Data Sheets (SDSs).  Instead, the SDS refers users to the USP Reference Standard label.  Storage conditions are lot–specific and may change from one lot to another.  If no specific directions or limitations are provided on the USP Reference Standard label, the conditions of storage shall include storage at room temperature and protection from moisture, light, freezing, and excessive heat.  Refer to General Chapter <659> Packaging and Storage Requirements in the USP-NF publication for definitions of storage and handling terms.   See Use and Storage for more details.

  1. Can USP Reference Standards be stored after opening for future use?

USP generally provides enough material for multiple preparations.  Any unused portions remaining after the container has been opened should be carefully stored in accordance with prudent laboratory procedures.  Many variables are outside of the control of USP.  Therefore, USP makes no warranties concerning the continued suitability of previously opened Reference Standards.  Decisions concerning the proper use of previously opened Reference Standards are the responsibility of the user.  View USP's policy statement on the storage and usage of Reference Standards.

  1. Why is the storage condition of a USP Reference Standard different from the storage condition provided in a USP compendial monograph?

The storage condition of a USP Reference Standard is determined based on the recommendation from the material’s supplier/manufacturer.  Data obtained during the collaborative study of a lot and historic data are also considered.  The provided storage condition of a USP Reference Standard is intended to preserve the integrity of the Reference Standard for the duration of its use as an RS.  The storage condition in a USP compendial monograph is based on the recommendation of the monograph’s sponsor.  The storage condition provided in a monograph is for the article of commerce. 

  1. Can a USP Reference Standard be stored at a different temperature other than what is provided on the label?

The provided storage condition is also how USP stores the specific item.  As Continued Suitability for Use (CSU) testing is performed on the item stored as per its label, we do not have data to support the continued suitability of the item stored at an alternate storage condition.  For this reason, we are unable to comment on the storage of a USP Reference Standard at an alternate temperature.  It is the responsibility of the user to determine if a material remains suitable for use when handled differently than the provided instructions.

  1.  Is a USP Reference Standard still suitable for use if a temperature excursion occurs?

USP does not comment on storage deviations and the potential effect of temperature excursions on the USP Reference Standard material.  The user should consult their own internal policies & SOPs and use their best scientific judgment to make the decision on whether or not to use the material(s).

  1.  Do USP Reference Standards require special shipping?

The storage condition of a USP Reference Standard is intended to preserve the integrity of the material for the duration of its use as an RS.  USP Reference Standards are not customarily shipped on ice or under refrigerated conditions.  Shipping conditions are determined based on the stability information for individual USP Reference Standards and transit times.  If scientific evidence suggests the need to ship a USP Reference Standard on ice or dry ice, USP will do so.  For these items, a statement that a cold shipment is required will be included in the Product Description [e.g. Endotoxin (10,000 USP Endotoxin Units) (COLD SHIPMENT REQUIRED)].  View USP's policy statement on the shipping conditions of USP Reference Standards.

Shipping on ice or dry ice is available for all USP Reference Standards on request and for an extra charge - Call USP Customer Service at 1–800–227–8772 (U.S. and Canada), +1–301–881–0666, or 00–800–4875–5555 (Select Europe) for details.

Availability and Validity

  1. What happens if a new USP Reference Standard that is specified in a new USP compendial monograph is not yet available for purchase?

As per Section 5.80 of the General Notices in the USP-NF publication, if any new USP or NF written standard requires the use of a new USP Reference Standard that is not yet available, that portion of the standard containing the requirement shall not be official until the specified USP reference material is available.  Please view the Medicine Compendium’s FAQs here regarding the unavailability of a USP Reference Standard listed in an MC monograph.

To learn when a new USP Reference Standard becomes available for the first time, use the New Reference Standards Release Notification Service.  This service is not available for the release of back-ordered items or lot changeovers.  To receive a monthly list of lot changeovers, please subscribe to our free monthly Email Notice.

  1. What happens if a USP Reference Standard is on back order?

The availability of USP Reference Standards is generally better than 99 percent.  USP strives to plan ahead to replace depleted lots in a timely manner.  However, despite our best efforts, some USP Reference Standards might occasionally be out of stock temporarily.  Contact your USP Account Manager or Reference Standards Technical Service (rstech@usp.org) to find out when the specific USP Reference Standard you are looking for might become available again.  You can also frequently check the product listings on USP's online store which are updated on a daily basis or sign up for our free monthly Email Notice which will keep you informed about USP Reference Standards that become available.

You can place an order for USP Reference Standards that are currently out of stock.  Products that become available within 30 days of your order will be shipped to you automatically.  If the product becomes available after 30 days, USP will send you a Notice of Availability to get your confirmation before shipping the order.

  1. Are the impurities listed in a table of a specific USP compendial monograph available from USP?

All USP Reference Standards that are required to carry out the tests or methods within a specific monograph will be provided in a list at the beginning or end of a monograph.  The Reference Standards are written as "USP <name> RS."  Other chemicals, reagents, impurities, etc. that are listed in the monograph are not available as USP Reference Standards.

  1. What is USP’s policy on Product Recalls and Withdrawals?

If a product is determined by USP to no longer meet the compendial requirements, USP will notify customers who purchased the product in the last 12 months that it is being recalled or withdrawn.  USP recommends referring to the online store and Daily Listings prior to using a USP Reference Standard to make sure the specific lot is valid for use.  These sources are updated on a daily basis.

  1. How do I determine if a USP Reference Standard is still valid for use or has expired?

Current lots of USP Reference Standards do not have valid use dates (expiration dates).  As long as a lot is listed as being the “current lot,” it is valid and suitable for use.  Once a current lot is depleted, it becomes the “previous lot.”  At this time a valid use date is assigned, which is typically a year from the date of depletion.  The last day of the indicated month represents the expiration date for the specified lot (e.g., "05/14" means the lot was considered official through May 31, 2014). 

The USP Reference Standards Catalog is published bimonthly online and annually in print.  Since the Daily Listings and online store are updated daily, USP recommends referring to one of these sources prior to using a USP Reference Standard to make sure the lot is valid for use.  It is the responsibility of the user to ascertain that a particular lot of a USP Reference Standard has official status either as a "Current Lot" or as a "Previous Lot" within the valid use date.  View USP's policy statement on expiration dating of Reference Standards.

Performance Verification Tablets (Prednisone Tablets)

Please visit the Dissolution Performance Verification Testing (PVT) page of the USP website for detailed information. This page is updated as necessary. You can also access a free Webinar on Dissolution Performance Verification Testing at the above link.

  1. Where are the acceptance criteria for the current lot of USP Prednisone Tablets Reference Standard catalog #1559505?  I have heard that you have to calculate the geometric mean and %CV of your data.  How is that done? 

The USP Certificate for the USP Prednisone Tablets RS provides the acceptance criteria and formulas for the calculations.  Although the certificate provides the procedure for calculating the geometric mean and %CV for your Performance Verification Test (PVT) data, a more detailed discussion was provided in a Stimuli to the Revision Process article by Walter Hauck, et al., entitled "Description of the Upcoming Change in Data Analysis for USP Dissolution Performance Verification Tests" PF 34(6) [Nov–Dec 2008].  To help analysts with this calculation, USP has provided a Web-based tool; see Calculation Tool for the PVT of Dissolution Assemblies.

  1. How many runs have to be performed for the Performance Verification Test (PVT)?

USP's current approach for PVT calls for the performance of two consecutive runs including all positions of a dissolution instrument (Single-Stage Test approach).  The combined results for both runs will be evaluated and compared with the acceptance criteria corresponding to the Single-Stage approach.

Moreover, USP has implemented a Two-Stage Test approach that allows the analyst to evaluate the results of the first run and compare it with the acceptance criteria corresponding to the first stage (run) of the Two-Stage approach.  If the results are within the first-stage acceptance criteria, the PVT test can be stopped at this stage.

In case of an assembly with 12 or 14 positions, a single run (with all positions tested) is required for the PVT.

  1. Did the method to perform the PVT using the current lot change from the previous lot?

The method to perform the PVT has not changed from the previous lot.  USP provides some recommendations to help customers achieve a successful PVT in the Dissolution Toolkit.  The procedure for the PVT is given in the USP Certificate.

  1. What is the storage condition for USP Prednisone Tablets RS catalog #1559505?

USP Prednisone Tablets RS should be stored as per the label.  Please refer to General Chapter <659> for storage and handling definitions.

  1. When does a particular lot of USP Prednisone Tablets RS catalog #1559505 expire?

Unlike other USP Reference Standards, a Period of Validity is provided on the USP Certificate of USP Prednisone Tablets RS.  This date is final and will not be extended.  A specific lot should not be used after its assigned valid use date.

  1. Can I round the PVT dissolution results to whole numbers for calculation?

Per General Notice Section 7.20, numbers should not be rounded until the final calculations for the reportable value have been completed. Intermediate calculations may be rounded for reporting purposes, but the original (not rounded) value should be used for any additional required calculations.  In particular, the percent dissolved values should be retained to at least three decimals prior to calculation of the geometric mean and %CV.

  1. What should I do if the PVT for Apparatus 1 passes and then fails for Apparatus 2?

If nothing but the stirring elements are changed when switching from Apparatus 1 to Apparatus 2, then the PVT for Apparatus 1 is considered to be successful.  The cause of failure should be investigated and any adjustments made.  If the cause is the paddle stirring elements and no other changes are made, the PVT has to be repeated for Apparatus 2 only.  If any changes are made other than the replacement of the paddle stirring elements, the PVT should be repeated for both Apparatus 1 and Apparatus 2.


Please contact Reference Standard Technical Services (rstech@usp.org) with USP Reference Standard questions.  For questions related to USP monographs, please email stdsmonographs@usp.org.  For questions related to NF monographs, please email nfmonographs@usp.org.  Please contact Customer Service (custsvc@usp.org) for questions related to orders.