With the exception of CRMs, USP does not provide COAs. All information for official uses of a Reference Standard may be found on the label of the standard and, where needed, in the additional data sheets shipped with the standard. Test results and data that are not included in these additional data sheets cannot be shared because of confidentiality rules. USP does provide Material Safety Data Sheets (MSDS) for all Reference Standards and USP Certificates for some Reference Standards. USP Certificates do not completely describe the test results obtained during evaluation. Rather, they are issued to provide customers with additional information such as a hard copy of the USP RS label text, storage & handling conditions, concentrations (special cases), and typical chromatograms (limited cases). These certificates, when available, can be viewed on our Web site by clicking on the Product Description link for an item in our online catalog. (View USP's policy statement on Certificates of Analysis for Reference Standards, or read our Document Disclosure Policy).
Unless otherwise specified on the label, all USP Reference Standards are 100.0% pure for compendial use in quantitative applications. This applies only to USP Reference Standards intended for quantitative purposes in compendial procedures. Those intended only for qualitative purposes are not assigned a purity value. The USP Catalog and RS label contains the labeled values for the current lot of all quantitative USP Reference Standards. These labeled values are intended for only specific quantitative USP compendial applications.
USP Endotoxin Units are identical to International Units. Relationships for other USP Reference Standards must be determined on a case–by–case basis. Please refer to the USP monograph of a specific material for further information.
In July 2002, USP decided to improve the numbering system for all of our Reference Standard products. USP added a "1" as the first digit of the item number and removed the "–". For example
Item Old Item No. New Item No. Acetaminophen (400 mg) 00300–9 1003009 Brompheniramine Maleate (125 mg)
The item numbers on labels of USP products were not changed until the next lot was available for each product. Based on inventory levels and the demand for each Reference Standard, this process could take an extended period of time to complete.
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.
It is not common for USP to have a product recall. If the product is determined to no longer meet the compendial requirements, USP will notify customers who purchased the product in the last 12 months.
Use and Applications
USP Reference Standards are intended for test and assay use only as per USP compendia; they are not intended for administration to humans or animals as drugs or medical devices. (View USP's policy statement on the storage and usage of Reference Standards).
You may be able to use USP Reference Standards for analytical or laboratory applications other than those specified in the USP–NF, but you are responsible for determining the suitability of the standards for the required purposes.
USP Reference Standards do not carry an expiration date as long as they are in distribution. A lot of USP RS may be used in its official applications as long as it is listed as "Current Lot" in the current (most recent) Official USP Reference Standards Catalog. Upon depletion, the lot is designated in the catalog as "Previous Lot" and a "Valid Use Date" is assigned. The last day of the indicated month represents the expiration date for the specified lot (e.g., "F–1 06/02" means lot F–1 was considered official through June 30, 2002). The official USP Reference Standards Catalog is published bimonthly online and every four months in print. The USP Daily Reference Standards Catalog is updated daily. It is the responsibility of the user to ascertain that a particular supply of 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)
Any specific directions for use are provided on the label of the Reference Standard and/or on its USP Certificate. Some standards can be used as–is but others may require drying before use or correction of the labeled valued 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. See Use and Storage for more details.
The USP Near Infrared 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 continuous suitability for use program. For more details, download our official statement.
Shipping and Storage
USP's policy is to include proper storage conditions for unopened Reference Standards on the container label. Storage conditions are lot–specific. 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 purchaser. (View USP's policy statement on the storage and usage of Reference Standards).
Labeling and storage information for USP Reference Standards is also provided in USP–NF General Chapter <11> USP Reference Standards. If the specific label instructions differ from the instructions in USP–NF (this may happen if the labels are updated before a new edition of USP–NF is published), the instructions on the label take precedence. See the Use and Storage section on our website for more details.
USP Reference Standards are not customarily shipped on ice or under refrigerated conditions. The storage conditions noted on the Reference Standard vial or packaging are intended to preserve the integrity of the Reference Standard during long–term storage. Shipping conditions are determined based on the stability information for individual Reference Standards and transit times. If scientific evidence suggests the need to ship a Reference Standard on ice or dry ice, USP will do so. (View USP's policy statement on shipping of Reference Standards.) Shipping on ice or dry ice is available for all 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.
Special instructions for orders from outside of the United States can be found in our purchasing support section, or by clicking here.
Requirements for any new standards, tests, or assays in USP compendia will typically not go into effect unless the specified USP Reference Standards are available from USP. The availability of new Reference Standards and the official dates of the USP compendial standards, tests, or assays requiring their use are announced in USP–NF or its Supplements, other official USP compendia (ie. FCC), or in the Interim Revision Announcements published in USP's Pharmacopeial Forum or in the FCC Forum. To learn when a particular new Reference Standard becomes available for the first time, use the New Reference Standards Release Notification Service.
The availability of USP Reference Standards is generally better than 99 percent and we strive to plan ahead to replace depleted lots in a timely manner. We project a depletion date for each Reference Standard lot based on historic trends. However, despite our best efforts, some Reference Standards might occasionally be out of stock temporarily. Contact your USP Account Manager or Reference Standards Technical Service (firstname.lastname@example.org) to find out when the specific Reference Standards you are looking for might become available again. You can also frequently check the product listings on USP's e–store or sign up for our email notices, which will keep you informed about Reference Standards that become available. To sign up for the email notice service, email email@example.com.
You can place an order now for Reference Standards that are not currently in stock. Products that become available within 30 days of your order will be shipped to you automatically. If the products become available after 30 days, USP will send you a Notice of Availability to get your confirmation before shipping the order.
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.
The certificate for Prednisone Tablets RS Lot Q1L136 provides the acceptance criteria and formulas for the calculations. Access this Certificate online. 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.
USP's current approach for the 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.
The method to perform the PVT has not changed from the previous lot. USP provides some recommendations to help customers achieve a successful PVT. These details are given in the USP Certificate of USP Prednisone Tablets RS Lot Q1L136. Access this Certificate online.
Lot Q1L136 should be stored in a dry place at controlled room temperature not exceeding 25°C. Per General Notices, controlled room temperature means a temperature maintained thermostatically that encompasses the customary working environment with the average relative humidity not exceeding 40%, and the temperature of 20° to 25° (68° to 77° F) allowing for excursion to 15° (59° F).
Per General Notices, intermediate results are not to be rounded. In particular, the percent dissolved values should be retained to at least three decimals prior to calculation of the geometric mean and %CV.
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.
Certified Reference Material (CRM)
A USP Certified Reference Material (CRM) is a USP Reference Standard with a "pedigree." It should be used as a USP Reference Standard. A CRM is a special class and the next generation of a USP Reference Standard that has undergone additional metrologically based testing and statistical analysis. The USP CRM is issued with a Certificate of Analysis (COA), listing a certified property value with its associated uncertainty, expiration date, and other information, according to ISO Guide 311. The one or more property values are certified by a procedure that establishes its traceability to an accurate realization of the unit in which the property values are expressed2.
Since a USP CRM is a USP Reference Standard, it should be used in the same way in which you would use a USP Reference Standard. The user should follow the current monograph and label instructions.
Nothing needs to be done concerning past and future results, since a CRM is also a Reference Standard. A measurement uncertainty may be calculated using information from the USP COA and your experimental data, if appropriate.
You may propagate the uncertainty of your house standard using the standard uncertainty of the USP CRM3,4.
USP is ISO Guide 34 accredited as a Reference Material producer (RMP) of Chemical CRMs.
USP is the first global pharmacopeia to produce CRMs to meet the increasingly demanding measurement needs of the industry. USP has always produced quality reference materials and the CRMs are a further improvement in the final product by advancing the metrological science of our Reference Standards. The purpose of the CRMs is to provide a higher degree of confidence in the analytical measurement that leads to decisions regarding product specification and acceptance limits.
A USP CRM is a means to establishing trueness and traceability to the measurement system, thereby allowing and enabling consistency and comparability of measurements and results over periods of time and among laboratories. Traceability and uncertainty of measurement are important components in the documentation for ISO 17025 requirement for testing labs.
The CRM COA provides confidence in the property value(s), measurement traceability, and internal and external quality assurance. The CRM certified property value may be used for calibration, comparison, or value assignment. The CRM user is able to propagate uncertainty to the final result, and is able to make meaningful comparisons of measurement results.
The acceptance criteria and certified property value and uncertainty (CRM) are completely different concepts derived from different principles. The CRM provides trueness of measurement, an assigned value and how far from that value the actual value can be with a stated level of confidence. The monograph limits are specified in the appropriate compendial monograph. Acceptance criteria are determined by the customer. The CRM contributes neither to the product specification nor the acceptance criteria. The proper implementation and integration of a CRM into the measurement process lends assurance the specifications and acceptance criteria are met.
Initially, the price of the USP CRM will be the same as the USP Reference Standard. This improvement in the final product is presently an additional bonus to your purchase at USP Reference Standard prices.
USP is committed to producing CRMs, and you can expect to find more available to purchase each year.
A copy of the certificate is available on the Reference Standards Web site listings; select the CRM name and then click on "View" next to "USP Certificate."
If the CRM is available, the reference material will be sold only as a CRM.
The expiration date (period of validity) of a CRM is required by ISO Guide 31 . The CRM property value and uncertainty is applicable to the unopened vial for the stated period of validity. It is expected that the USP Reference Standard will be used when opened. 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, hence CRMs. Decisions concerning the proper use of previously opened Reference Standards are the responsibility of the purchaser.
If a CRM/Reference Standard lot is exhausted, the earlier date takes precedence. For example, if the valid use date of a USP Reference Standard/CRM is September 2009 and the CRM COA is September 24, 2010, the valid use date of September 2009 should be used. The date that comes first (valid use date or period of validity) always takes precedence. The CRM certified property value is valid for the stated period of validity on the CRM COA. If the valid use date comes before the CRM COA period of validity and the valid use date has past, the material is no longer a Reference Standard and cannot be used for official compendial uses. FDA requirements for an official Reference Standard would not be met. However, the material may be used as a CRM (i.e., check standard).
1 ISO Guide 31, Reference Materials, Contents of Certificates and Labels. 2nd ed. Geneva, Switzerland: ISO; 2000.
2 ISO Guide 30, terms and definitions used in connection with reference materials. Geneva, Switzerland: ISO; 1992.
3 "Guide to the Expression of Uncertainty in Measurement", ISO, 1993.
4 Barry N. Taylor and Chris E. Kuyatt, "Guidelines for Evaluating and Expressing the Uncertainty of NIST Measurement Results", NIST Technical Note 1297, 1994 Edition.