usp reference standard exp date

Reference Standards

General

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

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 (62KB), or read our Document Disclosure Policy).

1.

What is the specific purity of individual USP Reference Standards?

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.

2.

How do USP Units convert to International Units?

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.

3.

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

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 "–"punctuations. For example

ItemOld Item

No.

New Item

No.

Acetaminophen (400 mg) 00300–9 1003009

Brompheniramine Maleate(125 mg)

07800–8 1078008

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.

4.

What is USP's Policy on Product Recalls?

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.

5.

Use and Applications

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 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).

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Are USP Reference Standards suitable for applications not specified in the USP–NF?

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.

7.

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

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)

8.

Do USP Reference Standards require any special preparation before use?

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.

9.

Why is USP not requiring annual recertification of the USP Near Infrared System Suitability Reference Standard?

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.

10.

Shipping and Storage

Where can I find information on labeling and storage of USP Reference Standards?

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.

11.

Do USP Reference Standards require special shipping?

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.

12.

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

Special instructions for orders from outside of the United States can be found in our purchasing support section, or by clicking here.

13.

Availablity

What happens if a new Reference Standard specified in a monograph is not yet available from USP?

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

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Standard becomes available for the first time, use the New Reference Standards Release Notification Service.

What if an existing Reference Standard is currently not available from USP?

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 ([email protected]) 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 protected].

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.

15.

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.

Where are the acceptance criteria for the new lot of Prednisone Tablets? I have heard that you have to calculate the geometric mean and

%CV of your data. How is that done?

The certificate for Prednisone Tablets RS Lot P1I300 provides the acceptance criteria and formulas for the calculations. Access this

certification 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 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.

16.

How many runs have to be performed for the Performance Verification Test?

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.

17.

What are the differences between Q0H398 and Lot P1I300?

The packaging configuration has been changed - lot Q0H398 tablets are now individually packaged in blister packages.1.

The certificate has added PVT limits for 14 positions.2.

18.

Did the method to perform the PVT of Lot Q0H398 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. These details are given in the USP Certificate of USP Prednisone Tablets RS Lot Q0H398. [Access this Certificate online]

19.

What is the storage condition for USP Prednisone Tablets RS Lot Q0H398?

Lot Q0H398 should be stored in a dry place at controlled room temperature not exceeding 25º 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 20º to 25º (68º to 77ºF) allowing for excursion to 15º(59º F).

20.

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

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.

21.

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

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replacement of the paddle stirring elements, the PVT should be repeated for both Apparatus 1 and Apparatus 2.

Why do the acceptance criteria use the geometric mean rather than arithmetic?

Experience with this lot of Prednisone Tablets RS and prior PVT collaborative studies have shown that the data are better analyzed in the log

scale to improve the normality assumption. The acceptance limits are actually for the arithmetic mean and standard deviation in the log

scale. The limits are converted back to the percent dissolved scale to make them more interpretable. This conversion changes the arithmetic

mean and standard deviation into a geometric mean and %CV. See the 2008 Stimuli Article for details.

23.

The %CV requirement in the new acceptance criteria seems incredibly tight. We have data that pass the current Lot P0E203 ranges and

yet would fail the new criteria based on the %CV requirement. Has USP made the test more difficult to pass?

There was no intent to make the test more difficult to pass. However, it is different, so some data that would pass the previous test could fail

the new one and vice versa. The %CV requirement is based on the estimate of within-laboratory variability from the participants in the

collaborative study for Lot P1I300.

24.

Have the storage conditions been changed for USP Prednisone Tablets RS Lot P1I300?

Historically, this standard has been stored at room temperature. Lot P1I300 should be stored in a dry place at 15°–25°.

25.

I failed %CV with the new lot. What should I do?

The limits on %CV are to ensure that the dissolution test assembly acts as an integrated unit. When a dissolution assembly fails to pass the

%CV limit, we recommend that lab personnel check the equipment and test procedure according to USP's published Dissolution Toolkit,

version 2 make the necessary adjustments, then repeat the PVT.

26.

What is the difference between Lot P0E203 and Lot P1I300?

Please see Notice to Purchasers of USP Prednisone Tablets Lot P1I300 Concerning Relabeling.

27.

Why is there a difference in the %CV acceptance limits between the Single-Stage and the second stage of the Two-Stage tests? Shouldn't

they be the same?

The current approach for the PVT is designed as a Single-Stage approach consisting of performing two consecutive runs. This means that

for an 8-position dissolution assembly, 16 individual values are generated and evaluated together at the end of the second run. A laboratory

may choose to implement the PVT as a Two-Stage approach (group sequential design). The Two-Stage approach allows the possibility to

stop the test at the first stage (run); however, a kind of penalty has to be paid for the possibility of stopping after the first stage (run). This is

to control the probability of falsely passing the test—the more opportunities there are to pass, the higher the false pass rate will tend to be. In

the acceptance table for the Two-Stage approach, the accept/reject decision rules are more stringent at the first stage than at the second.

The penalty is that the acceptance values for the second stage (run) are tighter than those of the Single-Stage approach although the

number of the individual values evaluated is the same. (If the limit at the end of the Two-Stage design were the same as for the Single-Stage,

there would necessarily be an increase in the false pass rate owing to the possibility of passing at the first stage.) The first stage values

were chosen to make the second stage values similar to those from a Single-Stage test. It happens that the limits for the geometric mean

appear not to change, but that is due to rounding and would show the same penalty if shown to more decimals.

28.

Certified Reference Material (CRM)

What is a USP 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.

29.

How do I use a CRM?

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.

30.

What should I do with my past and future results, if I am a current purchaser of a USP Reference Standard that has now become a USP

CRM?

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.

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What should I do about the uncertainty of my house standard, if I use the USP CRM to make the house standard?

You may propagate the uncertainty of your house standard using the standard uncertainty of the USP CRM3,4

.

32.

Why is USP authorized to produce CRMs?

USP is ISO Guide 34 accredited as a Reference Material producer (RMP) of Chemical CRMs.

33.

Why is USP producing 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.

34.

What are the benefits of a USP CRM?

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.

35.

What do I do with the certificate? What do I do with the certified property value and the uncertainty value?

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.

36.

Is there a difference between acceptance criteria and certified property value and uncertainty (CRM)?

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.

37.

Does the USP CRM cost more than the USP Reference Standard?

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.

38.

How many more USP CRMs will be available for purchase?

USP is committed to producing CRMs, and you can expect to find more available to purchase each year.

39.

What if the COA is lost or removed from the packaging?

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."

40.

May I buy just the USP RS without the certificate?

If the CRM is available, the reference material will be sold only as a CRM.

41.

Why does a USP CRM have an expiration date (period of validity) and what does the expiration date mean?

The expiration date (period of validity) of a CRM is required by ISO Guide 31 [1]. 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.

42.

If a CRM/Reference Standard lot is exhausted, which expiration date should be used, the valid use date of the Reference Standard/CRM lot

or the COA period of validity?

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

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Copyright © 2012 The United States Pharmacopeial Convention

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).

References

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.


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