How can I order NIBSC products?
NIBSC products can be ordered online via our web catalogue. Please go to https://nibsc.org/login to register for an account.
How much of a product can I order?
Where there is a formal sales restriction on a NIBSC product, details are typically provided in the “customer notes” section of the product webpage. Where a restriction is in place, this is typically to allow sufficient time to develop and produce the replacement for that product.
WHO International Standards are intended to be used for calibration of secondary standards. While we acknowledge that some WHO IS are used on a routine basis by some laboratories, it is important to note that the frequent supply of large quantities for this purpose cannot always be guaranteed. We must carefully curate stocks of WHO IS to avoid the need for their frequent replacement, due to the resource and regulatory burden that this may cause.
What documentation do you provide with NIBSC products?
Details of the intended use, contents, unitage and handling/storage instructions are provided in an Instructions for Use (IFU) which can be downloaded from individual product webpages in the NIBSC catalogue.
In addition, the development and evaluation of all WHO IBRS is described in a detailed report which is submitted to the WHO Expert Committee for Biological Standardisation (ECBS). These reports are typically referenced in the product IFU (Section 9: References). Reports can be downloaded from the WHO website (2014-onwards), or can be provided upon request, via email to enquiries@nibsc.org.
We do not provide Certificates of Analysis (CoA) with our products.
What is the expiry date of a NIBSC product?
Where a product has an expiry date, it is stated on the product label, and typically in the “customer notes” section of the product webpage. Where expiry dates are given, they are based on robust real-time stability studies conducted on multiple batches of the product.
If no expiry date is stated on the product label or webpage, then the product does not have an expiry date. This is common practise for WHO IBRS, which remain valid with the assigned potency and status until they are withdrawn or amended. WHO IBRS are typically freeze-dried to maximise long-term stability during storage and transportation at ambient temperatures. For each WHO IBRS this approach is supported by a robust accelerated thermal degradation study, which provides assurances of the long-term stability of the product.
For more details of approaches to stability assessment for WHO IBRS, including accelerated thermal degradation studies, see the WHO “Recommendations for the preparation, characterisation, establishment and use of WHO international biological reference standards”.
Why was my order shipped at ambient temperature?
The majority of WHO IBRS (as well as some NIBSC Reagents and Working Standards) are freeze-dried in the presence of excipients and stabilisers, which affords them very high stability and enables lower cost shipping at ambient temperature. This is supported by data from accelerated thermal degradation studies, during which products are stored at elevated temperatures (up to +45 or +56oC) for periods of time (months to years) which far exceed typical shipment transit times. A small number of liquid formulation products are also shipped at ambient temperatures due to demonstrated high stability.
Cold chain shipping of these products can be requested if desired, the costs of which are invoiced to the customer. For a limited number of products, such as those in a frozen liquid formulation, or where it is advised based on our stability studies, cold chain shipping is routinely applied.
How should I store products upon receipt?
The recommended storage temperature for our products is typically stated on the product label, and/or the Stability section of the product Instructions for Use.
What diluent should I use to reconstitute and dilute a product?
Guidance for reconstitution and dilution of products may be provided in the Use of Material section of the product Instructions for Use (IFU). Guidance will vary for different products, depending on the nature of the analyte and its excipients/matrix. In some cases, the use of water may be advised (e.g. products derived from freeze-dried or plasma) but in other cases it is expressly not recommended. Customers should carefully read the IFU before using a product.
In the absence of specific guidance in the IFU, we may advise the use of a common buffer solution such as PBS, containing 0.1-0.5% of a carrier protein such as bovine albumin, to protect against adsorption of the analyte to container surfaces, and thus maximise recovery of the analyte. In practise, a wide variety of diluents may be suitable, depending on the assay in which the product will be used, and end users may perform their own assessment of the suitability of a particular diluent. Users should also consider the matrix of both the product and a typical test sample, as differences between buffer systems and biological matrices (e.g. plasma) may influence performance.
For how long is a product stable after reconstitution/first use? Can I aliquot and freeze it?
Our stability studies are typically limited to the freeze-dried product. Due to limited resources, we cannot routinely undertake post-reconstitution studies in a representative number of diluents, storage temperatures and durations. In limited cases where we do have supporting data on stability after reconstitution, guidance is typically provided in the Use of Material section of the product Instructions for Use (IFU).
In the absence of specific guidance in the IFU, customers are advised to perform their own assessment of stability after reconstitution in their chosen diluent at their desired storage temperature.
What is an International Unit (IU)?
Whilst a small number of WHO IBRS are value-assigned in units of the System Internationale (SI), e.g. mass, the majority are assigned in International Units (IU), enabling the assessment of complex biological products in a consistent, internationally harmonised manner.
IU are typically assigned in situations where physicochemical determination of SI units is not possible or not appropriate. This may be because there are no agreed validated reference measurement procedures available for SI-traceable quantitation, or because a mass value may not adequately describe the biological activity of the product (e.g. glycoprotein hormones, where the presence of particular glycoforms is required to ensure activity). As a result, units defined by a suitable reference preparation are required to quantify biological activity.
For most WHO IBRS, biological activity is demonstrated by relevant assays and for many IS is stated in IU. The IS thus defines the IU and also has a role in qualitatively defining what is being measured (the measurand). It is implicit that the IU has no existence other than in relation to the IS. For any new WHO IBRS, the numerical value assigned will typically be arbitrary, whilst any subsequent replacement WHO IBRS will be value assigned relative to the previous WHO IBRS, ensuring as much as possible that the continuity of the IU is maintained. The value assigned to replacement WHO IBRS will therefore be dependent on the value assigned to the previous WHO IBRS and on the combination of methods used to make the comparison.
What is the uncertainty of measurement of an assigned value?
In a strict metrological sense, the International Unit (IU) of activity for a biological analyte is defined by the contents of the ampoule of its corresponding IBRS. Every effort is made to maintain the continuity of the IU when an IBRS is replaced, however a current IBRS is not formally traceable to its predecessor(s), only to the physical content of the existing IBRS. For this reason, no uncertainty of measurement is applied to an IBRS.
Where a WHO IBRS is value-assigned in SI (System Internationale) units, such as mass per vial/ampoule, a true statistically derived uncertainty of measurement is typically provided in the Unitage section of the product Instructions for Use (IFU).
Is there a conversion factor from IU to SI units?
In most cases, WHO IBRS are value-assigned in IU because assignment in SI units is not possible, or not advisable because expression of results in SI units does not adequately describe the biological potency of the test article. Value assignment in IU is therefore considered the best option to promote global harmonisation of products or tests from different manufacturers performed in different laboratories and thereby avoid the lack of harmonisation which may arise through attempting to express results in SI units or an absolute measure of biological response.
Consequently, where a WHO IBRS is value-assigned in IU, there is typically not an established or validated conversion factor into SI units. Establishing a formal link between IU and SI units would serve to define a “specific activity” (or “specific potency”) to the WHO IBRS, which is often not appropriate because the specific activity/potency of preparations of the same biological molecule(s) from different sources may vary.
In some cases, the IU value is derived from a study consensus value combining results reported in various alternative units (for example, NAT standards for infectious disease diagnostics are typically assigned in IU, using a value converted from a consensus of results from multiple laboratories expressed in NAT-detectable Units, or copies/mL). However, in such cases, the assignment in IU is not intended to establish a conversion factor from IU to an alternative unit and should not be treated as such.
In exceptional cases, where a robust conversion factor between IU and SI units has been experimentally determined, this will be stated in the Unitage section of the product Instructions for Use. For example, whilst human Insulin potency was historically measured in IU, subsequent advances in physicochemical methodology enabled accurate quantitation in mass units. Today, it is routinely quantified in mass units, with an established conversion factor into IU, as reflected by the value-assignment of the WHO International Standard.
The contents section of the Instructions For Use for a product which is assigned in IU states a nominal content in mass units – can I use this value instead?
Only the assigned value stated in the Unitage section of a product Instructions for Use (IFU) should be used for experimental purposes. The contents section of an IFU is intended to provide information about the full list of contents of a vial/ampoule of a product (including excipients) and is also important for customs purposes. This section of the IFU typically includes the quantity of the biological target in mass units, however these are nominal values; estimates based on dilutions made to bulk materials, prior to freeze-drying, during which small losses of material are to be expected. Nominal contents values are not experimentally derived values and should not be used for experimental purposes under any circumstances.
How should I use a WHO IBRS to calibrate my secondary standard or assay?
General guidance on the development and calibration of a secondary standard using a WHO IBRS is provided in the “Recommendations for the preparation, characterisation, establishment and use of WHO international biological reference standards” (Part B).
Further guidance is also provided in WHO manuals for different types of secondary standards:
WHO manual for the establishment of national and other secondary standards for vaccines
WHO manual for the preparation of secondary reference materials for in vitro diagnostics designed for infectious disease nucleic acid or antigen detection: calibration to WHO International Standards
WHO manual for the preparation of reference materials for use of secondary standards in antibody testing