SC III E. British Pharmacopoeia Chemical Reference Substances (BPCRS)

1. The current list of BPCRS may be found on the BP’s website at www.pharmacopoeia.com. The quantity of material supplied is sufficient to carry out in duplicate each of the tests in which it is used in any one monograph.

Requirement

2. The establishment of a new BPCRS is based on scientific necessity following advice from the British Pharmacopoeia Commission’s Expert Advisory Groups. A reference substance for the medicinal substance is usually required for specific, stability-indicating assays and may also be required for identification purposes. A reference substance for an impurity is required when control using a dilute solution of the substance being examined is not possible or is undesirable. Such cases include those where the response factor of the impurity is significantly different from that of the substance, or where it is necessary to limit a named impurity (see Supplementary Chapter I A).

The following criteria are taken into account when determining whether a new BPCRS is required.

Availability of the material A commercially available reagent is specified wherever it is found to be suitable and justified.

Analytical convenience Wherever possible, either the same EPCRS or the same BPCRS is specified throughout any one monograph.

Establishment

3. Manufacturers who have contributed to the development of the monograph(s) are asked to supply material for use as reference substances. Normally, about 50 g is required for an Assay standard and about 10 g for an impurity. In some cases it is possible to use a quantity of the medicinal substance admixed with smaller quantities of the impurities as an impurity reference standard. It would be helpful if manufacturers could indicate the likely availability of reference materials at an early stage during monograph development.

4. The materials are tested by the Laboratory to confirm their suitability for the intended purpose and are made available not later than the effective date of the monograph in which they are used.

Monitoring and replacement

5. All substances used for quantitative analyses are re-tested every three years and materials used for qualitative analysis every five years unless experience has shown that more frequent testing is necessary.

6. When a BPCRS is due for replacement (because of a fall in quality or exhaustion), a review of the use of the material and the number of units supplied is carried out.

Continued availability

7. When a monograph is omitted from the Pharmacopoeia the last published monograph remains the legal standard. As the usual reason for omission is low and declining use or withdrawal of the material from the market, demand for any associated reference substances from within the United Kingdom is normally low.

8. It is not possible to maintain reference substances for omitted materials indefinitely and, for materials no longer marketed in the United Kingdom, it is difficult to obtain replacement stocks. As a service to analysts, reference substances for monographs omitted from the current edition of the Pharmacopoeia are normally retained for about five years from the date of publication of the current edition unless the material becomes unsatisfactory or the supply is exhausted before that date.

9. Demand is monitored and any significant increase in demand for a reference substance for an omitted monograph is noted. If such increased demand appears to stem from a renewed interest in the medicinal or pharmaceutical product, consideration may be given to reinstating the monograph in the Pharmacopoeia.