Reference product and reference product are two different concepts, which have been clearly defined in the Chinese Pharmacopoeia: the reference product refers to the reference substance used for identification, inspection, content determination and calibration of the performance of the calibration instrument, while the standard product refers to the reference substance used for bioassay, antibiotic or biological drug content or titer determination. In the literature, the two concepts are often confused, and the reference product is the standard product, which is only one substance and two formulations. The reason for the error may be that some drugs have both reference products and standard products.

The question of what is the difference between the reference and the standard is a very common problem in medicine; In fact, the reference product and the standard product are two completely different concepts in a strict sense, but they have one thing in common, that is, they belong to the national standard substances, and there are clear records in the Chinese pharmacopoeia, next let's take a look at the difference between the reference product and the standard product, and the related issues involved.

First, the concept of standard products and reference products

Reference substance refers to the standard substance used for identification, inspection, content determination and calibration of the performance of the calibration instrument.

Reference substance refers to a reference substance used for the determination of content or titer in biological assays, antibiotics or biological drugs, expressed in titer unit (U).

National standard products and biological reference products refer to reference substances used for identification, inspection of content or titer determination, the preparation and calibration of which shall comply with the requirements of the "Preparation and calibration Procedures of National Standard Substances for Biological Products", and shall be distributed by the institution designated by the drug regulatory department under The State Council. Enterprise working standards or reference products must be standardized by national standards or reference products before use.

Reference line refers to a specific substance used for the physical and chemical determination of biological products, prepared by the production unit using the same method as the production process of the product. The reference product should be as consistent as possible with the formula of the product stock, and if the stability is poor, it can be added without appropriate stabilizer that interferes with the determination of substances. The reference product shall be reviewed and approved by the national drug verification agency, and its standard shall not be lower than the quality standard of the product.

The national drug standard material is the material basis of the national drug standard, which is a special measuring tool used to check the quality of drugs. It is the benchmark for measuring drug quality; It is also used as a material standard for calibration of test instruments and methods; In drug testing, it is a control to determine the authenticity of drugs, is an essential tool to control the quality of drugs. At present, the China Institute for the Inspection and Control of Pharmaceutical and Biological Products has been able to provide all kinds of national standard substances 1242, of which 288 kinds of traditional Chinese medicine chemical reference, 400 kinds of control medicinal materials, both of which account for more than half of the total. National drug standards and reference strains refer to the standard substances used in the national drug standards for identification, inspection, content determination, inspection of impurities and related substances, which are an integral part of the national drug standards.

2. Standard products and control varieties

Standard substances for biological products are divided into two categories:

1. National biological standards

Refers to a standard substance labeled with an international standard, or developed by our country (there is no international biological standard) for the quantitative determination of the titer or toxicity of a product, and its biological activity is expressed in international units (IU) or units (U).

2. National biological reference

National biological reference strain refers to a biological reagent, biological material or specific antiserum labeled with an international reference product, or developed by China itself (there is no international reference product) for the qualitative identification of microorganisms (or their products) or disease diagnosis; Or refers to a reference substance used to quantitatively detect the biological titer of certain products, such as a reference substance used to determine the titer of live measles vaccine or the flocculent unit of toxoid, where the titer is expressed in specific units of activity, not in (IU).

Third, how to distinguish between reference products and standard products

The standard is the reference standard for determination of content by microbial method.

Reference products are standards for the determination of content by instrumental analysis or other analytical methods, both of which are provided by the national designated department of China Biological Products Inspection.

Reference strains are reference substances used for identification, inspection, content determination, and calibration of the performance of testing instruments.

Standard strain refers to a standard substance used in bioassay, antibiotic or biologic drug determination of dosage or titer, expressed in titer unit (U).

The mixing of reference or standard, that is, the use of reference or standard for content determination other than its calibration method, is a frequent but neglected problem in drug testing. Although the content of different calibration methods in the same batch of reference products has a good correlation, it is not exactly the same, and sometimes the difference is very large. For example, the reference of cefuroxime ester provided by Glaxo Company in the UK was labeled as 96.9% by HPLC for content determination. UV was 98.8% for dissolution determination. Although the Chinese Pharmacopoeia Code clearly stipulates that the reference products issued by the Ministry of Health should only be used for the analytical methods specified in the text. But because:

(1) The manual for use of reference products provided by the Ministry of Health is not detailed enough, and most of them have no quality requirements and calibration methods for reference products;

(2) Lack of knowledge of the proper use of reference or standard products;

(3) It is extremely difficult to find corresponding control products in daily scientific research;

(4) There is often a problem of mixing reference products in the text of Chinese pharmacopoeia. For example, the standard product or reference product used for content determination is often used for dissolution check, and the content determination method is different from the dissolution analysis method, so it is easy to cause mixing.

The above content is the introduction of the concept of standard products and reference products, the difference between standard products and reference products using biochemical methods to determine the standard products, the current national standard products a total of 15 kinds, It is macroscopin, gentamicin, thalomycin, kanamycin, erythromycin, choriotrophin, guitin, bacitracin zinc, saltase, synthetic oxytocin, Lincoenzyme, streptomycin, amplase, ferricoside G, neomycin.