Laboratory Practice Session 01

COMMON APPROACHES FOR QUALITY CONTROL OF DRUGS. HARMONIZATION OF PHARMACOPOEIAS

I. Questions and tasks for discussion:

1. Explain the differences between the terms – «drug», «medicine», «pharmaceutical substance», «dosage form».
2. What are the regulations of medicines quality and at what stages of drug preparation it is necessary to use them?
3. What is Pharmacopeia, State Pharmacopeia?
4. Explain differences between the two types of regulations – «individual monographs» and «general monographs.
5. What do you know about the world's leading pharmacopoeias (Ph. Eur., USP and JP)?
6. List the features of the International Pharmacopoeia.
7. List the main features of the British Pharmacopoeia.
8. What is the harmonization of the pharmacopoeias?
9. Clarify the abbreviations: ICH, EDQM, PDG, PMDA, USP? What are the main purposes of these organizations?

II. Examine and compare general articles of leading world pharmacopoeias.

Examine the proposed articles (appendix 1) from different pharmacopoeias: European, Japanese and U.S. Pharmacopoeia. Pay attention to the article title and to the pharmacopoeial section, which includes this article. Find similarities and differences in the methods of analysis. Fill the table according to the plan:

1. Identify the purpose of the test – which drug qualities does it determine?
2. Depict the general scheme of the test, write (where possible) chemical reaction equation.
3. Indicate test conditions: reagent concentration, temperature, time, etc.
4. Make a conclusion about the harmonization degree of these pharmacopoeial articles.

№	Ph. Eur. (7^th ed.)	JP (16^th ed.)	USP (31^th ed.)
1	2. Methods of analysis 2.4. Limit tests   2.4.13. Sulfates	1. Chemical Methods   1.14. Sulfate limit test	Chemical tests and assays, Limit tests   221. Chloride and Sulfate
2	-	1. Chemical Methods   1.15 Readily carbonizable substances test	Chemical tests and assays, Limit tests   271. Readily carbonizable substances test
3	2. Methods of analysis 2.4. Limit tests   2.4.14. Sulfated ash	2. Physical Methods   2.44. Residue on Ignition test	Chemical tests and assays, Limit tests   281. Residue on Ignition test
4	2. Methods of analysis, 2.2. Physical and physicochemical methods   2.2.32. Loss on drying	2. Physical Methods   2.41. Loss on drying test	Physical tests and determinations   731. Loss on drying
5	Loss on ignition – test is included in monographs	2. Physical Methods   2.43. Loss on ignition test	Loss on ignition – test is included in monographs

III. Study the table below. Find and represent in writing form similarities and differences in Pharmacopoeias

European Pharmacopoeia (Ph. Eur.) Inter-governmental	United States Pharmacopoeia Independent of government	Japanese Pharmacopoeia Governmental
The European Pharmacopoeia of the Council of Europe is a pharmacopoeia, listing a wide range of active substances and excipients used to prepare pharmaceutical products in Europe. It includes more than 2000 specific and general monographs, including various chemical substances, antibiotics, biological substances; Vaccines for human or veterinary use; Immunosera; Radiopharmaceutical preparations; Herbal drugs; Homoeopathic preparations and homoeopathic stocks. It also contains Dosage forms, General monographs, Materials and Containers, Sutures; 268 General methods with figures or chromatograms and 2210 reagents are described. The monographs give quality standards for all the main medicines used in Europe. All medicines sold in the 36 Member States of the European Pharmacopoeia must comply with these quality standards so that consumers have a guarantee for products obtained from pharmacies and other legal suppliers. The European Pharmacopoeia is developed by the European Directorate for the Quality of Medicines (EDQM) and is a part of the Council of Europe, Strasbourg, France. It has been created by the Convention on the elaboration of a European Pharmacopoeia from 1964. Currently there are 37 members of the European Pharmacopoeia Commission: Austria, Belgium, Bosnia and Herzegovina, Bulgaria, Croatia, Cyprus, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Montenegro, Netherlands, Norway, Poland, Portugal, Romania, Serbia, Slovak Republic, Slovenia, Spain, Sweden, Switzerland, Republic of Macedonia, Turkey, United Kingdom, and the European Union. In these countries and the European Union the Ph. Eur. is the official pharmacopoeia. Additional local pharmacopoeias may exist (e. g. in United Kingdom and Germany). Not all of these countries are member states of the European Union. Observers from 20 member and non-member states of the Council of Europe and international organizations take part on sessions of the European Pharmacopoeial Commission: Albania, Algeria, Australia, Belarus, Brazil, Canada, China, Georgia, Israel, Madagascar, Malaysia, Morocco, Kazakhstan, Russian Federation, Senegal, Syria, Tunisia, Ukraine, United States of America, and the WHO.   7^th edition	It is the official pharmacopeia of the United States, published dually with the National Formulary as the USP-NF. The United States Pharmacopeial Convention (usually also called the USP) is the nonprofit organization that owns the trademark and copyright to the USP-NF and publishes it every year. Prescription and over-the-counter medicines and other health care products sold in the United States are required to follow the standards in the USP-NF. USP also sets standards for food ingredients and dietary supplements. The United States Pharmacopeia and The National Formulary (USP–NF) is a book of public pharmacopeial standards. It contains standards for (chemical and biological drug substances, dosage forms, and compoundded preparations), excipients, medical devices, and dietary supplements. USP–NF is a combination of two compendia, the United States Pharmacopeia (USP) and the National Formulary (NF). Monographs for drug substances, dosage forms, and compounded preparations are featured in the USP. Monographs for dietary supplements and ingredients appear in a separate section of the USP. Excipient monographs are in the NF. A monograph includes the name of the ingredient or preparation; the definition; packaging, storage, and labeling requirements; and the specification. The specification consists of a series of tests, procedures for the tests, and acceptance criteria. These tests and procedures require the use of official USP Reference Standards. Medicinal ingredients and products will have the stipulated strength, quality, and purity if they conform to the requirements of the monograph and relevant general chapters. Tests and procedures referred to in multiple monographs are described in detail in the USP–NF general chapters. The General Notices provide definitions for terms used in the monographs, as well as information that is necessary to interpret the monograph requirements. USP is proposing to revise the General Notices for the USP and NF. The U.S. Federal Food, Drug, and Cosmetics Act designates the USP–NF as official compendia for drugs marketed in the United States. A drug product in the U.S. market must conform to the standards in USP–NF to avoid possible charges of adulteration and misbranding. 31^th edition	Japanese Pharmacopoeia (JP) is a book of official pharmaceutical standards in Japan, prepared by the JP secretariat in PMDA and established by the MHLW. It is evaluated and reviewed in expert committees periodically held by the JP secretariat. Pharmaceuticals and Medical Devices Agency (PMDA) is an incorporated administrative agency, established under the Act on PMDA in 2004. It conducts scientific and technical evaluations and reviews on pharmaceuticals and medical devices under the entrustment and medical devices, under the entrustment from the Ministry of Health, Labor and Welfare (MHLW). 17^th edition

IV. Read the sentences. Say, if it is true (T) or false (F)?

1. Readily Carbonizable Substances Test is a method to examine the minute impurities contained in drugs, which are readily colored by addition of concentrated acetic acid.
2. Loss on ignition test is carried out for drugs of organic nature, which lose a part of the components or impurities during ignition.
3. Loss on Ignition Test is a method to measure the loss in mass when the sample is ignited under the conditions specified in monograph.
4. To conduct Loss on drying test you can dry the substance in exsiccator at 101,3 kPa or under vacuum (different pressure, sometimes with heating) and in the oven at temperature, specified in monograph.
5. In Sulfate limit test the solution of BaCl2 is used as a reagent, and the standard solution of H2SO4 is used as a control solution.
6. Residue on ignition test (Sulf ated ash) is necessary stage of heavy metals limit test. Residue on ignition test is carried out at T > 400^oC in the presence of H2SO4

V. Look at the scheme. Cross out the direction where sulfuric acid is not required during the test:

VI. Self-test:

1. What is pharmacopoeias harmonization (negotiation)?
   1. The development and implementation of standards of medicines as the basis of their safety and effectiveness.
   2. The free movement of medicines in Europe.
   3. Quality assurance of drug substances and excipients when importing or exporting from Europe.
   4. Coordinated control of production and quality of medical products in connection with the free movement of medicines.
2. Pharmacopoeia harmonization – is harmonization of requirements for quality of medicines between:
   1. European countries.
   2. Europe and Russia.
   3. Britain, France and the USA.
   4. European Pharmacopoeia, the U.S., Japan and other countries pharmacopoeias.
3. According Ph.Eur. in the test «loss on drying» the substance is dried under conditions:
   1. In an exsiccator over a reagent to absorb water.
   2. In vacuum.
   3. In vacuum at a given temperature.
   4. In an oven at a certain temperature.