International Conference on Harmonization ich. Report on the research work “Development of the Concept for ensuring the quality of medicines in the Russian Federation. Some progress in harmonization
- creating a forum for constructive dialogue between regulatory authorities and the pharmaceutical industry regarding the existing and objective differences in registration requirements in the US, EU and Japan in order to ensure faster implementation of new medical products and patient access to them; participation in the protection of public health from international prospects; monitoring and updating harmonized technical requirements leading to greater mutual recognition of drug research and development data; eliminating future different requirements by harmonizing selected areas necessary for the further development of therapeutics and new technologies for the production of medical products; ensuring the dissemination and understanding of harmonized guidelines and approaches that update or replace current provisions and allow for more economical use of human and material resources without compromising safety; ensuring the dissemination and understanding of harmonized guidelines, their use for the implementation and unification of common standards.
- From the European Union, the European Medicines Agency (EMEA) and the European Federation of Pharmaceutical Manufacturers and Associations (EFPIA) participate in the work of the ICH. From the USA, the ICH includes the US Food and Drug Administration (FDA) and the US Pharmaceutical Development and Manufacturers Association (PhRMA). From Japan, the Medicines and Medical Devices Agency of the Ministry of Health, Labor and Social Affairs of Japan and the National Institute of Health Sciences, as well as the Japanese Pharmaceutical Manufacturers Association (JPMA) are participating in the harmonization work.
- safety
Document code | Manual title |
Mutagenicity tests |
|
| S1A | The need to study the mutagenicity of drugs |
| S1B | Testing for mutagenicity of drugs |
| S1C(R1) | Selection of doses for mutagenicity studies of drugs and dose limits |
| S2A | Guidance on specific aspects of regulatory genotoxicity testing for drugs |
| S2B | Genotoxicity: A Standard Battery for Genotoxicity Testing of Pharmaceuticals |
| S3A | Toxicokinetics Guidance Note: Estimation of Total Exposure in Toxicity Studies |
| S3B | Pharmacokinetics: A Guide to Repeated Dose Tissue Distribution Studies |
Toxicity Test |
|
| S4 | Single dose toxicity tests |
| S4A | Duration of continuous animal toxicity testing (Rodent and non-rodent toxicity testing) |
Generative toxicology |
|
| S5(R2) | Detection of reproductive toxicity of medical products and reproductive toxicity in men |
| S5A | ICH Support Male Fertility Toxicity Guidelines |
Biotechnological products |
|
| S6 | Assessment of preclinical safety of biotechnologically derived drugs |
Pharmacology research |
|
| S7A | Safety pharmacology studies for human drugs |
| S7B | Non-clinical assessment of the potential for delayed ventricular repolarization (QT prolongation) of drugs in humans |
Immunotoxicological studies |
|
| S8 | Immunotoxicological studies on human drugs |
- efficiency
Clinical Trial Safety |
|
| E1 | Number of patients undergoing clinical safety studies of drugs intended for long-term treatment of non-life-threatening conditions |
| E2A | Clinical Safety Data Management: Definitions and Standards for Urgent Reporting |
| E2B(R3) | Clinical Safety Data Management: Data Element for Transporting Special Case Safety Messages |
| E2C(R1) | Clinical Safety Data Management: Periodic Update of Safety Reporting for Marketed Medicines E2C Supplement: Periodic Update of Safety Reporting for Marketed Medicines in E2C(R1) |
| E2D | Post-market safety data management: Definitions and standards for reporting |
| E2E | Pharmacovigilance planning |
Clinical trial reports |
|
| E3 | Structure and content of Clinical Trial Reports |
Dose-Response Studies |
|
| E4 | Dose-response information for entering data into the registration dossier |
Ethnic factors |
|
| E5(R1) | Ethnic factors in the acceptability of foreign clinical data |
GCP(Good Clinical Practice) |
|
| E6(R1) | GCP (Good Clinical Practice) |
Clinical trials |
|
| E7 | Supporting studies in specific populations: geriatrics |
| E8 | Basic review of clinical trials |
| E9 | Statistical principles for clinical trials |
| E10 | Selection of control group and associated data in clinical trials |
| E11 | Clinical study of medical products on children |
Clinical evaluation standards by therapeutic category |
|
| E12 | Principles for the clinical evaluation of new antihypertensive drugs |
Clinical assessment |
|
| E14 | Clinical assessment of QT/QTc interval prolongation and proarrhythmic potential for non-antiarrhythmic drugs |
Pharmacogenomics |
|
| E15 | Terminology in pharmacogenomics |
- quality
| Document code | Manual title |
Stability |
|
| Q1A(R2) | Stability Testing of New Drug Substances and Products |
| Q1B | Stability Testing: Photostability Testing of New Drug Substances and Products |
| Q1C | Stability Testing for New Dosage Forms |
| Q1D | Bracketing and Matrixing Designs for Stability Testing of New Drug Substances and Products |
| Q1E | Evaluation of Stability Data |
| Q1F | Stability Data Package for Registration Applications in Climatic Zones III and IV “The volume of stability data for registration dossiers for drugs used in climatic zones III and IV” |
Validation |
|
| Q2(R1) | New title: Validation of Analytical Procedures: Text and Methodology Previously: Text on Validation of Analytical Procedures New title: “Validation of Analytical Procedures: Content and Methodology” to replace the manuals “Content of Validation of Analytical Procedures” and “Validation of Analytical Procedures: Methodology” |
| Impurities | |
| Q3A(R2) | Impurities in New Drug Substances |
| Q3B(R2) | Impurities in New Drug Products |
| Q3C(R2) | Impurities: Guideline for Residual Solvents |
| Pharmacopoeia | |
| Q4 | Pharmacopoeias"Pharmacopeias" |
| Q4A | Pharmacopoeial Harmonisation |
| Q4B | Regulatory Acceptance of Analytical Procedures and/or Acceptance Criteria (RAAPAC) |
| Quality of biotechnological drugs | |
| Q5A(R1) | Viral Safety Evaluation of Biotechnology Products Derived from Cell Lines of Human or Animal Origin |
| Q5B | Quality of Biotechnological Products: Analysis of the Expression Construct in Cells Used for Production of r-DNA Derived Protein Products |
| Q5C | Quality of Biotechnological Products: Stability Testing of Biotechnological/Biological Products “Quality of biotechnological products; assessment of the stability of biotechnological/biological drugs" |
| Q5D | Derivation and Characterization of Cell Substrates Used for Production of Biotechnological/Biological Products |
| Q5E | Comparability of Biotechnological/Biological Products Subject to Changes in their Manufacturing Process |
| Specifications | |
| Q6A | Specifications: Test Procedures and Acceptance Criteria for New Drug Substances and New Drug Products: Chemical Substances (including Decision Trees) |
| Q6B | Specifications: Test Procedures and Acceptance Criteria for Biotechnological/Biological Products |
| Good Manufacturing Practice | |
| Q7 | Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients |
| Pharmaceutical Product Development | |
| Q8 | Pharmaceutical Development"Development of pharmaceutical products" |
| Quality Risk Management | |
| Q9 | Quality Risk Management"Quality Risk Management" |
| Q10 | Pharmaceutical Quality system “Quality system at a pharmaceutical enterprise” Stage 3. |
The introduction of uniform standards at the international level is a fairly long process, especially if these standards relate to complex processes. However, harmonization of regulatory requirements in the pharmaceutical sector at the global level is gaining momentum. At the root of this trend is the increasing degree of globalization of pharmaceutical production itself. In addition to increasing efficiency, harmonization of regulatory requirements should ultimately ensure broad access to quality medicines to all those who need them, regardless of where they are located geographically
Today, the harmonization process is still far from an acceptable level. This leads to significant waste of time and money in the pharmaceutical industry. For example, according to a review by the European Federation of Pharmaceutical Industries and Associations (EFPIA), in some cases the cost of preparing a dossier for a new drug can be 15–20% of the cost of the clinical trials involved. investing hundreds of millions of dollars. The study showed that there are a large number of inspection organizations, some of them unnecessary, that require hundreds of thousands of dollars a day to exist. After all, from 1000 to 2500 man-hours are spent on inspection of one production facility. Harmonization of approaches to dossier preparation and the introduction of uniform production inspection standards would help avoid unnecessary costs in the pharmaceutical sector as a whole and direct the saved resources to solve the necessary problems. (Europe Today)
Significant progress has been made over the past five years in standardizing R&D and clinical trial requirements, as well as harmonizing regulatory requirements for finished dosage forms, active pharmaceutical ingredients (APIs) and excipients.
The main driving force behind the regulatory harmonization process in the pharmaceutical sector is the International Conference on Harmonization of Technical Requirements for the Registration of Pharmaceuticals for Human Use (ICH). For 21 years, ICH has been focused on eliminating unnecessary documentation and simplifying the development, production and registration of pharmaceuticals. The ICH is composed of representatives from regulatory authorities, Pharmacopoeias and drug manufacturers from the USA, Japan and Europe. Through this organization, a general approach to the problem of harmonization was developed and priorities were set for the implementation of this complex and multilateral project.
In addition to the ICH, a number of other organizations are involved in the harmonization of regulatory requirements in the pharmaceutical sector, for example, the US's Pharmacopeias Discussion Group. The World Health Organization is also involved in the harmonization process, as is the American Society for Harmonization of Drug Regulation. Other groups working to harmonize regulatory requirements across countries have focused their efforts on specific issues in the area of active pharmaceutical ingredients and excipients.
Some progress in harmonization
An example is the progress made by the United States and European countries in harmonizing regulatory requirements in the pharmaceutical sectors of these countries. By applying ICH guidelines for quality standards and using a common technical documentation format, the US and Europe have adopted a common dossier format for a number of medicinal products.
Japan, which five years ago was moving towards national standards, is now showing significant interest in cooperation towards harmonizing regulatory requirements in pharmaceuticals.
Perhaps the most significant symbol of the progress in harmonization achieved in the 21st century is the single electronic form of technical documentation that companies use to prepare their registration dossiers. As a joke, they now remember the time when it was necessary to take a truck to deliver the entire volume of documents in the registration dossier to the regulatory authorities.
In the area of harmonization of pharmaceutical manufacturing standards, the process currently underway is a direct reflection of the reality of the supply of most APIs to the United States and European countries from India and China. Two years ago, the Food and Drug Administration and the United States (USP) opened offices in China, India and Latin America. The presence of representative offices and USPs directly in manufacturing countries has improved their interaction with local regulatory authorities, manufacturers and pharmacopoeias.
Progress in harmonization of Pharmacopoeias, APIs and excipients
The harmonization of Pharmacopoeias began about 10 years ago. Over time, good cooperation has been established between the Pharmacopoeias of the United States, Japan and Europe. However, harmonization in this area is a long and extremely labor-intensive process. For example, the USP's PDG has so far only completed 27 of 34 general provisions and 40 of 63 excipient monographs.
Attempts are being made to harmonize monographs down to finished medicinal products.
At the global level, one of the key points is the harmonization of quality parameters for APIs and excipients. It is planned that the USA will contain monographs on all pharmaceutical excipients according to the list. At the same time, an international working group will be created to disseminate best practices. The European Directorate for the Quality of Medicines & HealthCare (EDQM) has established bilateral ties with the US FDA and the similar agency in Australia
(Australia's Therapeutic Goods Administration - TGA) for the exchange of confidential information on APIs and excipients. As part of these agreements, mutual inspections began last year as a pilot project.
Several possibilities are being considered to harmonize the quality parameters of excipients at a global level. One of them is the application of requirements for the production of excipients; another is the participation of manufacturers in a voluntary program of inspection of production facilities by independent auditors. The International Pharmaceutical Excipients Auditing is seeking registration with the American National Standards Institute, which will allow it to serve as an independent quality auditor.
Remaining differences
Harmonization does not mean literally repeating all procedures for registering pharmaceuticals. There will always remain differences in the approaches taken by different regulatory agencies. Even within the framework of one European Union, new things can be registered “centrally”, i.e. through EU authorities, or by registering with national agencies. The US FDA's strategy is to harmonize pharmaceutical safety requirements between the US and the EU, although some differences in approaches and procedures will remain.
National specifics are visible in the example of inspection of pharmaceutical production. The US FDA, for example, focuses on anomaly investigations, validation rules, and the maintenance and cleanliness of equipment and production facilities. In EU countries, the main efforts are aimed at compliance with cleanliness of premises and their classification, equipment maintenance and laboratory control. In Japan, inspectors place increased demands on the quality of raw materials, the cleanliness of production equipment and the appearance of finished pharmaceuticals.
"Pharmaceutical industry", April No. 2 (19) 2010
To start your search, start typing the term you are looking for in the search field. The terms and phrases found in the dictionary will be shown in a drop-down list (the first 30). To get more accurate results, continue typing your search phrase or select a different search mode.
Depending on the selected search mode, the dictionary searches for the search term either from the beginning of each term/phrase, or anywhere in the term/phrase, or searches for its exact match. You can also use the alphabetical index above to search for a term/phrase.
You can select a term/phrase from the drop-down list with the mouse or with the up/down arrow keys (after selecting, press the Enter key to display the dictionary entry card)
On the right is a column with the last five terms added to the dictionary, as well as your dictionary search history (the last ten searches). The history is stored on your computer and can be deleted at any time (to do this, click on the “clear” link)
If you are searching in "from the beginning of the phrase" and didn’t find anything, then try switching to the mode "anywhere in the phrase".
Dictionary entry comprises: search term(displayed at the beginning along with a direct link to the dictionary entry) and translation options. Each translation option may include: information from canceled term or not, and recommended instead of him, definition of this term as specified in the original document (in italics), note to the definition specified in the document or the note of the dictionary compilers, document's name, from which the term/phrase is taken and date of addition to the dictionary.
We are constantly improving and expanding the dictionary. If you find an error, inaccuracy in the terminology or operation of the dictionary, or want to suggest a new feature, please contact us by mail: [email protected] .
We hope that the dictionary will help you in your daily work. We wish you pleasant use!
Page Content
The Eurasian Economic Commission has developed draft Rules for conducting research on biological medicinal products on the territory of the Eurasian Economic Union (EAEU). The purpose of the document is to simplify the collection and presentation of data accompanying applications for registration of biological drugs.
The rules are necessary for the formation of a common drug market in the EAEU, which will begin operating on January 1, 2016. From this date, safe, effective and high-quality drugs will be able to move freely throughout the Union.
The draft Rules were developed on the basis of the provisions set out in the relevant documents of the International Conference on Harmonization of Technical Requirements for the Registration of Medicines (ICH) and the European Medicines Agency (EMA).
The document regulates the development, research of safety, effectiveness and quality of both new biological drug molecules and biosimilar drugs. At the same time, the Rules contain chapters dealing with general research issues: from banks producing cells to finished drugs. There is a separate chapter that contains drug-specific requirements for the development, production and research of biosimilar drugs.
Strict adherence to the Rules will help pharmaceutical manufacturers complete the full cycle of studying biological products, confirm their safety, quality and effectiveness, ensuring that the reproduced biomolecules correspond to their prototypes. This will make it possible to replace drugs taking into account their comparable safety and effectiveness.
It should be noted that the Rules are mandatory for authorized bodies and expert organizations when performing the procedure for examining the safety, quality and effectiveness of this group of drugs in the process of assessing their registration dossiers.
A high degree of harmonization of the Rules with the requirements of relevant international documents will facilitate the process of entry of these drugs into foreign markets, will facilitate the recognition of data on pharmaceutical development and the results of confirming safety, quality and effectiveness when registering them outside the Union.
The draft decision of the EEC Council on approval of the Rules for conducting research on biological medicinal products on the territory of the Eurasian Economic Union was published on the websites of the Eurasian Economic Union in the section “Public discussions and RIA” and of the Eurasian Economic Commission on the page of the Department of Technical Regulation and Accreditation of the EEC in the section “Public discussion of draft regulatory documents” legal acts".
All interested parties can submit comments to the EEC Department of Technical Regulation and Accreditation within 30 days from the date of publication of the draft document.
Reference
TO biological medicines include immunobiological and biotechnological drugs, drugs obtained from human blood plasma, probiotic (eubiotic) drugs, bacteriophage drugs, high-tech drugs.
International Conference on Harmonization of Technical Requirements for Drug Registration (ICH) is an organization that brings together regulatory authorities and the pharmaceutical industry in Europe, Japan and the USA to discuss the scientific and technical aspects of drug registration.
European Medicines Agency (EMA) is an EU agency responsible for the scientific evaluation of medicines developed by pharmaceutical companies for use in the EU.