Good manufacturing practice

Under Good Manufacturing Practice ( English Good Manufacturing Practice , abbreviated GMP ) refers to guidelines for quality assurance in production processes and environments in the production of medicines and drugs , but also in cosmetics, food and feed . In pharmaceutical manufacturing , quality assurance plays a central role here because quality deviations directly affect the health of consumers may have. A GMP-compliant quality management system ensures product quality and the fulfillment of the health authorities' binding requirements for marketing.

Corresponding guidelines for the pharmaceutical sector are, for example, by the European Commission , by the Pharmaceutical Inspection Co-Operation Scheme (PIC / S), by the US Food and Drug Administration (FDA) and on a global level by the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use ( ICH ) (previously for active ingredients and quality risk management). The term “Good Manufacturing Practice” was introduced in 1962 by the Food and Drug Administration through the current good manufacturing practice (cGMP) initiative .

Elements of a GMP-compliant quality management system

A GMP-compliant quality management system (QMS) must contain the following elements:

• Document management for specification documents (e.g. SOPs and forms) and records. Specification documents such as work instructions, forms and plans must be version controlled and be subject to a defined life cycle (approval, release, regular updating and revision). Records (in paper form or electronically) must be created in accordance with the principles of good documentation practice and data integrity (complete, correct, traceable / assignable, timely, legible) and appropriately archived (protection against loss, damage, manipulation, ensuring readability over the entire prescribed archiving period) become. Computer systems must have an audit trail that records all actions, especially changes, in a tamper-proof manner.
• Deviation management: Processes, procedures and methods are described in specification documents (SOPs, manufacturing and test regulations). Unplanned deviations from this or from GMP principles must be documented and evaluated in a documented, formal process by the process owner and quality assurance. Unplanned and unapproved changes are also deviations. The resulting corrections, corrective measures (eliminating the cause of the error) and preventive measures (Corrective and Preventive Action, CAPA) must be documented and tracked.
• Change management : If processes, procedures or the condition of equipment are to be changed in a planned manner, the change must be justified, planned and approved by quality assurance before implementation, and the implementation must then be documented.
• Qualification of equipment (systems and devices as well as, if necessary, buildings and rooms): It must be shown in a planned and documented process that the equipment is suitable for the planned purpose and that it actually works reliably under the conditions on site (during commissioning and then on a regular basis Intervals). To do this, 4 phases are run through (each with its own plan and report):
  • Design qualification (DQ): Definition of the requirements (DQ plan, specification sheet) and selection of equipment corresponding to the requirements (DQ report, specification sheet or offer);
  • Installation qualification (IQ): on-site installation and verification of whether all planned components and functions are available;
  • Functional or operational qualification (OQ): Verification by means of a functional test whether the requirements according to DQ are met;
  • Performance Qualification (PQ): Test under real conditions, e.g. B. Production of three batches with one system for test purposes, or analysis on typical samples and comparison with results from other devices.
• Validation of processes and methods: It must be shown in a planned and documented process that processes (e.g. manufacturing processes) and methods (e.g. analytical methods in quality control) achieve results that meet the requirements of the product, and deliver reliably reproducible results.
• Training of employees: Before starting an activity, employees must be adequately trained (e.g. SOP, practical training on the device or system, training in method) and the training must be documented.
• Risk management
• Internal audits

EU GMP guidelines for human and veterinary medicinal products

The EU GMP guidelines for human and veterinary medicinal products (often referred to as the EC GMP guidelines before the Lisbon Treaty came into force) specifies the 2003/94 / EC guideline for establishing the principles and guidelines of good manufacturing practice for medicinal products for human use and for use in Investigational medicinal products intended for humans as well as Directive 1991/412 / EEC laying down the principles and guidelines of good manufacturing practice for veterinary medicinal products and is structured as follows:

Part I - Essential Requirements for Medicinal Products

• Chapter 1 - Quality Management
• Chapter 2 - Personnel
• Chapter 3 - Rooms and Facilities
• Chapter 4 - Documentation
• Chapter 5 - Manufacture
• Chapter 6 - Exam
• Chapter 7 - Outsourced Activities
• Chapter 8 - Complaints and Product Recalls
• Chapter 9 - Self-Inspections
• glossary

Part II - Good Manufacturing Practice for Active Ingredients

• Section 1 - Introduction
• Section 2 - Quality Management
• Section 3 - Personnel
• Section 4 - Buildings and Facilities
• Section 5 - Process Equipment
• Section 6 - Documentation and Logs
• Section 7 - Materials Management
• Section 8 - Production and In-Process Controls
• Section 9 - Packaging and Labeling
• Section 10 - Storage and Distribution
• Section 11 - Laboratory Controls
• Section 12 - Validation
• Section 13 - Change Control
• Section 14 - Rejection and Reuse of Materials
• Section 15 - Complaints and Recalls
• Section 16 - Contract Manufacturers
• Section 17 - Agents, Brokers, Dealers, Wholesalers, Repackagers, Relabellers
• Section 18 - Specific Instructions for Active Ingredients Produced Using Cell Culture / Fermentation
• Section 19 - Active Ingredients for Use in Clinical Trials
• Section 20 - Glossary

Part III - GMP relevant documents

• Company Description - Site Master File
• Q9 - quality risk management
• Q10 Pharmaceutical Quality Assurance System
• MRA batch certificate
• Template for the "written confirmation" for active ingredients that are exported to Europe from third countries for use in human medicinal products

Attachments

• Appendix 1 - Manufacture of Sterile Medicinal Products
• Appendix 2 - Manufacture of Biological Medicines for Human Use
• Appendix 3 - Manufacture of radiopharmaceuticals
• Annex 4 - Manufacture of veterinary medicinal products (excluding animal vaccines)
• Appendix 5 - Manufacture of Animal Vaccines
• Appendix 6 - Manufacture of Medical Gases
• Appendix 7 - Manufacture of Herbal Medicines
• Appendix 8 - Samples of starting and packing material
• Appendix 9 - Manufacture of liquids, creams and ointments
• Appendix 10 - Production of aerosols
• Appendix 11 - Computerized Systems
• Appendix 12 - Use of Ionizing Radiation for Pharmaceutical Manufacturing
• Appendix 13 - Manufacture of Investigational Medicinal Products
• From human blood or human production of products - Annex 14 plasma derived
• Appendix 15 - Qualification and Validation
• Appendix 16 - Batch certification and release by the competent person
• Appendix 17 - Parametric Release
• Appendix 18 - (since 2005, moved to Part II) Good Manufacturing Practice for Active Ingredients
• Appendix 19 - Reference and retention samples
• Appendix 20 - (since 2011, moved to Part III) Quality Risk Management

Regulations in individual countries

Germany

The implementation of good manufacturing practice is regulated by the Medicines and Active Substance Manufacturing Ordinance of November 3, 2006. In addition, the Federal Ministry of Health publishes a translation of the EU GMP guide.

United States

In the USA the guidelines are the Current Good Manufacturing Practice (cGMP) , the small "c" makes the difference between USA and EU. In order to ensure that they are up-to-date, unlike in the EU, these guidelines are checked for up-to-dateness every April 1st and modified if necessary. The cGMP is incorporated into the Code of Federal Regulations (CFR), the collection of US legal texts, under 21 CFR 210 and 21 CFR 211. There are also other chapters of the CFR that are relevant in the context of GMP (e.g. 21 CFR 11, or 21 CFR 820).

International standardization

International standards that include good manufacturing practice are for example

• ISO 15378 "Primary packaging for pharmaceuticals - Special requirements for the application of ISO 9001 in accordance with Good Manufacturing Practice (GMP)" and
• ISO 22716 "Cosmetics - Good Manufacturing Practice (GMP) - Guide to Good Manufacturing Practice".

GMP +

The "+" stands for the integration of hazard analysis and critical control points (HACCP). In 2013 the first standard for feed sustainability was published, for which two modules were developed: “GMP + Feed Safety Assurance” (which focuses on feed safety) and “GMP + Feed Responsibility Assurance” (which focuses on sustainable feed). In addition to HACCP regulations for the quality management system (ISO 9001), product standards, traceability, monitoring, programs with basic conditions, the chain approach and the early warning system, the module “GMP + Feed Safety Assurance Scheme” has been integrated.

See also

• Good Automated Manufacturing Practice

Individual evidence

1. ↑ Outsourced activities
2. ↑ Production of liquids, creams and ointments
3. ^ Federal Ministry of Health - Announcements
4. ↑ Code of Federal Regulations: Title 21 - Food and Drugs ( Memento of the original dated February 7, 2007 in the Internet Archive ) Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. 
5. ↑ Archived copy ( Memento of the original from April 2, 2015 in the Internet Archive ) Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. 
6. ↑ Archived copy ( memento of the original from February 21, 2015 in the Internet Archive ) Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. 
7. ↑ Archived copy ( memento of the original from February 21, 2015 in the Internet Archive ) Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. 

Web links

• EU GMP guidelines (EU GMP guidelines for human and veterinary medicinal products, English)
• WHO information (English)
• Documents of the US FDA GMP in the pharmaceutical sector (English)
• Quality guidelines of the ICH (English)
• Austrian Medicines Works Regulations (German)
• GMP in cosmetics, US FDA (English)