In the development and manufacture of a therapeutic product (a drug or a biologic), Good Manufacturing Practices (GMP)* activities help ensure that a manufacturer can consistently control and produce these products to meet the identity, strength, purity and quality appropriate to their intended use.1-9
In the US the cGMP* are based on the fundamental principles of quality assurance:9
- Quality, safety and effectiveness must be designed and built into the product.
- Quality cannot be inspected or tested into the product.
- Each step of the manufacturing process must be controlled to maximize the likelihood that the product will be acceptable.
Sponsors (companies) that develop therapeutic products are ultimately responsible for ensuring that their products comply with relevant GMP regulations at all stages of the product lifecycle. This holds true even if part or all of the manufacturing activities are outsourced to a third party (such as a contract manufacturing organization).
Safeguarding product quality with GMP
Regulatory authorities safeguard product quality via routine inspections of manufacturers to verify their compliance with relevant GMP regulations.1-8 These regulations contain the minimum requirements for the methods, facilities, equipment, personnel and control activities used in the manufacturing, processing and packaging of a therapeutic product.2 Aside from the finished product, GMP also applies to the active pharmaceutical ingredients (APIs). The development and manufacture of the API should follow the principles described in the Q7A and Q11 guidance documents of ICH (International Conference on Harmonisation).10,11
The ICH guidelines Q8, Q9 and Q1012-14 relate to the development of quality systems in the pharmaceutical industry. These guidelines describe principles such as “quality by design,” quality risk management and quality systems. In addition to these general requirements, it is recommended to adhere to any other specific GMP guidance documents that may apply to the development of your product (for example, those governing sterile products produced by aseptic processes).15
GMP throughout the product lifecycle
GMP should be applied throughout the product lifecycle9. As the product moves through the product development phases, the GMP stringency increases with progression from clinical trials through to commercialization. For instance, the chemistry, manufacturing and control (CMC) information that is included with the early-stage clinical trials may be less detailed than with the licensing application and post-approval amendment applications. Data requirements (such as process validation) for GMP increase as knowledge about product accumulates. Such information is submitted in the Quality section of the clinical trial and licensing applications. The Quality section contains detailed information on the quality aspects, characteristics and manufacture of the drug substance and drug products.
Examples: GMP activities
GMP regulations address all areas that affect process performance and product quality, including personnel, materials, procedures, equipment, facilities and records. The following are some brief, general examples of GMP activities:1,9
- Personnel must be qualified and trained to perform their function.
- Materials used in the process must meet specified quality attributes and be controlled in a manner to prevent mix-ups.
- Procedures must be established and followed for the manufacture, testing, cleaning, validation and stability activities associated with the product (from raw materials and the drug substance to the finished product to packaging materials).
- Equipment must be properly identified, cleaned and maintained to prevent cross-contamination.
- Facilities must be suitable for their intended purpose with proper lighting, air handling, plumbing and sanitation.
- Records to demonstrate GMP compliance must be properly maintained.
* In the US, it is referred to as Current Good Manufacturing Practices, or cGMP.
The information presented in these articles is intended to outline the general processes, principles and concepts of the healthcare product development lifecycle. Since regulatory requirements are ever-changing, it is current only as of the date of publication and not intended to provide detailed instructions for product development. Every healthcare product is unique and therefore so is its associated product development lifecycle. Specific advice should be sought from a qualified healthcare or other appropriate professional.
Published: October 17, 2012
- Health Canada. (2011). Good Manufacturing Practices. Retrieved June 1, 2012, from http://www.hc-sc.gc.ca/dhp-mps/compli-conform/gmp-bpf/index-eng.php.
- U.S. Food and Drug Administration. Drug Applications and Current Good Manufacturing Practice (CGMP) regulations. Retrieved June 1, 2012, from http://www.fda.gov/drugs/developmentapprovalprocess/manufacturing/ucm090016.htm.
- Canada. Part C, Division 2 of the Food and Drugs Regulations. Retrieved August 13, 2012, from .
- United States Code. (2012, April 1). Title 21, Part 210, Current Good Manufacturing Practice in Manufacturing Processing, Packing, or Holding of Drugs; General. Retrieved August 13, 2012, from http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFRPart=210&showFR=1.
- United States Code. (2012, April 1). Title 21, Part 211, Current Good Manufacturing Practice for Finished Pharmaceuticals. Retrieved August 13, 2012, from http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFRPart=211&showFR=1.
- United States Code. (2012, April 1). Title 21, Part 606, Current Good Manufacturing Practice for Blood and Blood Components. Retrieved August 13, 2012, from http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFRPart=606&showFR=1.
- Commission Directive 2003/94/EC of 8 October 2003 laying down the principles and guidelines of good manufacturing practice in respect of medicinal products for human use and investigational medicinal products for human use. Retrieved August 13, 2012, from http://ec.europa.eu/health/files/eudralex/vol-1/dir_2003_94/dir_2003_94_en.pdf.
- European Commission. (2011, February 7). EudraLex – Volume 4 Good manufacturing practice (GMP) Guidelines. Retrieved June 1, 2012, from http://ec.europa.eu/health/documents/eudralex/vol-4/index_en.htm.
- Buckley, B. & Koepke, S.R. (2008). Chapter 8. Overview of the GxPs for the regulatory professional. In D.J. Pisano & D.S. Mantus (Eds.) FDA regulatory affairs. A guide for prescription drugs, medical devices, and biologics (2nd ed.). New York: Informa Healthcare.
- International Conference on Harmonisation. (2000, November). ICH Q7A: Good Manufacturing Practice Guidance for Active Pharmaceutical Ingredients. Retrieved August 13, 2012, from http://www.fda.gov/downloads/regulatoryinformation/guidances/ucm129098.pdf.
- International Conference on Harmonisation. (2012, May). ICH Q11: Development and Manufacture of Drug Substances (Chemical Entities and Biotechnological/Biological Entities). Retrieved August 13, 2012, from http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q11/Q11_Step_4.pdf.
- International Conference on Harmonisation. (2009, August). ICH Q8(R2): Pharmaceutical development. Retrieved August 13, 2012, from http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q8_R1/Step4/Q8_R2_Guideline.pdf.
- International Conference on Harmonisation. (2005, November). ICH Q9: Quality risk management. Retrieved August 13, 2012, from http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q9/Step4/Q9_Guideline.pdf.
- International Conference on Harmonisation. (2008, June). ICH Q10: Pharmaceutical quality system. Retrieved August 13, 2012, from http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q10/Step4/Q10_Guideline.pdf.
- U.S. Food and Drug Administration. (2004, September). Guidance for Industry: Sterile Drug Products Produced by Aseptic Processing – Current Good Manufacturing Practice. Retrieved August 13, 2012, from http://www.fda.gov/downloads/Drugs/…/Guidances/ucm070342.pdf.