The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use, or simply ICH, stands as a cornerstone in the realm of pharmaceutical development and regulation. The goal of ICH is to create global standardization for clinical trials. Each country or region’s regulatory authorities (the FDA in the US, EMA in Europe, Health Canada, etc) creates unique guidelines and requirements for conducting clinical research. However, many clinical trials aim to test on diverse populations, and eventually, distribute the resulting treatment across borders. By standardizing these requirements, ICH hopes to improve efficiency and safety in drug development worldwide.
At the heart of this mission lie the ICH guidelines, which serve as comprehensive frameworks for conducting clinical trials and maintaining quality standards. In this blog post, we will delve into the significance of ICH guidelines, their categorization, and their impact on the pharmaceutical industry and public health.
The ICH GCP guidelines are divided into four key categories, each with a topic code:
Quality Guidelines (Topic Code = Q)
These guidelines encompass various aspects of quality control throughout the drug development lifecycle, aiming to ensure the consistent production of safe, effective, and high-quality pharmaceutical products. This includes milestones such as stability studies, impurity testing, and flexible approaches based on Good Manufacturing Practices (GMP) risk management.
The current Quality guidelines are outlined as follows:
| Q1 | Stability |
| Q2 | Analytical Validation |
| Q3 | Impurities |
| Q4 | Pharmacopoeias |
| Q5 | Quality of Biotechnological Products |
| Q6 | Specifications |
| Q7 | Good Manufacturing Practice |
| Q8 | Pharmaceutical Development |
| Q9 | Quality Risk Management |
| Q10 | Pharmaceutical Quality System |
| Q11 | Development and Manufacture of Drug Substances |
| Q12 | Lifecycle Management |
| Q13 | Continuous Manufacturing of Drug Substances and Drug Products |
| Q14 | Analytical Procedure Development |
Safety Guidelines (S)
Safety guidelines are designed to uncover potential risks; for example, carcinogenicity or genotoxicity.
The current Safety guidelines are outlined as follows:
| S1 | Carcinogenicity Studies |
| S2 | Genotoxicity Studies |
| S3 | Toxicokinetics and Pharmacokinetics |
| S4 | Toxicity Testing |
| S5 | Reproductive Toxicology |
| S6 | Biotechnological Products |
| S7 | Pharmacology Studies |
| S8 | Immunotoxicology Studies |
| S9 | Nonclinical Evaluation for Anticancer Pharmaceuticals |
| S10 | Photosafety Evaluation |
| S11 | Nonclinical Paediatric Safety |
| S12 | Nonclinical Biodistribution Considerations for Gene Therapy Products |
Efficacy Guidelines (E)
Ensuring the efficacy of investigational products is imperative for advancing medical knowledge and improving patient outcomes. The ICH GCP guidelines delineate procedures for accurately assessing the efficacy of interventions through robust study design, conduct, safety, and reporting.
The current Efficacy guidelines are outlined as follows:
| E1 | Carcinogenicity Studies |
| E2 | Genotoxicity Studies |
| E3 | Toxicokinetics and Pharmacokinetics |
| E4 | Toxicity Testing |
| E5 | Reproductive Toxicology |
| E6 | Biotechnological Products |
| E7 | Pharmacology Studies |
| E8 | Immunotoxicology Studies |
| E9 | Nonclinical Evaluation for Anticancer Pharmaceuticals |
| E10 | Photosafety Evaluation |
| E11 | Nonclinical Paediatric Safety |
| E12 | Nonclinical Biodistribution Considerations for Gene Therapy Products |
| E14* | Clinical Evaluation of QT |
| E15 | Definitions in Pharmacogenetics / Pharmacogenomics |
| E16 | Qualification of Genomic Biomarkers |
| E17 | Multi-Regional Clinical Trials |
| E18 | Genomic Sampling |
| E19 | Safety Data Collection |
| E20 | Adaptive Clinical Trials |
| E21 | Inclusion of Pregnant and Breastfeeding Individuals in Clinical Trials |
| E22 | General Considerations for Patient Preference Studies |
*Note, there is no “E13”
Among the myriad guidelines established by the ICH, the Good Clinical Practice (GCP) guidelines (Code E6) stands out as a fundamental pillar in clinical trial conduct. These guidelines outline the ethical and scientific standards for designing, conducting, recording, and reporting clinical trials involving human subjects. Embracing principles of quality, safety, and data integrity, the ICH GCP guidelines ensure that clinical trials are conducted with utmost respect for the rights, safety, and well-being of trial participants. ICH is currently in the process of revising E6 for the third time (referred to as E6 R3). The draft protocol is available on the ICH site.
Multidisciplinary Guidelines (M)
Basically a catch-all for anything that doesn’t fall into Quality, Efficacy, or Safety, the Multidisciplinary guidelines include things like medical terminology (MedDRA), Common Technical Document guidelines (CTD), and Electronic Standards for the Transfer of Regulatory Information (ESTRI).
The current Multidisciplinary guidelines are outlined as follows:
| M1 | Stability |
| M2 | Analytical Validation |
| M3 | Impurities |
| M4 | Pharmacopoeias |
| M5 | Quality of Biotechnological Products |
| M6 | Specifications |
| M7 | Good Manufacturing Practice |
| M8 | Pharmaceutical Development |
| M9 | Quality Risk Management |
| M10 | Pharmaceutical Quality System |
| M11 | Development and Manufacture of Drug Substances |
| M12 | Lifecycle Management |
| M13 | Continuous Manufacturing of Drug Substances and Drug Products |
| M14 | Analytical Procedure Development |
| M15 | General Principles for Model-Informed Drug Development |
Of note: eCTD v4.0 has been in the process of rolling out over the past few years. For an in-depth look at the updates, read our article “Everything You Need to Know about eCTD 4.0”.
Are ICH Guidelines Mandatory?
One might wonder whether adherence to ICH guidelines is obligatory or merely discretionary. In many regulatory jurisdictions, compliance with ICH guidelines is not legally mandated; however, non-compliance may raise concerns during regulatory inspections and approvals. Moreover, adherence to ICH guidelines demonstrates a commitment to best practices in pharmaceutical development and enhances the credibility and reliability of clinical trial data. Therefore, while not legally binding, adherence to ICH guidelines is widely regarded as essential for maintaining regulatory compliance, ensuring patient safety, and fostering international collaboration in drug development.
How to Cite ICH Guidelines
Proper citation of ICH guidelines is crucial for acknowledging their contribution to scientific literature and ensuring traceability of regulatory standards. When citing ICH guidelines in academic or regulatory documents, adherence to citation styles such as the American Psychological Association (APA) is recommended. The following format can be used for citing ICH guidelines in APA style:
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use. (Year of publication). Title of Guideline (ICH Guideline No.). Retrieved from URL
For example:
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use. (1996). Good Clinical Practice (ICH E6). Retrieved from https://database.ich.org/sites/default/files/E6_R1_Guideline.pdf
Conclusion
In conclusion, the ICH guidelines serve as indispensable frameworks for ensuring the quality, safety, and efficacy of pharmaceutical products worldwide. By adhering to these guidelines, stakeholders in the pharmaceutical industry uphold ethical standards, promote patient welfare, and facilitate international collaboration in drug development. Whether in clinical trial conduct or pharmaceutical quality control, the principles outlined in ICH guidelines underscore a commitment to excellence and public health.
Kivo's software is designed to support a variety of ICH best practices, including GCP and eCTD 4.0. We also offer over 400 pre-formatted ICH templates. If you have questions about how to conform to ICH standards, reach out to our team at any time.
