News and innovation
line
Best practices for phase 1 investigational drugs trials
line
Facebook LinkedIn Emailline
Contact Us

Best practices for phase 1 investigational drugs trials

Before pharmaceutical products are released onto the market, they undergo extensive screening as an investigational drug (IND, or investigational new drug) to ensure the new molecule’s safety and adherence to regulations.1,2 In contrast to commercially available medications, the safe processing and dispensing of investigational drugs has not been widely standardised.3 Read on to discover the latest guidance on safe investigational drug manufacturing and administration.

More on this topic: New clinic study: Reduce hazardous drug contamination with BD

Hazards involved with these kinds of drugs

Investigational drugs must follow current good manufacturing practices (CGMPs) when they reach phase 1 clinical trials, as this stage represents their first introduction to human subjects.2,4 However, there is still room for error: the Institute for Safe Medication Practices (ISMP) found potential for errors in naming practices, drug labels, packaging, product appearance, and expiration dating among study sponsors.3 As well, phase 1 investigational drugs are still new chemicals, meaning there is often little information on potential toxicity.5

According to Valdeolmillos et al, investigational drugs should be considered hazardous until they can be fully excluded, “as it is not frequent to have hazard studies available or the information about safety is usually insufficient.”6 Hazardous drug exposure, even in small concentrations, can cause adverse effects such as internal organ damage, genetic mutations, cancer and higher rates of reproductive issues.7-12

More on this topic: Make the safety switch: 4 potential everyday safety hazards

Safety in phase 1 clinical trials of investigational drugs

The United States Food & Drug Administration’s CGMPs for phase 1 investigational drugs include rigorous written instructions for safe receipt, handling, storage, dispensing, retrieval and return of the drug during trials.13 The European Directive 2001/83/EC, which outlines the requirements for medicinal products intended for human use, requires an extensive written summary of product characteristics as well.2

As with all hazardous drugs, the US CGMPs also state that the use of closed-system transfer devices, ensuring that the investigational drug is not exposed to the environment during processing, can alleviate the need for stricter room classification for air quality.4 Studies show that the use of closed-system transfer devices may help reduce hazardous drug contamination.7 The European CGMPs mention that special attention should be paid to ensure safe handling of investigational drugs to avoid cross contamination, identifying the importance of establishing a sufficient quality control system.14

References

  1. US Food & Drug Administration (FDA). Investigational New Drug (IND) Administration. Published 20 July 2022. Accessed 20 December 2023 at: https://www.fda.gov/drugs/types-applications/investigational-new-drug-ind-application.
  2. Official Journal of the European Union. DIRECTIVE 2001/83/EC OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL of 6 November 2001 on the Community code relating to medicinal products for human use. Published 1 January 2022. Accessed 16 January 2024 at: https://eur-lex.europa.eu/legal-content/EN/TXT/?uri=CELEX%3A02001L0083-20220101&qid=1705406082924.
  3. Cruz JL, Brown Jn. Safety risks with investigational drugs: Pharmacy practices and perceptions in the veterans affairs health system. Ther Adv Drug Saf. 2015 Jun; 6(3): 103–109. DOI: 10.1177/2042098615584924.
  4. US Food & Drug Administration (FDA). Guidance for Industry CGMP for Phase 1 Investigational Drugs. Published July 2008. Accessed 20 December 2023 at: https://www.fda.gov/media/70975/download.
  5. Occupational Safety and Health Administration (OSHA). Controlling Occupational Exposure to Hazardous Drugs. Accessed 20 December 2023 at: https://www.osha.gov/hazardous-drugs/controlling-occex.
  6. Valdeolmillos L, Pastor CG, Alonso MS, Arregui CL, Castiella EM. Use of closed system transfer devices with investigational drug products. European Journal of Hospital Pharmacy. 2023;30:A170-A171.
  7. Brechtelsbauer E. Identification and reduction of hazardous drug surface contamination through the use of a novel closed-system transfer device with a point-of-care hazardous drug detection system. AM J Health Syst Pharm. 2023 Mar 21;80(7):435-444. DOI: 10.1093/ajhp/zxac336.
  8. Sotaniemi EA, Sutinen S, Arranto AJ, et al. Liver damage in nurses handling cytostatic agents. Acta Med Scand. 1983;214(3):181-189. doi:10.1111/j.0954-6820.1983.tb08593.x
  9. McDiarmid MA, Oliver MS, Roth TS, Rogers B, Escalante C. Chromosome 5 and 7 abnormalities in oncology personnel handling anticancer drugs. J Occup Environ Med. 2010;52(10):1028-1034. doi:10.1097/JOM.0b013e3181f73ae6
  10. Cavallo D, Ursini CL, Perniconi B, et al. Evaluation of genotoxic effects induced by exposure to antineoplastic drugs in lymphocytes and exfoliated buccal cells of oncology nurses and pharmacy employees. Mutat Res. 2005;587(1-2):45-51. doi:10.1016/j.mrgentox.2005.07.008
  11. Skov T, Maarup B, Olsen J, Rørth M, Winthereik H, Lynge E. Leukaemia and reproductive outcome among nurses handling antineoplastic drugs. Br J Ind Med. 1992;49(12):855-861. doi:10.1136/oem.49.12.855
  12. Lawson CC, Rocheleau CM, Whelan EA, et al. Occupational exposures among nurses and risk of spontaneous abortion. Am J Obstet Gynecol. 2012;206(4):327.e1-e8. doi:10.1016/j.ajog.2011.12.030
  13. US Food & Drug Administration (FDA). E6(R2) Good Clinical Practice: Integrated Addendum to ICH E6(R1) Guidance for Industry. Published March 2018. Accessed 20 December 2023 at: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/e6r2-good-clinical-practice-integrated-addendum-ich-e6r1.
  14. Official Journal of the European Union. 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. Published 14 October 2003. Accessed 16 January 2024 at: https://eur-lex.europa.eu/legal-content/EN/TXT/?uri=celex%3A32003L0094.

This list of references to third-party peer-reviewed material and the sites they are hosted on are provided for your reference and convenience only, and do not imply any review or endorsement of the material or any association with their operators.  The Third-Party References (and the websites to which they link) may contain information that is inaccurate, incomplete, or outdated. Your access and use of the Third Party Sites (and any websites to which they link) is solely at your own risk. 

BD-112280