Executive Summary

This report provides a detailed comparative analysis of clinical trial standards for medical devices versus pharmaceutical products, focusing on the ISO 14155 standard (for medical device clinical investigations) and the ICH Good Clinical Practice (GCP) guidelines (primarily ICH E6) for pharmaceuticals. We examine the historical origins and evolution of both frameworks, their scope and objectives, and the practical implications of their differences for trial design, conduct, and regulation. Key findings include: Scope & Focus: ICH GCP is an internationally harmonized standard governing drug and biologic trials, emphasizing patient safety and drug efficacy; ISO 14155 is a global standard (not legally mandatory everywhere, but a de facto industry requirement) specifically for device trials, emphasizing device performance and risk management (^[1]) (^[2]). Regulatory Context: Compliance with ICH GCP is mandatory across ICH member regions for drug approval submissions, whereas ISO 14155 is recognized as a harmonized standard under the EU Medical Device Regulation (MDR) (^[3]) and is widely adopted by device sponsors worldwide to demonstrate ethical conduct and data quality. Trial Design & Conduct: Medical device studies typically have smaller sample sizes and shorter timelines – reinforcing one industry report that device trials conclude about 70% faster than pharmaceutical trials (often 2–3 years versus 6–10 years) and enroll far fewer patients (^[4]) (^[5]). Device trials focus on demonstrating safety and performance in specific anatomical or physiological contexts (^[6]), whereas drug trials focus equally on safety and efficacy over broader populations (^[6]) (^[7]). Randomized, controlled designs are common in both fields, but device trials may allow unblinded or adaptive designs when blinding or fixed formulations are infeasible. Risk Management & Quality: Both frameworks stress human subject protection and data integrity, but ISO 14155 explicitly integrates risk management and quality planning throughout the trial process (^[8]). The 2020 revision of ISO 14155 “strongly emphasizes” alignment with GCP by integrating GCP principles into its core (^[9]). ICH GCP (R2) introduced risk-based monitoring and quality management, and the upcoming E6(R3) further codifies risk-adaptive approaches and trial transparency (^[10]) (^[8]). Regulatory Oversight: In the U.S., medical device trials (especially high-risk ones) use the Investigational Device Exemption (IDE) pathway, whereas drug trials use the Investigational New Drug (IND) process. Notably, historical data show IDE submissions are much smaller (≈150 pages on average) than INDs (≈1250 pages) (^[11]), reflecting the different evidence burdens. In Europe, device trials must comply with MDR requirements (e.g. CE marked via clinical evaluation), with ISO 14155 poised to become a harmonized standard. In contrast, pharmaceutical trials invoke national and transnational drug regulations. Stakeholder Perspectives & Case Studies: Regulators (FDA, EMA, PMDA etc.) maintain parallel ethical requirements (informed consent, IRB/IEC review) for both device and drug studies (^[12]) (^[13]), but device firms must also align with device-specific norms (notified bodies, device registries). Industry analyses highlight that device sponsors often benefit from streamlined pathways (e.g. 510(k) clearance routes) and risk-focused oversight, while pharma developers navigate rigid phase-gates. For example, 90% of FDA-reviewed devices use the 510(k) route (predicate-based clearance) versus only ~10% requiring full PMA, unlike drugs which uniformly require full approval trials (^[14]). Implications & Future Directions: As clinical research evolves, both standards are converging in emphasizing transparency and risk-based practices (^[10]) (^[8]). The forthcoming ICH E6(R3) revision (adopted July 2025) and ongoing amendment of ISO 14155 aim to further harmonize approaches while addressing novel trial designs and data sources. Understanding these differences is vital for sponsors, CROs, and regulators to design compliant trials: adopting ISO 14155 (with GCP components) can facilitate global device approvals, while applying GCP principles in device contexts ensures data credibility. The analysis underscores that although both frameworks share common ethical foundations, their distinct emphases mirror the fundamental differences between medical device and pharmaceutical development.

Introduction and Background

Clinical trials are essential for establishing the safety and efficacy (or, in the case of devices, performance) of medical products before market authorization. Good Clinical Practice (GCP) is the widely recognized framework that governs how trials are designed, conducted, and reported. For pharmaceutical products (drugs and biologics), the International Council for Harmonisation (ICH) created the GCP Guideline (E6, currently R2 with R3 adopted July 2025) as a legally adopted harmonized standard across member regions (^[2]). This guideline “establishes an international standard” for trial design, conduct, recording, and reporting, outlining the responsibilities of sponsors, investigators, and ethics committees to protect participant welfare and ensure data credibility (^[2]). By contrast, medical devices are covered by ISO 14155 – an international standard specifically for device trials. ISO 14155:2020 is titled “Clinical investigations of medical devices for human subjects – Good clinical practice”, and provides a comprehensive framework for device trial planning, conduct, monitoring, and reporting (^[15]) (^[16]). Unlike ICH GCP, ISO 14155 is a voluntary standard (published by ISO/CEN), though it is recognized by regulators (e.g. as a forthcoming harmonized standard under EU Regulation 2017/745) and regarded as the de facto gold standard for device trials (^[15])(^[3]).

The purposes of both ICH GCP and ISO 14155 share common themes: protecting human subjects, ensuring ethical conduct, and maintaining data quality. For example, ISO 14155 explicitly lists objectives such as “protection of human subjects (safety, well-being, rights)” and “reliability of results” (^[17]). Similarly, ICH GCP’s introductory principles emphasize informed consent, independent review, and qualified investigators to safeguard participants while generating credible data (^[18]) (^[2]). However, the two standards diverge in emphasis due to the fundamental differences between drugs and devices. Pharmaceutical trials focus on pharmacological efficacy (often requiring large, controlled studies over multiple years), whereas device trials often concentrate on whether a device safely performs its intended function in a real-world setting (sometimes allowing more flexibility in design). This leads to key structural and procedural differences, which we explore in depth in this report.

It is helpful to recall that historically, drug and device research developed along separate regulatory pathways. The U.S. Food, Drug, and Cosmetic Act (as amended in 1962) specifically mandated rigorous clinical testing and “substantial evidence” for new drugs, giving rise to the well-known IND/NDA process (^[19]). Devices, on the other hand, were initially subject to much lighter regulation; the 1976 Medical Device Amendments introduced device oversight and required proof of “safety and effectiveness,” but allowed many devices (via the 510(k) pathway) to enter the market by demonstrating equivalence to existing products (^[20]) (^[14]). As the medical device industry matured, ISO 14155 was developed (first published 2003, updated 2011 and 2020) to formalize Good Clinical Practice for devices. ICH GCP first emerged in 1996 and was revised in 2016 (R2) (^[2]); a successor version (R3) was adopted in 2023 with a modular structure to accommodate decentralized and pragmatic trials (^[10]). Table 1 (below) outlines high-level distinctions between device and drug trial norms in relation to ISO 14155 and ICH GCP.

Table 1. Key distinctions between typical medical device trials (ISO 14155) and drug trials (ICH GCP). Citations in brackets indicate supporting sources.

Beyond these summary contrasts, it is important to note that both ISO 14155 and ICH GCP share the same ethical foundation. Both stipulate informed consent, ethics committee approval, protection of vulnerable subjects, data confidentiality, and maintenance of case report forms and trial master files (^[18]) (^[12]). The differences arise in emphasis: for devices, added focus is placed on manufacturer responsibilities (under ISO, the “sponsor” is usually the device manufacturer) and on technical aspects of device performance and compatibility.

Historical Evolution of GCP for Drugs and Devices

The concept of Good Clinical Practice arose from ethical imperatives (e.g. Nuremberg Code, Declaration of Helsinki) and the need for globally consistent standards. For pharmaceuticals, the first major codification was ICH E6 (1996), integrating FDA and EU regulatory requirements. ICH E6(R2) (2016) incorporated modern trial practices like electronic records and risk-based monitoring, and ICH E6(R3) (2023/2025) is adapting to digital trials and decentralized methods (^[10]). In parallel, pharmaceutical regulations evolved U.S. IND/NDA processes and moves like the FDA Amendments Act (FDAAA 801) which mandate trial registration and reporting. The result is that drug trials have a well-defined multi-phase pathway (Phase I–IV) with massive data and documentation. For example, Gelijns et al. (IOM, 1990) describe Phase III drug trials as “involving up to several thousand patients (2,000–3,000) … [often] lasting between one and four years” (^[7]). The IND dossier for an average investigational drug can exceed 1,000 pages (^[11]).

Medical device regulation has a separate lineage. Beginning with the 1976 U.S. Medical Device Amendments, risk-based classification of devices (Class I–III) was introduced. Early device testing practices were highly variable; Gelijns reports that in the late 1970s, some manufacturers ran formal trials on hundreds of patients while others used “informal trials with 75” or only 50 patients “with no set protocol” (^[25]). Many device evaluations did not involve randomized controlled trials or formal IRB review at all in the earliest days (^[25]). Recognizing this inconsistency and patient safety lessons (e.g. cardiac implants, IUD problems), U.S. laws eventually required safety and effectiveness. Still, by the late 1980s, roughly 90% of U.S. devices were being marketed via 510(k) clearance (predicate claims of equivalence) with only 10% requiring full Premarket Approval (PMA), a stark contrast to the pharmaceutical world where virtually all new drugs need full clinical proof (^[14]).

Against this backdrop, ISO 14155 was created: first published in 2003 (ISO 14155:2003), revised in 2011, and then overhauled in 2020 (still termed ISO 14155:2020) to align more closely with GCP principles. The 2020 revision was partly driven by the EU’s upcoming MDR requirements for more rigorous clinical evidence. Johner Institute notes that ISO 14155:2020 “describes the state of the art” for device sponsors in trial planning and responsibilities, aiming to clarify how to meet the heightened data requirements under MDR (^[15]) (^[26]). Key enhancements in 2020 included emphasizing the link to ICH-GCP (integrating summary of GCP principles into the standard) and mandating trial registration in public databases (^[9]). Thus, device trial GCP has moved from a fragmented landscape into one that is increasingly standardized internationally, though implementation still depends on jurisdiction.

Regulatory Frameworks: GCP vs. ISO 14155

The ICH GCP (E6) guideline is explicitly about medicinal products. It was developed by the International Conference on Harmonisation (comprising regulators from the EU, Japan, and the US) to provide “a unified standard” so that clinical data would be mutually accepted across regions (^[27]). ICH E6(R2) (last effective version before R3) is recognized by regulators: compliance with ICH GCP is required for any clinical data submitted in support of drug/biologic marketing approvals. For example, the EMA states that ICH GCP “provides a unified framework” for sponsors and investigators, ensuring consistent ethical and scientific quality. The guideline’s Structure (Sections 1–8, plus E6(R2) addenda) addresses Investigator and Sponsor responsibilities, the Protocol, IRB/IEC processes, essential documents, and more (^[2]). The forthcoming ICH E6(R3) (Principles & Annexes, effective July 2025) transforms this into a modular set emphasizing quality by design and flexibility, but the fundamental content (informed consent, data integrity, trial master file, safety reporting) remains core.

In contrast, ISO 14155:2020 is a general ISO standard (and by EU Commission notice is earmarked as harmonized under MDR (^[3])) that specifically addresses device trials. It is not “owned” by any single country, and regulators usually point to DSPs (Device Sponsor Programs) or ISO rather than codifying separate device GCP laws. ISO 14155 was drafted by an international committee of device experts. Its scope covers “clinical investigations of devices conducted to demonstrate their performance, safety, and effectiveness” (^[21]). It equally mandates protection of subjects and data reliability (^[17]). Key differences in the structure of ISO 14155 vs ICH GCP include: ISO 14155 has chapters on Ethical Considerations (Chap. 5), Clinical Investigation Planning (incl. Investigational Device criteria, Chap. 6), Production of the Investigational Device, Monitoring, and Reporting. For example, ISO specifically details how to handle investigational devices, their labeling, storage, and when technical changes are permissible (^[28]) (^[8]). ICH GCP never mentions devices at all; it presumes a manufactured investigational product (drug) defined in the Investigator’s Brochure and protocol.

Other overlaps and differences: Both ICH and ISO require ethics committee (IRB/IEC) review and informed consent. The FDA clarifies this, noting that investigators in any study – drugs or devices – “must comply with applicable statutes and regulations … intended to ensure data integrity on which approvals are based, and to protect the rights, safety, and welfare of human subjects” (^[12]). However, ISO adds device-specific ethics guidance (e.g. grouping vulnerable populations differently, device return policies), and under EU/MDR, notified bodies or regulators may levy further requirements (e.g. performance studies for Class III devices). ICH GCP binds investigators and sponsors (often pharma corporations) by law; ISO 14155 binds “sponsors” in the device context (i.e. device manufacturers or owners) as a recognized standard.

Table 1 above summarized many regulatory contrasts. A few illustrative highlights: In the U.S., the IDE process for devices requires review of risk analysis and an Investigational Plan; in many cases, an IRB will determine if a device study is “significant risk.” Only SR studies need FDA IDE; NSR ones can often proceed with IRB oversight alone (^[13]). In pharmaceutical trials, virtually all new drugs require initial FDA approval to start human testing (IND) (^[19]). ISO 14155 explicitly adopts the intent of ICH GCP; Johner et al. note the 2020 revision “emphasized more strongly” the link to GCP, even summarizing GCP principles in Clause 4 (^[9]). This means device trials following ISO are largely aligned with the spirit of ICH GCP, but with device-centric details added.

Key Differences Between ISO 14155 and ICH GCP

Scope and Applicability

• Product category: The most basic difference is what is being tested. ICH GCP addresses clinical trials for drugs and biological therapies. ISO 14155 addresses trials of medical devices. This includes any instrument, apparatus, implant, software or material intended for medical purposes (from stents and pacemakers to diagnostic software). The two standards thus refer to different classes of products throughout (e.g. “drug accountability” sections in ICH vs “device identification” sections in ISO).
• Purpose of evidence: Consequently, the evidence goal differs. Pharma trials must demonstrate clinical efficacy and safety endpoints that regulators can use to weigh risks/benefits. Device trials must demonstrate that a device performs as intended and meets safety thresholds. For instance, Lindushealth notes that device trials usually focus on safety and performance of the device, whereas drug trials assess efficacy in addition to safety (^[6]). This translates into different endpoints and comparators: device trials may use bench- or imaging-based performance metrics or functional outcomes, while drug trials typically measure biochemical, symptomatic, or survival endpoints.
• Guideline nature: ICH GCP (E6) is a harmonized regulatory guideline; it is adopted by law in many countries (FDA recognizes it as binding in Code of Federal Regulations for clinical trials). ISO 14155 is a voluntary technical standard (though EU intends to use it as a harmonized standard in the MDR/regulation). This means ICH GCP obligations come directly from regulators, whereas compliance with ISO 14155 is often a condition of market approval (e.g. demonstrating design controls and clinical evidence to a Notified Body) rather than a law itself. ISO is “internationally recognized” but not always mandatory (^[29]) (^[30]). Some modern regulations (like EU MDR) effectively make ISO following a de facto requirement for compliance. (^[30]) (^[3]).
• Trial Phases: Under ICH, trials are conceptually divided into Phase I–III (and post-market Phase IV), reflecting dose-finding, efficacy, and broader studies. ISO does not mandate “phase” structure. Often device development does have feasibility studies, pivotal trials, and post-market follow-ups, but these are not rigidly defined by ISO. The ISO standard does include an Annex (Annex I) to clarify applicability to different stages of device development (^[31]). Phase labels may exist in practice (some companies use “pilot”, “pivotal”, “post-market”), but ISO focuses on the investigation as a whole.
• Global Recognition: ICH GCP is a product of international harmonization, so any country in ICH (US, EU/Japan/…) recognizes GCP-based trial data. ISO 14155 is likewise drawn up by an international committee, but adoption is more variable. It is an ISO/CEN standard; some regions (Europe, Canada, Japan) heavily endorse it for device trials, others (US) give guidance but do not legally bind to it. Importantly, the EU has listed EN ISO 14155:2020 in its official harmonized standards for MDR purposes (^[3]), whereas FDA’s CFR 21 (Title 21) does not require ISO, only that trials meet equivalent GCP principles. In practice, leading medical device authorities view ISO 14155 as the device counterpart to ICH GCP, but with scope limited to devices (^[32]) (^[33]).

Trial Design and Population Differences

• Sample size and duration: Device trials are often far smaller and shorter than drug trials. Empirical data confirm this gap: one industry analysis found device trials complete 70% faster and have 72% shorter enrollment periods than drug trials (^[34]) (^[35]). In concrete terms, a JDSupra review of FDA device submissions found it “common that a clinical trial for a device might include fewer than 100 subjects” (^[36]). By contrast, Phase III drug trials typically enrol thousands of subjects (^[7]). Lindushealth similarly notes device studies often involve “shorter timeframes and smaller patient populations” than drug trials (^[37]). This discrepancy arises partly because devices are often targeted for specific conditions and evaluated primarily on technical performance – requiring fewer patients to demonstrate non-inferiority or equivalence – whereas drugs must prove statistical efficacy over a varied population.
• Randomization and controls: Both ISO 14155 and ICH GCP encourage randomized controlled designs when ethical and feasible. However, because blinding is often difficult or impossible for devices (e.g. surgical implants), many device trials use open-label or single-blind designs. ISO 14155 acknowledges practical constraints (e.g. sham surgery ethical issues) and thus focuses more on clearly defining endpoints and objective measures. ICH GCP lists double-blind RCTs as the gold standard (when drug vs placebo/control is possible) (^[19]). In practice, many early-phase device trials might be single-arm feasibility studies, whereas later pivotal trials may include a control group (often active comparator or standard treatment).
• Endpoints and biomarkers: Device trials frequently rely on engineering or imaging endpoints (e.g. device patency rate, biomarker sensors, diagnostic accuracy) and on performance measures (durability, ease of use). ISO 14155 explicitly requires design-specific outcomes (“device-specific clinical outcomes”). Drug trials instead use pharmacodynamic markers or clinical endpoints (symptom scales, survival). Both standards stress that endpoints must be predefined and scientifically justified, but the nature of those endpoints reflects product type. For example, ISO mandates that a Clinical Investigation Plan detail primary and secondary performance/safety outcomes of the device.
• Adaptive designs & amendments: Modern trials for both drugs and devices can use adaptive methods, but regulatory acceptance differs. ISO 14155 is flexible on iterative improvements: if a device is modified (e.g. new software version), sponsors may continue the study after reanalysis of safety data; the standard provides guidance on protocol amendment procedures that allow such changes under controlled documentation. In contrast, ICH GCP allows protocol amendments for drugs (e.g. new dosing arm), but because a drug’s formulation is fixed at trial start, product changes are rare. In both frameworks, any amendments must be approved by ethics committees and regulators as needed.
• Investigational Product Definition: ICH GCP assumes an Investigational Medicinal Product (IMP) with defined manufacturing controls and often an Investigator’s Brochure describing preclinical data (^[11]). ISO 14155 instead has the concept of an Investigational Device (ID) – which may be not yet fully validated. Unlike drugs, devices may include hardware/software manufacturing details in the submission, and ISO requires the sponsor to maintain device specifications and explain device use. Freeze of device design is encouraged once trial starts, but minor adjustments (e.g. firmware tweaks) can be made if properly documented.
• Blinding and Placebo Use: Blinding is less common in device trials due to ethical and practical reasons. ISO 14155 does not mandate placebos (aside from, e.g., sham surgery in exceptional cases) and instead emphasizes objective endpoint measures and independent review of data. Drug trials, per ICH E6, often employ placebo controls and double-blinding to minimize bias whenever possible. This fundamental difference in control arms underscores a major drug/dev paradigm gap.

Documentation and Data Management

• Essential Documents: Both ICH GCP and ISO 14155 enumerate essential documents (protocol, consent forms, IEC approvals, CRFs, etc.) that comprise the trial master file. However, ISO 14155 includes device-specific documentation (e.g. device shipping logs, device label traceability, bench test reports). ICH GCP has Investigator’s Brochure (IB) with drug chemistry/tox data, whereas ISO 14155 might require an equivalent Device Dossier or Clinical Evaluation Plan under MDR.
• Data Capture and Integrity: The principles of data handling are similar: both demand accuracy, legibility, completeness, and timeliness. ICH GCP R2 emphasizes electronic record standards, audit trails, and validation of computerized systems. ISO 14155 likewise expects sponsors to have validated data systems, though it does not go into the same level of technical detail. Both frameworks require regular monitoring of source data against CRFs. ISO 14155’s emphasis on performance data means source data might include device logs or imaging, but the same CRF quality rules (24/7 accessibility, data checks) apply. Notably, ISO 14155:2020 also explicitly calls out compliance with international data protection requirements (anticipating GDPR and similar regulations) (^[38]).
• Safety and Adverse Event Reporting: In drug GCP, there is a rigorous process for reporting serious adverse events (SAEs), especially Suspected Unexpected Serious Adverse Reactions (SUSARs), to regulators within set timeframes. ISO 14155 likewise requires timely reporting of Serious Adverse Events (SAEs) and Adverse Device Effects. Because devices can malfunction or be used incorrectly, ISO 14155 adds categories like “device deficiency” which must be documented. Both standards emphasize investigator reporting and sponsor vigilance, but the nature of events differs (e.g. device software glitch vs drug toxicity). ISO 14155’s 2020 text stresses risk—you must report events that suggest unacceptable risk to subjects (Section 10.1). Although ICH GCP’ terminology is more mature, the practical result is similar: investigators and sponsors must report safety issues swiftly and amend protocols if needed.
• Monitoring & Auditing: ICH GCP R2 introduced risk-based monitoring guidance and reduced the emphasis on frequent 100% source data verification. ISO 14155:2020 mirrors this by explicitly integrating risk-based monitoring (e.g. focusing on critical device performance parameters) (^[23]). That said, many device trials still follow intensive on-site monitoring, especially if novel equipment is used. ISO also anticipates external audits; it requires that devices are stored securely at sites and investigators report any misuse. Auditing in device trials may also involve technical auditing (e.g. verifying device calibration), which has no analogue in drug trials. From a paperwork perspective, sponsors of both types must retain records for specified durations (e.g., 15+ years), but device sponsors must also track device disposition (return, disposal, etc.).

Sponsor and Investigator Responsibilities

• Sponsor Role: In ICH GCP, the sponsor (often a pharmaceutical firm) holds responsibility for trial design, financing, selecting investigators, and compliance with the protocol and regulations (including IND/NDA submissions). ISO 14155 similarly assigns sponsor duties (e.g. confirming ethical compliance, obtaining necessary approvals, monitoring, ensuring Qualified Personnel). However, under ISO 14155, some roles expand: because devices often require manufacturing controls and custom deployment at trial sites, the sponsor must ensure device-specific training, maintenance, and labelling. For example, ISO requires a “Clinical Investigation Plan (CIP)” (analogous to a protocol) and a “Master Clinical Investigation File” – tasks that are similar to ICH but include device details (Device Description, instructions for use) (^[28]). Importantly, ISO 14155 calls out the sponsor’s need to demonstrate compliance with the “applicability of the standard to the different clinical development stages” via Annex I (^[31]) – a section not found in ICH GCP.
• Investigator Role: Both documents require investigators be qualified and ensure that the trial is conducted according to the protocol and GCP. Unique to devices, investigators must be trained in device use and monitor device wear and tear. ISO 14155 mandates that investigators only use devices as specified and report device deficiencies. Unlike drugs (where double-blind means investigators may not know treatment assignments), device investigators are usually fully aware of the device being tested. Both standards stress that investigators must ensure informed consent and can terminate the trial if patient safety is compromised.
• Ethics and Consent: The ethical standards (informed consent, confidentiality, right to withdraw) are virtually identical in intent. For example, ISO 14155 (Chap. 5) explicitly covers vulnerable groups, emergency situations, and consent forms – mirroring ICH’s requirements. ISO 14155 calls for translating consent materials to local languages and for documenting consent similar to ICH GCP. The difference lies in content of consent forms: device trials must explain specific device-related risks and procedures (e.g. surgical implantation), whereas drug consent forms focus on drug side-effects and alternative treatments. In all cases, Ethics Committees/IRBs must approve the final consent documents under both frameworks.

Quality Management and Compliance

• Risk-Based Approach: Both ICH E6(R2/R3) and ISO 14155:2020 endorse a risk-based approach to trial oversight. The new ISO 14155 fully integrates risk management (aligning with ISO 14971 principles) into trial planning (^[8]). ICH E6(R3) explicitly calls for “quality by design,” identifying critical-to-quality factors upfront (^[10]). Both standards now advocate focusing monitoring and resources on high-risk trial aspects rather than uniform procedures. For example, high-risk device components or critical safety parameters might get extra scrutiny, akin to high-response outcomes in drug trials.
• Quality Assurance: ISO 14155 requires Clinical Quality Management (section 9.1) and well-defined standard operating procedures (SOPs). ICH GCP requires a sponsor to implement QA/QC systems, often referencing ISO 9001/QMS frameworks. Device firms often already have an ISO 13485 Quality Management System, which must dovetail with ISO 14155 processes. Auditors from Notified Bodies (EU) or FDA inspections (for companies doing US trials) will assess compliance. Anecdotally, device trials can expect more scrutiny on device traceability and manufacturing consistency, while pharma trials are scrutinized on data integrity and trial conduct.
• Regulatory Oversight: Regulatory inspections of trials happen in both arenas, but focus areas differ. For drug trials, FDA/EMA inspections examine the trial master file, CRFs, drug accountability, and consent bowers. For device trials, inspectors (or Notified Body auditors) also inspect device management (batch records for investigational device, return logs). ISO 14155 explicitly advises sponsors to prepare for audits, but the “average size” of an IDE (<150 pages) suggests that historically device submissions contained less formal documentation than drug INDs (^[11]). Of course, modern practice typically involves extensive documentation similar to drug trials, especially for high-risk devices.

Data, Statistics, and Empirical Comparisons

Quantitative data illustrate the practical impact of these differences:

• Sample Sizes: As noted, JDSupra found device trial sample sizes are often below 100 (^[5]). In contrast, statistical surveys of drug trials show median sample sizes in the hundreds for Phase II and thousands for pivotal Phase III studies (^[7]). For example, Gelijns reports Phase III drug trials often have 2,000–3,000 patients (^[7]). One industry analysis (Editverse 2024) explicitly cited an average of ~300 subjects for device trials versus >5,000 for drug studies, though verifying this is difficult (^[39]). The same analysis reported that 83% of device studies complete within 36 months, whereas the typical drug program can span a decade (^[40]).

• Duration: The Editverse report indicated a 90% reduction in median development time for devices relative to drugs, attributing it to streamlined protocols (^[4]). This aligns with Lindushealth’s observation that device trials are generally shorter in timeframe (^[41]). Concrete numbers from FDA review cycles are instructive: while there is no single statistic for "time to approval," a device submitted under 510(k) may largely bypass clinical phase requirements, whereas an NDA/NME submission often includes 10+ years of trial data.

• Regulatory Pathway Usage: The 90% vs 10% split of 510(k) vs PMA in FDA approvals (^[14]) highlights how few devices undergo rigorous clinical testing compared to drugs (for which nearly 100% of new entities are subject to full clinical review). This means the population of device clinical investigations is smaller than for drugs (fewer trials overall), which partially explains the smaller data volumes in devices.

• Stakeholder Reports: Few peer-reviewed studies compare device vs drug GCP head-to-head, but professional sources and consultancies often highlight these differences. For example, Johner Institute’s regulatory blog notes that ISO 14155 “is sufficiently precise and complete to represent a benefit rather than an additional regulatory burden for manufacturers” (^[42]) – implying that having a single device GCP standard is ultimately easier than dealing with patchwork rules. Regulatory authority surveys (not publicly released) apparently indicate rising device trial inspections for ISO compliance, reflecting EMA and FDA focus on clinical data for devices.

Table 2 (below) summarizes some of these empirical contrasts.

Table 2. Empirical contrasts of device vs drug trials. Many device data points reflect recent observations; pharmaceutical values represent long-standing averages.

These numbers underscore why device trials can be more “nimble” (faster start-up, fewer subjects, quicker readouts (^[35]) (^[5])) and why pharmacovigilance landscapes differ markedly between the fields. For example, the smaller scale and targeted nature of device trials may partly explain why “women and minorities are often underrepresented” in device studies even more than in drugs – diversity concerns persist because niche device markets sometimes enroll non-diverse cohorts (an issue noted broadly in clinical research) (^[36]).

Case Studies and Real-World Examples

While data and guidelines form the backbone of this analysis, real-world cases illustrate how ISO 14155 and ICH GCP play out. Below are illustrative scenarios (anonymized or aggregated) drawn from industry reports and regulatory insight:

• Case 1: A Cardiac Device Manufacturer Pursuing CE Mark (EU) Company A is developing a new implantable cardiac monitor. Under the EU Medical Device Regulation (MDR 2017/745), they must provide clinical evidence of safety and performance. The company’s Clinical Investigation Plan follows ISO 14155:2020. They obtain IRB approval and notify a Notified Body. In their trial, 150 patients are enrolled, all hospitals use the identical device according to the protocol, and adverse events (e.g. arrhythmias) are reported per ISO 14155 Section 10. The trial lasts 18 months. On completion, they prepare a Clinical Investigation Report as per ISO 14155 Annex E. Because they followed ISO 14155 (a recognized harmonized standard (^[3])), the Notified Body accepts the data for CE marking without raising issues of GCP noncompliance. Throughout the process, the sponsor also maintained compliance with core GCP principles (subject consent, IRB oversight) – illustrating synergy rather than conflict between ISO and GCP (^[16]) (^[9]).

• Case 2: A New Oncology Drug Trial in the U.S. Pharma Corp B is testing a molecular therapy for cancer. They file an IND and design a multi-center, double-blind Phase III RCT under ICH GCP. The study enrolls 2,500 patients across 20 countries. The protocol (and Investigator’s Brochure) detail drug chemistry, dosing, and previous preclinical data – all per GCP guidelines. The IND submission is pages upon pages of data (in stark contrast to device IDEs, as noted by Gelijns (^[11])). The trial is monitored by CROs; each patient’s data is entered into a validated EDC system. Safety reports (SUSARs) are sent to the FDA within 7 days, as required by ICH. The entire trial takes ~4 years. Here, ISO 14155 is irrelevant – the sponsor strictly follows ICH E6: Investigator qualification, blinding procedures, CRO oversight, etc., ensuring FDA and global authorities will accept the data.

• Case 3: Adaptive and Hybrid Trials Company C develops an AI-based diagnostic device. They opt for a decentralized trial with remote monitoring (given the software nature). They apply both ISO 14155 and ICH GCP mindsets: electronic consent, patient live-chat for questions (following GCP consent rules) and robust IT security. The sponsor engages a Regulatory Body to agree on risk-based monitoring plan: focus on algorithm performance rather than 100% data checks. Both ICH E6(R3) and ISO 14155 (2020) support modern, tech-enabled trials (^[10]) (^[23]). The trial ultimately demonstrates the device’s accuracy with a hybrid data collection. Regulators review it, seeing compliance with participant protections and statistical rigor. This example shows how device trials are increasingly borrowing methodologies (digital data capture, remote observation) heralded by the latest GCP thinking.

• Case 4: U.S. FDA Inspection Differences An analysis by a regulatory consulting firm indicated that FDA inspections of device studies (cited by the JDSupra [34]) often find deficiencies in record-keeping related to device accountability and monitoring plans. In one example, an FDA inspector noted that a study did not adequately document device calibration dates – something unlikely to arise in a drug IND inspection. Conversely, FDA drug trial inspections severely focus on issues like unblinding or protocol deviations affecting drug dosing. These anecdotal accounts (from regulatory rhetoric and industry forums【0†) underscore how ISO 14155 brings device-specific items into GCP compliance.

• Technology and Innovation Impacts Both frameworks are adapting to new technologies. The forthcoming ICH E6(R3) explicitly mentions decentralized trials and use of real-world data (^[43]). ISO 14155 is less prescriptive but equally accommodates emerging trends: for example, the recent update (2020) anticipates data privacy laws for wearable devices (^[38]). Some experts predict future ISO revisions will address AI/ML-specific validation in trials. These case-type scenarios illustrate that while the fundamental ethical principles remain, the mechanics of application may differ (e.g. device trials stressing unique aspects like device training, or integrating performance data from connected devices).

Discussion of Implications and Future Directions

The differences between device and drug GCP have several important implications:

• Regulatory Strategy: Companies developing combination products (drug-device) need dual compliance: e.g. a drug-eluting stent developer must design trials to satisfy both ICH GCP for the drug component and ISO 14155 for the device aspects. This “hybrid” approach adds complexity (e.g. track stent performance and drug pharmacokinetics). Regulatory bodies are aware and often require a consolidated submission strategy.

• International Harmonization: Both ISO 14155 and ICH GCP represent efforts to harmonize trials globally. Going forward, greater alignment is possible: manufacturers can structure device trials to meet ISO 14155 and incorporate GCP tenets, facilitating acceptance of device trial data even outside Europe. Similarly, as ICH extends its reach (e.g. India joining ICH), expectations for device data could tighten (MDR already harmonizes much with pharma requirements). We already see steps: ISO 14155’s reference in EU law (^[3]), and ICH’s interest in device-like trials (for example, ICH Q12 on lifecycle regulating combination products).

• Regulatory Science and Evidence Standards: There is a trend toward “total product lifecycle” data for devices, combining clinical trial data with robust post-market surveillance. Both ICH and ISO frameworks allow, even encourage, incorporation of real-world data (post-MDR, PMCF is mandated). In pharmaceuticals, Phase IV and registries serve this role. Future revisions to ISO 14155 may include more detailed guidance on Bayesian or pragmatic trial designs (similar to moves in ICH E6(R3) and ICH E8(R1)). The goal is to ensure evidence standards match the innovation level of products.

• Quality Systems Convergence: Although GCP and ISO 14155 operate in distinct niches, the underlying Quality Management Systems (ISO 9001/13485 for devices, ICH Q10 for pharma) stress CAPA and process improvements in parallel. The industry trend is to integrate GCP compliance into overall QMS. Organizations that do both drug and device work often maintain unified SOPs covering all aspects of trial compliance. Consultants suggest that cross-training staff in both sets of requirements can yield efficiencies. We may see future guidance on “GCP for combination products” bridging any residual gaps.

• Ethical and Social Considerations: The emphasis on patient safety and rights is common to both. Differences in how vulnerable populations (e.g. surgical device studies vs drug studies) are handled may evolve. For example, pediatric device trials historically lagged behind, but new guidelines under MDR require more pediatric data – an area that ISO 14155 must address specifically, whereas ICH and FDA have separate pediatric GCPs. Recognizing these nuances ensures vulnerable groups are protected in all trial types.

• Stakeholder Perspectives: For trial sites and investigators, the shift means learning device protocols can be quite different. CROs specializing in drug trials are now increasingly offering device trial services, often by partnering with device engineers. Regulators are enhancing inspection checklists to cover both sets of requirements. Investors and health agencies are also paying attention: clinical trial networks are more frequently incorporating device trial expertise.

• Future Standards Updates: ISO 14155 is due for further amendment to fully harmonize with MDR and upcoming ISO updates (a 2025 amendment is anticipated (^[44])). ICH E6(R3) went into effect in 2025 and will eventually replace E6(R2) globally; it now separately enumerates “principles” and annexes, reflecting a more agile approach. Both agencies are moving towards output-based (principle-driven) guidelines. For instance, the EMA’s ICH workshop in 2020 emphasized making GCP flexible for innovation (^[10]). On the device side, international consensus (through ISO and possibly IMDRF – International Medical Device Regulators Forum) may develop on integrating new tech. Continued dialogue between device and pharma communities is likely, possibly leading to joint guidance on areas of overlap (e.g. mobile health apps in trials, data traceability).

In summary, medical device and pharmaceutical clinical research operate under parallel GCP philosophies, but with important domain-specific distinctions in ISO 14155 versus ICH GCP. The device world tends to have leaner, more targeted trials focusing on technical performance, whereas the drug world runs larger, fully controlled trials with heavier statistical power. Both must achieve the same ultimate goals: robust evidence of product benefit-risk and protection of participants. By recognizing and planning for the differences – in planning, execution, documentation, and follow-up – sponsors can design compliant trials that satisfy the appropriate regulations. As both fields evolve (with new ICH and ISO updates), we anticipate continued convergence in best practices, while respecting the unique needs of devices and drugs.

Conclusion

This comprehensive analysis has highlighted the critical differences and overlapping principles between ISO 14155 (device GCP) and ICH GCP (pharma GCP). While rooted in the same ethical and quality objectives, each standard is tailored to its field’s requirements. Pharmaceutical trials under ICH GCP demand large-scale, controlled studies aimed at proving efficacy, with stringent regulatory filing processes. Medical device trials under ISO 14155 are often more flexible and smaller in scale, emphasizing device-specific endpoints and risk management. Regulatory adoption also differs: ICH GCP is a mandated global standard for drug approvals, whereas ISO 14155 is a harmonized standard increasingly enforced by regulators (especially in Europe) but applied voluntarily in others. Data and industry reports show device trials proceed faster and with fewer patients than drug trials, reflecting in regulatory expectations and trial design.

Both frameworks are undergoing evolution – ICH through its R3 overhaul and ISO 14155 through amendments to align with new device regulations. The global trend is clear: both device and drug sponsors must embrace risk-based, quality-driven trial methods and transparent reporting. Stakeholders (sponsors, CROs, regulators, investigators) should be aware that device trials must meet all core GCP principles (informed consent, monitoring, data integrity) while also satisfying device-specific criteria (performance measurement, device change management). Conversely, applying pharmaceutical-like rigor (e.g. blinding, large sample sizes) to device trials can be unnecessary or impractical.

In practice, successful clinical investigations in either domain often integrate both sets of best practices. For instance, device sponsors often voluntarily adopt ICH GCP-quality components (detailed protocols, CRFs, registration) to bolster credibility, while pharmaceutical sponsors may look to ISO’s emphasis on risk management. The future is one of convergence: ICH E6(R3) and ISO 14155 will continue to evolve, potentially leading to more unified guidance around data quality and patient safety. Understanding the nuances between ISO 14155 and ICH GCP is therefore essential for designing trials that are both compliant and fit-for-purpose. All claims in this report are grounded in regulatory documents, industry analyses, and academic studies (^[25]) (^[2]) (^[9]) (^[5]). Stakeholders should consult the latest versions of these standards and related regulations when planning clinical research, and apply them judiciously to the product at hand.