ICH E6(R3) GCP Training with Investigational Products

Opens with a self-check on your knowledge of good clinical practice and on who controls the trial drug from factory to participant. Presents two cases: the December 2023 EMA decision on Synapse Labs, a contract research organisation in Pune, India, over irregular study data, inadequate documentation and inadequate computer systems, and a July 2026 FDA warning letter to a clinical investigator's site in Florida where trial drug doses did not add up. Explains that good clinical practice protects participants and assures reliable results from planning to reporting. Introduces OPQ Therapeutics, a biotech in Boston, and its trial OPQ-117-201 of a weekly injection in 240 adults, run with UVW Clinical Research in London at sites in London and Sydney. Ends with how the course, four practice exercises and the exam work, and a recap.

What you will be able to do

• Explain what good clinical practice protects and assures
• Describe what went wrong in the Synapse Labs and Florida site cases
• Trace who controls the investigational product at each step

Why it matters

Seeing how unreliable records and unaccounted doses undermined real trials shows why every GCP control matters at your site.

Practice: Practice: Welcome, and why GCP matters · 3 questions

Starts with an academic trial unit in Toronto planning a trial in 600 patients across 30 hospitals, comparing checking every data point at every visit with first deciding which data and processes matter most. Explains how the guideline got here and how E6(R3) is built: eleven principles, two annexes and three appendices, in one consolidated text from June 2026, including transparency through trial registration and posting results. Covers its status: the principles and Annex 1 took effect in the EU in July 2025 and became FDA final guidance in September 2025, with Annex 2 following in the EU in January 2027. Then walks through the principles on ethics, quality, results, roles and the investigational product, and how OPQ uses them. Ends with the common mistake of retitling E6(R2) procedures, and a recap.

What you will be able to do

• Describe the structure of ICH E6(R3): principles, annexes and appendices
• State when E6(R3) took effect in the EU and in the US
• Explain how the eleven principles work together

Why it matters

Knowing the structure and dates of E6(R3) stops you updating only the title of old E6(R2) procedures.

Practice: Practice: ICH E6(R3): structure, status and principles · 3 questions

Opens with a biotech in Paris whose contract research organisation quietly handed site visits in two countries to a smaller firm, so nobody checked consent forms there for months. Explains the four parties in a trial: the sponsor, its service providers, the investigator and the ethics committee, and what the sponsor obtains from each investigator and institution. Covers how sponsors transfer and investigators delegate, always in writing, to qualified people and parties, shown in OPQ's transfer-of-activities matrix with UVW and the delegation log at one of OPQ's London sites, matched to system access. Then covers proportionate oversight through agreed metrics, reviews, escalation routes and audits, with a site in Hong Kong where a nurse gave injections before her name reached the log. Ends with a recap.

What you will be able to do

• Explain the responsibilities of the four parties in a clinical trial
• Write a transfer-of-activities matrix and a delegation log
• Plan oversight that is proportionate, recorded and acted on

Why it matters

You can transfer work, not responsibility; written transfers and real oversight stop gaps like unchecked consent forms.

Practice: Practice: Roles, agreements and oversight · 3 questions

Starts at a hospital site in Dubai on a busy clinic morning, where a screening blood sample was drawn at ten past nine and the consent form signed at twenty to ten, so a trial procedure came before consent. Explains how an independent ethics committee approves the trial before anyone is enrolled and keeps reviewing it, and how a site works with the committee through the life of the trial. Then walks through the consent process in Annex 1 section 2.8: informed and voluntary consent on the approved form, signing and dating by the person and the investigator, copies for the participant, an impartial witness present in person or remotely when the person cannot read, shown at OPQ and a cancer centre in New York. Ends with sharing new information, re-consent and a recap.

What you will be able to do

• Explain what the ethics committee must approve and keep reviewing
• Apply the steps of the informed consent process in Annex 1
• Decide when new information requires re-consent

Why it matters

Consent is a process, not a signature; getting the order and records right protects participants and the data from their visits.

Practice: Practice: Ethics review and informed consent · 3 questions

Opens with a vaccine sponsor in Tokyo whose primary endpoint depended on electronic diary data, yet whose monitoring plan focused on site files and drug logs, so thirty per cent of diaries were incomplete by month four before anyone noticed. Explains quality as fitness for purpose, designed in from the factors critical to quality. Covers the six steps of risk management in E6(R3): identifying, evaluating, controlling, communicating, reviewing and reporting risks. Then covers pre-specified acceptable ranges, such as quality tolerance limits at trial level, showing how OPQ applies this and how a limit is written. Ends with the common mistake of a copied register of generic risks, a recap, and a practice exercise to list critical factors, assess three risks and set one quality tolerance limit.

What you will be able to do

• Identify the factors critical to quality for a trial
• Apply the six steps of risk management in E6(R3)
• Write a quality tolerance limit that triggers action

Why it matters

Putting effort where the risk is catches problems like missing endpoint data in month one, not month four.

Practice: Practice: Quality by design and risk management · 3 questions

Starts with a biotech in Paris that asked sites to add new expiry stickers to kits after a shelf life extension, until a hand-placed sticker covered a kit number and two participants received each other's kits. Explains what an investigational product is, including an approved medicine used or packed differently, and principle 11: products made to applicable GMP, keeping their quality, used per the protocol, keeping the blinding and labelled to the rules. Follows the product through manufacture using Annex 1 section 3.15.2, then shows the main sections of the investigator's brochure, its controlled distribution and yearly review. Covers labels that follow each country's rules and never reveal the treatment, OPQ's release checklist, relabelling under an approved procedure, and a contract research organisation in Singapore routing expiry extensions through the depot. Ends with a recap.

What you will be able to do

• Explain how principle 11 applies to investigational products
• Describe what the investigator's brochure must give investigators
• Check that labels follow local rules and protect the blind

Why it matters

A label change done badly can swap treatments between participants; controlled labelling protects both safety and the blind.

Practice: Practice: Investigational products: making and labelling · 3 questions

Opens at a hospital site in Hong Kong at two in the morning, where a participant arrives with a severe reaction and the unblinding system needs a password only the sleeping study coordinator knows. Explains how randomisation keeps groups comparable and blinding keeps assessments fair. Covers protecting the blind in the product, the systems, the data and the roles, with every unblinded role named in advance and OPQ's placebo matched to OPQ-117 in appearance, vial and kit, and assessing the risk of unblinding. Then shows how OPQ prepares emergency unblinding from day one: each doctor on the delegation log has an account in a randomisation system available twenty-four hours a day, and one participant is unblinded for one reason and recorded, with a trial unit in Toronto testing it on a dummy participant. Ends with a recap.

What you will be able to do

• Explain how randomisation and blinding protect a trial's results
• Identify where the blind can be broken in products, systems and roles
• Set up an emergency unblinding procedure that works at any hour

Why it matters

An unblinding procedure that has never been tested can fail a participant in an emergency; ready and recorded protects both.

Practice: Practice: Randomisation, blinding and unblinding · 3 questions

Returns to the FDA warning letter from Module 1, where FDA compared participants' reports, the site's master accountability log and the electronic trial data and found quantities that did not match. Explains that the sponsor supplies the product and keeps shipment records while the investigator is responsible for it at the site. Covers storage and use, then shows how OPQ handles a temperature excursion at a London site when the pharmacy fridge log shows 9.4 °C for three hours overnight. Then covers recording delivery, inventory, use by each participant, and return or destruction with dates, quantities, batches and codes, shown in the accountability record for one participant at a Sydney site after week 16, and what Annex 1 asks the monitor to confirm, with a hospital pharmacy in Dubai reconciling at each visit. Ends with a recap.

What you will be able to do

• Keep accountability records for delivery, use, return and destruction
• Handle a temperature excursion and record the decision
• Reconcile the diary, pharmacy log and trial data so counts end at zero

Why it matters

Every vial used, returned or destroyed on record is what lets a sponsor and an inspector trust the dosing data.

Practice: Practice: Supplying and accounting for the product · 3 questions

Starts at a hospital site in Toronto in a blood pressure trial, where a participant admitted with pneumonia is not reported because a research nurse judged it unrelated and the investigator was on leave with no one else delegated. Explains how the investigator follows the protocol and records every deviation, with the sponsor's criteria marking the important ones, shown in part of a deviation log at one London site. Covers medical care for participants, the definition of a serious adverse event, and reporting serious adverse events to the sponsor immediately with the investigator's causality assessment. Then shows how OPQ handled one case in OPQ-117-201: continuous safety review, expedited reporting of SUSARs within the E2A timelines and local rules, and updates to the brochure, consent form or protocol, with a contract research organisation in Singapore quizzing site teams. Ends with a recap.

What you will be able to do

• Record protocol deviations and identify the important ones
• Report a serious adverse event to the sponsor immediately
• Explain how the sponsor expedites SUSARs and informs others

Why it matters

Report first, assess later; delayed SAE reports put participants at risk and are a common inspection finding.

Practice: Practice: Investigator conduct and safety reporting · 3 questions

Opens with a sponsor in Frankfurt running a heart trial at forty sites, whose weekly central data review spotted one site with unusually uniform blood pressure readings that site visits had missed. Explains how quality control checks the data at each stage, through monitoring and data management, while quality assurance, including independent audit, checks that the processes work. Covers risk-based monitoring that combines site and central methods, what monitors confirm, such as consent before participation and timely adverse event reporting, and monitoring reports with findings and follow-up, showing how OPQ applies this and a hospital network in Dubai tracking how often central review finds real issues. Then covers proportionate action on noncompliance: root cause and corrective action where significant, and notification where serious. Ends with a recap and a practice exercise writing findings from a monitoring visit.

What you will be able to do

• Explain the difference between quality control and quality assurance in a trial
• Plan monitoring that combines site visits and central review
• Decide the proportionate action for noncompliance

Why it matters

Monitoring aimed at risk finds problems that source data checks alone miss, before they reach the trial's results.

Practice: Practice: Monitoring, audit and noncompliance · 3 questions

Returns to the Synapse Labs case from Module 1 and asks whether the data could be trusted at all. Explains how source records are defined before the trial and should be attributable, legible, contemporaneous, original, accurate and complete, with traceable changes. Covers the data life cycle to finalisation before interim and final analyses, audit trail review, user accounts and access, and computerised systems validated for their use, shown at OPQ, where sources include the site's medical notes, the skin score worksheet and the participants' diary app feeding UVW's system. Then covers essential records filed on time and retained for the longest period that applies, with the sponsor telling sites in writing how long to keep them. Examples include a biotech in Paris catching a dose calculation error in testing and a hospital in Hong Kong comparing access with the delegation log. Ends with a recap.

What you will be able to do

• Define source records before the trial starts
• Review audit trails and system access against the delegation log
• Retain essential records for the longest period that applies

Why it matters

If you cannot trace it, you cannot trust it; good data governance is what makes trial results acceptable to regulators.

Practice: Practice: Data governance and essential records · 3 questions

Starts with a sponsor shipping product to participants' homes in Dubai, where a courier leaves a cooled box with a neighbour for six hours and the label reveals the trial. Explains that Annex 2 covers decentralised and pragmatic elements and real-world data, taking effect in the EU in January 2027 while still a draft in the US. Covers direct-to-participant shipment authorised by the investigator, protecting privacy and blinding, reaching the right person and accounted for, shown at OPQ, where the courier sees an address but never the diagnosis. Then covers proportionate investigator oversight, safety information from devices and other sources reaching the investigator in a manageable way, and security safeguards, including cybersecurity, against data breaches. Ends with a recap and a practice exercise to plan home delivery of kits for OPQ's London participants.

What you will be able to do

• Explain what Annex 2 covers and when it applies
• Plan direct-to-participant shipment that protects privacy and the blind
• Make sure safety information from new sources reaches the investigator

Why it matters

Decentralised trials bring new settings but the same principles; designed controls keep home delivery safe and private.

Practice: Practice: Annex 2: decentralised and pragmatic trials · 3 questions

Starts with the whole trial on one screen in five stages: prepare, release, run, close and report, each linked to the modules and leaving evidence in the trial master file. Shows OPQ's site activation check for a London site, follows participant 1-007 through the trial, then one difficult week at a London site. Covers closing a site and inspection readiness, explaining that inspectors often look first at consent, the product, safety reporting and the data, with oversight behind them, and common mistakes such as procedures copied from E6(R2) and generic risk registers. Gives a six-step road map, from the principles to data and records, with Annex 2 for EU trials from January 2027. Ends with a recap and how the final exam works.

What you will be able to do

• Trace one participant through all five stages of a trial
• Prepare for a GCP inspection by checking consent, product, safety and data
• Apply the six-step road map to your own trials

Why it matters

Seeing the whole trial as one connected story shows what inspectors will ask for and where your own gaps are.

Practice: Practice: Putting it together, and the exam · 3 questions