Import, Export and Regulatory Considerations for Investigational Product

Part of Good Clinical Practice (GCP) — ICH E6(R3): Investigational Product (IP) Management.

About 6 minutes. Free, in your language, no account needed.

Why this matters

A shipment held at customs for three weeks can stop enrollment across a whole country. A broken cold chain can destroy a batch that took nine months to make. These are common causes of delay in global trials. They are also where people most often assume Good Clinical Practice (GCP) has an answer, and it does not.

Start with what E6(R3) does not say

International Council for Harmonisation (ICH) guideline E6(R3) for GCP does not set import or export rules for investigational product.

The words import, export, customs, cold chain and Qualified Person do not appear in the E6(R3) Principles and Annex 1. There is no ICH import license requirement and no ICH transit temperature limit.

What E6(R3) does is defer. Section 2.10.9 states: "Investigational product management should be arranged and conducted in accordance with applicable regulatory requirements, and safeguards should be in place to ensure product integrity, product use per protocol and participant safety." Section 3.15.3(a) repeats that wording for the sponsor's supply activities.

Principle 11.1 requires manufacture under applicable Good Manufacturing Practice (GMP) standards. Principle 11.5 requires labeling to follow applicable regulatory requirements. The operative words each time are "applicable regulatory requirements", and those come from national and regional law.

The sponsor's supply responsibilities, which E6(R3) does set

3.15.3(a) — the sponsor is responsible for supplying the investigator and institution with the investigational product. "Investigational product should be supplied after obtaining the required approval/favorable opinion from the IRB/IEC and the regulatory authority(ies) for the trial." IRB/IEC means institutional review board or independent ethics committee.
3.15.3(c)(i) — timely provision of product to avoid any interruption to the trial and to continue treatment for participants.
3.15.3(c)(ii) — the sponsor maintains records of the identity, shipment, receipt, return and destruction or alternative disposition of the product.
3.15.3(c)(v) — steps to ensure the product is stable over the period of use and "only used within the current shelf life."
3.15.3(c)(vi) — batch samples retained to reconfirm specifications, kept "either until the analyses of the trial data are complete or as required by the applicable regulatory requirement(s), whichever represents the longer retention period."

Section 3.15.3(c)(i) is the hook for the rest of this lesson. In E6(R3) terms, a customs delay is a failure of timely provision.

Import and export as national and regional law

Everything below is context, not guideline text. Requirements vary by country and they change. Confirm the current position with your sponsor's regulatory affairs group. The recurring themes across jurisdictions are these.

Trial authorization before import — many countries will not permit investigational product to enter until the trial is authorized nationally. Section 3.15.3(a) points the same way.
Import licenses or permits — a country may require a specific license, sometimes per shipment and sometimes per trial.
An importer of record — many customs regimes require a named legal entity in the destination country to act as importer.
Customs documentation — shipments typically travel with invoices, a packing list, the import authorization, and a certificate of analysis.
Export controls — the country of manufacture may impose its own requirements. Both ends of the route have rules.
Controlled substances — additional national licensing usually applies, often from a different authority, with permits per shipment and capped quantities.

Do not assume a route that worked for one trial works for the next.

Cold chain in transit

Section 3.15.2(b) makes the sponsor responsible for determining acceptable storage temperatures and conditions, and for informing monitors, investigators, pharmacists and storage managers. Section 3.15.2(c) requires packaging that prevents contamination and unacceptable deterioration during transport and storage.

Beyond that, transit temperature control is operational practice, not ICH text. It relies on validated shipping containers, temperature data loggers traveling with the shipment, and documented courier handling instructions.

When a shipment arrives with an excursion, the site workflow from lesson 2 of this module applies unchanged. A long customs hold is a frequent cause, because it can exceed the shipper's validated duration.

GMP and batch release: the European Union context

Principle 11.1 requires manufacture in accordance with applicable GMP standards. E6(R3) says nothing about how GMP compliance is certified.

In the European Union, the established practice is that investigational medicinal products are made under European Union GMP and that a Qualified Person certifies each batch before release for use in a trial. The European Union Clinical Trials Regulation 536/2014 has been applicable since 31 January 2022.

Treat that as regional context a regional expert should confirm. The Qualified Person concept is European Union law and has no equivalent in many jurisdictions.

The records that prove the chain

Appendix C of E6(R3) lists essential records. Four relate directly to supply and import:

Shipping records for investigational product and trial-related materials
Certificates of analysis of investigational product shipped
Documentation of investigational product storage conditions, including during shipment
Records of relabeling of investigational product at the investigator site

Together they are the evidence that a shipment arrived intact and lawfully. Note that relabeling at the site is itself an essential record.

In practice

ABC Pharmaceuticals is opening three sites in a new country. The product requires storage at 2 to 8 degrees Celsius.

Kwame is the regional clinical supply manager. He does not look in E6(R3) for the import rules, because they are not there. He works from the national regulatory authority's requirements, the country's customs requirements, and the sponsor's procedures. His planned sequence is national trial authorization, IRB/IEC favorable opinion, import permit, then first shipment. Section 3.15.3(a) supports that ordering.

The first shipment is held at the border for four days over a public holiday. The shipper was validated for 96 hours, and Kwame receives a data logger alert at hour 92. The site pharmacist quarantines the product on arrival and records the logger data. The manufacturer evaluates the excursion against the product's stability data and releases the batch with a documented justification.

Kwame then changes two things. The next route avoids the holiday period, and the sponsor moves to a shipper validated for 120 hours. Under section 3.10.1.4 the risk and mitigation are communicated to the sites and monitors. The sites lost no dosing days, because Kwame planned around a legal system E6(R3) never described.

Key takeaways

E6(R3) does not set import or export rules; sections 2.10.9 and 3.15.3(a) require investigational product management to follow applicable regulatory requirements, which are national and regional law.
Section 3.15.3(a) requires investigational product to be supplied only after the required IRB/IEC approval or favorable opinion and regulatory authority approval are obtained.
Section 3.15.3(c)(i) makes timely provision a sponsor responsibility, so customs and import failures become a GCP problem through their effect on trial continuity.
Section 3.15.3(c)(vi) requires batch samples to be retained until the trial data analyses are complete or for the period applicable regulation requires, whichever is longer.
The Qualified Person batch certification model is European Union law, not an E6(R3) requirement.
When the guideline says "applicable regulatory requirements", that is an instruction to find the local law, not permission to stop reading.