5. Investigator and Investigational Product

5.1 Does the local regulation require PI/CI to be approved/registered by any regulatory authority (e.g., RA/EC)?  

The Korean GCP Guidelines state that Korean PIs must be well educated, trained, and have foreign language abilities. It is assumed that local medical certification is required.

5.2 Does the local regulation require any specific documents if PI/CI is based outside the country?  

Not applicable. PI must be based in Korea.

5.3 Does the local authority allow electronic ICF administration including electronic signatures?

Yes, electronic ICF is allowed. 

The Digital Signature Act provides the basic guidelines for eSignatures as well as the legal validity, enforceability, and accessibility in agreements and contracts.

South Korea has a tiered eSignature legal model and recognizes digital signatures as a distinct type of eSignature.

eSignatures are valid in South Korea as long as certain guidelines stated in The Digital Signature Act are met. An important requirement is for the eSignature to be identifiable to the signatory and associated with the signed document. Additional documentation may need to be provided in court to prove a valid contract.

In some stances, when digital signatures are required, they need to meet the following criteria to be equivalent to handwritten signatures:

• The digital signature-creating key shall be held by and known only to the subscriber.
• The subscriber shall be controlling and managing the digital signature-creating key at the time of signing.
• It shall be ascertained whether there has been any alteration in the digital signature concerned since it was affixed.
• It shall be ascertained whether there has been any alteration in the electronic message concerned since the digital signature was affixed.

The tiered eSignature legal model in South Korea allows companies to select the type of eSignatures to use while conducting their business.

Key Restrictions

eSignatures are not recommended for:

• Documents requiring notarization.

5.4 Does local regulation require ICF to be administered as audio/visual and do these need to be recorded? 

There is no requirement for ICF to be administered as audio/visual in South Korea. However, due to cultural and language barriers, it must be ensured that the subject is fully aware of the undertaking and this may mean that the ICF be presented verbally.

5.5 Are there any specific information/requirements on data capture/management (e.g., privacy regulations, etc.)? 

South Korea’s Personal Information Protection Act (PIPL) outlines the protection of ‘sensitive data’ which encapsulates ‘health’ data. Sensitive data is defined below:

Sensitive data: Sensitive data is defined as 'personal information regarding an individual's ideology, faith, trade union or political party membership, political views, health, sexual orientation and other personal information that may cause a material breach of privacy', and further includes genetic information, criminal records, information on an individual's physical, physiological, and behavioral characteristics generated through certain technical means for the purpose of identifying a specific individual and racial/ethnic data as stated in Article 18 of the Enforcement Decree of the Personal Information Protection Act 2011 (as amended in 2021 and 2022) (English version with 2020 Amendments available here; up-to-date version only available in Korean here) ('the PIPA Enforcement Decree').

Health data: The PIPA only stipulates that health data is deemed sensitive data without providing a direct definition of 'health data'. According to the PIPC guidelines, health data is data about an individual's current and past medical history and physical/mental disabilities (e.g., disability rating).

For more information regarding the PIPL, see the below link to the English translation.

https://iapp.org/resources/article/south-korea-privacy-law-personal-information-protection-act/

5.6 If a clinical study involves a study product such as OTC and this is provided via pharmacy/amazon, etc., are there any specific regulations for IP management that need to be followed?

Investigational Products must be provided directly by the Sponsor.

5.7 For a marketed study product/OTC, can a participant be compensated after confirmation of the purchased study product, or upfront prior to product acquisition? Does compensation in any way impact how the study is viewed (i.e. RWE vs interventional study)?

Investigation Products must be provided directly by the Sponsor.

5.8 Is it permitted to pay participant stipends (i.e., is it permitted to pay the patients for their participation in the clinical trial?) If so, what is the average range? 

In accordance with the Korean GCP Guidelines, the IRB/IEC shall review both the amount and method of payment to subjects to ensure that neither presents problems of coercion or undue influence on the trial subjects. Payments to a subject shall be prorated and not wholly contingent on the completion of the trial by the subject.

The IRB/IEC shall ensure that information regarding payment to subjects, including the methods, amounts, and schedule of payment to trial subjects, is set forth in the written informed consent form and any other written information to be provided to subjects. The compensation for subjects in the event of premature discontinuation shall be specified.

Payments to subjects are typically small and only cover travel expenses.

5.9 Specific labeling requirements for the clinical study product 

The sponsor shall ensure that the investigational product(s) (including active comparator(s) and placebo, if applicable) is characterized as appropriate to the stage of development of the product(s), is manufactured in accordance with any applicable GMP, and is coded and labeled in a manner that protects the blinding, if applicable. In addition, the labeling shall comply with applicable regulatory requirement(s).

The sponsor shall determine, for the investigational product(s), acceptable storage temperatures, storage conditions (e.g. protection from light), storage times, reconstitution fluids and procedures, and devices for product infusion, if any. The sponsor shall inform all involved parties (e.g. monitors, investigators, pharmacists, and storage managers) of these determinations.

The investigational product(s) shall be packaged to prevent contamination and unacceptable deterioration during transport and storage.

In blinded trials, the coding system for the investigational product(s) shall include a mechanism that permits rapid identification of the product(s) in case of a medical emergency but does not permit undetectable breaks of the blinding.

If significant formulation changes are made in the investigational or comparator product(s) during the course of clinical development, the results of any additional studies of the formulated product(s) (e.g. stability, dissolution rate, bioavailability) needed to assess whether these changes would significantly alter the pharmacokinetic profile of the product shall be available prior to the use of the new formulation in clinical trials.

Further information regarding the Labeling Requirements for Clinical Study Products can be found here: Regulation on the Labeling of Medicinal Products, etc. (No.2020-82).

5.10 What documents need to be submitted (including relevant fee if any), and to whom, if a permit is needed for an investigational/study product being shipped from outside the country? Are there any specific requirements for biologics? 

An import license is not required for Investigational medical products. Investigational medical products are exempt from import requirements. Please see below information regarding the exemptions of import licenses under Item 4.

Guidelines for Recommending Drugs and Cosmetics for Exemption from Import Requirements

Article 2 (Scope of Exemptions for Import Requirement Certification) 

(1) The pharmaceuticals and cosmetics exempt from import requirements are items imported for the following purposes:

• For medicines for a rare disease or that are hard to come by (less than USD 2,000)
• For emergency relief
• Quasi-drug for emergency quarantine
• For the production of starter packs
• For research
• As promotional or reference samples
• As quasi-drugs and cosmetics for consumer surveys
• As active pharmaceutical ingredients (APIs) needed for pharmaceutical manufacturing upon consignment from abroad and entirely exported (hereinafter referred to as the “APIs of pharmaceuticals manufactured under overseas contract”)

The recommendation criteria for Exemptions for Import Requirements for pharmaceuticals and cosmetics are as follows:

1. Medicine for a rare disease or that are hard to come by shall be provided with a written diagnosis issued by the head of a national or public hospital, the head of a public health center, or the head of a medical institution (excluding midwives) pursuant to Article 3 (2) of the Medical Service Act. However, if the required amount for the minimum treatment cycle is specified for a product that requires a certain treatment cycle, and if a pharmaceutical for two or more people is imported by attaching a written diagnosis for each individual, the product may be recommended even if the total amount is valued at USD 2,000 or more.
2. Emergency pharmaceuticals imported in preparation for the treatment of emergency patients or for other emergency relief purposes shall be accompanied by a plan for usage from the head of the relevant medical institution.
   1. Quasi-drug for emergency quarantine is for the prevention or quarantine where infectious disease breaks out under the Infectious Disease Control and Prevention Act, the drug should follow a plan for usage from the person who intends to use the quasi-drug for non-commercial and non-marketing use. However, if the import agency handles the imports, the quasi-drug can be recommended only when the entire amount of the product is circulated to the user in the plan.
3. The amount of a product imported for the production of starter packs shall be based on a manufacturing plan but shall not exceed 2 kilograms for APIs. However, the quantity may be increased or decreased depending on the product or the manufacturing tests.
4. Research products shall be accompanied by a research (or study) plan, and the quantity shall be limited to the minimum necessary for testing the product to be imported or manufactured.
5. Products to be used as samples shall be classified as either promotional or reference samples. Products for reference purposes shall be limited to two for the same product, and products for promotional use may be recommended according to the following criteria:
   1. The quantity shall be limited to 5 per distributor based on the original packaging unit at the time of import of the product.
   2. Each sample unit shall bear a label that clearly distinguishes it from the same products imported for other purposes, e.g. “sample”, and those that are not labeled as such may be recommended on condition that they are labeled separately after customs clearance.
6. Quasi-drugs and cosmetics for consumer surveys shall be recommended according to the following criteria:
   1. The recommendation shall be based on a consumer survey plan, and the quantity shall be the minimum required for a consumer survey.
   2. Each unit shall bear a label that clearly distinguishes quasi-drugs and cosmetics for consumer surveys from the same products imported for other purposes (e.g., “a quasi-drugs for consumer survey” or “a cosmetic product for consumer survey”), and units not labeled as such may be recommended on condition that they are marked separately after customs clearance.
7. APIs of pharmaceuticals manufactured under the overseas contract shall be limited to APIs with the consignment manufacturing contract or documents that can prove the consignment relationship (in case the API cannot be identified, supporting documents such as the product standard may be attached). However, APIs for pharmaceuticals that have already been approved or notified are excluded.

For products other than Investigational Medicinal Products, please see the below process.

KC Certification, or Korea Certification, is a product certification that is mandatory for many products. It exists to ensure that goods comply with Korean safety standards. As with other countries we have written articles about, this country-specific certification is in place to protect the health and safety of Korean users, and to reduce the impact on the environment. 

The certification is very similar to the European CE mark and is valid for 730 different products, spanning automotive parts, machines, and anything electronic.

The manufacturer of the goods is the responsible party for getting their goods tested and certified with the KC mark.

In order to obtain the KC certificate, manufacturers must go to the Korean Agency for Technology and Standards (KATS) in South Korea. KATS is part of the Ministry of Trade, Industry, and Energy (MOTIE), and it is responsible for the regulatory framework for the market launch of different consumer goods to comply with consumer safety standards. 

Detailed Steps of the KC Certification:

• Preparation of application documents and application
• Registration at the Korean certification authority
• Factory inspection (only for Korea Safety Certificate)
• Product tests in an accredited test lab
• Checking of all documents and issuance of the KC Mark Certificate

KC Certification application documents:

The following application documents are needed to apply for the KC Mark Certification – all documents must be in Korean:

• Application form
• Business License
• Complete contact details of the Korean importer and the production plant
• Product descriptions and/or user manuals 
• List of critical components
• KC or CB certificates of critical components
• Circuit diagrams (only for electronic products)
• Example of the marking
• If available, CB certificate and test report of the products according to IEC standards, which include 220V (AC) 60Hz

After submission, all these documents are reviewed and then, crucially, the products are tested for safety by an internationally recognized testing institute. These tests are carried out in accordance with national and international standards. 

If CB certificates and test reports according to IEC standards are available, the certification and testing process for the respective products can be simplified and shortened. However, an important requirement is that the CB certificate must include the Korean voltage of 220V (AC) / 60 Hz.

Manufacturers of safety products also have to undergo a factory inspection and will continue to have follow-up audits and product testing at regular intervals.

The KC Certification process can usually be completed within 3-6 months, although products requiring factory inspections may take longer. This includes the preparation of the application documents, assuming that all required information is available.

Products that have succeeded in getting KC-certified must display the KC Mark label, along with other product information (Korean is mandatory, English is optional).

Importing

Once goods have a KC license, they can be imported into Korea, but it is important that the license is available before the goods are shipped to be imported. If a consignment enters Korean customs without a KC license, they will simply reject the shipment.

https://www.mouseandbear.com/blog/importing-goods-into-south-korea.htm

5.11 What is the turn-around time to get an import permit? 

Import permits are issued within 2 days.

https://m.blog.naver.com/PostView.naver?isHttpsRedirect=true&blogId=creatper&logNo=220881115953

5.12 Does the local authority allow the destruction of clinical supplies at an off-site location (e.g. third-party vendor in or outside the country) after study completion? Are certificates of destruction required?

There is no specific guidance on this topic.