Pharmaceutical Regulations and Registration in South Korea (MFDS)

The Ministry of Food and Drug Safety (MFDS) priorly known as the Korean Food and Drug Administration (KFDA) is the regulatory authority in South Korea. For a product to enter into the market it must satisfy certain requirements and must comply with all the relevant regulations to ensure the arrival of only safe, effective and quality medicines.

In this article we talk about the product registration in South Korea, MFDS regulations, labelling requirements, pharmaceutical classification and more.

Classification of Pharmaceuticals in South Korea (MFDS)

and are classified into drug products and pharmaceutical ingredients. Drug products are categorized into three classifications:

New drugs - Any new pharmaceutical material that is different in chemical structure or original composition from pharmaceutical products previously approved in Korea, or a multiple preparation containing a new material as an active drug substance.

Pharmaceuticals that require data submission - Pharmaceuticals required for the evaluation of safety and efficacy that is not referred to a new drug e.g., pharmaceuticals with enhanced effectiveness, new composition of active drug substance, and pharmaceuticals administered via new route of administration.

Generic drugs – Pharmaceuticals that are regarded as a new drug for which there is a reference drug that is similar to the new drug with respect to the active ingredient, dosage form, and strength.

Pharmaceutical Regulations and Registration in South Korea (MFDS)

In the MFDS official website there are a number of regulations available out of which the key regulations are:

• Regulations on the Criteria for Classification of Drugs

• Regulation on Pharmaceutical Approval, Notifications and Reviews

• Standard Manufacturing Criteria for Drugs

• Regulation on Safety of pharmaceuticals, etc

• Regulation on Renewal of Drugs

• Regulation on Approval for Investigational New Drug Application of Drugs

Apart from these regulations, The Pharmaceutical Affairs Act is also essential to comply with.

Good Manufacturing Practices (GMP) Regulation for medicinal products –

The Good Manufacturing Practices (GMP) for Medicinal Products (No.2021-87, Nov 4 2021) specifies detailed requirements for enforcement, expiration dates of GMP compliance certificates, and submission of documents for certain medicinal products. The document covers various articles and annexes under different acts and regulations, detailing procedures for GMP compliance, validation methods, and contract manufacturing and analysis. 

Annex	Products Covered in the Annex
Annex 1	Manufacture Of Sterile Medicinal Products
Annex 2	Manufacture Of Biological Medicinal Substances And Products For Human Use
Annex 3	Manufacture Of Radiopharmaceuticals
Annex 4	Manufacture Of Medicinal Gases
Annex 5	Manufacture Of Herbal Medicinal Products
Annex 7	Manufacture Of Liquids, Creams And Ointments
Annex 8	Manufacture Of Pressurised Metered Dose Aerosol Preparations For Inhalation
Annex 10	Use of Ionising Radiation in the manufacture of Medicinal Products
Annex 11	Manufacture of Investigational Medicinal Products
Annex 12	Manufacture Of Medicinal Products Derived From Human Blood Or Plasma
Annex 15	GMP Guide for active Pharmaceutical Ingredients
Annex 17	Good Manufacturing Practice for Medicinal Products

 Key Labeling Requirements for Pharmaceuticals in South Korea (MFDS)

Some of the key MFDS labelling requirements for pharmaceuticals are as follows:

• The trade name and address of the person with permission by item for drugs or an importer.

• Name of the product

• Manufacturing number and expiration date

• The number of product, weight and capacity

• Storing conditions/methods

• Dose, dosage regimen

• Precautions and warnings

• Name (all ingredients included), quantity of active ingredients and preservatives

• The letters “prescription drug” or “over-the-counter” must be provided as suitable

• The labelling of packages, inserts, containers must be as per the Korean Pharmacopoeia for the drugs listed under Korean Pharmacopoeia.

• Any other information that is prescribed by the Ordinance of Prime Minister

  
  

Clinical Trial Requirements for Pharmaceuticals in South Korea (MFDS)

Clinical trials are significant to the healthcare industry. It is through clinical trials that we accumulate and establish evidence for the safety and effectiveness of the drug. To conduct any clinical trial, a clinical trial protocol and its approval is a must. Similar to the protocol, an IND (Investigational New Drug) application is also a must for new drugs. IND is applicable for:

• Drugs that are under development

• Drugs with new formulation

• Drugs with new route of administration

• Drugs with new indications or dosage.

The IND application along with the application dossier is submitted and the application is received by the Clinical Trials Management Division. The next step is the request for consultation of the Drug Evaluation Department and after that the submitted data are reviewed by the Drug Evaluation Department. The review result is notified. If there is any nonconformity noted, then the applicant is requested to submit supplement data. Finally, the Clinical Trials Management Division approves or rejects (nonconformity) the application.

Documents required for clinical trial approval

Clinical trial Plan; Information on the evidence of chemical structure and the physicochemical and biological properties; non-clinical tests; Clinical trial protocol; Investigator’s Brochure

• IND application

• Clinical trial Plan; Information on the evidence of chemical structure and the physicochemical and biological properties; non-clinical tests

• Clinical trial protocol

• Investigator’s Brochure

• Data proving the manufacture of investigational drug as per the GMP standards

• Informed consent forms

• Compensation rules for victims of clinical trial

• Data on the quality and manufacturing of the investigational drug

• Prior clinical use data of the product, if available

• Data regarding the investigator, clinical trial institution, or contract research institute as per the article 34-2 (2) of the Act.

  
  

Registration Process for Pharmaceuticals in South Korea (MFDS)

Submission: The application for a new drug is submitted by the applicant to the NIFDS (National Institute of Food and Drug Safety Evaluation) or through e-Drug service.

Pre-review: In this stage the data submitted by the applicant is reviewed to check and confirm that they meet the requirements of the data. A product manager is appointed, and they check the data requirements adequacy. In this stage they check for whether requested for product briefing, history of civil petition… The submission and pre-review stages are done by the Drug Review Management Division.

Review: The applications that satisfy the data requirements are sent to the appropriate responsible divisions. The documents and other requirements are reviewed and reconfirmed. The applicant is requested to supplement data if the data submitted are insufficient. This is done up to 2 times and still the data is not sufficient, the application is rejected.

Approval & Issuance: The license of approval is granted, and the certificate is issued. After drug approval completion, the applicant is requested to provide consent to disclose information which include the safety and efficacy review result, test methods and BE (bioequivalence) test review results.

Amidst of these processes consultation with Central Pharmaceutical Affairs Advisory Committee (CPAC) can be done, if necessary.

5. Validity of License for the sale of medicinal products is generally granted for five years. The license holder must file a renewal application with the MFDS six months before expiration. A renewal application must include necessary information on drug safety and quality control and sales during the authorization period which are as follows:

• The safety control data collected during expiry period and follow-up actions conducted.

• Use state and relevant actions which concern the safety in foreign countries

• Quality control data collected during expiry period

• Matters relating to labelling

• Data regarding the manufacture and import performance

• Copy of marketing approval certificate or certificate of completion of product report.

6. Fee structure is given below:

   
   

Category	Fee in KRW (online)	Fee in KRW (In person or mailing)
New Drug	7,72,350	8,53,650
Orphan drugs	3,87,350	4,30,040
Other than new and orphan drug	1,93,440	2,14,930
GMP Inspection	6,17,500	6,82,500
Pharmaceutical Import	3,85,700	4,26,300
Pharmaceutical Export	7,73,300	8,54,700
Renewal application	3,63,000	4,04,000

• For a detailed fee structure please look into Regulation on fees for Pharmaceutical Approval, etc on MFDS website. Documents Required for New Drug Approval for MFDS
  

• Drug manufacturing or marketing application

• Safety and efficacy data

• Test methods and specifications

• API manufacturer’s name and address

• Data required for GMP inspection evaluation

• If DMF used, DMF application and attached data

• Agreement for contract manufacturing including name and address of subcontractors, if any

• Patent certificates and supporting data, if applicable

  
  

  Documents Required for Generic Drugs for MFDS

  
  

  The documents needed to submit for generic drugs are the bioequivalence test data, quality data. These are submitted instead of the safety and efficacy data like the toxicity, pharmacology, clinical trials.

  Documents Required for Pharmaceutical Required for Data Submission for MFDS From the submission data for new drugs, selectively submit the data required for evaluating the safety and efficacy.

  Import & Distribution Requirements and Documentation

• Commercial Invoice

• Certificate of Origin

• Self-certification of origin by the producer or exporter

• Import Declaration to clear customs

• Certificate of Pharmaceutical Product (CPP)

• Product Registration

• Good Manufacturing Practice (GMP) Compliance

• Distribution License

MFDS Post Marketing Surveillance for Pharmaceuticals

In South Korea, the Korea Institute for Drug Safety and Risk Management (KIDS) under the MFDS is responsible for the assurance of high quality, safe medicines. Along with other tasks , they also focus on collection, analysis and evaluation of drug safety information. To facilitate the management and reporting of adverse event reports, the KIDS has developed a system called KAERS (Korean Adverse Event reporting System). Anybody who experiences an adverse event can report via KAERS.

Regional Pharmacovigilance Centres (RPVC’s) are also a part of the KAERS system. They evaluate the causal relationship of the AE (adverse event) information in the region and report this through KAERS. The KIDs also submit the ICSR (individual Case Safety Reports) reports to the WHO UMC Uppsala.

Apart from these, Risk Management Plans, risk mitigation plans, Periodic Safety Update Reports, audits are also involved in the post market surveillance. The Annex 6-2 of the Regulation for Pharmaceutical Approvals, Notifications and Reviews states the preparation tips for RMP, risk mitigation measures and more.

Conclusion

It is important to comprehend the MFDS regulations as drug approval process in South Korea, product registration in South Korea, clinical trial requirements and all other things are under MFDS. Prior approval of drugs from highly regulated authorities like the EMA or FDA can help in approval of pharmaceuticals. With proper navigation, the pharmaceuticals can gain faster approval thereby leading to an expedited market entry.

Artixio can help you in the approval process of pharmaceuticals. Our region-specific regulatory experts are well versed with the MFDS guidelines and regulations which can aid in a speedy approval process including the documentation and all other activities concerning pharmaceuticals. Connect with us through info@artixio.com

FAQ’s

Q. Can I withdraw my product approval, if so how?

A. Yes, you can withdraw the approval of the pharmaceutical by submitting a cancellation application to the MFDS or Regional Office of Food and Drug Safety Commissioner. Along with the application the following must also be included: Business name, contact information, location, application details (product registration/ approval/notification number, details and reason for cancellation, business type, signature or sealing of application date, applicant) and attachment (product approval or notification certificate).

Q. What are the documents required for safety and efficacy evaluation of new drugs under MFDS?

A. Origin that leads to discovery & development, structural data (physical, chemical, biological nature), drug substance & product data, toxicology, pharmacology, clinical data, uses in other countries, stability test data, domestic copy comparison and special drug features are the required documents. 

Q. What are the factors involved for a drug to be classified as a prescription drug under the MFDS?

A. The factors considered for a drug to be prescription drug whether it is to be used under the provisional diagnosis supervision, instruction of a medical professional due to its pharmacological action, ADR, dosage regimen or route of administration. Habituation & dependence, significant drug interaction, misuse/abuse, new drug, narcotic drugs, psychotropic substance, ultra narcotic drugs, toxicant or violent toxins are some of the other factors considered.

Q. What is the validity for marketing approval for pharmaceuticals and when should i renew it?

A. 5 years is the validity period, and it must be renewed by submitting a renewal application 6 months before the expiration date.