Q&A: marketing authorisation for pharmaceuticals and medical devices in China

Marketing authorisation

How long does it take, in general, to obtain an authorisation from application to grant, what fees are payable and what is the normal period of validity of the authorisation?

According to the Measures for the Administration of Drug Registration, the time limit for a drug marketing authorisation review is 200 days but, in practice, it might be longer. According to the Regulations on the Supervision and Administration of Medical Devices, the period for obtaining approval for medical device registration is generally 23 days or less but, in practice, it generally takes around three months.

Registration fees are charged separately for drug clinical trial applications and drug marketing authorisation applications. The fees are different for new drugs and chemical generic drugs.

In the case of medical device registration applications, registration fees are different for the initial registration, change of registration and renewal of registration.

Both the drug registration certificate and the medical device registration certificate are valid for five years. The holder can apply for re-registration or renewal of registration six months before expiry.

What protections or exclusivities apply to the data submitted by originators to gain initial approval and, on variation or new application, to add indications or pharmaceutical forms?

China protects undisclosed test data and other data submitted by manufacturers or distributors who have obtained licences to produce or sell drugs containing new chemical ingredients. No one can make improper commercial use of such undisclosed test data and other data. Within six years, if other applicants use the aforementioned data to apply for a licence to produce or sell the same or similar drugs without the consent of the approved applicant, the NMPA will not grant the authorisation. The data protection provided does not equate to market exclusivity and the NMPA does not exclude applications based on self-acquired data.

On 26 April 2018, the NMPA announced the Implementation Measures for the Protection of Drug Test Data (Interim) (Exposure Draft), which expands the data protection of innovative drugs and special drugs – such as orphan drugs and paediatric drugs – and proposes mechanisms for application, review, authorised publicity, objection and revocation of data protection.

To what extent and when can third parties make freedom of information applications for copies of research data submitted by applicants for authorisation to market medicinal products or medical devices?

With regard to drugs, the NMPA makes public the conclusion and basis for the evaluation of drugs approved for marketing. The main published information includes the acceptance number, acceptance date, drug name, type, instruction sheet and drug marketing technical review report. The publication time varies depending on the specific circumstances but is generally within one to two years of the acceptance date of the Centre for Drug Evaluation (CDE). However, the data submitted by the applicant will not be published and there is no provision regarding third parties’ applications to obtain a copy of that data.

As for medical devices, the drug regulatory authority publishes, through the information platform, daily supervision and management information, but does not publish copies of data submitted by applicants for marketing approval. There is no provision regarding third parties' applications to obtain relevant data.

What are the specific requirements and processes for marketing approval of the major categories of regulated products?

Regulated drugs mainly include narcotic drugs, psychotropic drugs, poisonous substances for medical use, radiopharmaceuticals and pharmaceutical precursor chemicals, among others. The management of such drugs shall be subject to relevant special management regulations, such as, among others:

• the Regulation on the Administration of Narcotic Drugs and Psychotropic Drugs;
• the Regulation on the Administration of Poisonous Substances for Medical Use;
• the Regulation on the Administration of Radiopharmaceuticals; and
• the Measures for the Administration of Pharmaceutical Precursor Chemicals.

These regulations clearly stipulate the development, production, operation, packaging, transportation, use, import and export requirements for regulated drugs.

Regarding marketing authorisation for the aforementioned drugs, the Drug Administration Law  stipulates that marketing authorisation holders may not outsource the manufacture of blood products, narcotic drugs, psychotropic substances, poisonous substances for medical use or pharmaceutical precursor chemicals. Therefore, in principle, the holder of the marketing authorisation should only be the manufacturer. The research and development organisation without production capacity cannot be the applicant and holder of any marketing authorisation.

In addition, the Drug Administration Law stipulates that the required marks shall be printed on the labels and package leaflets of narcotic drugs, psychotropic substances, poisonous substances for medical use, radiopharmaceuticals, medicinal products for external use and non-prescription medicinal products. Vaccines, blood products, narcotic drugs, psychotropic substances, poisonous substances for medical use, radiopharmaceuticals, pharmaceutical precursor chemicals and other medicinal products under special administration of the state shall not be sold online. Import or export licences issued by the CDE shall be required for the import or export of narcotic drugs and psychotropic substances within the scope specified by the government.

What pharmacovigilance or device vigilance obligations apply to the holder of a relevant authorisation once the product is placed on the market?

In the case of drugs, marketing authorisation holders have the following pharmacovigilance obligations:

• taking responsibility for the drugs’ non-clinical research, clinical trials, production, distribution, post-marketing research, monitoring, and reporting and handling of adverse reactions;
• formulating a post-marketing risk management plan and taking the initiative to conduct post-marketing studies, further validating the safety, efficacy and quality control of drugs, and strengthening the continuous management of the marketed drugs;
• conducting post-marketing adverse reaction monitoring and actively collecting, tracking and analysing information on suspected adverse reactions, and taking risk control measures for drugs with identified risks in a timely manner; and
• stopping the sale of drugs immediately if there are quality problems or other safety hazards, notifying relevant drug distributors and medical institutions to stop sales and use, recalling the drugs that have been sold, and disclosing recall information in a timely manner as well as, if necessary, stopping production immediately and reporting to the relevant authorities the situation of the recall and disposal of the drugs.

In the case of medical devices, the manufacturer and distributor have the following vigilance obligations:

• carrying out adverse event monitoring and reporting adverse events or suspicious adverse events to the government agency; and
• immediately stopping production, notifying the relevant manufacturers and distributors, users and consumers to stop sales and use, if necessary recalling medical devices on the market, taking remedial and destruction measures, recording the relevant situation, releasing relevant information, and reporting the recall and handling of the medical devices to relevant authorities upon discovering that the product does not meet the mandatory standards or the technical requirements concerned, or other defects.

What authorisations are required to manufacture, import, export or conduct wholesale distribution and storage of medicinal products and medical devices? What type of information needs to be provided to the authorities with an application, what are the fees, and what is the normal period of validity?

The production of drugs requires a drug manufacturing certificate (valid for five years), the application for which requires the information of relevant personnel – such as the pharmaceutical technicians, engineering and technical personnel – as well as the conditions of the plant, facilities, equipment and sanitary environment, among others. The wholesale and retail sale of drugs requires a drug supply certificate (valid for five years), the application of which requires information similar to that for a drug manufacturing certificate.

Imported drugs must apply for registration in accordance with NMPA regulations. For drugs produced abroad, the imported drug registration certificate is required before importation. After the imported drugs arrive at the port, the importing drug company must make a filing with the drug regulatory authority at the port location, and customs handles the customs clearance procedures. For drug exports, an application for a drug export sales certificate is required.

In respect of medical devices, the medical device production licence and the distribution licence are both valid for five years.

There is no uniform fee schedule for the aforementioned permits; different fees are charged in different regions.

What civil, administrative or criminal sanctions can authorities impose on entities or their directors and officers for breach of the requirements concerning controlled activities?

The drug regulatory authority may impose the following administrative penalties on the manufacturer and distributor or their directors and officers for breach of the relevant regulations:

• a warning;
• confiscation of illegal income;
• confiscation of drugs and medical devices illegally produced and sold, as well as tools, equipment, raw materials and other things used in illegal production and distribution;
• an order to suspend production and distribution;
• fines;
• revocation of the production or distribution licence; or
• if the violation is serious, the legal representative, the principal person in charge, the directly responsible person and other responsible persons may be subject to administrative penalties, such as confiscation of the income obtained from the company during the period of the violation, fines, prohibition from production and distribution for life or for a certain period of time, and detention.

If the acts constitute the crime of producing or selling medical equipment that does not meet the required standards, or the crime of producing or selling counterfeit or inferior drugs, the defendant may be sentenced to fixed-term imprisonment, life imprisonment, the death penalty, criminal detention, fines or confiscation of property.

What, if any, manufacture and supply of medicinal products is exempt from the requirement to obtain an approval to market?

Medical institutions may set up preparation laboratories upon approval by the health administration of the provincial government and the drug regulatory authority, and they may make preparations (except for narcotic drugs and biological preparations) according to clinical needs. However, these preparations can only be prescribed by the medical institutions themselves and are not allowed to be offered for sale.

Are imports allowed into your jurisdiction of finished products already authorised in another jurisdiction, without the importer having to provide the full particulars normally required to obtain an authorisation to market? What are the requirements?

These imports are normally not allowed. If the drug is already authorised in another jurisdiction, it falls into the category of generic drugs, which means that the review would focus on ethical sensitivity and bridge studies instead of a full clinical study. Nonetheless, the importer must apply for marketing authorisation in accordance with the detailed classification of drugs and corresponding materials provided in the Measures for the Administration of Drug Registration and other related regulations. The CDE reviews the application and issues the drug registration certificate if the comprehensive review conclusion is passed.

In the case of medical devices, an overseas manufacturer exporting products to China must, through its representative office established in China or a corporate legal person designated in China as its agent, submit to the drug regulatory authority the filing or registration materials and the documents, as requested depending on the category and classification of the products.