China Pharmaceuticals Registration & Regulatory Consulting | GRP

Committed to your success, from Concept to Approval.

China / PHARMACEUTICALS & BIOLOGICS CONSULTING

CHINA REGULATORY STRATEGY

The regulatory process from product design to market entry for a new drug is oftentimes complicated and unclear. Most of the Chinese regulations are in Chinese and are changing continuously. Our regulatory  team stays current with the latest legislation, regulatory requirements and interpretations and industry initiatives in China.

Our regulatory team in China makes sure that our clients are kept informed of all changes that occur at the CFDA that may impact their regulatory and business strategies in china.

Our regulatory team in China has many years of experience developing effective and tailored regulatory strategies for pharmaceutical companies that help them register successfully their drugs in China and with minimum risk.

CHINA CFDA DRUG REGISTRATION IN CHINA

The process of drugs registrations in china depends on the category they belong to. CFDA classifies drugs is three categories, Chemical, Biological or Traditional Chinese Medicine.

All drugs and drug substances (APIs) manufactured outside China must be registered via the imported drug application. Foreign-made APIs need to undergo a process like drug registration. Even if a product is approved elsewhere, the CFDA will most likely still require the foreign manufacturer to conduct at least some clinical testing in China before the drug is approved in China.

Global Regulatory Partners can help your medical company with all aspects of pharmaceutical product or API registration in china.

REGISTRATION PATHWAYS

The different types of drug applications in China are:

  1. New drug application
  2. Generic drug application
  3. Imported drug application (includes foreign new drugs)
  4. Supplemental application
  5. License renewal

Application and Approval Procedures and Timeline for Imported Drugs

  1. Submit application
  2. Dossier content and format checking/notification of quality testing and specifications verification by the CFDA (35 days)
    o If needed, proceed with samples testing and standards verification by the NICPBP (65 days / 95 days for special drugs and vaccine products)
  3. Technical evaluation for clinical trials by the CDE (90 days regular/80 days fast track review)
    o If needed, submit complementary data (4 months)
    o If needed, submit supplementary data for CDE evaluation (40 days)
  4. Administrative approval by the CFDA (30-40 days)
    o If the CFDA does not approve, must begin application process again
  5. Approval for Clinical Trials
  6. Notification of clinical trial protocol and list of investigators to the CFDA
  7. Commencement of Clinical Trials
  8. Submission of clinical trial results and other amended or supplementary data
  9. Acceptance by the CFDA
  10. Technical evaluation by the CDE (150 days regular/120 days fast-track review)
    o If needed, then submit complementary data (4 months)
    o If needed then submit supplementary data for CDE evaluation (40 days)
  11. Administrative approval by the CFDA (30-40 days)
    o If the CFDA does not approve, must begin application process again
  12. Approval of imported drug application

CHINA CFDA QUALITY COMPLIANCE

The CFDA has issued various regulations to strengthen management and organization at medical device manufacturing sites. This includes implementing Good Manufacturing Practice (GMP) standards for all medical devices, a more stringent adverse events and recalls system, additional on-site inspections, and other new industry standards. In addition to the CFDA, the General Administration of Quality Supervision, Inspection and Quarantine (AQSIQ) also carries out safety, certification, and inspection of certain medical devices to ensure adherence to quality standards.

However, despite the improving standards and implementation of GMP regulations for medical devices in China, there are still many scandals regarding defective products due to poor quality systems. Foreign companies will need to conduct audits in order to ensure that their Chinese operations or partners are performing according to expected standards.

There are two types of on-site audits that are required in China: a one-time quality management system (QMS) audit for registration that domestic and foreign manufacturers must complete, and a GMP audit for a manufacturing license after registration that local manufacturers must complete annually. Requirements for these audits include an on-site audit checklist as well as multiple company meetings.

CFDA GMP Requirements

All Chinese drug manufacturers also require Good Manufacturing Practice (GMP) certification. This includes manufacturers of IVD reagents, medicinal gases, and drugs. However, foreign manufacturers should note that Chinese GMP is not equivalent to U.S. FDA GMP. Currently, many chinese factories still encounter many challenges to meet CFDA GMP requirements.

Global Regulatory Affairs quality team in China helps pharmaceutical companies identify their deficiencies and address them in a timely manner to become compliant with CFDA and International GMP requirements.

Local Representation

When marketing a drug or medical device in China, it is important to have an independent in-country representative for your products that is a legal entity registered in China, even if you are marketing through a Chinese distributor.

This representative serves as the required local entity that deals with the China Food & Drug Administration (CFDA) regarding product registration and renewal, adverse event reporting, etc. There are three local agents required:

  1. Registration Agent: The company that registers the product is the registration agent.
  2. After Sales Agent: The after sales agent provides technical service and support for the medical device product. The business scope described in the business license of the local legal Chinese entity must include a provision stating that the after sales agent will provide such services.
  3. Legal Agent: The legal agent’s key responsibilities include: a) reporting any adverse events regarding the medical device that occur inside or outside China to the CFDA; and b) handling any recall issues as they arise, as well as other regulatory matters.

Having an independent third party allows for confidentiality of technical information and less reliance on a distributor, whose primary motive may only be sales. In cases where your distributor is acting as your local agent, if your distributor does not perform well and you wish to end the relationship, the distributor may attempt to charge a large fee to transfer the existing registrations or refuse to transfer them at all.

Clinical Trials

Medical Device clinical trials in China must comply with China’s GCP requirements. It is important to determine if the device requires the clinical trials. This can be decided based on the type of the drug.

As is the case in many countries around the world, a local clinical trial is almost always required for the registration of drugs in China. Since drug registration in China follows global International Conference on Harmonization (ICH) guidelines, data requirements in China are like those in the United States and other developed countries. However, companies may encounter difficulties if they want to keep sensitive data confidential from copying competitors.

In some cases, as an alternative to local clinical studies, a bioequivalence (BE) study will be required instead. The BE study will test similarities between two drugs believed to have the same active ingredients and use. The filing process for clinical trials in China begins with submitting a Clinical Trial Application (CTA) dossier to the CFDA. The Center for Drug Evaluation (CDE) reviews the submission dossier, test report, and verified specification, and requests a panel meeting if any concerns or questions are raised. The CDE may issue supplementary requests if any additional documents are needed from the applicant. The National Institute of Food and Drug Control (NIFDC) tests and analyzes the quality of the drug samples, while the Center of Food and Drug Inspection (CFDI) inspects sponsors and manufacturing sites.

After the CDE’s review, a recommendation on whether to grant the applicant a Clinical Trial Permit (CTP) is submitted for confirmation to the CFDA. The CTP approval requires an extensive length of time—about 18 months after the initial CTA dossier is submitted to the CFDA. The CFDA prioritizes which clinical trial proposals to review first according to the product’s level of importance. Drugs that aim to cure serious diseases, such as AIDS and cancer, are normally fast tracked to get clinical trial approval.

After obtaining a CTP, the company is free to initiate clinical trials at any approved site in China, as long as they follow Good Clinical Practices (GCP) throughout the clinical trials.

clin-trials-china

The CFDA’s Drug Regulatory Department oversees local clinical trials and affirms compliance with GCP. Generally, clinical trials in China involve four phases:

  1. Phase I – an initial review of the drug’s safety to humans
  2. Phase II – an evaluation of the effectiveness of the drug
  3. Phase III – a confirmation for the effectiveness of the drug
  4. Phase IV – a post-marketing study

The clinical trial’s sample size must meet statistical requirements by satisfying the minimum number of subjects outlined by the CFDA. If the institution is unable to reach the minimum sample size because of the rarity of a disease, the institution should appeal to the appropriate provincial-level FDA (PFDA) to reduce the sample size.

The trial must be carried out by an organization certified to conduct drug clinical trials, using drugs from manufacturing facilities that follow Good Manufacturing Practices (GMP).

If there is a serious adverse event, investigators must notify the PFDA and applicants within 24 hours, and the ethics committee thereafter. If an event is serious, the PFDA may suspend or terminate the trial. A trial may also be terminated due to fraud, ethical concerns, and failure to report adverse events.