In China, 40% of the biologics market comprises biosimilars. The usage of biosimilars in oncology has increased as cancer overtook heart disease as the second-leading cause of mortality in the nation. The size of the Chinese biosimilars market, which was anticipated to be worth US $1.54 billion in 2022, is predicted to grow at a CAGR of 23.7% from 2022 to 2030 and reach US $8.46 billion in 2030.
China's regulations and registration framework for biologics and biosimilars is overseen by the National Medical Products Administration (NMPA), formerly known as the China Food and Drug Administration (CFDA). Biologics are complex molecules derived from living organisms, and they include products such as monoclonal antibodies, vaccines, and cell therapies.
On June 30, 2020, National Medical Products Administration (NMPA) has released regulations on the registration of biologics and the December 11, 2020 has subsequently released "Decree No. 33" on focusing on lot release of biological product. According to the decree, domestic and overseas drug marketing authorization holders (MAHs) holding drug approval documents are eligible to apply for lot release. However, overseas drug MAHs must designate an enterprise legal person within China to handle the lot release process, emphasizing the importance of local representation and compliance with Chinese regulatory standards. It is essential for stakeholders to understand the implications of these changes.
Biologic medication patentability is not specifically constrained by law. Biologic medications may be registered as long as they comply with patent eligibility conditions.
NMPA Classification of Biologics and Biosimilars in China
Under the regulations for Biologics and Biosimilars, the products are classified into Preventive or Therapeutic or IVD Reagent Products. For the purpose of registration, each category is further classified into different sub-categories -
Preventive Biologics | Therapeutic Biologics | IVD Reagent Products |
Vaccine Biologics - Immunization and non-immune planned vaccines for prevention and control of disease and prevalence | Used in treatment Eg - Proteins, peptides, derivatives from engineered cells | Eg - Blood sourcing screening IVD reagents labeled with radionuclides |
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Important Documents:
Chemistry, Manufacturing, and Control (CMC) Documents:
Drug Substance Information: Detailed information about the manufacturing process, characterization, and specifications of the active pharmaceutical ingredient (API) or biologic substance.
Drug Product Information: Manufacturing details, formulation, specifications, stability studies, and packaging information for the final drug product.
Analytical Methods: Detailed descriptions of analytical methods used to assess the quality and characteristics of the biologic or biosimilar.
Nonclinical Study Data:
Pharmacology Studies: Data from in vitro and in vivo pharmacological studies that demonstrate the biologic's intended mechanism of action and potential effects.
Toxicology Studies: Information on nonclinical safety studies that evaluate the toxicological profile of the product.
Clinical Trial Data:
Study Protocols and Reports: Detailed protocols for clinical trials, including design, patient populations, endpoints, and statistical analyses. Clinical study reports (CSRs) for completed trials should also be included.
Pharmacokinetic and Pharmacodynamic Data: Data on the pharmacokinetics (PK) and pharmacodynamics (PD) of the biologic or biosimilar.
Comparability Studies (Biosimilars): Extensive data comparing the biosimilar to the reference product, including analytical data, in vitro assays, and clinical comparability studies.
Quality Assurance and Control Documents:
Quality Control Testing: Information on quality control tests performed on both the drug substance and drug product.
Batch Records and Process Validation: Detailed records of manufacturing processes, including batch records and process validation data.
Specifications: Detailed specifications for various aspects of the product, including purity, potency, identity, and impurities.
Labeling and Package Insert:
Product Labeling: Proposed labeling for the biologic or biosimilar, including package inserts, prescribing information, and patient information.
Regulatory Documentation:
Product Information: Comprehensive information about the biologic or biosimilar, including its proposed indications, dosing, administration, and usage instructions.
Administrative Forms: Completed application forms and administrative documentation required by the NMPA.
Regulatory Pathway for biosimilars and biologics in China
Dossier Submission:
Prepare a comprehensive registration dossier that includes data from preclinical studies, clinical trials, comparability studies, manufacturing details, quality control measures, and other relevant information.
Regulatory Review:
Submit the registration dossier to the NMPA for regulatory review. The NMPA assesses the data to ensure the quality, safety, and efficacy of the biologic or biosimilar.
The review process involves multiple stages, including document evaluation, on-site inspections, and scientific assessment.
Approval and Marketing:
Upon successful review, the NMPA grants marketing approval, allowing the biologic or biosimilar to be launched in the Chinese market.
Biosimilars are typically assigned a unique trade name that includes the common name of the active substance along with a specific suffix or code.
Timelines: It takes around 2 years to get a biologic approved by the NMPA.
Fees: Applicable fees remain the same as original drugs or biologics.
Post Marketing Surveillance is a critical component of the regulatory oversight of biologics and biosimilars in China. It involves ongoing monitoring of the safety and effectiveness of these products after they have been approved similar to other pharmaceutical products.
Pharmacovigilance System:
Biologic and biosimilar manufacturers are required to establish a robust pharmacovigilance system to collect, analyze, and report adverse events and other safety-related data associated with their products.
Adverse Event Reporting:
Healthcare professionals, patients, and consumers are encouraged to report any adverse events, unexpected reactions, or product-related issues to the regulatory authority or the manufacturer. Timely reporting of such events is crucial for monitoring product safety.
Periodic Safety Update Reports (PSURs):
Manufacturers are typically required to submit periodic safety update reports to the regulatory authority. These reports provide a comprehensive overview of the safety profile of the biologic or biosimilar based on accumulated post-marketing data.
Signal Detection and Analysis:
Regulatory authorities continuously monitor and analyze reported adverse events to detect any potential safety signals or trends. If a new safety concern arises, appropriate actions may be taken, including labeling changes or further investigations.
Risk Communication:
Regulatory agencies and manufacturers communicate safety-related information to healthcare professionals, patients, and the public. This includes updates to product labeling, safety advisories, and educational materials.
Risk Management Plans (RMPs):
Manufacturers may be required to develop risk management plans outlining strategies to minimize identified and potential risks associated with their products.
Inspections and Audits:
Regulatory authorities may conduct inspections or audits of manufacturing facilities, distribution processes, and pharmacovigilance systems to ensure compliance with post-marketing surveillance requirements.
Collaboration and Information Sharing:
Regulatory agencies collaborate with international partners and organizations to share safety information and best practices for post-marketing surveillance.
Quality Management and Continuous Improvement:
Manufacturers should have systems in place to continuously monitor and improve the quality and safety of their biologic or biosimilar products.
While China presents immense opportunities for biologic manufacturers, navigating the regulatory landscape can pose significant challenges. Complex approval processes, language barriers, and evolving regulations require diligent attention and expertise to ensure compliance. However, with the right strategic approach and regulatory support, companies can leverage China's burgeoning market to expand their global footprint and deliver innovative biologic therapies to patients in need.
Artixio: Your Partner in Regulatory Compliance
At Artixio, we understand the complexities of regulatory compliance in the pharmaceutical industry, particularly in emerging markets like China. With our expertise in navigating regulatory frameworks and facilitating market access, we empower companies to navigate the evolving landscape with confidence. Whether you're seeking guidance on clinical trial design, market authorization strategies, or post-market surveillance, our team of regulatory experts is here to support your journey. Contact us at info@artixio.com to learn more about how we can help you succeed in the dynamic world of biologics regulation in China.
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