Point 1: Applicants must comprehensively understand the products applied for
This latest Draft for Comment of Technical Requirements ("Draft") has high requirements for the strategic visions of applicants. The original text says: Applicants shall comprehensively understand the marketing backgrounds in China and abroad, safety and effectiveness data and post-marketing adverse reaction monitoring situations of the marketed injections and evaluate and confirm their clinical values. This requirement is appropriate under the background of in-depth and comprehensive advancement of current R&D. To successfully promote and apply for a project, the project leader of a pharmaceutical company must possess rich professional knowledge, accurately grasp regulations, appropriately master the R&D and industry combination and possess proper internal and external resources of the company. If an applicant cannot comprehensively understand and grasp the project taken charge of, the quality of the application data will be worrying. Therefore, this requirement of the NMPA makes sense.
Point 2: The guidelines for RLD selection are clear
The NMPA has issued guidelines for the selection of RLDs in the consistency evaluation of oral solid preparations, which also apply to the consistency evaluation of injections according to the Draft: Applicants shall select the RLDs according to the Procedures for the Selection and Determination of Reference Listed Drugs for Chemical Generic Drugs issued by the NMPA and carry out the consistency evaluation research with reference to those Technical Requirements and relevant technical guidelines in China and abroad. As mentioned above, there have been many aseptic preparations (including eye drops and injections) in the latest official list of RLDs.
Point 3: Document retrieval plays a key role in the formulation and process determination process
Unlike oral solid preparations, simple dosage forms of small molecule chemical pharmaceutical products generally do not need to be conducted clinical trials, in which case, the international Q1/Q2 guidelines shall be followed to ensure the generic injection drugs to have highly consistent quality effects and attributes with original drugs. The Q1/Q2 guidelines refer to that generic drugs of chemical drug injections need to be kept consistent with the original drugs in terms of API and excipient varieties and kept consistent therewith as far as possible in terms of API and excipient feeding quantity. To achieve this, pharmaceutical enterprise researchers need to strengthen their information retrieval ability.
For example, the Draft mentions the following details:
※Formulation-Excipient varieties and dosage in the injections shall normally be the same as those in the reference listed drugs (RLDs). Same excipient dosage refers to that the excipient dosage in the generic drugs shall be 95%-105% of the corresponding excipient dosage of the RLDs, and if there are special solvents, they shall be consistent with the special solvents of the RLDs in terms of formulations.
※Applicants may submit formulations different from the RLDs’ bacteriostatic agents, buffers, pH regulators, antioxidants and metal ion complexing agents, however, they shall indicate the differences, state reasons for choosing them and study and prove that the above differences do not affect the safety and effectiveness of the products applied for.
※Excipient concentration or dosage shall meet the limit requirements of FDA IID or be well-founded. In the event of excessive feeding, reference with relevant requirements of ICH Q8 is recommended.
Point 4: Aseptic processing and sterilization process research levels must meet the latest requirements of the industry
Aseptic products may be produced using the terminal sterilization process or non-terminal sterilization process, however, whichever process, the final aseptic products must have sterility assurance levels that meet the latest regulation requirements and industry consensus.
The Draft mentions the following details: (1) To effectively control the pyrogen (bacterial endotoxin), control over the APIs, excipients, and pharmaceutical packaging materials,...
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