Point 7: The quality research must follow the ideas of ICH Q8 Guideline
Quality research is a priority in all pharmaceutical product development stages. Regarding the consistency evaluation of chemical drug injections, the Draft newly mentions the R&D route required by ICH Q8: QTPP-CQA-CPP-CP. For example, the Draft stipulates: The critical quality attributes (CQAs) of the preparation shall be established according to the quality target product profile (QTPP); the CQAs of injections normally include but are not limited to the research of the followings: character, identification, redissolution time, dispersion time, particle size distribution, re-dissolved solution character, solution clarity, solution color, osmotic pressure/osmotic pressure ratio, pH value, moisture, filling, filling/weight variation, content uniformity, visible foreign matter, insoluble particle, bacterial endotoxin, sterility, elemental impurities, residual solvent, related substance (isomer), and API crystal form/particle size and content, etc.
Injections are pharmaceutical products that directly enter human bodies, therefore, their safety has been a focus of regulators and applicants. The Draft increases the requirements for mutagenic impurities besides continuing to emphasize the necessity of related substance inspections, for example, it stipulates as follows: The occurrence of potential mutagenic impurities shall be determined according to relevant documents and RLD situation and by analyzing the production process and product degradation pathway, and targeted research shall be conducted if necessary, to control them according to the research results and relevant technical guidelines.
The valsartan event that occurred in the middle of 2018 was an oral solid product event, however, it’s very normal that the regulator extends its regulation to the injection area with the expansion of impacts of the problem. In general, it’s internationally recommended that the ICH M7 Guideline be used to research and control genotoxic impurities.
Another new characteristic of the Draft is the requirement for the elemental impurities: According to the provision of ICH Q3D, the elemental impurities in the preparations shall be determined through scientific and risk-based assessments, including the elemental impurities possibly brought in by APIs, excipients, pharmaceutical packaging materials, and production equipment, etc.
Point 8: Requirements for generic injection drugs’ comparison with RLDs are higher than those for oral preparations’ comparison therewith
It’s a general requirement in the consistency evaluation work that the products shall be compared with RLDs, however, as to the comparison degree, the requirements for oral solid preparations are generally not high. The Draft requires applicants to comprehensively compare their developed products with RLDs, specifically as follows: The developed products shall be comprehensively compared with the RLDs in terms of quality (including impurity profile), to guarantee their quality consistency. Investigation data of multiple batches of samples of the RLDs shall be provided in principle, which are data of the investigation into the CQAs closely related to the consistency evaluation.
Predictably, RLD procurement and standard procurement will also consume a large part of project funds.
Point 9: Many new requirements are increased to the stability study
The stability study is undoubtedly important in the lifecycles of pharmaceutical products. Besides the common requirements in the past, the Draft also proposes new requirements for injections: The accelerated and long-term tests of injection stability studies shall be conducted under conditions that meet the GMP; the stability study plans can be designed by taking into account characteristics of the injection products applied for, such as product specification, container, filling, and API and excipient concentrations and according to relevant technical guidelines, to investigate items that are subject to changes during the storage and may affect the preparation quality, safety, and/or effectiveness. If the injection formulation contains excipients such as antioxidant and bacteriostatic agent, the stability stu...
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