已上市化学药品变更研究的技术指导原则_英文版

已上市化学药品变更研究的技术指导原则_英文版内容摘要：

determine whether the impurity levels are acceptable or not with rationales according to the Appendix 1 or 2 of “Technical Guideline for Study of Impurities in Chemical Drug Products”； If it is not acceptable, then a decision tree should be referenced to decide the subsequent step of work including consideration for carrying out any needed toxicology studies. In addition to the studies suggested under each change type in this guideline, it is also necessary to perform other selected important studies by taking into consideration of the characteristics and specifics of the change. For example, for some changes to a tablet manufacturing process, besides paring dissolution/release performances, it is also necessary to assess if there are any changes to other physical parameters. 2. Evaluation of Sameness or Equivalence prior to and post Change 4 Strictly speaking, it is unnecessary for a product to remain pletely identical before and after a change, however, the product must keep the sameness and equivalence, namely, the product must have the same quality and clinical equivalence. Based on the study and qualification about the chemistry, physics, microbiology, biology, biology equivalence and stability of a product, prehensive analysis should be carried out to evaluate how a change would impact drug safety, efficacy and quality controllability. In general, by paring and analyzing of the results before and after a change, it can be determined whether the results pre and post change are equivalent. The parison studies include dissolution and release as well as a thorough parative analysis of a property, such as drug product stability, etc. In some cases, however, the products are unable to retain the same equality or equivalence after the change, ., the change may have affected the product safety, efficacy and quality controllability. If a pharmaceutical manufacturer still wishes to implement the change, it must prove that the change will not negatively impact the product quality through a series of pharmacological and biological studies. For example, if the studies found that certain manufacturing process changes could result in new degradation products. However, further study shows that the degradation products will not raise concerns about the drug safety. Therefore, this change still can be implemented. 3. Considerations about the samples used for studies If a change occurs at the manufacturing phase after a drug product has been approved for marketing, samples used for change studies and qualification should e from manufacturing at a scale greater than the pilot scale. In general, quality parison studies (., dissolution, release parison experiments) for a drug product in support of a change are performed using samples from 3 production batches prior to the proposed change and from 13 batches manufactured with the proposed changes incorporated. Post change drug product stability study is usually performed using samples from 1~3 batches stored for 3~6 months under an accelerated and a longterm storage conditions. The stability results are pared with that of the 3 batches obtained from the manufacturing scale prior to the change. Specifics on the number of batches and testing duration should be determined based on the level of impact caused by the change to the product quality and stability. As for major change, or products with test results revealing a poorer product stability, it is suggested that more samples batches be selected and extended testing duration be adopted. With respect to a change for an injection product, 5 stability sample batches and testing duration should be in accordance with the relevant technical requirements. 4. Related Changes A change required to a product seldom occurs alone. For example, manufacturing site change may occur in parallel with changes to manufacturing equipments and processes。 a change to a pharmaceutical excipient in a formulation may lead to changes to drug product specifications。 or may result in changing packaging materials at the same time. In this guideline, changes paralleled to or consequential to another change are called Related Changes With respect to Related Changes, studies can be performed according to the guiding principles for various types of changes in this guideline. Because these changes may affect the product’ s safety, efficacy and quality controllability to different extents, ., related changes may be classified to different change types in this guideline, and studies may be carried out according to the respective technical requirements。 however, the overall studies should be carried out to meet the higher technical requirements. For example: a change to an excipient in a drugs tablet formulation is within the scope of Type III chang。