In order to implement the spirit of the Opinions on Deepening the Reform of the Review and Approval System and Encouraging Innovation in Pharmaceuticals and Medical Devices by the General Office of the Central Committee of the People's Government of the People's Republic of China and the General Office of the State Council (Office of the [2017] No. 42), and the Opinions on Reforming and Improving Policies on the Supply Guarantee and Utilization of Generic Drugs by the General Office of the State Council (State Office of the People's Government of the People's Republic of China [2018] No. 20), and to perfect the technical standards of the application for registration of orally solid generics
Assurance of commercial production batch samples and bioequivalence study (referred to as "BE study").
Taking into account the current situation of R&D and production of generic drugs in China, the following requirements have been formulated for the batch size of BE study samples of chemical generics (oral solid dosage forms) in Registered Classification 4 and 5.2.
I. For tablets and capsules (including extended-release preparations, chewable tablets, orally disintegrating tablets, etc.), the sample batch size of the BE study (in terms of the amount of feeding, the same below) shall not be less than 100,000 preparations. For bulk dosage and granule dosage, the sample batch size of BE study batch shall not be less than 1/10 of the proposed commercial production batch size.
II. If the above requirements are not met, the supplementary study of batch amplification shall be conducted in accordance with the above requirements. In principle, the amplification study should be carried out in the same production line. If the production equipment is changed, the working principle of the production equipment should be consistent.
A comprehensive quality consistency comparison study should be conducted between the amplified samples and the BE study batch samples and reference preparations. If the quality of the enlarged research batch samples is considered consistent with that of the BE research batch samples and reference preparations after comprehensive assessment, the batch size of the enlarged research batch shall be recognized as the maximum batch size for commercial production; if the research data cannot prove that the quality of the enlarged research batch samples is consistent with that of the BE research batch samples and reference preparations after comprehensive assessment, the BE study shall be repeated with samples that meet the batch size requirements.
Third, under special circumstances, such as drugs used in the treatment of rare diseases, drugs controlled in accordance with national regulations, the sample batch size of the BE study batch may be lower than the above requirements, but the batch size shall be within the normal batch size of the actual production line.
Fourth, for oral solid preparations applying for passing the consistency evaluation of quality and efficacy of generic drugs or deemed to have passed the consistency evaluation, if it involves the sample batch size of the BE study batch, the above requirements shall be referred to.
V. These technical requirements have been formally implemented since the date of publication, and varieties initiating BE study after the official implementation date will not be recognized if the sample batch does not meet the requirements.