2014-03-08 Lachman CONSULTANTS
CMC批准后的生产变更年度报告指南姗姗来迟，影响非凡
好消息是部分变更由需要递交补充调低为年度报告申明，监管有所放宽；坏消息是行业可能需要花费一定时间领会指南，通过诸如与仿制药办公室的监管项目经理电话沟通，摸清立场变化，理清这一文件所能涵盖的具体变更。
这份13页的文件修订稿，同时涵盖了与NDA与ANDA有关的变更，背景介绍与标准声明与所有FDA指南文件无异，但是附件A与附件B含有重要内容，其中说明了现在可以作为年度报告提交的变更类型。如果变更不太可能对产品质量带来不利影响（这是标准具有灵活性的地方，企业可能由此别出心裁的解释自己对变更影响的看法—所以需小心），这些类型的变更可作为年度报告提交，列于附件A中。附件B则重新列出了在不同放大与上市后批准变更（SUPAC）指南中认定的年度报告的变更。
FDA提醒行业仍要对之前的“已获批NDA与ANDA变更”指南予以关注，同时指出需要充分罗列支持变更的数据，以支持申请者做出的变更不需要递交补充的判断。
新指南覆盖了成分及组成、生产场地、生产工艺、批量规模与设备变更、质量标准、容器密封、标签变更以及其它相关变更（例如规格与说明的变更）。对该指南不同条款的解读需要谨慎，决定在年度报告中提交变更时，务必考虑对产品质量带来影响的可能性，而非最终认定没有影响。
Lachman CONSULTANTS - Bob Pollock先生 2014-03-04
校译：识林-Kapok 2014-03-08
A Little Late, But CMC Annual Reportable Postapproval Changes Guidance Hits the Street
Written by Bob Pollock • March 04, 2014
The good news is that there is some regulatory relief for the down-regulation of some changes from supplements to Annual Report notifications; the bad news is that the industry will likely spend as much time figuring out the Guidance and trying to position changes such that they can reasonably be read to be covered by the document as trying to get a Regulatory Project Manager on the phone at OGD.
The revised 13 page document covers changes to both NDAs and ANDAs and provides a general background section and the standard disclaimers found in all FDA guidance documents, but the real meat is found in Appendix A and Appendix B, which describe the types of changes that can now be submitting in the Annual Report. Appendix A contains those types of changes that can be submitted in the Annual Report if the change has minimal potential to have an adverse effect on product quality (this is where the rubber meets the road and where firms are likely to be maybe too creative in their views of the impact of change- so be careful). Appendix B restates the annual reportable changes found in the various Scale-up and Post-approval Changes (SUPAC) Guidances.
FDA reminds the industry to continue to pay attention to the older “Changes to an Approved NDA and ANDA” Guidance and also notes that data supporting the change should be adequately presented to support the applicant’s determination that the change did not require the submission of a supplement.
The new Guidance covers changes to components and composition, manufacturing sites, manufacturing process, batch size and equipment changes, specifications, changes in container closures, and labeling changes associated with other related changes (e.g., how supplied or description changes). The complete guidance document can be found here. Please be careful in your interpretation of the various provisions of this Guidance and remember the decision to submit a change in the Annual Report must take into consideration the potential for impacting the product quality and not the ultimate finding that it did not.
For questions related to this guidance or for help in its interpretation please contact Joan Janulis at j.janulislachmanconsultants.com or one of the Lachman Regulatory team.