新冠肺炎疫情对美国食品和药物管理局（FDA）的检查计划造成了前所未有的破坏。由于疫情而暂停了绝大多数检查活动，FDA被迫试行新的检查计划，包括远程交互式评估，更多地使用21 USC 374(a)(4)下的记录请求（通常称为704项请求），以及更多地依赖互信协议下的其他卫生当局检查。

The COVID-19 pandemic resulted in an unprecedented disruption to the U.S. Food and Drug Administration (FDA) inspection program. With the vast majority of its inspectional activities suspended due to the pandemic, FDA was forced to pilot new and unfamiliar inspectional initiatives, including remote interactive evaluations, increased use of records requests under 21 USC 374(a)(4) — commonly known as 704 requests — and increased reliance on other health authorities’ inspections under the Mutual Reliance Agreement.

2022年7月22日，FDA发布了新的指南草案“进行远程监管评估问答”（RRA指南），其中描述了FDA在COVID-19大流行之后继续使用这些指南替代检查措施的计划。FDA继续使用这些定义为“远程监管评估”或RRA的工具，反映了FDA向“现代化方法”监督产品和设施的转变¹。

On July 22, 2022 the FDA released new draft guidance, “Conducting Remote Regulatory Assessments Questions and Answers” (the RRA Guidance), describing the agency’s plan to continue to use these alternative inspectional initiatives beyond the COVID-19 pandemic. FDA’s continued use of these tools, broadly defined as “remote regulatory assessments” or RRAs, reflects the agency’s shift toward a “modernized approach” to oversight of FDA-regulated products and establishments¹.

FDA正式采用RRA作为监督工具，这使得FDA能够以基于风险的方式优先考虑有针对性的现场检查方法，并通过RRA获得的记录来准备现场检查²。它还可能为行业创造一个额外的监管步骤来证明持续的合规性。管理和响应RRA与FDA 483大不相同，生产商需要相应地调整其方法以确保成功的结果。

FDA’s formal adoption of RRAs as an oversight tool allows the agency to prioritize resources in a risk-based manner for a targeted on-site inspectional approach and use records obtained through RRAs to prepare for on-site inspections². It also potentially creates an additional regulatory step for industry to demonstrate ongoing compliance. Managing and responding to an RRA differs significantly from managing an inspection and responding to an FDA 483, and manufacturers will need to adjust their approach accordingly to ensure successful outcomes.

FDA的RRA指南是一种问答文件，广泛地定义了远程监管评估，包括“对FDA监管的机构及其记录的检查，完全远程进行，以评估是否符合适用的FDA要求。”根据所涉及的评估类型，RRA可能包括记录请求、与机构的虚拟会议和使用直播来检查设施数据、操作和信息的组合³。

FDA’s RRA Guidance, which is styled as a question-and-answer document, broadly defines remote regulatory assessments to include “an examination of an FDA-regulated establishment and/or its records, conducted entirely remotely, to evaluate compliance with applicable FDA requirements.” Depending on the type of assessment involved, an RRA may include a combination of record requests, virtual meetings with the establishment, and/or the use of livestream to examine the facilities data, operations, and information³.

根据此指南，FDA打算在“有助于履行FDA的监管职责、保护人类和动物健康……以及支持监管决定和监督活动⁴”时请求RRA，包括，例如，当旅行限制阻挡了FDA进行现场检查、机构监督或执行监管决策时⁵，尽管此指南也明确表明，FDA不接受进行RRA的请求。值得注意的是，FDA并不认为RRA可以替代检查，这意味着目前处于OAI（指示官方行动）状态的工厂不太可能通过RRA获得许可。

According to the guidance, FDA intends to request RRAs whenever it is “appropriate to help fulfill the Agency’s regulatory responsibility and protect human and animal health … and to support regulatory decisions and oversight activities⁴.” This includes, for example, when travel restrictions limit the agency’s ability to conduct in-person inspections, to conduct establishment oversight, or to support regulatory decisions⁵, although the guidance also makes clear that FDA is not accepting requests to perform RRAs. Notably, FDA does not consider RRAs to be replacements for inspections, meaning that sites currently on OAI (official action indicated) status are unlikely to be cleared through an RRA.

此指南描述了两类RRA：

The guidance describes two categories of RRAs:

1、自愿性RRA，包括“根据行业自愿参与进行的记录评估和/或交互式评估（例如，操作的远程直播视频，电话会议和屏幕共享）⁷。”

1.Voluntary RRAs have included “records assessments and/or interactive evaluations (such as remote livestreaming video of operations, teleconferences, and screen sharing) conducted pursuant to voluntary participation by industry⁷.”

拒绝参与自愿RRA不会导致FDA采取任何强制措施，但可能会延迟FDA的评估或导致FDA考虑采取其它行动（例如，检查）来行使FDA的监督职责⁸。

Declining to participate in a voluntary RRA will not result in any enforcement action by the agency but may delay FDA assessments or lead FDA to consider other actions, such as an inspection, to exercise the agency’s oversight responsibilities⁸.

2、强制性RRA，包括“根据FD&C法案第704(a)(4)条向药品生产企业索取记录或其他信息的请求，以及根据21 C.F.R. 1.510(b)(3)和1.512(b)(5)(ii)(C)索取[外国供应商核查计划]记录的请求⁹”。

2. Mandatory RRAs have included “requests for records or other information from drug establishments under section 704(a)(4) of the FD&C Act, and requests for [Foreign Supplier Verification Program] records under 21 C.F.R. 1.510(b)(3) and 1.512(b)(5)(ii)(C)⁹.”

根据指南，撤回参与或拒绝提供记录可能被视为拒绝参与强制性RRA。拒绝强制性RRA的机构可能违反了食品、药品和化妆品法案，FDA可能会采取“适当措施”¹⁰。

According to the guidance, withdrawing participation or refusing to provide records may be considered declining to participate in a mandatory RRA. An establishment that declines a mandatory RRA may be in violation of the Food, Drug, and Cosmetic Act, and FDA may take “appropriate action¹⁰.”

FDA可以将RRA期间收集的观察项与后续检查中的任何观察项结合起来使用¹¹。当FDA完成RRA时，FDA可能会与公司管理层会面。FDA还可以提供一份观察到的表明潜在违规行为的条件和/或做法的书面清单¹²。尽管FDA在RRA结束时不会发布FDA 483表（检查结果列表），但可能会在RRA期间提供关于观察结果和问题的更新，并鼓励公司在会议期间做出回复或在15个美国工作日内提供书面回复¹³。FDA通常会编写一份总结报告，在RRA结束时将其提供给公司。

FDA may combine observations gathered during an RRA with any observations from a subsequent inspection¹¹. When FDA completes an RRA, the agency may meet with establishment management. The agency may also provide a written list of conditions and/or practices observed that indicated a potential violation¹². Although FDA does not issue a Form FDA 483, List of Inspectional Observation, at the conclusion of an RRA, it may provide updates on observations and issues during RRA and encourages establishments to respond during the meeting or to provide written responses within 15 U.S. business days¹³. FDA will typically prepare a report summarizing its review and findings, which it will provide to the establishment when the RRA is closed.

此指南还详细说明了在检查之前进行RRA的潜在好处。这些潜在的好处包括，促进公司为下一次检查做好准备，通过减少FDA需要审核的记录数量来优化FDA在现场的时间，以及在符合适当条件时允许FDA在不经检查的情况下做出监管决定¹⁴。

The guidance also details potential benefits of having RRAs precede inspections. These potential benefits include identifying issues that may enhance an establishment’s preparation for its next inspection, optimizing FDA’s time on site by reducing the number of records the agency needs to review, and allowing FDA to make regulatory decisions without an inspection when appropriate conditions are met¹⁴.

下一步该怎么做?

What to Expect Next？

RRA指南证实了我们一直以来的怀疑：即使FDA恢复正常的现场检查，FDA也将继续使用其记录请求权限和远程交互式评估工具来履行其监管职责。一方面，更多地使用RRA可以使FDA进行更有针对性的现场检查，并更灵活地解决短缺和潜在短缺问题。另一方面，RRA可能导致加强对关键生产工厂（尤其是国外）的审查，以及FDA对生产商整体的额外监督层级。

The RRA Guidance confirms what we suspected all along: that FDA will continue to use its records request authority and remote interactive evaluation tools to carry out its regulatory oversight responsibilities even if the agency resumes normal on-site inspections. On the one hand, the increased use of RRAs could allow FDA to conduct more targeted on-site inspections and to more nimbly navigate shortages and potential shortages. On the other hand, RRAs could lead to enhanced scrutiny of critical, especially foreign, manufacturing sites and additional layers of FDA oversight of manufacturers overall.

生产商还需要权衡参与“自愿RRA”的好处与回应多轮信息请求的负担，以及RRA导致FDA采取行动的可能性。此外，生产商应评估其现有流程和技术能力，以确保此类请求已准备就绪，并确保以与现场检查类似的专业水平、勤勉程度和紧急程度处理RRA。

Manufacturers will also need to balance the benefit of participation in “voluntary” RRAs against the burden of responding to what can end up being multiple rounds of information requests and the potential that the RRA will lead to action by FDA. In addition, manufacturers should assess their existing processes and technological capabilities to ensure readiness for such requests and to ensure that RRAs are handled with a level of professionalism, diligence, and urgency similar to on-site inspections.

¹ 见FDA声明，FDA Details Optimized Approach for Regulatory Oversight Tools to Better Protect Public Health（2022年7月22日）；FDA，Conducting Remote Regulatory Assessments: Questions and Answers: Draft Guidance for Industry 5（2022年7月）。

² Conducting Remote Regulatory Assessments: Questions and Answers: Draft Guidance for Industry 8-9。

³ Id. at 10.

⁴ Id. at 7.

⁵ Id. at 7-8.

⁶ Id. at 6；见FDA声明，FDA Details Optimized Approach for Regulatory Oversight Tools to Better Protect Public Health。

⁷ Conducting Remote Regulatory Assessments: Questions and Answers: Draft Guidance for Industry 5。

⁸ Id. at 11.

⁹ Id. at 6.

¹⁰ Id. at 11.

¹¹ Id. at 8.

¹² Id. at 15.

¹³ Id.

¹⁴ Id. at 9.

¹ See FDA Statement, FDA Details Optimized Approach for Regulatory Oversight Tools to Better Protect Public Health (July 22, 2022); FDA, Conducting Remote Regulatory Assessments: Questions and Answers: Draft Guidance for Industry at 5 (July 2022).

² Conducting Remote Regulatory Assessments: Questions and Answers: Draft Guidance for Industry at 8-9.

³ Id. at 10.

⁴ Id. at 7.

⁵ Id. at 7-8.

⁶ Id. at 6; See FDA Statement, FDA Details Optimized Approach for Regulatory Oversight Tools to Better Protect Public Health.

⁷ Conducting Remote Regulatory Assessments: Questions and Answers: Draft Guidance for Industry at 5.

⁸ Id. at 11.

⁹ Id. at 6.

¹⁰ Id. at 11.

¹¹ Id. at 8.

¹² Id. at 15.

¹³ Id.

¹⁴ Id. at 9.