FDA Form 483 Frequently Asked Questions
Q: When is an FDA Form 483 issued?
A: An FDA Form 483 is issued to firm management at the conclusion of an inspection when an investigator(s) has obrved any conditions that in their judgement may constitute violations of the Food Drug and Cosmetic (FD&C) Act and related Acts. FDA investigators are trained to ensure that each obrvation noted on the FDA Form 483 is clear, specific and significant. Obrvations are made when in the investigator’s judgement, conditions or practices obrved would indicate that any food, drug, device or cosmetic has been adulterated or is being prepared, packed, or held under conditions whereby it may become adulterated or rendered injurious to health.
Q: What is the purpo of an FDA Form 483?
A: The FDA Form 483 notifies the company’s management of objectionable conditions. At t
he conclusion of an inspection, the FDA Form 483 is prented and discusd with the company’s nior management. Companies are encouraged to respond to the FDA Form 483 in writing with their corrective action plan and then implement that corrective action plan expeditiously.
Q: Is the FDA Form 483 intended to be an all-inclusive list of every possible deviation from law and regulation?
A: No, it’s not. The FDA Form 483 is a report which does not include obrvations of questionable or unknown significance at the time of the inspection. There may be other objectionable conditions that exist at the firm that are not cited on the FDA Form 483. FDA investigators are instructed to note only what they saw during the cour of the inspection. Companies are responsible to take corrective action to address the cited objectionable conditions and any related non-cited objectionable conditions that might exist.
Q: How is the FDA Form 483 shared with the company?
A: FDA Form 483s are discusd with a company’s management at the conclusion of the inspection. Each obrvation is read and discusd so that there is a full understanding of what the obrvations are and what they mean.
Q: What are the implications of the FDA Form 483 for agency enforcement and what happens next?
A: The FDA Form 483 does not constitute a final Agency determination of whether any condition is in violation of the FD&C Act or any of its relevant regulations. The FDA Form 483 is considered, along with a written report called an Establishment Inspection Report, all evidence or documentation collected on-site, and any respons made by the company. The Agency considers all of this information and then determines what further action, if any, is appropriate to protect public health.
美国FDA483回复的10条技巧
每次FDA检查官完成现场检查时，都会给药业负责人发一份CGMP现场检查缺陷报告（48
3表），483报告决不是表彰药业在哪些方面做得好或是达到CGMP的要求，而是列举出检查官在药企进行CGMP检查期间所观察到的哪些不足之处。483缺陷报告也不是对药企是否通过CGMP现场检查的最后结论。下面就483报告回复的技巧介绍如下：
1. 483表报回复的格式：通常药企回复483报告的回复格式是将按流水号将483缺陷上列出的不足一字不差的打印出来，然后另起一行对这一不足做出回答。按一问一答的格式对483报告的每一条不足逐条进行回复。
2. 483表报回复的内容：回复的内容与形式完全是根据483报告中列出的不符合项根据回具体情况来决定。但无论如何回复一定要表达了药企对不符合项改进的态度或决定，所采取的方案与措施。
3. 回复正文力求简明，并列出相关的改进措施和方法，具体内容以附件的形式出现。回复正文内容包括同意或不同意，必要时要解释，提供必要的背景情况。每一条的回复正文中FDA最不愿意在看到是的反复地重申造成这一项缺陷的各种原因，并进行辨解；FDA希望读到回复是药企对改进这些不足的承诺和如何改进的具体方法。
4. 回复要提供全面的整改计划（包括已实施的和计划中的）和完成时间表。整改计划：1）要有针对性，2）要完整准确，3）要可行，4）要实现对整改诺言，5）要评估所有受影响的产品。药企不应当仅仅是为了回复好而改进这些缺陷项，而是为了提高GMP的执行水平。比如同样的问题也出现在其它车间或部门的，也要进行全面的改进。检查官提出的缺陷属于“点”上的问题，回复要以“面”上进行改进。如果FDA检查官提出的缺陷属于“面”上的或“系统”上的共性问题，回复必须在更深层次方面进行改进。
5. 回复报告除了简明的叙述其改进的方法和具体措施外，还要提供相应的证据。如：新批准或修订的SOP复印件和相应的记录（包括该文件的英文文件）；验证方案或/和验证报告；购置仪器或设备的照片和发票复印件；改进后的各种照片；车间或实验室扩建的图纸等等。
6. 如果改进措施需要较长的时间，比如新建一个专用车间或改建一个车间，回复应当包括设计图纸，时间进度表。
7. 如果483表报告中有一条缺陷是较为严重的缺陷，回复必须有详细的改正步骤和采取的实际措施的时间表。同时还要附上企业总裁的承诺书。
8. 回复应及时。时间要求是当企业收到FDA的483报告后，应当在15天日对483报告的回复寄出（原规定是15天到30天内）。药企可以用传真的方式或电子邮件以扫描的文件形式将483报告回复发送到指定的地区FDA办公室，与此同时还必须用国际快递将483报告回复原件寄到FDA办公处，并采用提供邮件回执的报务以确保FDA办公处收到药企的483报告回复。
