FDA factory inspection is actually a common name, and is a relatively large proposition. Because we are currently exposed to the "FDA" factory inspection, there are medical device FDA factory inspection, that is, QSR820 factory inspection, food FDA factory inspection (according to the U.S. GMP110 regulation 21CFR Part110), OTC drug factory inspection (according to the 21 CFR chapter of the Drug Enforcement Agency), cosmetics The four major categories of factory inspection.
1. History of the FDA:
The FDA's office in China, located in Beijing, was established in 2008 as the first overseas office of the FDA, with the primary function of overseeing the compliance of U.S. exporters. It currently has about 18 regular employees (including several Chinese Americans). Dr. Leigh Verbois, Gurley, is the Director, Peter Baker, the famous killer prosecutor, is the Assistant Director for Drugs, Nicole Smith is the Assistant Director for Devices, and Patrick Bowen is the Assistant Director for Food and Feed.
2. Audit Chances
According to statistics, the current number of FDA audits of Chinese pharmaceutical and device companies is about 130-160 per year. For pharmaceutical companies, the number of registered companies is about 800. For devices, there are more than 3,400. For Class I products, they are inspected every four years, and for Class II/III products, they are inspected every two years.
3. FDA inspection focus:?
Review of documents; according to the QSIT method - based on 7 subsystems
4 major subsystems (management, design, corrective prevention, production process);
3 support subsystems (documents, materials, production tools and equipment control); FDA inspection work will be a point of view to bring the surface, to seize a point, can be a few back and forth on an issue, but also may be checking the entire company's quality management system. The company's quality management system.
4. Inspection time and personnel arrangements:
A class of two devices are one prosecutor; three devices for one or two prosecutors, 4-5 working days
5. Related documents
FDA inspection of common documents are Form 483, the EIR report, a warning letter and import ban. Briefly introduce the definition and use of the 4 documents.
1) Form 483
Form 483 is used by the FDA inspector who performs the inspection to record the defects found. The inspector issues the form at the conclusion of the inspection, and the inspected company is required to formally respond to the deficiencies. Responses to deficiencies on the form need to be submitted within 15 business days of its signing. Only after the response is received will the FDA be able to make a decision on whether or not to issue a warning letter. Prosecutors will not issue a Form 483 if no deficiencies are found during the inspection.
? Note: In addition to Form 483, there are also Forms 482 and 484
FDA482: Notice?of?Inspection: Notice of Inspection
FDA483: Inspectional?Observations: Notice of Inspection Observations
FDA484: Receipt? for?Samples: Sample Receipt Form
2) EIR: Establishment Investigation Report Factory Investigation Report
In addition to the Form 483, the inspector has to produce an EIR. The EIR will be completed within 30 working days, and then it will be sent to the FDA regional office or central office for inspection. The person in charge of the inspection will be identified with the following statuses:
NAI: No Action Indicated - there were noobjectionable items found during the inspection
NAI: No Action Indicated - during the inspection No non-compliant items found
VAI: Voluntary Action Indicated -objectionable items were found, but no action is required on the part of theauthority. All of the company's actions are on a voluntary basis. All of the company's actions are on a voluntary basis.
VAI: Voluntary Action Indicated -objectionable items were found, but no action is required on the part of theauthority. All of the company's actions are on a voluntary basis.
OAI: Official Action Indicated -Objectionable items were found and further regulatory measures will be derived (e.g. Warning Letter).
OAI: Official Action Indicated -objectionable items were found and further regulatory measures will be derived(e.g. Warning Letter).
The FDA sends the EIR to the inspected company. As part of the so-called "Freedom of Information Act", other companies can also request to see the EIR, but experience has shown that it takes a long time to publicize foreign EIRs.
3) Warning Letter
The FDA will issue a warning letter if the inspection reveals serious deficiencies and the response to the Form 483 is deemed inadequate. The company must respond within 15 business days with a detailed explanation of how the deficiencies were addressed and how to prevent them from recurring. Warning letters are typically posted on the official FDA website.
4) After that, the company may face the following consequences:
Influence on the approval The FDA will stop granting approval for one or more drugs, and stop reviewing the filings.
Import Stop / Import Alert Import Suspension / Import Ban
The company's products can no longer be exported to the US. The products will be subject to DWPE (detention without inspection) by US Customs. There are also instances where a 483 does not open a warning letter that leads directly to a ban.
Debarment List
The Debarment List includes all companies that are not permitted to manufacture drugs for sale in the United States. The exclusion list is public.
Court - Consent Decree Court - Decree
For U.S. companies and their subsidiaries, it may be necessary to have a consultant company inspect the company for a few months to a few years and improve systems and processes. At the end of the process there will be an inspection and at the same time there will be a loss of profit.
The FDA inspector's personality type and inspection ideas
1. Inspector's personality type
1) Questioning + Killer type
Characteristics: Questioning inspectors are generally technical experts, have a strong technical background, and know a lot about the product's R & D and design, process, and other key points. They are under 40 years old, energetic, and have a clear mindset.
Check the characteristics: questioning type of prosecutor on any material you provide, especially records are distrustful attitude. He will be from the document paper old and new, handwriting, the sequence of signature time, the user's familiarity with the document to determine whether there is forgery. When checking, he likes to go around the company first, checking the function of each area, signage, placed items to see if there are obvious violations. Special attention is paid to uncontrolled document records and explanations are requested; even the presence of uncontrolled document records in desks is checked. This type of prosecutor aims to find as many problems as possible, and will dig deeper once they find something suspicious. They don't care if every point in 21 CFR is checked. This kind of is typical not to find the problem of death will not stop, can also be called "find fault type" inspector.
Response strategy: never take the initiative to explain their major defects. If you have a lot of defects that you can't handle, you can try to take the initiative to expose some minor defects to see if you can guide the focus of the inspection. For any defects they question, try to explain them from a technical point of view.
2) dogmatic + facetious type
Characteristics: dogmatic prosecutors to the quality system experts, very familiar with the provisions of the regulations, logical thinking, but not necessarily understanding of the product.
Inspection characteristics: the inspection basically follows the requirements of 21 CFR, the inspection will pay attention to the control of time to ensure that no aspects will be missed. They like to sit in the conference room to check the documents, supplemented by on-site inspection.
Response strategy: Cooperate with the prosecutor's requirements, especially for the documents they need to try to provide quickly. The defects found by the prosecutor can be explained from the point of view of the actual risk to the product is small.
3) Learning + vacation type
Characteristics: Learning prosecutors are generally novice and almost retired veterans. Mild-mannered and easy to communicate with, they are often inspecting China for the first time.
Inspection characteristics: With the mindset of learning about the product and the way the business operates, they are more patient in listening to the company's explanations.
Response strategy: serve tea and water to entertain, nothing to open a small joke to ease the tension, as far as possible to keep a good mood and state.
Of course, these observations, just let us in the process of factory inspection a little smoother, but can not put all the hopes are pinned on this above, well-prepared to have the courage to meet the factory inspection, in order to successfully pass the factory inspection.