What are USFDA microbial limits for WFI?

As per USFDA guidelines, 10 CFU/100 ml is an acceptable action limit. The sample size should be 100-300 ml for a sampling of WFI for testing. The WFI should pass for both endotoxins and microorganism microbial action limits.

What are USFDA microbial limits for purified water?

According to USFDA guidelines, purified water should have less than 100 CFU/ml will be acceptable. If any action limit crosses in purified water then all finished manufactured by the purified water should be evaluated thoroughly and investigated for any possible growth of microbial.

What are the biofilms in the water system?

Biofilms are the organisms attached to the inner surface of pipes in a water system.

Does FDA notify upcoming FDA inspection?

It is not absolutely sure that you will be notified by FDA before inspecting your facility, If you have issued any warning letter for a quality issue in a product in the US market then there are big chances you face a sudden inspection. Sometimes you get a notice of an upcoming inspection. The FDA inspector will reach your facility with a form 482 notice at the time of inspection.

USFDA inspection checklist for pharmaceutical facility

USFDA approval is a big milestone for any pharmaceutical manufacturing facility. If you are looking to export medicines to the US then you must have your facility approved by the USFDA. A pharma company can only sell direct products in the US market if they have got approval from the USFDA department. Every drug manufacturer needs to get inspected by FDA to ensure that the products are manufactured in accordance with GxP standards. In this article, we will elaborate on all USFDA inspection checklists that will help you to comply with different inspections by USFDA.

The frequency of inspection for a facility is at least once every two years.

The company which has any objection or has got a warning letter may get more inspections than once every two years.

Manner of company premises FDA inspection?

USFDA inspection is the same as other cGMP inspections conducted by local drug inspectors. In FDA inspection the level of authenticity and criteria of acceptance of the system become more stringent than other cGMP inspections. Some very important concepts most relevant to FDA inspections are given below that may provide you a framework for preparation. While starting the inspection FDA inspector will explore the quality management system (QMS) that may include:-

A competent management representative
Deviation report(if any)
Regular management reviews: You must have an authentic record for conducting management reviews on a periodic basis.
Record of self-inspection:- A valid self-inspection record that includes QC manager, production manager, Q.A. manager, and management representatives.

Quality Plan or Master Quality plan- A quality plan is an established document that ensures the degree of quality adopted for products manufactured in the plant.

Data of statistical evaluation of product data.

All CAPA record:- You must have a complete and authentic CAPA record of the period between the last inspection and the current inspection date. The corrective action and preventive action made for the process or product should be presented to the inspection team.

Risk analysis record or SOP:- The inspector will like to see the SOP and practical record maintained for risk analysis during operations at various stages of production and quality control process and utility works.

Calibration record of instruments.
Validation records of machinery and lab equipment.
Training record of technical and non-technical staff:- Training record is a very essential document of all GMP inspections. You must have the record containing all practical information of training conducted.

E.H.S control charts:-

Manufacturing process validation record:- Manufacturing process validation reports are very crucial documents that prove the quality of the product manufactured in the plant is up to the mark. Process validation is a periodical warranting process that investigates the error in the system. Those errors are eliminated and recalibrated the equipment to the desired standard.

Product performance reviews:- Product performance review refers to the stability check-ups of quality products. It is a routine process done by the Q.C. department with the old products stored in control samples and humidity chambers for accelerated stability checkups. If the products found any deterioration in quality or physical appearance then the whole manufacturer's method of that product is reviewed and revalidated.

Inspection closeout meeting:- FDA inspectors discuss the short-finding or other issues with the management body of the company. Inspectors will provide their view on the system of the company and the credibility of the record you showed them.

Post Inspection works:- You will get a letter after a few weeks of inspection from the FDA. There are two options: first, you will get FDA approval, second, you will find FDA 483 letter where you will find all deficiencies found in your facility during the inspection.

An affixed time frame will be provided to you to remove the deficiencies listed by inspectors, and you have to submit your response to FDA.

Also Read: Best cough syrup names in India 2021

Types of FDA inspections

All pharmaceutical manufacturing companies that sell products to the US market are abiding to comply with USFDA inspection.

The type of inspection may be different from previous inspections. There are four main types of FDA inspection:-

Pre-approval Inspection
Routine Inspection
Compliance follow-up inspection
For Cause Inspections

Pre-approval Inspection:- This type of inspection is conducted on the request of a company that is not approved by USFDA until. Any new company that is willing to sell medicines in the US market needs to apply for USFDA approval. After receiving an application from the company along with required documents the USFDA conducts an inspection and decides whether the facility is capable to manufacture quality medicines that will be acceptable in the US market, and the infrastructure of the company is according to the cGMP compliance.

Routine Inspection:- These inspections are usually conducted after every two years of FDA approval. In such inspections, the USFDA inspector checks whether the company following the USFDA and GMP norms for manufacturing the products, and documents are maintained to ensure the transparency of the process followed during. Inspectors check the Quality system, change in the system of manufacturing, quality and premises are checked. It is also checked whether any responsible personnel changed during the period of 2 years if any significant person joined the company, inspector check does the SOP for induction of new responsible person is followed or not.

Records of all manufacturing records like BPR, BMR, MFR and logbooks of instruments and machineries are verified. Calibration record of lab instruments along with validation is checked. Validation record of manufacturing process, analytical method validation and validation of manufacturing machinery is checked thoroughly.

Compliance follow-up inspection:- This type of inspection is conducted as the result of a review action and corrective action taken by a facility against the warning letter or 483 observations. The inspector checks the facts that the company submitted documents of corrective actions are valid or not.

For Cause Inspections:- This inspection is conducted to investigate a specific problem developed or registered by USFDA.

Reference:

Meddeviceonline.com/understanding the 4 types of FDA inspection
FDA’s investigations operations manual/202110M
What happens during an inspection?

New cancer drugs approved by FDA

What is the concept of GxP?
Best liver tonic names in India
ICH Guidelines

USFDA inspection checklist for pharmaceutical facility