Calibration and FDA 483 Letters in 2020

Background

In the event of a violation of the Federal Food, Drug, and Cosmetic Act, depending on its nature, FDA may give individuals and firms an opportunity to take voluntary and prompt action to correct the violation before FDA initiates an enforcement action. Untitled letters are used for violations that may not meet the threshold of regulatory significance for a warning letter and request correction of the violations. Unlike a warning letter, an untitled letter does not include a statement that warns the individual or firm that failure to promptly correct the violation may result in enforcement action. FDA generally is under no legal obligation to warn individuals or firms about violations before taking enforcement action.

Source :https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/compliance-actions-and-activities/issuance-untitled-letters

• Matters described in FDA warning letters may have been subject to subsequent interaction between FDA and the letter recipient that may have changed the regulatory status of issues discussed in the letter.
  
  

Source: https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/compliance-actions-and-activities/warning-letters

Observations are listed on a Form 483 in order of significance by the investigator. The format of any single observation begins with a statement based in a citation of law, regulation or Act and is followed by a statement of specific conditions observed during the inspection. For a description of the citations and the data in the attached spreadsheets, please see A Short Description of Citations.

You really don't want to receive this letter from the FDA. As of December 11, 2020 the FDA has issued 595 483 letters. Calibration and measurement are specifically called out in many letters.

What are the common issues for those receiving an FDA 483 letter that mention calibration?

• Stay On Schedule

• Keep Calibration Records

• Have Written Procedures

Here are some snippets from FDA 483 letters issued in 2020:

"you should also provide evidence that you have reviewed other validations for the presence of all required testing, calibration of all equipment used for each study for the range of use, number of samples used as required and adequacy of sampling plans."

Stay On Schedule

"The press sensors (b)(4) were not calibrated prior to executing the performance qualification. The IM 08 sensors have not been calibrated since the unit was initially placed in service prior to 2009 and were overdue for calibration per your Injection Molding Machine Calibration Schedule."

"You failed to calibrate instruments and controls you use in manufacturing or testing a component or dietary supplement, as required by 21 CFR 111.27(b). Specifically, our investigator observed your (b)(4) model scale contained a calibration sticker stating the last calibration date was July 23, 2012, that expired on July 23, 2013, and you could not provide evidence this scale has been recalibrated since this date."

Keep Calibration Records

"The validation records lack calibration reports, a record of the personnel that performed the individual task, the date, and an adequate description of the manufacturing process that would be supported by the validation activities."

"In addition, you did not provide records that document calibration of (b)(4) used to measure (b)(4) in your acidified products."

"Your  response states you have contacted a calibration company and included an invoice from this company but documentation was not provided to show your equipment was calibrated."

Have Written Procedures

"Your firm has not established a procedure to provide specific directions and limits for accuracy and precision for the calibration of the flow meters."

"Specifically, your firm has not adequately validated, reviewed, or approved the manufacturer change for the calibration heater test fixtures. "

"You did not establish and implement written procedures for the method and frequency of calibrating verification instruments as required by 21 CFR 117.165(b)(1). Your firm utilizes a (b)(4) Thermometer to monitor the temperature of incoming refrigerated/frozen ingredients. You did not establish a written calibration procedure to verify the accuracy of your thermometer. Further, during our inspection you stated that your firm has not been performing calibration or verification activities for your (b)(4) thermometer."

"It is unclear if procedure (b)(4) is a new procedure developed as a result of this observation; however, this procedure has not been provided for review nor have any records of PQ (or calibration) results been provided for review. It is also unclear how your firm determined a calibration window of (b)(4) was acceptable to ensure acceptable performance of your (b)(4). "

"your firm has not established and maintained procedures for all steps you perform, including but not limited to, performance of communicable disease testing, documentation of test kit lot numbers, equipment used during testing, incubation times, steps in reporting results to clients, and calibration/maintenance of testing equipment."

The FDA regulates $1 trillion worth of products a year. It ensures the safety of all food except for meat, poultry and some egg products; ensures the safety and effectiveness of all drugs, biological products (including blood, vaccines and tissues for transplantation), medical devices, and animal drugs and feed; and makes sure that cosmetics and medical and consumer products that emit radiation do no harm.

Source: FDA.gov

Whose Job Is it To Be Responsible For Calibrations Due?

This may come as a surprise, but it is NOT the responsibility of your calibration company. Many companies, including Alliance Calibration do send out a notice when items are coming due for calibration. However, it is the end user of calibrations responsibility to ensure their gages are calibrated. Click here for more details.

Alliance Calibration provides online 24/7 access to calibration data to help you in the event of an audit. In addition, we inform you when measurement & test equipment is due for calibration.

You may want to read 3 Big Mistakes When Changing Calibration Intervals.