The document defines FDA warning letters and describes the process of FDA inspections that can lead to warning letters. It explains that warning letters notify companies of violations found during inspections and investigations. Companies must promptly correct issues and FDA will check that corrections are adequate. The document also describes different types of warning letters for various regulated industries and how to browse existing warning letters on the FDA website.
2. DEFINITION
An FDA warning letter is an official message from the United
states Food & Drugs Administration (FDA) that it has found
that a manufacturer has violated some rule in a regulated
activity.
While the FDA generally determines violations through its own
inspections, they can also issue one based on evidence from
state personnel
the FDA does not consider a warning letter a final action on
which it can be issued
3. The FDA defines an FDA warning letter as:-
“A correspondence that notifies regulated industry about violations
that FDA has documented during its inspections or investigations.
Typically, a Warning Letter notifies a responsible individual or firm
that the Agency considers one or more products, practices, processes,
or other activities to be in violation of the Federal Food, Drug, and
Cosmetic Act (the Act), its implementing regulations and other
federal statutes.
Warning Letters should only be issued for violations of regulatory
significance, i.e., those that may actually lead to an enforcement
action if the documented violations are not promptly and adequately
corrected. A Warning Letter is one of the Agency’s principal means
of achieving prompt voluntary compliance with the Act.
4. The agency has a computer application called the Compliance
Management System (CMS) that district offices use to
electronically submit warning letter recommendations to FDA
Centers.
All district office must use the CMS to submit the warning
letter recommendation, the Form FDA 483 that supports the
alleged violations, the Establishment Inspection Report (EIR),
and any written response from the firm.
5. WHY FDA COMES FOR INSPECTION
The person who involved in the manufacturing of bulk
API or involved in the formulation of product are willing
to sale or market there product in the regions of the united
states
The dossier is submitted according NDA for new product
and ANDA for generic drug and 502(f)(1) for
an API or bulk chemical
6. After the dossier or application is accepted by the USFDA and
send a reply for the inspection of the premises
FDA FORM 482- Notice Of Inspection
It is an official notice of FDA for inspection signed by the FDA
officials. It is produced by the inspector and has the authority
to inspect the manufacturing facility
Inspection coordinator will receive the notice and manage the
inspection accordingly
7. Coordinator should ask for notice, if it is not presented by
the FDA inspector
A copy of this shall be attached with the inspection file
FORM 482 shows that inspector has authorization from
FDA to inspect the facility
An inspector can ask for the manufacturing records of the
regulated product and can enter in the area where the
product is being manufactured.
8. He can review online records, collect samples and
interview the personnel working in area
An inspector cant review the product price list, financial
data of firm, product marketing data, research documents
and employee data excluding the training records.
These documents are considered as firms confidential
documents
9.
10. FDA FORM 483 – Observations of inspection
Inspector shall provide the list of his observations about
inspection on FORM 483
It has all the points noticed by the FDA inspectors. An
observation made in previous inspection or as mentioned in the
GMP are not followed or corrected can be added in 483
The original copy of the FDA Form 483 is presented to the
form management, generally to the person who had received
the notice of inspection
11. FDA Form 484- recipient of Samples
During the inspection if FDA inspectors want to take any
sample they have to issue a receipt of those samples on
Form 484
It has a quantity of simple with the lot number of the
product sampled Form 484 is used for samples only but
not for promotional material, labels, photographs or any
record taken by FDA investigators
12.
13. TYPES OF WARNING LETTERS
General FDA Warning Letters
Tobacco Retailer Warning Letters
Drug Marketing and Advertising Warning Letters (and
Untitled Letters to Pharmaceutical Companies)
14. General FDA Warning Letters
When FDA finds that a manufacturer has significantly violated
FDA regulations, FDA notifies the manufacturer. This
notification is often in the form of a Warning Letter.
The Warning Letter identifies the violation, such as poor
manufacturing practices, problems with claims for what a
product can do, or incorrect directions for use.
The letter also makes clear that the company must correct the
problem and provides directions and a timeframe for the
company to inform FDA of its plans for correction.
15. FDA then checks to ensure that the company’s
corrections are adequate. Matters described in FDA
warning letters may have been subject to subsequent
interaction between FDA and the recipient of the letter
that may have changed the regulatory status of the issues
discussed in the letter.
16. Tobacco Retail Warning Letters
Compliance check inspections of tobacco retailers occur
periodically, and are conducted to determine a retail
establishment’s compliance with the Federal Food, Drug, and
Cosmetic Act, as amended by the Family Smoking Prevention
and Tobacco Control Act (Tobacco Control Act) and its
regulations in effect
such as the Regulations Restricting the Sale and Distribution of
Cigarettes and Smokeless Tobacco to Protect Children and
Adolescents, found at Title 21 of the Code of Federal
Regulations, Part 1140
17. 21 C.F.R. Part 1140
CIGARETTES, SMOKELESS TOBACCO, AND COVERED
TOBACCO PRODUCTS
Prohibition of sale and distribution to the persons younger then
18yrs of age and Format and content requirements for labeling
and advertising.
Tobacco products covered in compliance check inspections of
tobacco retailers include cigarettes and smokeless tobacco.
All other Warning Letters issued by CTP for violations of the
Federal Food, Drug, and Cosmetic Act, as amended by the
Tobacco Control Act and its applicable regulations, can be
found at FDA’s main Warning Letter page at the Inspections,
Compliance, Enforcement, and Criminal Investigations -
Warning Letters page.
18. Drug Marketing and Advertising Warning
Letters
These letters are supplied by the CDER Freedom
of Information Office (FOI). This page only covers letters
issued by Headquarters and the Office of Prescription Drug
Promotion (formerly the Division of Drug Marketing,
Advertising, and Communications).
"Cyber" letters are sent electronically via the Internet to web
sites that offer to sell online prescription drugs that may be
illegal. The letters warn these web site operators that they may
be engaged in illegal activities and informs them of the laws
that govern prescription drug sales.
19. Warning Letter Close-Out Letter Program
(Applies to letters issued on or after Sept. 1, 2009)
FDA may issue a Warning Letter close-out letter ("close-out
letter") once the Agency has completed an evaluation of
corrective actions undertaken by a firm in response to a
Warning Letter.
A close-out letter may issue when, based on FDA’s evaluation,
the firm has taken corrective action to address the violations
contained in the Warning Letter. This procedure applies to
Warning Letters issued on or after September 1, 2009.
20. A close-out letter will not be issued based on representations
that some action will or has been taken. The corrective actions
must actually have been made and verified by FDA.
If the Warning Letter contains violations that by their nature are
not correctable, then no close-out letter will issue.
Future FDA inspections and regulatory activities may further
assess the adequacy and sustainability of these corrections.
Should violations be observed during a subsequent inspection
or through other means, enforcement action may be taken
without further notice
21. HOW TO BROWSE WARNING LETTERS
Use any of these "Browse" functions:
Browse Warning Letters by Company
Browse Warning Letters by Issuing Office
Browse Warning Letters by Subject
Browse Warning Letters with Response Letters
Browse Warning Letters with Closeout Letters
