Tuesday, June 26, 2012

FDA's Regulatory Procedures Manual Effective May 2012 Regarding Advisory Actions Such as Warning Letters

Regulatory Procedures Manual – May 2012 Chapter 4 Advisory Actions
____________________________________________________________________
4-1
Chapter 4
ADVISORY ACTIONS
This chapter defines and establishes uniform guidance and procedures for
Warning Letters and Untitled Letters.
This chapter includes the following sections:
Section Topic _____Page
4-1 WARNING LETTERS ......................................................................................... 4-2
4-1-1 Warning Letter Procedures................................................................................. 4-2
4-1-2 Warning Letters To Government Agencies......................................................... 4-3
4-1-3 Issuing Warning Letters - Factors to Consider.................................................... 4-4
4-1-4 Center Concurrence And Letters Issued By Centers.......................................... 4-6
4-1-5 Letters For Illegal Promotional Activities........................................................... 4-11
4-1-6 Multiple Center Review..................................................................................... 4-12
4-1-7 Time Frames..................................................................................................... 4-12
4-1-8 Warning Letter Follow-Up ................................................................................. 4-13
4-1-9 Firm Profile Updates in FACTS......................................................................... 4-16
4-1-10 Warning Letter Format...................................................................................... 4-16
4-1-11 Warning Letter Distribution ............................................................................... 4-20
4-1-12 Warning and Untitled Letters Addressed to Importers, Custom Brokers,
and Foreign Firms............................................................................................................ 4-21
4-1-13 Freedom of Information (FOI)........................................................................... 4-22
4-1-14 Center For Biologics Evaluation And Research (CBER)................................... 4-23
4-1-15 Center For Drug Evaluation And Research (CDER)......................................... 4-25
4-1-16 Center For Devices And Radiological Health (CDRH) ...................................... 4-29
4-1-17 Center For Food Safety And Applied Nutrition (CFSAN) and Center for
Veterinary Medicine (CVM).............................................................................................. 4-31
4-1-18 Center for Tobacco Products (CTP) ................................................................. 4-31
4-1-19 Tracking................................................................................................................ 4-32
4-2 UNTITLED LETTERS....................................................................................... 4-33
4-2-1 Policy ................................................................................................................ 4-33
4-2-2 Center Concurrence and Letters Issued By Centers ........................................ 4-33
4-2-3 Tracking ............................................................................................................ 4-34
4-3 USE OF STATE EVIDENCE FOR FDA WARNING LETTERS AND
UNTITLED LETTERS.......................................................................................................... 4-34
4-4 EXHIBITS ......................................................................................................... 4-36Regulatory Procedures Manual – May 2012 Chapter 4 Advisory Actions
____________________________________________________________________
4-2
4-1 WARNING LETTERS
4-1-1 Warning Letter Procedures
When it is consistent with the public protection responsibilities of the agency and
depending on the nature of the violation, it is the Food and Drug Administration’s

FDA's Unapproved Drugs Initiative

In June 2006, the FDA announced a new drug safety initiative to remove unapproved drugs from the market, including a final guidance entitled "Marketed Unapproved Drugs—Compliance Policy Guide (CPG)," outlining its enforcement policies aimed at efficiently and rationally bringing all such drugs into the approval process. The FDA uses a risk-based enforcement program in order to concentrate its resources on those products that pose the highest threat to public health and without imposing undue burdens on consumers, or unnecessarily disrupting the market. For all unapproved drugs, the CPG gives highest enforcement priority to the following:

Drugs with potential safety risks
Drugs that lack evidence of effectiveness
Health fraud drugs
Drugs that present direct challenges to the new drug approval and OTC drug monograph systems
Unapproved new drugs that are also violative of the Act in other ways
Drugs that are reformulated to evade an FDA enforcement action

Summary of Compliance Policy Guide

The Marketed Unapproved Drugs—Compliance Policy Guide (CPG):

provides official notice that any illegally marketed product is subject to FDA enforcement at any time
clarifies that the FDA intends to use a risk-based approach to enforcement
- once the risk-based assessment has been made, the FDA can and will take any number of enforcement actions, including but not limited to:
  - requesting voluntary compliance
  - providing notice of action in a Federal register notice
  - issuing an untitled letter
  - issuing a warning letter, or
  - initiating a seizure, injunction, or other proceeding

What are unapproved drugs and why are they on the market?

From FDA website:

What are unapproved drugs and why are they on the market?

The original Federal Food and Drugs Act of 1906 brought drug regulation under federal law. That Act prohibited the sale of adulterated or misbranded drugs, but did not require that drugs be approved by FDA. In 1938, Congress required that new drugs be approved for safety. In 1962, Congress amended the 1938 law to require manufacturers to show that their drug products were effective, as well as safe. As a result, all drugs approved between 1938 and 1962 had to be reviewed again for effectiveness. To be consistent with current regulations and to ensure that all drugs have been shown to be safe and effective, all new drugs are required to have an approved application for continued marketing.

Many healthcare providers are unaware of the unapproved status of drugs and have continued to unknowingly prescribe them because the drugs’ labels do not disclose that they lack FDA approval. In addition, since many unapproved drugs are marketed without brand names and have been available for many years, it is often assumed that these unapproved drugs are generic drugs. This is not correct. Generic drugs have been evaluated and approved by FDA to demonstrate bioequivalence to a brand name reference drug. Healthcare professionals and consumers can be assured that FDA-approved generic drug products have met the same quality, strength, purity and stability as brand name drugs. Additionally, the generic manufacturing, packaging, and testing sites must meet the same quality standards as those of brand name drugs. Unapproved drug products have not been evaluated and approved by FDA. Unapproved drugs are not generic medications, and neither their safety nor their efficacy can be assured.

Show all related FDA Basics Questions

The FDA website also contain the following:

All the above can be found here.

Counterfeit Version of Avastin in U.S. Distribution

Statement Issued: Feb. 14, 2012

FDA sends letters to 19 medical practices about counterfeit product and other unapproved cancer medicines

The U.S. Food and Drug Administration (FDA) is warning health care professionals and patients about a counterfeit version of Avastin 400mg/16mL, which may have been purchased and used by some medical practices in the United States. Avastin is an injectable medicine used to treat cancer and is administered to patients in clinics, hospitals, and doctors’ offices. The counterfeit version of Avastin does not contain the medicine’s active ingredient, bevacizumab, which may have resulted in patients not receiving needed therapy.

In a related action, FDA has issued letters to 19 medical practices in the United States that purchased unapproved cancer medicines that may include the counterfeit Avastin. The counterfeit version is labeled as Avastin, manufactured by Roche. Roche is the company that manufactures Avastin approved for marketing outside of the United States.

Roche conducted laboratory tests that confirmed the counterfeit version of Avastin. Packages or vials may be counterfeit if they:

are labeled with Roche as the manufacturer
display batch numbers that start with B6010, B6011 or B86017

The only FDA-approved version of Avastin for use in the United States is marketed by Genentech (a member company of Roche). The FDA-approved version does not include the Roche logo on the packaging or vials. In addition, Genentech’s FDA-approved version of Avastin vials and packaging have a 6-digit numeric batch number and expiration dates in a 3-letter month and 4-digit year format (e.g., JAN 2014). Genentech’s Avastin products are safe and effective for their intended uses.

The 19 medical practices in the United States purchased unapproved cancer medicines and, potentially, the counterfeit Avastin, from Quality Specialty Products (QSP), a foreign supplier that may also be known as Montana Health Care Solutions. Volunteer Distribution in Gainesboro, Tennessee is a distributor of QSP’s products. FDA has requested that the medical practices stop using any remaining products from these suppliers. FDA cannot ensure the safety or efficacy of any of these unapproved products.

Letters to Doctors About Purchasing Unapproved Injectable Cancer Medications

Based on information to date, FDA has determined that none of the unapproved cancer medicines received by these medical practices from Volunteer Distribution are in shortage in the United States. FDA-approved versions of these medicines are available in adequate supply to meet current demand.

Medical practices that have obtained unapproved products from foreign sources, in particular from Volunteer Distribution and/or QSP, should stop using them and contact the FDA. These products should be retained and securely stored.

To report suspect counterfeit products and other suspect unapproved products obtained from Volunteer Distribution or QSP/Montana Health Care Solutions or other sources:

Call FDA’s Office of Criminal Investigations (OCI) at 800-551-3989, or
Visit OCI’s Web site (www.accessdata.fda.gov/scripts/email/oc/oci/contact.cfm), or
Email - DrugSupplyChainIntegrity@fda.hhs.gov

Health care professionals and consumers are asked to report adverse events related to the use of suspect injectable cancer medicines to the FDA’s MedWatch Safety Information and Adverse Event Reporting Program either online, by regular mail, by fax, or by phone. Health care profssionals and consumers can either:

Complete and submit the report online: www.fda.gov/MedWatch/report.htm, or
Download form or call 1-800-332-1088 to request a reporting form, then complete and return to the address on the pre-addressed form, or submit by fax to 1-800-FDA-0178.

FDA continues to evaluate this counterfeit medicine situation and we will provide updates.

For information about this counterfeit medicine, see Roche’s statement: http://www.gene.com/gene/news/press-releases/press_statements/ps_021412.html

For more information about counterfeit medicine: http://www.fda.gov/Drugs/ResourcesForYou/Consumers/BuyingUsingMedicineSafely/CounterfeitMedicine/default.htm.

Pictures of the counterfeit version of Avastin are shown below:

The Law of Compounding Medications And Drugs

Tuesday, June 26, 2012

FDA's Regulatory Procedures Manual Effective May 2012 Regarding Advisory Actions Such as Warning Letters