FDA Issues 22 Warning Letters to Web site Operators

December 1, 2009

FDA’s Office of Criminal Investigations (OCI), in conjunction with the Center for Drug Evaluation and Research and the Office of Regulatory Affairs, Office of Enforcement, targeted 136 Web sites that appeared to be engaged in the illegal sale of unapproved or misbranded drugs to U.S. consumers.


None of the Web sites are for pharmacies in the United States or Canada.

What did the agency issued?

The agency issued 22 warning letters to the operators of these Web sites and notified Internet service providers and domain name registrars that the Web sites were selling products in violation of U.S. law.

Guidance: Patient-Reported Outcomes

September 15, 2009

Source:  http://www.fdanews.com/ext/files/06d-0044-gdl0001.pdf

This guidance describes how the FDA evaluates patient-reported outcome (PRO) instruments used as effectiveness endpoints in clinical trials.
It also describes our current thinking on how sponsors can develop and use study results measured by PRO instruments to support claims in approved product labeling.

PRO instruments provide a means for measuring treatment benefits by capturing concepts related to how a patient feels or functions with respect to his or her health or condition.

The concepts, events, behaviors, or feelings measured by PRO instruments can be either readily observed or verified (e.g., walking) or can be non-observable, known only to the patient and not easily verified (e.g., feeling depressed).

The (FDA) is proposing to amend its postmarket medical device reporting (MDRs) regulation

August 28, 2009

The Food and Drug Administration (FDA) is proposing to amend its postmarket medical device reporting regulation to require that manufacturers, importers, and user facilities submit mandatory reports of individual medical device adverse events, also known as medical device reports (MDRs) to the agency in an electronic format that FDA can process, review, and archive.

Benefit/ Advantage

  1. Mandatory electronic reporting would improve the agency’s process for collecting and analyzing postmarket medical device adverse event information.
  2. The proposed regulatory changes would provide the agency with a more efficient data entry process that would allow for timely access to medical device adverse event information and identification of emerging public health issues.

FDA is also announcing a draft guidance document that provides recommendations on how to prepare and submit electronic MDRs to FDA in a manner that satisfies the requirements of this proposed regulation.

Date to Submit:

November 19, 2009. Submit comments on information collection
issues under the Paperwork Reduction Act of 1995 (the PRA) by September 21, 2009.

Addresses to Submit:

You may submit comments, identified by Docket No. FDA–2008–N–
0393 and/or RIN number 0910–AF86, by any of the following methods

Electronic Submissions
Submit electronic comments in the following way:

• Federal eRulemaking Portal: http://www.regulations.gov. Follow the
instructions for submitting comments

Written Submissions

Submit written submissions in the following ways:
• FAX: 301–827–6870.
• Mail/Hand delivery/Courier (for paper, disk, or CD–ROM submissions):
Division of Dockets Management (HFA– 305), Food and Drug Administration,
5630 Fishers Lane, rm. 1061, Rockville, MD 20852


All submissions received must include the agency name and Docket No(s). and Regulatory Information Number (RIN) (if a RIN number has been assigned) for this rulemaking. All comments received may be posted without change to http:// http://www.regulations.gov, including any personal information provided.

Source: – http://edocket.access.gpo.gov/2009/pdf/E9-19683.pdf

Also I have found some webinars which are related to MDR medical device reports which can be helpful

  1. Complaint Handling, MDR’s & Recalls
  2. Medical Device Complaints, MDR’s and Recalls
  3. Development and Audit of Complaint Handling and MDR Processes

Source:- http://www.complianceonline.com

Tight Regulation Over Cigarettes: Got Approved

June 15, 2009

More than four decades after the surgeon general declared smoking a health hazard, the Senate on Thursday cleared the final hurdle to empowering federal officials to regulate cigarettes and other forms of tobacco for the first time.

The Congressional Budget Office has estimated the new law would reduce youth smoking by 11 percent and adult smoking by 2 percent over the next decade, in addition to reductions already achieved through other actions, like higher taxes and smoke-free indoor space laws.

Law gives power to FDA:

  • Law would give the F.D.A. power to set standards that could reduce nicotine content and regulate chemicals in cigarette smoke.
  • The law also bans most tobacco flavorings, which are considered a lure to first-time smokers.
  • The law would also tighten restrictions on the marketing and advertising of tobacco products.
  • Colorful ads and store displays will be replaced by black-and-white-only text.

Beginning next year, all outdoor advertising of tobacco within 1,000 feet of schools and playgrounds would be illegal.

What Cigarette Makers required to do:-

Cigarette makers will be required to stop using terms like “light” and “low tar” by next year and to place large, graphic health warnings on their packages by 2012.

Source: The New York Times

FDA revises ICH Q8 guidance

June 11, 2009

The FDA has revised its guidance on ICH Q8, adding an annex that clarifies the original document and adds the principles of quality by design (QbD).

The US Food and Drug Administration’s (FDA) guidance states that different drug delivery methods will have varying CQAs, such as adhesion properties for transdermal patches, but raw materials such as excipients and intermediates are common factors.

Using the framework devised by the International Conference on Harmonisation (ICH) the guidance details the importance of identifying CQAs and using knowledge of them to guide product and process development.

Source: in-pharmatechnologist

FDA issues final guidance on ICH Q10

April 9, 2009

The FDA has provided a model for implementing the ICH Q10 quality control system in its final guidance, which is intended help manufacturers adapt processes throughout a product’s lifecycle.

By building upon good manufacturing practices (GMP) the International Conference on Harmonization’s (ICH) Q10 attempts to provide a comprehensive model for an effective quality management system.

The implementation of aspects of ICH Q10 not covered by GMP is optional. However, by adopting the additional processes outlined in the US Food and Drug Administration’s (FDA) guidance manufacturers should benefit from the innovation and continual improvement that are central tenets of ICH Q10.

In addition unlike GMP ICH Q10 explicitly covers all aspects of a product’s lifecycle, from development through to discontinuation, and is designed to strengthen the link between pre- and post-commercialization manufacturing activities.

Within this framework the FDA identifies three main objectives: achieve product realisation, establish and maintain a state of control and facilitate continual improvement.

To achieve these goals the FDA recommends companies use knowledge and quality risk management, with the guidance detailing how these ICH Q10 “enablers” should be used.

The complete guidance can be found here .

Source: In-PharmaTechnologist.com

On the Road Again: FDA’s Mobile Laboratories

March 31, 2009

mobile_labs_011FDA’s mobile laboratories are part of the agency’s nationwide network of laboratories, where scientists are continually testing food and drugs for contaminants.The chemistry mobile lab is shown here on the road near its base of operations in Jefferson, Ark.

This modified 44-foot trailer is one of three units that make up FDA’s chemistry mobile laboratory.

This 34-foot command center, outfitted in a modified motor home, is part of FDA’s chemistry mobile laboratory. Two other units, the sample preparation unit and the analytical unit, complete the lab.

An FDA scientist, who doubles as a driver, loads cable covers into the chemistry mobile laboratory. The covers protect communication cables, water hoses, and other cabling necessary to run the lab equipment.

Source: FDA News

HHS/FDA Indian offices Opened

February 4, 2009

Two new HHS/FDA food and drug safety offices in Dehli and Mumbai, India are the latest outpost of the US regulators.

This is how it is going to impact

HHS/FDA will post 10 experienced officials in India to work closely with industries that ship food and medical products to the United States, to improve safety and quality, which will facilitate the smooth flow of trade.

Along with the Office Director, HHS/FDA will have four inspectors and five senior technical experts who will cover food, medical devices and medicines.

This is what HHS/FDA personnel will provide :

These HHS/FDA personnel will provide technical advice, conduct inspections of facilities that export to the United States, and work with Indian government agencies and the private sector to develop certification programs to allow the efficient flow of safe HHS/FDA-regulated goods between the United States and India.

India is the fourth-largest exporter of drugs and biologics to the US with bilateral trade growing from $13.5bn (€10bn) in 2001 to $32bn in 2006.

Various Training based companies like ComplianceOnline conducts series of seminars regularly in India on topics like:

  • Computer System Validation and Part 11 Compliance in Practice
  • Applying Lean Principles to Controlled Documents
  • Critical Cleaning Validation for Pharmaceuticals & Biotech Industry
  • 21 CFR Part 11 Compliance in Practice and Computer System Validation
  • How To Comply With FDA Quality Systems Regulations And Pass FDA Inspections
  • Understanding US trends in Pharmaceutical and Building a Successful CMO

Click here to find more about ComplianceOnline seminars/webinars.

Source: Embassy of United States ComplianceOnline

FDA officially opens its doors in China

December 2, 2008

The US Food and Drug Administration has opened offices in three Chinese cities – Beijing, Shanghai and Guangzhou – to help improve the safety of medicines and ingredients imported into the US.

The FDA’s main office will be in Beijing, with the Shanghai and Guangzhou locations serving as inspection stations. This is part of a major plan by the agency to expand its international presence, with additional branches due to open in Europe, Latin America and India before the end of the year.

The Beijing office was opened in a formal ceremony last week attended by US Secretary of Health and Human Services Michael Leavitt, FDA Commissioner Andrew von Eschenbach, and Shao Mingli, China’s deputy health minister and head of the State Food and Drug Administration (SFDA).

“We’re opening up a new era, not just new offices, ” Secretary Leavitt said.

By having a presence in other parts of the world, we can work more closely with manufacturers and other governments, better share best practices and further ensure that quality and safety are built into … products at the point of manufacture.

The opening of the new offices is timely, coming at the tail end of a series of scandals involving Chinese products in the US and other world markets, including contaminated medicines, foods, and personal care products such as toothpaste. China is also at the top of the list of countries for products which have had import permission to the US refused.

With a headcount of just eight, plus five Chinese nationals, the FDA’s presence in China is considered mainly advisory, providing advice on US quality standards and training local inspectors, although it will also maintain an inspection function.

The FDA has been under fire from US politicians in recent weeks, with questions raised about the agency’s oversight of the pharmaceutical supply chain in the wake of the heparin scandal, which saw product from around the world recalled after contaminated heparin sourced from China found its way into medicines, the ongoing probe into quality standards at India’s Ranbaxy and slew of food safety incidents.

One of the persistent criticisms is that the agency should do more inspections of overseas plants. The FDA carried out 13 visits to Chinese production facilities, out of more than 700 sites in 2007. That compared with 24 to France, which has 162 drug manufacturing plants.

Source:Outsourcing Pharma

US bans import of 30 generic drugs of Ranbaxy

September 17, 2008

The Food and Drug Administration (FDA) today issued two Warning Letters to Ranbaxy Laboratories Ltd., of the Republic of India, and an Import Alert for generic drugs produced by Ranbaxy’s Dewas and Paonta Sahib plants in India.

The Warning Letters identify the agency’s concerns about deviations from U.S. current Good Manufacturing Practice (cGMP) requirements at Ranbaxy’s manufacturing facilities in Dewas and Paonta Sahib (including the Batamandi unit), in India. Because of the extent and nature of the violations, FDA today issued an Import Alert, under which U.S. officials may detain at the U.S. border, any active pharmaceutical ingredients (API) (the primary therapeutic component of a finished drug product) and both sterile and non-sterile finished drug products manufactured at these Ranbaxy facilities and offered for import into the United States.

The problems at these two Ranbaxy plants relate to deficiencies in the company’s drug manufacturing process. These actions are proactive measures that the FDA is taking in order to assure that all drugs that reach the American public are manufactured according to cGMP requirements. While this action does not involve removing products from the market, FDA has no evidence to date that Ranbaxy has shipped defective products. We will continue to monitor the situation.

Today’s announcement does not impact products from Ranbaxy’s otherplants which are not affected by today’s actions. FDA has inspected those facilities and, to date, they have met U.S. cGMP requirements for drug manufacturing.

The FDA recommends that consumers continue taking their medications manufactured by Ranbaxyand not disrupt their drug therapy, which could jeopardize their health. Patients who are concerned about their medications should discuss their concerns with their health care professional.

Earlier today, the FDA informed Ranbaxy that until it resolves the deficiencies at each of these two facilities and the plants come into compliance with U.S. cGMP requirements, FDA’s drug compliance office will recommend denial of approval of any New Drug Applications (NDAs) and Abbreviated New Drug Applications (ANDAs) that list the Paonta Sahib or Dewas plants respectively as the manufacturer of APIs or finished drug products

Ranbaxy is one of the largest foreign suppliers of generic drugs to the United States. The company makes a number of drug products.

The FDA Import Alert covers more than 30 different generic drug products (Drug List) produced in multiple dosage forms and dosage amounts ( i.e., 25 mg, 50 mg, and 100 mg) at these two locations.FDA has evaluated whether these actions would create any potential drug shortages in the United States, and has determined that other suppliers can meet market demand, with one exception. Because Ranbaxy is the sole supplier to the U.S. of one drug product, Ganciclovir oral capsules (an antiviral drug), to avoid creating a shortage of the drug, FDA generally will not detain shipments of this product, and plans to arrange for additional oversight and controls until the company resolves these manufacturing issues.

“With this action we are sending a clear signal that drug products intended for use by American consumers must meet our standards of safety and quality,” said Janet Woodcock, M.D., director, FDA’s Center for Drug Evaluation and Research (CDER). “The FDA has notified other agencies and health care professionals to make them aware of today’s actions so that they can take appropriate action and advise patients as needed.” The Warning Letters issued today document the results of FDA investigations at these two sites.

One Warning Letter addressed problems at Ranbaxy’s Dewas facility found during an inspection conducted by FDA in early 2008. During that inspection, FDA investigators documented significant cGMP deviations in the manufacture of sterile and non-sterile finished products and violations with respect to the manufacture and control of APIs. Specific areas of concern included the following aspects of the firm’s quality control program:

  • The facility’s beta-lactam containment program (measures taken to control cross-contamination), which appeared inadequate to prevent the potential for cross-contamination of pharmaceuticals;
  • Inadequate batch production and control records;
  • Inadequate failure investigations; (A failure investigation is done to address any manufacturing control or product rejection to determine the root cause and prevent recurrence); and,
  • Inadequate aseptic (sterile) processing operations.

The second Warning Letter addressed the Paonta Sahib facility following an inspection at its Batamandi unit, also in early 2008.This inspection documented various cGMP deficiencies, including the following:

  • The lack of assurance responsible individuals were present to determine the firm was taking necessary steps under cGMP;
  • Inaccurate written records of the cleaning and use of major equipment;
  • Incomplete batch production and control records; and,
  • Inadequate procedures for the review and approval of production and control records for drug products.

Following the two inspections, FDA provided Ranbaxy with a separate list of inspectional findings for each of the facilities. In mid-April and May, Ranbaxy responded in writing to these findings in lengthy submissions to FDA. The agency then evaluated its findings, Ranbaxy’s responses, and the firm’s overall inspectional history, an evaluation that required substantial time due to the complex scientific and technical nature of both the identified deficiencies, particularly at the Dewas site, and the firm’s responses. Ultimately, FDA concluded that the firm’s responses were not adequate and that the Warning Letters were the appropriate regulatory response.

“Today’s actions are clearly warranted by the serious violations established by FDA’s investigations at these two sites,” said Deborah M. Autor, director, CDER’s Office of Compliance, FDA. “Until the company addresses these deficiencies, APIs and finished drug products from these plants will remain on the Import Alert, and we will not approve any Abbreviated New Drug Applications or New Drug Applications that list either of the two facilities as the manufacturer of APIs or finished drug products.”

This represents the second time in less than three years FDA has issued a Warning Letter to Ranbaxy. In 2006, FDA cited Ranbaxy for violations of U.S. cGMP at its Paonta Sahib facility.

The FDA will continue to work with Ranbaxy’s Dewas and Paonta Sahib plants to resolve these issues.
Consumers and health-care professionals can report adverse events to FDA’s MedWatch program at 1-800-FDA-1088; by mail at MedWatch, HF-2, FDA, 5600 Fishers Lane, Rockville, MD 20852-9787; or online, at the following Internet address: www.fda.gov/medwatch/report.htm

Source: FDA News