Showing posts with label FOREIGN-MANUFACTURED DRUGS. Show all posts
Showing posts with label FOREIGN-MANUFACTURED DRUGS. Show all posts

Saturday, December 22, 2012

FDA Warns Against Unapproved Drugs From Foreign Suppliers

Dec 21, 2012

More than 350 medical practices in the United States may have received unapproved medications, including unapproved versions of Botox, from a foreign supplier, the US Food and Drug Administration (FDA) warned on its Web site this week.
"These medications may be counterfeit, contaminated, improperly stored and transported, ineffective, and/or unsafe. Medical practices that purchase and administer illegal and unapproved medications from foreign sources are placing patients at risk and potentially depriving them of proper treatment," the agency said.
The FDA has sent a letter to the physicians or medical practices involved informing them of the situation.
A list of the doctors and clinics that received the letter is available here.
Products Not FDA Approved
To reduce the chance of patients receiving an unapproved, counterfeit, unsafe, or ineffective medication, the FDA is asking that medical practices stop administering the unapproved versions of Botox and any other products they have received from foreign suppliers owned and operated by Canada Drugs and known under the following names: Quality Specialty Products (QSP), A+ Health Supplies, QP Medical, Bridgewater Medical, or Clinical Care.
"Many, if not all, of the products sold and distributed by these suppliers have not been approved by FDA. Therefore, FDA cannot confirm that the manufacture and handling of these products follow U.S. regulations or that these medications are safe and effective for their intended uses," the FDA said. Medications not approved by the FDA may also lack the necessary and required labels that ensure their appropriate and safe use, the agency reminds clinicians.
So far in 2012, the FDA has issued letters to medical practices in the United States that purchased unapproved medications from foreign suppliers 5 times: on February 10, April 5, April 23, June 28, and September 10.
The FDA is asking healthcare providers to examine their purchasing practices to ensure that products are purchased directly from the manufacturer or from state-licensed wholesale drug distributors in the United States.
"Health care professionals, pharmacies, and wholesalers/distributors are valuable partners in efforts to protect consumers from the risks of unsafe or ineffective products that may be stolen, counterfeit, contaminated, or improperly stored and transported. The receipt of suspicious or unsolicited offers from unknown suppliers should be questioned, and extra caution should be taken when considering them," the FDA said.
Healthcare providers are asked to report suspected criminal activity to FDA's Office of Criminal Investigations (OCI) by calling 1-800-551-3989 or visiting the OCI Web site.
The FDA has provided information on its Web site on how to verify that a wholesale drug distributor is licensed in the state(s) where it is conducting business.
Adverse events related to the use of suspect medications may be reported to MedWatch, the FDA's safety information and adverse event reporting program, either online at https://www.accessdata.fda.gov/scripts/medwatch/medwatch-online.htm by telephone at 1-800-FDA-1088, by fax at 1-800-FDA-0178, or with postage-paid FDA form 3500, available at http://www.fda.gov/MedWatch/getforms.htm to MedWatch, 5600 Fishers Lane, Rockville, Maryland 20852-9787.
Source found here

Tuesday, August 14, 2012

FDA REGULATION OF FOREIGN-MANUFACTURED DRUGS and US Customs Role



Although the testimony below was given before Congress in 2007, it has been updated in 2011 and is very helpful in understanding the FDA's foreign drug inspection program.

The statement is found here.
Statement by
Andrew von Eschenbach M.D.
COMMISSIONER OF FOOD AND DRUGS
FOOD AND DRUG ADMINISTRATION
on
FDA's Foreign Drug Inspection Program
before
Committee on Energy and Commerce
Subcommittee on Oversight and Investigations
U.S. House of Representatives

Thursday November 1, 2007
INTRODUCTION
Mr. Chairman and Members of the Subcommittee, I am Andrew C. von Eschenbach, M.D., Commissioner of Food and Drugs at the United States Food and Drug Administration (FDA or the Agency). I am pleased to be joined here today by my Agency colleagues, Ms. Margaret Glavin, Associate Commissioner for Regulatory Affairs, and Ms. Deborah Autor, Director, Center for Drug Evaluation and Research (CDER) Office of Compliance. Thank you for the opportunity to discuss the important issues relating to FDA’s foreign drug inspection program.
FDA-regulated products include human and animal drugs, vaccines and other biological products, food and animal feed, cosmetics, and medical devices. FDA’s regulation of these products is considered the “gold-standard” around the world and our goal is not only to maintain that standard but to continuously strive for improvement. Yet, in keeping this commitment to the American consumer, we do face significant challenges. We recognize that the world is evolving and our local markets now provide products largely from a global marketplace.
FDA is keenly aware that we must systematically assess these global market issues as they relate to drug products and other FDA-regulated products manufactured overseas. Therefore, we are developing comprehensive solutions to face these global challenges.
FDA REGULATION OF FOREIGN-MANUFACTURED DRUGS
FDA’s monitoring of foreign-manufactured drugs is based on far more than foreign inspections. To comply with the Food, Drug, and Cosmetic (FD&C) Act, any entity that intends to import drugs into the U.S. must ensure that the drug meets a number of quality and labeling requirements.
In the FD&C Act, Congress enacted provisions to create a relatively “closed” distribution system for imported drug products to help ensure the domestic supply is safe and effective by limiting the drugs and biologics that may be imported into the U.S. All “new drugs,” which includes all finished prescription drug products, must be approved by FDA as safe and effective for their intended use. FDA approvals are manufacturer-specific and product-specific, and include many requirements related to the product, such as manufacturing location, formulation, source and specifications of active ingredients, manufacturing controls, the container/closure system, and labeling. Facilities that manufacture drugs for the U.S. market must meet FDA’s current good manufacturing practice (cGMP) requirements.
When an FDA-regulated drug product is offered for import into the U.S., U.S. Customs and Border Protection (CBP) notifies FDA. If the product appears to violate the FD&C Act, FDA will give notice advising its owner or consignee of the violation and the right to provide testimony demonstrating why the article at issue is not violative or to request permission to recondition the product. If the product is ultimately refused admission, it must be destroyed unless exported by the owner or consignee within 90 days from the date of refusal.
FDA performs 100 percent screening of active pharmaceutical ingredients (API) and drug products entering into the U.S. to establish whether, if required, FDA has approved the drug product or the API is consigned to a plant that corresponds with its designated approval in the drug product application. Also, FDA screens whether the manufacturing plant is registered and the drug is listed. FDA performs surveillance examinations of imported goods to check for compliance with U.S. requirements.
Another key tool is the Import Alert, which signals FDA field personnel to pay special attention to a particular product, manufacturer, shipper and/or importer. FDA issues Import Alerts for Detention Without Physical Exam (DWPE) when we have information that would cause future shipments of a product offered for entry to appear violative within the meaning of section 801 of the FD&C Act. This allows FDA field personnel to detain the product without physical examination, based on the appearance of a violation as documented in the Import Alert. Once FDA detains a product under 801(a) the burden shifts to the importer to demonstrate why, in fact, its product complies with U.S. law. In addition, FDA personnel also perform periodic filer evaluations to ensure import data provided to the Agency are accurate.
U.S. manufacturers also have a responsibility to ensure the safety of foreign-manufactured ingredients used for their finished dosages. U.S. manufacturers of finished dosage drugs that import APIs from abroad are to examine and test ingredients before using them in their drug products under cGMP. FDA may inspect a firm’s foreign facilities and/or their domestic facilities to determine if the manufacturing facility meets the Agency’s quality standards. In addition, FDA inspections routinely evaluate manufacturers’ testing and controls of ingredients and supplies. FDA inspects all API manufacturers for compliance with cGMP prior to the approval of the dosage form’s new drug application (NDA), abbreviated new drug application (ANDA), or biological license application (BLA). If during a domestic or foreign inspection, FDA determines that an imported API fails to meet specifications or is manufactured using unsafe practices, an import bulletin can be used to trigger testing of future shipments, or the drug can be subject to automatic detention at the U.S. border.
Foreign Inspections
FDA performs over 200 foreign drug manufacturing inspections per year. Exercising FDA’s regulatory authority abroad can be challenging. In some countries, we need authorization from the relevant government to enter and inspect facilities and other countries have travel alerts that require FDA to take special precautions to ensure the safety of our investigators. Many of these firms are motivated to have FDA inspect their facilities because they have an application pending with the Agency that may require a pre-approval inspection.
Foreign inspections are more costly because of travel costs and special needs associated with travel in a foreign country. Foreign drug inspections are typically scheduled for five days. Depending on the product involved, we have scheduled inspections for as short a period as three days for a control testing laboratory, and up to two weeks for a sterile product.
There are approximately 800 FDA investigators trained to conduct foreign inspections in all program areas and 335 specifically for the drug program area. Also, CDER supports these inspections with additional technical experts and trained investigators. FDA typically solicits for volunteers from this specially trained cadre of investigators. The inspections are often conducted by one investigator who will conduct three, five-day inspections consecutively.
FDA foreign investigators are highly experienced and well-equipped. They often have many years of domestic experience and are dedicated to working long hours to accomplish an inspection in the allotted time. Some investigators speak foreign languages. FDA also relies on assistance from the firms’ U.S. agents and representatives to translate if needed and help with logistical challenges that arise in traveling to a foreign firm. The investigators travel on official U.S. government passports requiring FDA to notify the U.S. Department of State and relevant embassies. We are planning to strengthen our collaboration with embassy staff to assure our investigators are well prepared for local conditions.
Drug Ingredient Safety
Foreign activity in drug counterfeiting and contamination is an on-going concern for the U.S. and other nations. Ten years ago, counterfeit glycerin contaminated with diethylene glycol (DEG) killed nearly 100 children in Haiti. Last year in Panama, glycerin contaminated with DEG, traced to China, again caused scores of deaths. Recently, toothpaste imported from China was also found to contain DEG. To minimize the potential of DEG contamination of ingredients in the U.S., the Agency immediately issued guidance alerting drug manufacturers to perform testing for DEG contamination on all shipments of glycerin used in the formulation of drugs. FDA’s CDER formed a task force, which developed a series of action items aimed at pro-actively addressing our susceptibility to similar pharmaceutical ingredient contamination and misbranding incidents.
As more pharmaceutical ingredients are sourced from abroad, an increased number of foreign intermediaries become involved in the supply chain. Discussions with the International Pharmaceutical Excipient Council (IPEC-Americas), a trade organization comprised of drug manufacturers and excipient manufacturers and distributors, has echoed our concerns and findings regarding the complexity of global supply chains and the lack of traceability of excipients to their original manufacturers. Pharmaceutical manufacturers can reduce the associated risks by obtaining intelligence about the distribution chains for each imported ingredient by establishing more robust systems and procedures to qualify suppliers of pharmaceutical ingredients and assure the identity and purity of batches of incoming ingredients.
IMPROVING THE OVERSIGHT OF FOREIGN MANUFACTURED DRUGS
Information Technology (IT) Enhancements
Since taking the position as FDA Commissioner, upgrading FDA’s IT systems has been one of my top priorities. We expect these improvements will help address the challenges we face in the area of foreign inspections. Logistically, foreign firms are more difficult to track and more challenging to inspect than domestic firms. The data we have regarding foreign firms is not easy to confirm or check for accuracy because we cannot easily gain access to the firms. Foreign firms must register with FDA before shipping to the U.S. Because there is no cost to register, some firms register, but do not actually produce a product or ship products to the U.S, or discontinue shipping without any notice to FDA. The practice of registering without producing or shipping can create uncertainty at any given moment about the precise number of FDA registered firms from which to target inspections, often necessitating secondary data-source checking.
FDA does have the ability to capture the importation of drug products and the manufacturer of those products through its Operational and Administrative System for Import Support (OASIS) system. The information provided by the importer often leads to duplicate entries of manufacturers due to name, configuration, and address changes or does not accurately identify the site-specific manufacturer of the product.
We are working on more effective and efficient solutions to ensure the accuracy and validity of the data in our registration and import IT system. FDA has set up the Bio-informatics Board (BiB) to address this issue for FDA. The Product Quality subgroup focuses on the issue of establishing accurate information on firms and their products. We are actively seeking other means to identify duplicate entries, such as those caused by variations of the same name and address (e.g. use of third-party validation of non-confidential business information). Additionally, the Agency’s current initiative to implement electronic registration of firms holds promise to redirect our resources from data entry, enabling us to focus instead on quality assurance of the data bases. In addition, the BiB directs the work and approves recommendations set forth by the Business Review Boards (BRBs). BRBs define business processes, driving outcomes enabled by IT services.
The Office of the Chief Information Officer is leading enterprise-wide IT transformation initiatives and establishing an aggressive two-year plan to rebuild FDA’s critical IT infrastructure. Several key projects are underway that will sustain the transformation.
  • FDA’s Decision Support System will be enhanced to boost performance and expand the ability to rapidly access information critical to managing FDA’s foreign drug inspection program. OASIS and FACTS will be migrated into 21st century database and hardware platforms to enhance critical functionality (target date: February 2008).
  • FDA is implementing upgrades to the Agency’s IT systems to increase efficiency of import entry review by allowing users to access multiple databases across the Agency under a single sign-on capability. Included systems are DRLS, Document Archiving, Reporting and Regulatory Tracking System, Mission Accomplishments and Regulatory Compliance Service (MARCS), OASIS and FACTS.
  • FDA is developing and implementing a firm management and tracking system called Firm Management Services (FMS) that will allow users to input and search for firms in multiple repositories, improving the quality of data received by FDA and enabling the Agency to better screen imported products and identify firms shipping to the U.S. FMS will replace older, less effective technology used by FACTS/OASIS and older components of MARCS’s applications.
  • FDA is also developing a Firm Finder application to allow users to search firms in multiple repositories from one access point. Identifying and retrieving information about these firms is a key step in the evaluation of imports. Firm finder will use web services to integrate with legacy (FACTS/OASIS) and MARCS’s applications.
  • FDA is re-engineering MARCS, a major FDA IT program, to integrate and enhance several FDA systems, including OASIS and FACTS, by collecting and processing information obtained by or needed to support FDA field operations.
  • FDA is working on FDA’s Unified Registration and Listing System (FURLS) to integrate Center for Food Safety and Applied Nutrition, Center for Devices and Radiological Health, CDER, Center for Biologics Evaluation and Research, Center for Veterinary Medicine, registration and listing systems.
  • FDA has initiated software development of the Electronic Broker Information Center, a universal data interface application for filers, importers, or consignees to use a secure communication means to submit documents in support of entry review processes, location and availability data, view import entry and FDA line statuses, Notices of FDA Action, and perform firm and product data queries.
  • FDA is working with CBP to ensure its planned Automated Commercial Environment (ACE) upgrade, a component of the International Trade Data System (ITDS), will provide real-time data feeds, ensuring that FDA receives all needed data elements electronically while harmonizing and validating information across centers.
  • FDA is also engaging in ongoing cleanup of internal data to ensure rapid access to information in support of FDA import safety operations and upgrade of internal systems to synchronize and validate data across centers.
  • FDA is developing and testing a system, which will utilize artificial intelligence in conjunction with analytical and inspectional data (foreign and domestic), and multiple data sources to identify products and shipments posing the greatest safety risks. The system is currently being evaluated for seafood products entering in the Port of
  • Los Angeles and if successful will be expanded to other commodities.
  • FDA is developing an Import Portal to allow Customs Brokers to more quickly exchange information with Import Reviewers about shipments/entries submitted for FDA review. The target for completion of development of this Import Portal is late FY 2009.
  • FDA is making substantial improvements in its IT infrastructure critical to ensuring the exchange of data between its field offices and Headquarters, including CBP as it monitors products entering the U.S. FDA completed the network circuit upgrade in early 2007. The router, server, and Laboratory Storage Area Network (LABSAN) upgrade, installation, and operation lease agreement is in place and will be executed through October 2008. LABSAN is an infrastructure built to manage data and provide effective quality assurance to maintain data credibility and centralized data storage. LABSAN ultimately reduces time spent accessing and analyzing drug import data.
  • FDA’s Program Quality System is an Agency-wide initiative that encompasses an electronic mechanism for manufacturers’ registration and product listings, as well as capturing inspection data from compliance reviews. FDA’s Product Quality Business Review Board has completed the second phase of a three-phase project to harmonize the processes for tracking regulated establishments and their products. Initial planning for this initiative should be completed by the end of December 2007.
International Efforts
FDA has a variety of cooperative relationships with foreign regulators, ranging from cooperation under a Free Trade Agreement, to agency-to-agency Memorandums of Understanding (MOUs), to informal arrangements established by exchanges of letters. A list of FDA’s commitments appears on FDA’s Office of International Programs, International Arrangements, web page (http://www.fda.gov/oia/default.htm).
FDA exchanges inspectional information with many foreign partners. Our relationships with some of these partners have become quite sophisticated and intense, developing to the point where we are communicating with them on a daily, and sometimes hourly, basis. FDA is currently engaged in the formal assessment of the efficacy of one foreign regulatory agency for more systematic use. Under the MOU between FDA and Swissmedic, the Swiss Agency for Therapeutic Products, technical experts have cooperated for three years on inspection collaboration with a desired endpoint of utilizing each other’s inspection reports in making regulatory decisions. Both sides, however, would retain the authority to inspect manufacturers in the other country at any time.
FDA is also in the process of joining the Pharmaceutical Inspection Co-operation Scheme (PIC/S). PIC/S fosters cooperation among pharmaceutical inspection authorities in pharmaceutical good manufacturing practices (GMP), as well as developing and promoting harmonized GMP standards and guidance documents, training competent authorities (in particular inspectors), and assessing and re-assessing inspection authorities. FDA submitted a formal application to join PIC/S in September 2005. Upon acceptance, it will enable the exchange of inspection reports and other inspection information with regulatory authorities. The PIC/S application process typically takes two years or more.
Another development on this front has been the establishment this year of the European Union (E.U.)-U.S. Bilateral Technical Working Group on Medicines Quality and Manufacturing. This group will have a major focus on utilizing shared resources through information exchange of inspectional data for plants in the U.S. and E.U. Another important planned activity of this group will be to share inspectional information from companies located in countries.
To promote and enhance the safety of all imported products, the President issued an Executive Order on July 18, 2007, that established the Interagency Working Group on Import Safety (Working Group). The Working Group, which includes representatives from 12 Federal departments and agencies, is tasked with reviewing the procedures, regulations, and practices for ensuring imported drugs, food, and other consumer products are safe. Secretary of Health and Human Services (HHS), Michael O. Leavitt, chairs the Working Group and FDA plays a key role. Secretary Leavitt and I traveled extensively throughout the country during the past few months visiting ports of entry and reviewing FDA field operations.