FDA News – Page 5 – by Liberty Management Group Ltd.

ANIMAL DRUGS

According to FD&C Act, the term “drug” means articles intended for use in diagnosis, cure, mitigation, treatment, or prevention of disease in man or other animals; and articles other than food intended to affect the structure or any function of the body of man or other animals which also includes articles intended for use a component of a drug.

As per FD&C Act “new animal drug” is a drug intended for use in animals which is not in GRASE (Generally Recognized as Safe and Effective) , in other words, if a drug is in GRASE list, then it is not a new animal drug under FDA&C Act.

Unapproved Animal Drugs are new animal drugs that cannot be marketed legally. FDA does not approve or index them. It is not legal to market unapproved new animal drugs as they didn’t gone through FDA pre-market review and got legal marketing status under FD&C Act. Unapproved animal drugs may not meet FDA’s standard for safety and effectiveness and also may not be properly manufactured or labeled.

There are three ways to get a Legal Marketing status of an animal drug.

Approval
Conditional Approval
Indexing

Approval: An approved animal drug has to go through NADA (New Animal Drug Application) process or for an ANADA (Abbreviated New Animal Drug Application) process for an approved generic animal drug. FDA approval means the drug is safe and effective when the drug is used as per the label and also it makes sure that the drug’s strength, quality are consistent for each production and the labeling is correct not misleading.

Conditional Approval: Conditional approval is only for drugs for major species with minor uses. FDA‘s Conditional approval means the drug is safe to use and has reasonable effectiveness when used as per the label instruction. This approval is valid only for one year. Drug companies can ask FDA to renew the approval for up to four more years. So during that 5 year period, companies can sell the drug legally and can also collect effectiveness data. After collecting the data, the company can submit the application to FDA for full approval.

Indexing: An indexed animal drug is a drug listed on the FDA’s Index of Legally Marketed Unapproved New Animal drugs for minor species which is unapproved by FDA but has legal marketing status. Indexing is allowed for drugs used on minor species such as pet birds, hamsters and ornamental fish which are non-food producing. Indexing is different from regular drug approval process. A panel of qualified experts outside FDA will review the drug’s safety and effectiveness in the specific minor species. If FDA agrees with the panel, it will add the drug to the Index.

All domestic and foreign establishments that manufacture, repack, or re-label animal drug products in the United States are required to register with the FDA and also list all of their drugs that are commercially. Also all the establishments that are registered with FDA are required to renew their registration between October 1^st and December 31^st every year to keep their registration active.

Liberty Management Group Ltd, a leading FDA consulting firm provides assistance with drug establishment registration, drug listing and US agent service to foreign establishments.

Sudha S

Regulatory Consultant

Mail: office@libertymanagement.us

http://www.fdahelp.us

MEDICAL DEVICES – WHO NEEDS TO REGISTER?

Establishments that are involved in the manufacturing and distribution of medical devices that are used in commercial distribution in the United States which includes import for export only devices are required to register with FDA annually.

As per 21 CFR Part 807, most establishments that are registered with FDA are also required to list the devices with FDA.

Below are the list of requirements for registration and listing depending on the type of activity conducted in the establishment.

Manufacturer: Establishments engaged in manufacture, preparation, propagation, compounding, and assembly or processing of a medical device intended for commercial market in the United States are required to register, list and pay FDA fees. This also includes the manufacturers of accessories that are packed or labeled for commercial distribution for health related issues to an end user, kit assemblers and also manufacturers of custom device and U.S establishment that manufactures for export only.

Contract Manufacturer: Manufactures a finished device as per other establishment’s specification are called as contract manufacturer. Since contract manufacturer meets the definition of finished device manufacturer they are also required to register, list and pay FDA fees.

Specification Developer: Specification developerare the ones who creates the specification for a device which are marketed under the establishment’s name but do not manufacture the device. In addition to that, they also arrange for the manufacturing of devices labeled with another establishment’s name by a contract manufacturer. Specification developers are required to register, list with FDA and pay the fees.

Contract Sterilizer: Establishments that provide sterilization service for another establishment’s device are required to register, list with FDA and pay the fees.

Re-processor of Single Use Device: Establishments that remanufacture single use device are required to register, list with FDA.

Re-packager or Re-labeler: Establishments that packages finished devices from bulk or re-package devices manufactured into different containers are required to register and list with FDA. Also establishments that changes the content of the labeling from the original manufacturer for distribution under establishment’s own name.

Remanufacturer: Any person or a firm who processes, refurbishes, conditions, repackages or does any other operation to a finished device that considerably changes the finished device’s performance are required to register, list with FDA.

Foreign Exporter: Establishments in a foreign country that exports finished device to United States for commercial distribution are also required to register and list their devices with FDA.

Initial Importer: Any establishment with a physical address in the United States which furthers the marketing of a medical device from a foreign manufacturer, who make the final delivery to the end user, but does not repackage or relabel or change the device package are required to register with FDA and also needs to identify the foreign manufacturer.

All companies that register with FDA are required to renew their registration and pay FDA fees for the following Fiscal year between Oct 1^st and Dec 31^st every year to keep their registration active.

Liberty Management Group Ltd, is a leading FDA consultant provides assistance with FDA registration, medical device listing and registration renewal and U.S agent service for foreign facilities.

Sudha S

Regulatory Consultant

Mail : office@libertymanagement.us

http://www.fdahelp.us

MEDICAL DEVICE REPORTING (MDR)

Every year FDA receives thousands of reports of deaths associated with medical devices, serious injuries and device faults. Medical Device Reporting (MDR) is one of the monitoring tool that FDA uses to check the device performance, to find device –related safety issues and contribute to risk and benefit assessment of medical devices.

Who needs to report?

Manufacturers: Manufacturers are required to report to FDA when they find any of their devices may have caused or contributed to a death or serious injury and device malfunction. They must also report if there is any death or serious injury if the malfunction were to recur.

Importers: Importers are required to report to FDA and the manufacturer as soon as they find out that one of their devices may have caused to contribute to a death or serious injury. However the importer must report only to the manufacturer if their imported devices have malfunctioned and would likely to cause death or serious injury if the malfunction were to recur.

Device User Facilities: A “device user facility” is a hospital, nursing home, ambulatory surgical facility, outpatient diagnostic or treatment facility (not a physician’s office). User facilities are required to report to both FDA and the manufacturer. If the manufacturer is unknown, user facilities are required to report only to FDA if there is any medical device related injury or death. User facilities are not required to report any device malfunction but can voluntarily report to FDA by using MedWatch through Electronic Medical Device Reporting (eMDR)

Voluntary Medical Device Reporting: FDA urges healthcare professionals, patients, caregivers and consumers to submit voluntary reports if there is any significant adverse events or device malfunction through MedWatch program.

Liberty Management Group Ltd, is a leading US FDA consulting group provides assistance with food, drug, medical device and cosmetic registration and US Agent service to foreign facilities.

Sudha S

Regulatory Consultant

Mail: office@libertymanagement.us

www.fdahelp.us

COMBINATION PRODUCTS

A combination product is a product consist of any combination of a drug and a device; a biological product and a device; a drug and a biological product; or a drug, device, and a biological product.

As per FDA 21 CFR 3.2, a combination product is defined as

A product consist of two or more elements for example, drug/device, biologic/device, drug/biologic or drug/device/biologic that are physically, chemically combined to form a single unit which is often referred as “single-entity” combination product. Some examples of single entity combination products are Syringes, insulin injector pen metered dose inhalers.
Two or more products packaged together in a single packet or as a package that has drug/device products, device/biologic products or biologic/drug products are often referred as “co-packaged” combination product. Examples of co-packages combination products are first aid kits containing devices(band aids and gauze) and drugs (antibiotic ointments and pain killers)
A drug/device/biological product packaged separately that as per the label it is intended for use only with an approved individually specified drug/device/biological product, where both are required to attain the intended use and upon the approval of proposed product, the labeling of the approved product needs to be changed are referred as “cross-labeled” combination product. Examples of cross-labeled combination product is Photosensitizing drug and activating laser/light source
Any investigational drug/device/biological products packaged separately and as per its proposed labeling it can be used only another individually specified investigational drug/device/biological product where both are required to have the same intended use which are referred as another type of “cross-labeled” combination product.

Section 503(g) (1) of FD&C act requires FDA to assign a component of the agency to primary jurisdiction for the regulation of combination product. The assignment of jurisdiction is based on the “primary mode of action” of the combination product. For example, if the primary mode of action of a combination product is a biological product, then it is assigned to FDA component which is responsible for the premarket review of that biological product.

Combination products are marketed under an authorization type connected with the constituent part that gives the primary mode of action (PMOA) for the combination product. For example, it should have NDA or ANDA if it has drug PMOA, a biologic license application (BLA) if it has a biologic PMOA or PMA (Pre-market approval) or 510K clearance if it has a device PMOA.

GMP requirements are applicable to all combination products that has drug/device/biologic constituent part.

Liberty Management Group, a leading FDA consulting firm in the United States will provide assistance with FDA registration of combination products.

Sudha S

Regulatory Consultant

Mail : office@libertymanagement.us

http://www.fdahelp.us

WHAT DOES FDA REGULATES

The Food and Drug Administration (FDA) is in charge for protecting public health by assuring the safety and efficacy of human and animal drugs and biologics, medical devices, tobacco products, human food and animal food for consumption, cosmetics, and electronic products that emit radiation. It also provides precise science based health information to the public.

FDA regulates the following which is a list of traditionally-recognized products that comes under FDA’s regulatory authority.

Foods, which includes

Dietary Supplements
Bottled water
Vegetable and fruit products
Food additives
Infant formulas
Other food products (some of the food products are regulated by USDA such as meat, poultry and egg products).

Drugs, which includes

Over the counter (OTC) drugs
Prescription drugs( Brand name and generic)

Medical devices, which includes

Simple items from bed board and cane
Dental devices
Surgical devices, implants and prosthetics
Complex medical devices such as intraocular lens and pacemakers.

Vaccines, Blood & Biologics, which includes

Allergenics
Blood and Blood products
Tissue and it products
cellular and gene therapy products

Radiation emitting products, which includes

Laser products
X-ray equipment
Ultrasonic therapy equipment
Mercury Vapor lamps
Sunlamps

Cosmetics, which includes

skin moisturizers and cleansers
Color additives found in makeup and personal care products
Nail polish and perfumes

Animal & Veterinary, which includes

Pet foods
Livestock feeds
Animal drugs and devices

Tobacco Products, which includes

Cigarattes
cigarette tobacco
roll-your-own tobacco
smokeless tobacco

Alcohol products are regulated by The Department of the Treasury’s Alcohol and Tobacco Tax and Trade Bureau (TTB) which monitors the production, importation, wholesale distribution, labeling and advertising.

Consumer Product Safety Commission(CPSC) ensure the safety of consumer goods such as children toys, power tools, cigarette lighters, household chemical products and products that cause a fire, electrical, chemical or mechanical hazard.

Meats, Poultry and certain egg products are regulated by US Department of Agriculture (USDA).

The Environmental Protection Agency (EPA) regulates many traits of pesticides which determines the amount of pesticide used during cultivation, processing and how much can remain on the food we buy. EPA also regulates drinking water, which develops the national standards of drinking water from municipal tap water to limit the level of impurities.

Liberty Management Group, a leading FDA consulting firm provides assistance with registration of food, drug, medical devices and cosmetic companies and also provides assistance with US agent service to foreign companies.

Sudha S

Regulatory Consultant

Mail: office@libertymanagement.us

www.fdahelp.us

SELF IDENTIFICATION – AN OVERVIEW

The Generic Drug User Fee Amendments of 2012 (GDUFA) requires that the manufacturers of human generic drugs, active pharmaceutical ingredients manufacturers (API) and the organizations which support the manufacture or approval of generic drugs to identify themselves electronically and update the information annually to FDA.

Self-identification is a vital requirement to help global supply chain transparency and provide assistance in building an accurate inventory of facilities and organizations involved in the manufacture of generic drugs and also simplifies inspections and compliance.

Who requires Self-Identification?

Facilities that manufacture human generic drug APIs or Finished dosage form of drugs (FDF) or both.
Packager and labeler of generic drugs.
Facilities identified in generic drug submission where the applicant remove the drug from a primary container and subdivide in to different primary containers.
Labs that are performing Bioequivalence (BE)/bioavailability (BA) tests.
Facilities identified in a generic drug submission where the testing is performed to check the characteristics of the FDF or the API pursuant to a contract with the applicant to satisfy a cGMP testing requirement

Who requires to pay the fees?

Facilities manufacturing, or intending to manufacture, API of human generic drugs and/or finished dosage form (FDF) human generic drugs.
Facilities that engage in generic drug packaging and labeling (FDA consider these as manufacturing facilities)

Who does not require to pay the fees?

Firms that engages in testing, repackaging or relabeling are not required to pay the fees.

Penalty for not submitting Self– Identification

Under GDUFA, all FDF or API products manufactured at the facility will be considered as misbranded.
Products manufactured in foreign facilities are considered misbranded and it is a violation of federal law to market misbranded products in interstate commerce or to import the products into the United States.

Drug manufacturers’ needs to submit their Self – Identification information to FDA through Electronic Submission Gateway (ESG) by creating Structured Product Labeling (SPL) files.

For FY 2019, the Self-Identification period starts from May 1^st 2019 to June 1^st 2019.

Liberty Management Group, a leading FDA consulting firm provides assistance with SPL preparation and submission of Self-Identification to FDA.

Sudhs S

Regulatory Consultant

Mail: office@libertymanagement.us

http://www.fdahelp.us

BASICS OF IMPORTATION – MEDICAL DEVICES

FDA regulates a range of products which includes food (human and animal consumption), medical products (drugs, devices and biological products), radiation-emitting electronic products, tobacco products and cosmetics. All imported shipments of FDA regulated products are evaluated by FDA and needs to comply with same regulations as of domestic products. The products that are offered into U.S including personal items must be declared to U.S. Customs and Border Protection (CBP). CBP will refers all FDA –regulated products to FDA for review. Mostly, importers will hire a custom broker to help them in submitting necessary entry documents and applicable payments to CBP on behalf of the importer. FDA regulated products are refused to enter in US commerce, if they appear to be adulterated, misbranded, or restricted for Sale. Refused products needs to be destroyed or exported from U.S within 90 days.

MEDICAL DEVICE IMPORTATION

Foreign medical device manufacturers are required to meet applicable US FDA medical device regulations in order to import devices into the U.S although the product is permitted for marketing in another country. The following are the requirements which FDA checks at the time of importation

Medical device establishment registration
Device listing
Medical Device Labeling
Premarket Notification(510K) or Premarket approval(PMA) if applicable
GMP Regulations
U.S Agent for foreign manufacturers.

The Initial importer of the device are required to register their establishment with FDA.

As per FDA, an initial importer is any importer who furthers the marketing of a device from a foreign manufacturer to the person who makes the final delivery or sale of the device to the ultimate consumer or user, but does not repackage, or otherwise change the container, wrapper, or labeling of the device or device package. FDA medical device establishment registration and listing can be found at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfRL/rl.cfm

Manufacturers, Initial importers and device user facilities are subject to Medical Device Reporting (MDR) regulation, where they have to report device-related adverse events and problems to FDA. Importers are required to maintain a MDR event file for each adverse event and also they have to forward all product complaints (MDR and non MDR events) to the manufacturer.

Medical devices that are imported into the United States must meet Custom Border Protection (CBP) requirements in addition to FDA regulations.

Liberty Management Group, a leading FDA consulting group in the United States provides assistance with medical device establishment registration, device listing, medical device label review and US agent service for foreign medical device establishment firms.

Sudha S

Regulatory Consultant

Mail: office@libertymanagement.us

http://www.fdahelp.us

BASICS OF IMPORTATION – DRUGS

DRUGS IMPORTATION

FDA will verify compliance with the following requirements at the time of importation.

FDA Drug Establishment Registration
Drug Listing
NDA or ANDA approval (If applicable)
Conducts field examination and analyzes samples of drugs products to make sure they comply with standard and label requirements.
FDA will make sure that the manufacturer is in not is the list of foreign manufacturers who are not in compliance with drug GMP or import alert.

FDA will verify the manufacturer’s registration and listing by comparing the submitted information to CDER’s registration and listing databases. If the information does not match, FDA will ask for additional information or may detain the product. If the product requires a NDA, ANDA or IND and if does not have it, then FDA will subject the product to refusal.

Foreign establishments whose drugs are imported into United States are required to register with FDA and submit their drug listing information of their products intended for marketing in U.S. If the manufacturer has not registered, they need to register with FDA within 5 days after submitting their application. Also all foreign manufacturers are required to identify a U.S. Agent. FDA Drug establishment Registration and drug listing must be submitted to FDA electronically via CDER unless waiver is granted.

Drug products imported into the United States are subject to FDA labeling requirements. FDA will review the drug labels at the time of importation to check whether they are in compliance with FDA regulations. Specific drug labeling requirements are determined by the type of drug product. OTC drugs, prescription drugs, and drugs imported for drug effectiveness studies are subject to specific labeling requirements in addition to the general drug label requirements.

Liberty Management Group , a leading FDA consulting group in the United States provides assistance with drug establishment registration, drug listing and label review and US agent service for foreign drug establishment firms.

Sudha S

Regulatory Consultant

Mail: office@libertymanagement.us

www.fdahelp.us

NATIONAL DRUG CODE (NDC) – AN OVERVIEW

According to the Drug listing act of 1972, all registered drug establishments must provide the current list of all drugs manufactured, processed, prepared, propagated, compounded or processed for commercial distribution in their facility to FDA. These drugs products are identified and reported by using a unique three segment number called National Drug Code (NDC), which serves as universal product identifier for human drugs.

NDC number is a unique 10-digit, 3–segment numeric identifier assigned to each drug listed under Section 510 of FD&C act. Each NDC number identifies the labeler, product and the trade package size of the drug.

The first segment of NDC is known as labeler code, which is a unique 5 digit number assigned by FDA to each establishment that manufactures (including contract manufacturers, re-packers or re-labelers) or distributes (under its own name- Private label distributor).
Second segment, which is the product code, identifies the specifications (strength, dosage form and formulation) of a drug for a particular manufacturer. This denotes that different formulations or different strengths of the same formulation should be assigned different product codes.
The third segment, the package code, classifies package sizes and types. The second and third segments of NDC should be assigned by the labeler. The NDC will be in one of the following configurations: 4-4-2, 5-3-2, or 5-4-1.

NDC Labeler code request to FDA should be submitted in SPL (structured Product Labeling) format via FDA ESG (electronic submission gateway). Labeler is responsible for each NDC directory entry submitted through SPL files. Entry in NDC directory doesn’t indicate that FDA approved or verified the information of the drug. Assignment of NDC number to non-drug products is strictly prohibited. Under FD&C act, registration of a drug establishment or assignment of NDC number does not denote that FDA’s approval of the company or its products.

Even though NDC number is a mandatory requirement, but it is not required to appear on all drug labels and including the label of any prescription drug carton given to a consumer. However, if the same drug product that are sold or used in the hospitals are required to put bar code on their products.

NDC Directory does not include animal drugs, blood products, API (Active Pharmaceutical Ingredients), drugs manufactured exclusively for a PLD, or drugs that are marketed as a part of a kit or combination product or inner cover of a multi-level packaged product not marketed separately.

Liberty Management Group Ltd, provides assistance with drugs establishment registration , NDC labeler code request, Drug Listing and US agent service to foreign facilities.

Sudha S

Regulatory Consultant

Mail: office@libertymanagement.us

http://www.fdahelp.us

ACTIVE PHARMACEUTICAL INGREDIENT (API)

According to FDA, an active pharmaceutical ingredient is defined as “any substance or mixture of substances intended to be used in the manufacture of a drug product and that, when used in the production of a drug, becomes an active ingredient in the drug product. Such substances are intended to furnish pharmacological activity or other direct effect in the diagnosis, cure, mitigation, treatment or prevention of disease or to affect the structure and function of the body.”

API is the part of a drug that creates its effectiveness. In some cases, for example in combination therapies there may be multiple active ingredients to treat different symptoms in various ways.

All drugs are manufactured with two main components one: the API which is the main ingredient and others are called inactive ingredients also known as excipients which helps to deliver the medication into the system. Inactive ingredients are components of a drug product that do not surge or affect the medicinal action of the active ingredients. Inactive ingredients are added during the manufacturing process of the pharmaceutical products. Even though inactive ingredients don’t have any therapeutic effects, they are important and necessary components for any medication which plays an important role in drug composition, absorption, delivery and much more.

Manufacturers are using certain standard to determine the potency of the API in each drug. However it varies from one manufacturer to another. But all the manufacturers are required to register their manufacturing establishment with FDA and prove the effectiveness of their drugs through clinical trials.

Under Section 510 of FD&C Act, all firms that manufacture or processing of human drugs are required to register with FDA. The “manufacture” includes the manufacture, prepare and propagation drugs, drug compounding or processing of a drug. The scope of drug manufacturing include drug analysis, active pharmaceutical ingredient (API), final dosage form (FDF), analytical testing, repackaging or relabeling of any drug.

All API manufacturers are required to register their establishment and list their drugs with FDA. API drug manufacturers needs to submit their registration to FDA through Electronic Submission Gateway (ESG) by creating Structured Product Labeling (SPL) files API manufacturer’s drug establishment registration can be verified at https://www.accessdata.fda.gov/scripts/cder/drls/getdrls.cfm and listing can be verified at https://www.accessdata.fda.gov/scripts/cder/ndc/index.cfm

Liberty Management Group Ltd, provides assistance with API drugs establishment registration , NDC labeler code request, Drug listings and US agent service to foreign facilities.

Sudha S

Regulatory Consultant

Mail: office@libertymanagement.us