Category: fda registration drug

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.

  1. Approval
  2. Conditional Approval
  3. 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 1st and December 31st 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

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?

  1. Facilities that manufacture human generic drug APIs or Finished dosage form of drugs (FDF) or both.
  2. Packager and labeler of generic drugs.
  3. Facilities identified in generic drug submission where the applicant remove the drug from a primary container and subdivide in to different primary containers.
  4. Labs that are performing Bioequivalence (BE)/bioavailability (BA) tests.
  5. 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?

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

Who does not require to pay the fees?

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

Penalty for not submitting Self– Identification

  1. Under GDUFA, all FDF or API products manufactured at the facility will be considered as misbranded. 
  2. 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 1st 2019 to June 1st 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 – DRUGS

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.

DRUGS IMPORTATION

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

  1. FDA Drug Establishment Registration
  2. Drug Listing
  3. NDA or ANDA approval (If applicable)
  4. Conducts field examination and analyzes samples of drugs products to make sure they comply with standard and label requirements.
  5. 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

www.fdahelp.us

GENERIC DRUGS – AN OVERVIEW

A generic drug is a medicine created to be the equivalent to an already marketed brand-name drug in dosage form, safety, strength, route of administration, feature, physical characteristics, and intended use. The similarities between generic drug and brand-name medicine helps to demonstrate bio-equivalence, which shows  that a generic medicine works in the same way and gives the same clinical benefit as its brand-name type. In other words, generic medicine can be taken as an equal substitute for its brand-name equivalent.  FDA Generic Drugs program conduct inspections of manufacturing plants every year and monitor the drug safety after it has been approved and marketed.

Even though generic drugs and brand-name drugs share the same active ingredients, safety, strength, efficiency and the intended use, the trademark laws in the United States do not allow them to have the same look exactly like other drugs which is already on the market.

Cost difference between Generic medicine and Brand-name medicine

Companies that develop new drugs, like other new products are protected by patents that restrict other companies from manufacturing and marketing the same drug. The patent protects the company’s investment in developing the drugs by giving the sole right to market the drug till the patent is in effect.  FDA allows certain period of marketing exclusively the brand-name medicine till the patents and marketing exclusive rights expire. After that, it approves the generic version of the same drug.  Generic drugs cost less than their brand-name equivalent because they do not need to repeat animal and clinical studies that were required for brand-name drugs to demonstrate its safety and efficiency.  This is also known as “abbreviated new drug application.” The competition between the brand-name drug and multiple generic drugs is the main reason for low-cost generic drug.

Demonstration of ANDA

ANDA must demonstrate the generic medicine is equivalent to its brand-name counter part by the following ways.

  • Contain the same active ingredients as the brand-name drug. Active ingredients make the drug effective against the disease or condition it is treating. Inactive ingredients may vary.
  • Be identical in strength, dosage form and route of administration. If the brand-name drug is a capsule and is taken orally, so is the generic.
  • Treat the same medical condition.
  • Be absorbed into the bloodstream at a similar rate and over the same period of time.
  • Meet the same requirements for identity, strength, purity and quality.
  • Be manufactured under the same strict standards that FDA demands of brand-name drugs.

FDA will make sure that the medicines both generics and brand- name sold in the United States are safe and effective by conducting testing in its laboratories or through research contract and grants.  Also FDA encourages physicians and consumers to notify FDA of any adverse side effects when using the drugs and medical devices which FDA regulates by reporting them at MedWatch.

Liberty Management Group , a leading FDA consulting firm in the United States provides assistance with drug establishment registration, drug listing and label review.

Sudha S

Regulatory Consutltant

Mail : office@libertymanagement.us

http://www.fdahelp.us

CERTIFICATE TO FOREIGN GOVERNMENT (CFG)

Certificate to Foreign Government (CFG) is document prepared by FDA issued for legally marketed devices in the U.S that are in compliance with the regulations of FD&C act.

Medical devices that are legally marketed in the United States can be exported to anywhere in the world without getting approval from FDA.  Although FDA does not restrict the export of legally marketed, certain importing countries require a certification from FDA stating that the firm, or its devices are in compliance with U.S. FDA regulations. Foreign government will ask for official assurance that the products exported to their countries are in compliance with US FDA regulations such Good manufacturing Practice (GMP) requirements. In that cases, U.S companies can request a certificate to foreign government (CFG) also known as Certificate of Free sale to FDA.

The certificate to foreign government (CFG) is a self-certification process. By completing the required form, a firm confirms that it is registered with FDA and listed their device with FDA, that each product is legally marketed in the U.S. and is not the subject of an open recall, that all facilities involved in the manufacturing process are complying with the FDA’s regulations, and that each product is being exported from the U.S.

Requirements to get the Certificate to Foreign Government (CFG)

  1. The manufacturing facility must have a valid medical device establishment registration
  2. All devices must be listed with FDA
  3. The devices must have cleared Premarket notification (510K) or Premarket Approval (PMA) unless it is exempted by the regulation.
  4. The device should meet all the medical device labelling requirements as of 21 CFR 801 and 809.
  5. The device should be manufactured in accordance with 21CFR 820 also known as Good Manufacturing practice unless it is exempted by the regulation.

Certificate to Foreign government can be requested through CECATS system.  It is a voluntary electronic system that allows the manufacturers and initial importers to request export documents online. CECATS can be accessed by logging into FDA Furls account.

The fees for export certificate from CDRH is $175 for the first certificate and $85 each for additional certificate upon the request from the customer.

Liberty Management Group, a leading FDA consulting firm provides assistance with FDA Medical device registration, device listing and certificate to foreign government application.

Sudha S

Regulatory Consultant

Mail : office@libertymanagement.us

http://www.fdahelp.us

OVER-THE-COUNTER (OTC) DRUG PRODUCTS

Over-the-Counter drugs (OTC)  also known as nonprescription drugs are medications sold directly to consumers without a prescription from a physician. OTC drugs are in general considered as safe and effective for use by the consumers without getting treatment from a healthcare professional.  There are more than 300,000 OTC drugs are marketed with about 800 active ingredients.

Although there are more than 80 therapeutic categories of OTC drugs, starting from acne products to weight management drugs, FDA is not approving OTC products, but Center of Drug Evaluation and Research (CDER) ensures that OTC drugs are properly labeled and its ingredients listings. For each category, FDA developed an OTC drug monograph and published in the Federal Register. OTC drug monograph provided guidance which covers doses, acceptable ingredients, formulations and labelling requirements.  When the company adheres to OTC monograph, it can make and market an OTC drugs without FDA’s pre-approval.  OTC monographs defines the safety, efficiency and labeling of all OTC active ingredients. The drugs for which the active ingredients is not OTC monograph, has to apply for New Drug Application (NDA) or Abbreviated New Drug Application (ANDA).

FD&C acts requires firms that manufacture, contract manufacture, repack or re-label or salvaging of OTC drugs in the United States or that are offered for import in the U.S are required to register with FDA and renew their registration annually. Also domestic and foreign establishments must list all drugs that they manufactured, prepared, propagated, compounded, or processed for commercial distribution in the U.S. Foreign firms are required to identify a U.S agent and importers at the time of registration.

FDA Drug establishment registration needs to be submitted electronically using Extensible Markup Language (XML) files in the Structured Product Labeling (SPL) format. The firms must use FDA’s Electronic Submission Gateway (ESG) to submit SPL files.

Private Label Distributors (PLD) are not required to register their establishment with FDA, however they have to apply for their own Labeler code and list their drugs with FDA. FDA has a released a list of summary of registration and listings requirements for the manufacture or distribution of human pharmaceuticals, which can be seen at https://www.fdahelp.us/Pdf/Drug.pdf

Drug establishments that are registered with FDA must list all the products they manufacture for commercial distribution under their own labeler code, which includes the API manufacturers, bulk manufacturers, contract manufacturers, re-packers and re-labelers.

FDA has published a regulation establishing standardized content and format for the labeling of OTC drug products (Drug Facts labeling). The Drug Facts labeling for OTC drug products is intended to make it easier for consumers to read and understand OTC drug product labeling and use OTC drug products safely and effectively. All drugs or drug products in finished package form is considered as misbranded if it does not comply with FDA labeling requirements.

Liberty Management Group provides assistance with drug establishment registration, drug listing and label review.

Sudha S

Regulatory Consultant

Mail: office@libertymanagement.us

http://www.fdahelp.us

DMF – DRUG MASTER FILES

A Drug Master File (DMF) is a document submitted by a drug manufacturer to US FDA which is used to provide confidential detailed information about facilities, procedures, or things used in the manufacturing, processing, packaging, and storing of one or more human drugs. A DMF is submitted when more companies work in partnership to manufacture a drug product, which allows the company to protect is its intellectual property rights from its partner while complying with regulatory constraints as well for disclosing of processing procedures.

DMF’s are submitted to support regulatory regulations and prove the quality, safety and effectiveness of a product for getting Investigational New Drug Application (IND), New Drug Application (NDA), Abbreviated New Drug Application(ANDA), another DMF and Export Application. However, DMF submission is NOT a substitute for an IND, NDA, ANDA or Export Application. As per FDA regulation, DMF submission is not required by law, it is solely depends to submitters discretion.

As per FDA, there are five types of DMF’s

  • Type I  : Manufacturing Site, Facilities, Operating Procedures, and Personnel (no longer applicable)
  • Type II  : Drug Substance, Drug Substance Intermediate, and Material Used in Their Preparation, or Drug Product
  • Type III :  Packaging Material
  • Type IV  : Excipient, Colorant, Flavor, Essence, or Material Used in Their Preparation
  • Type V :  FDA Accepted Reference Information

All DMF submissions must be in the English language which should contain transmittal letter, administrative information about the submission and must include specific information about the DMF type.

All foreign DMF holders are required to appoint an U.S agent, however domestic DMF holders do not need a representative to submit it.

DMF holders should submit an annual report on the same date of their original submission.  Annual report should contain all the information including name and address of DMF holder, corporate headquarters, Manufacturing/ processing facility, contact for FDA communication, agents (if any),statement of commitment and signed statement by the DMF holder assuring that the DMF is current.

Starting from May 5, 2018 onwards, new DMFs other that Type III, as well as all documents submitted to existing DMFs excluding Type III are required to submit DMF using Electronic Common Technical Document (eCTD).  DMFs that are not submitted through eCTD after May 5, 2018 will be rejected, however for Type III DMFs the requirement will be effective from May 5, 2020 onwards.

Liberty Management Group Ltd, a leading FDA consulting group in the United States, provides assistance DMF eCTD submissions, US agent service, DMF closure and reactivation request submission to FDA.

Sudha S

Regulatory Consultant

Mail: office@libertymanagement.us

http://www.fdahelp.us