A Joint Collaboration Between FDA and AIFBA

A Joint Collaboration Between FDA and AIFBA
FDA Import Outreach A Joint Collaboration Between FDA and AIFBA November 8, 2016 Atlanta, GA

This presentation represents the Atlanta District Food and Drug Administration's current thinking on these topics. It does not create or confer any rights for or on any person and does not operate to bind FDA or the public. You can use an alternative approach if the approach satisfies the requirements of the applicable statutes and regulations. If you want to discuss an alternative approach, contact the FDA staff responsible for implementing this guidance. If you cannot identify the appropriate FDA staff, call the Atlanta District Office for the correct contact.

This presentation is intended as a quick reference tool for filer/brokers/forwarders/consignees importing FDA regulated products. This does not provide all- encompassing guidance. For a complete listing of all applicable regulations, please reference the Code of Federal Regulations at

Top Detention Reasons Labeling Pesticides and Industrial Chemicals
Chemotherapeutics Filth Device Listing Device Facility Registration (Domestic or Foreign Facility)

Products Regulated by FDA
Human foods (exceptions: most meat and poultry) Animal feeds Cosmetics Drugs (both human and animal) Biologics (including human cells and tissues) Medical devices Electronic products that emit radiation Tobacco

OR the ACE AofC Document
PLEASE READ! Several Affirmation of Compliance Codes have changed with ACE implementation. Refer to the Supplemental Guidance for the Automated Commercial Environment/International Trade Data System (ACE/ITDS) OR the ACE AofC Document

Food Entry Requirements
George Jackson Supervisory Investigator/Import Program Manager FDA Atlanta District

All Products Covered in This Section will Require Food Facility Registration and Prior Notice

Food Labeling FDA does not pre-approve labels for food products.
Questions concerning the labeling of food products may be directed to: Food Labeling and Standards Staff (HFS-820) Office of Nutrition, Labeling, and Dietary Supplements Center for Food Safety and Applied Nutrition Food and Drug Administration 5100 Paint Branch Parkway College Park, MD Telephone: (240)

Food Labeling To help minimize compliance action and delays, it is recommended that manufacturers and importers become fully informed about the applicable laws and regulations before offering foods for distribution in the United States.

Common Food Label Violations
Label is not in English Incorrect or missing statement of identity, or name of the food Label lacks the name and place of business of the manufacturer, packer, or distributor Fails to list potential allergens Fails to declare ingredients

Common Food Label Violations
Fails to bear nutrition labeling or the nutrition label is in incorrect format. Color additives Food Additives that are unsafe or not declared in label. (i.e. sulfites agents in seafood). Net Quantity (both Metric and U.S. Customary System ) e.g. Net wt. 1 lb. 8 oz. (680g) 21 CFR

Low Acid Canned Foods/Acidified Foods
Any food (other than alcoholic beverages) with a finished equilibrium pH greater than 4.6 and a water activity greater than 0.85 Is the RAW pH of the product is greater than 4.6, which is thermally processed and packaged in a hermetically sealed container Acidified Foods A low-acid food to which acid(s) or acid food(s) are added and which has a finished equilibrium pH of 4.6 or below and a water activity (aw) greater than 0.85.

Low Acid Canned Foods/Acidified Foods
How to tell if a product is LACF/AF Is the product stored at room temperature? Is the product is packaged in a hermetically sealed (airtight) container – metal cans, glass bottles/jars, plastic bottles/jars, laminated pouches, plastic bags? Does the finished product have a water activity of greater than 0.85? (product will be moist) Is the RAW pH of the product greater than 4.6? If you answered yes to all above questions, your product appears to be a LACF or AF

LACF/AF “Buzzwords” Canned ________ In Brine Preserved Pickled
________ In Vinegar Tetra Pak Aseptic

Exclusions from LACF/AF Regulations
Alcoholic Beverages Carbonated Beverages Jams, Jellies, and Preserves IF they meet the definition of 21 CFR 150 Fermented Foods low-acid foods subjected to the action of certain microorganisms, which produce acid during their growth and reduce the pH of the food to 4.6 or below (i.e. some green olives, pickles, and sauerkraut) The FDA entry reviewer will most likely ask for a process flow chart for these types of products

LACF/AF Requirements Manufacturers must register with FDA and File scheduled processing information for their products FCE number: Food Canning Establishment number. Example: 04321 Processors must file a separate scheduled process for each product and product style, and for each container size of all LACF/AF. SID number: Submission Identifier. Example: Container dimensions in inches and sixteenths. Example: 300 x 407

Container Dimensions A Total of 3 Fields
Height, Diameter and Thickness (Pouches, Oval Cans and Irregularly Shaped Containers ONLY) Each field can contain up to 4 numerals (ex. 1008) Measurements are in inches and sixteenths inches Example: a can which is 2 1/2 inches in diameter and 3 3/16 inches in height would be listed as Chart for converting Metric (mm) to English (inches and sixteenths)

NEW – Volume (ACE) Used to communicate the container volume and unit of measure of an Acidified Food (AF) or Low-Acid Food product that is packaged in a container that does not have a traditional size/dimension. The VOL code is acceptable for glass or ceramic containers and semi- rigid container, large steel or plastic drums, pails, fiberboard. (Large industrial sized containers.)

Product Code Tip Fourth Field Will Be Either:
“E” – Commercially Sterile “F” – Aseptic Pack “I” – Acidified

Acidified & Low-Acid Canned Foods REASONS FOR PRODUCT DETENTION
Acidified & Low-Acid Canned Foods REASONS FOR PRODUCT DETENTION Establishment is not registered (FCE #) Establishment has not filed process information with the FDA (SID #) Maybe subject to Import Alert and 99-12

LACF Information and Help Center

Dietary Supplements A dietary supplement is a product taken by mouth that contains a "dietary ingredient" intended to supplement the diet. The Dietary Supplement Health and Education Act (DSHEA) of 1994 places dietary supplements in a special category under the general umbrella of "foods," not drugs, and requires that every supplement be labeled a dietary supplement. Dietary ingredients include vitamins, minerals, amino acids, and herbs or botanicals, as well as other substances that can be used to supplement the diet.

Common Imported Dietary Supplements
Vitamins – Vitamins C, E; Multiple Vitamins Minerals - Zinc Proteins Herbals and Botanicals Fish Oil

Dietary Supplement Health Claims
Common Violations Product labeling is making unauthorized health claims. “Assists in the treatment and prevention of diabetes.” " Better Than Viagra” “is … a natural anti-inflammatory and is commonly used to ease stiffness and pain [from] arthritis….” If a dietary supplement claims to cure, mitigate, or treat a disease, it would be considered an unauthorized new drug and in violation of the applicable regulations and statutes.

Dietary Supplement Health Claims
Undeclared Active Ingredients in Products Marketed as Dietary Supplements FDA investigations have discovered products marketed as dietary supplements that contain the same active ingredients as in FDA-approved drug products, analogs of such drug ingredients, or other compounds of concern, such as novel synthetic steroids.

Common Labeling Problems
Lacks a (“Supplement Facts” panel), which is required under 21 CFR

Common Labeling Problems
Label lacks name of product and the term “dietary supplement” or “ herbal supplement” (see 21 CFR 101.3(g)) Net quantity of contents Name and place of business of manufacturer, packer, or distributor Directions for use / Warnings Label is not in English Import alerts 54-13, and 54-11 “Disclaimer”: this product is not intended to "diagnose, treat, cure or prevent any disease,"

Overview of Dietary Supplements

Supervisory Investigator/Import Program Manager
Cosmetic Entries George Jackson Supervisory Investigator/Import Program Manager FDA Atlanta District

Cosmetics–Scope Used by most consumers every day Examples:
Moisturizers, other skin preparations Hair care, hair dyes, hair straighteners Makeup, nail polishes Shaving preparations Perfumes Toothpastes, mouthwashes Face and body cleansers, deodorants Over 8 billion personal care products sold in U.S. annually Over $60 billion in annual sales

Cosmetic Defined in the Federal Food, Drug, and Cosmetic Act (FD&C Act), Section 201 (i) Articles intended for: Cleansing Beautifying Promoting attractiveness Altering the appearance Excludes “Soap”

Cosmetic, Drug, or Soap? No Yes Consists of alkali
salts of fatty acids? Detergent properties are due to alkali salts? Not Soap No Consists of detergents? Product is marketed solely as soap? No Yes Yes Intended solely to cleanse body & has characteristics like soap Has other non- cleansing properties? Intended to treat disease or alter structure/function of body? This is a WONDERFUL, WONDERFUL slide (and algorithm). With your permission (and with proper attribution given henceforth to YOU), I’m going to place this slide in my permanent archives for future use !!! Many thanks. Yes Marketing claims? Yes Yes Yes May be called soap but regulated as cosmetic Cosmetic Drug

Cosmetic vs. Drug Products can be cosmetics, drugs, or both
Antimicrobial cleanser Antidandruff shampoo Anticaries toothpaste Antiperspirant-deodorant If it meets definition of drug, it must comply with drug requirements—even if it is also a cosmetic No legal definition of “cosmeceutical” or “personal care product” under the FD&C Act

Cosmetics–FDA’s Authority
The law does NOT provide for FDA pre-market approval FDA’s authority is post-market only

Cosmetic Regulatory Requirements
Safe for the intended use Properly Labeled Not Adulterated or Misbranded

Cosmetics Regulations (21 CFR 700-740)
General (21 CFR Part 700) Definitions Requirements for Specific Cosmetic Products Cosmetic Labeling (21 CFR Part 701) Voluntary Registration of Cosmetic Product Establishments (21 CFR Part 710) Voluntary Filing of Cosmetic Product Ingredient Composition Statements (21 CFR Part 720) Cosmetic Product Warning Statements (21 CFR Part 740)

Cosmetic Labeling Guide

Prohibited/ Restricted Cosmetic Ingredients (21 CFR 700) “Negative List”
Prohibited cosmetic ingredients: Bithionol (21 CFR ) Halogenated Salicylanilides (21 CFR ) Chloroform (21 CFR ) Methylene chloride (21 CFR ) Prohibited as ingredients of cosmetic aerosol products: Vinyl Chloride (aerosol ingredient) (21 CFR ) Zirconium complexes (in aerosols) (21 CFR ) Restricted ingredients of cosmetic products unless used as specified in the regulations: Hexachlorophene (21 CFR ) Mercury (21 CFR ) Chlorofluorocarbons (21 CFR and 2.125) Certain Cattle Materials (21 CFR )

Color Additives (21 CFR 73, 74, 82) “Positive List”
Color additives – only ingredients in cosmetic products that require pre-market approval Uses - Color Additives in all ranges of FDA-regulated products… certifiable and certification-exempt… must be listed by regulation to be used legally in U.S. marketed products. Colorant (21 CFR ) vs. Color Additive Some color additives subject to “batch certification “ requirements 1960 Color Additive Amendments to the FD&C Act User Fee Program (21 CFR 80.10) Color additives are the only class of cosmetic ingredients that require pre-market approval by FDA and, of course, I need to re-emphasize that all color additives…whether used in cosmetics, foods, drugs, or medical devices…are subject to pre-market approval. Approved color additives are listed in codified CFR regulations with very specific compositional specifications and uses/restrictions requirements, and only these color additives can be used in the U.S. The regulations specify how they are to be used, as not all colors can be used interchangeably in foods, drugs, and cosmetics, and those color additives listed for ‘external use’ cannot be used for ‘eye area use’ unless specifically permitted by regulation. [21 CFR 70.5 (a)]. Of course our main interest here is to keep color additives with harmful chemical contaminants or which claim to be equivalent to listed colors but which do not meet the chemical specifications or other requirements in the listing regulation off the market.

Import Refusals for Cosmetics
Reasons for refusal Drugs/medical devices improperly marketed as cosmetics 39% Labeling violations 33% Color additive violations 26% Poisonous/harmful contaminants, filth/insanitary conditions 2%

VCRP Voluntary Cosmetic Registration Program

Voluntary Cosmetic Registration Program (VCRP)
Voluntary (“Self-Regulatory”) Program VCRP established 1972 (paper) e-VCRP (website) launched 2005 21 CFR 710 (Establishments) 21 CFR 720 (Product Formulations and Ingredients

Medical Device Entries
George Jackson Supervisory Investigator/Import Program Manager FDA Atlanta District

Preparing for Filing

Filing a Medical Device Entry
Determine whether the imported item is a medical device and/or radiation-emitting electronic product regulated by FDA Determine the regulatory requirements Requires 510(k), PMA, or is exempt Requires radiation-emitting product, abbreviated and annual reports Requires establishment registration and device listing Requires compliance with Quality Systems regulation Needs impact-resistant lens certification documentation Needs electrode lead wires and patient cables certification documentation Determine the product code to be submitted

Additional Information to Collect
Registration number Listing number Accession number Radiation-Emitting Electronic Products Marketing application number PM# (510K, PMA), IDE

Product Codes 3-letter code that CDRH creates for all regulated devices and radiation-emitting products, e.g., FRN For import entry purposes, the product code is expanded to include a two-digit industry code, e.g., 80F- -RN The code has no built-in intelligence unlike other FDA product codes that indicate type of packaging used, etc. CDRH maintains two publicly available web sites to search for FOI-releasable product codes Radiation-Emitting Electronic Products: Devices:

Product Codes

Determining Product Code
CDRH assigns the product code when it reviews each PMN and PMA application. Since around 1992, CDRH has included the product code on all clearance and approval letters. If you know your client’s PMN or PMA number, you can also query the appropriate database found at: For products that are exempt from the PMN clearance process, your client would have either used the CDRH Product Classification database or contacted CDRH staff for assistance to determine appropriate product code It is critical that you enter the correct product code during the entry process

Product Code Review Panel

Find the review panel in the product code builder and put the 2-digit code in the first box, the first letter in the 2nd box, and the last 2 letters in the last box:

Confirm that it is valid in the product code builder by clicking Next:

PM# (PMN & PMA)

Data needed from shipper– not publically releasable
IDE number and product code Radiation-emitting electronic product accession number From Product report, Annual report, or Abbreviated report Device listing number

Verifying a Firm’s Registration and Listing Status
CDRH maintains a web site with establishment registration and listing data - This data is updated weekly If you have a firm’s registration number you can easily check their status This site does not give device listing numbers since this is proprietary information

Registration and Listing

Device A of C: DEV DEV = Device Foreign Manufacturer Registration Number The qualifier for this code should be the device registration number issued by CDRH for the firm manufacturing the product identified in the FDA line. Example: or NOTE: should always be the DEV associated with the foreign manufacturer and not U.S. Specifications Developer

Device A of C: DFE DFE = Device Foreign Exporter Registration Number
The qualifier for this code should be the device registration number issued by CDRH for the exporter who exports or offers for export to the United States (U.S.), a device manufactured or processed by another individual, partnership, corporation or association in a foreign country, as well as devices originally manufactured in the U.S. Example: or

Device ACE Data Element (DII)
DII = Device Initial Importer Registration Number The qualifier for this code should be the device registration number issued by CDRH for the importer who takes first title to devices imported into the U.S. Example: or

Device ACE Data Element (DII)
DII = Device Initial Importer Registration Number The qualifier for this code should be the device registration number issued by CDRH for the importer who takes first title to devices imported into the U.S. Example: or No Longer an AOC in ACE

Device A of C: DDM DDM = Device Domestic Manufacturer
Must be transmitted with A of C KIT The qualifier for this code should be the device registration number issued by CDRH for the firm manufacturing the product identified in the FDA line. This Affirmation should only be provided for finished devices manufactured in the U.S. and claimed as part of a convenience kit

Device A of C: LST LST = Device Listing Number
The qualifier for this code should be the device listing number issued by CDRH for the product identified in the FDA Line. Example: E100100

Device A of C: PM# (PMA) PMA (PM#)= Device Premarket Approval Number
The qualifier for this code should be the device Premarket Approval (PMA) number, product development protocols (PDP) number or Humanitarian Device Exemption (HDE) number issued by CDRH for the product identified in the FDA line. Example: P979999

Device A of C: PM# (PMN) PMN (PM#) = Device Premarket Notification Number (510(k)) The qualifier for this code should be the device premarket notification (510(k)) number issued by CDRH for the product identified in the FDA line. Example: K979999

Device A of C: IDE IDE = Investigational Device Exemption Number The qualifier for this code should be the investigational device exemption number issued by CDRH for the product identified in the FDA line.

Device A of C: IRC IRC = Impact Resistance Lens Certification
This code is used to certify that the filer has on hand the test results or a certificate that shows that the product on the FDA line has met the standards for impact resistance lens.

What is a drop ball test and what are the labeling requirements for lenses/sunglasses?
Lenses for spectacles and/or sunglasses must be certified as impact resistant under 21 CFR Part A certificate illustrating the lens' compliance with the 21 CFR must accompany each lot of spectacle lenses/sunglasses seeking entry into the U.S.

The certificate must reflect that the lenses have been "sampled" and are impact resistant, using a statistically significant method. Manufacturers MAY conduct drop ball tests, as described in (d)(2), OR use an equal or superior test method.

EXAMPLE of Certificate
" (Name of manufacturer or seller) hereby guarantees that the articles listed herein are impact-resistant within the meaning of 21 CFR and have been tested pursuant to that section. Impact-resistant lenses are not unbreakable or shatterproof. Records of testing will be maintained for a period of three (3) years from the date of shipment, and copies will be forwarded to FDA upon request.” Certificate shall include the signature and street address of manufacturer or seller

Lens Labeling Statement of Identity common name of the device followed by an accurate statement of the principal intended action(s) of the device. Declaration of net quantity of contents Ex – “One Pair of Sunglasses” Name and place of business of manufacturer, packer or distributor. EXEMPT from adequate directions for use

Resources for Lens Products
Medical Device Labeling Regulations: Impact-Resistant Lenses – Questions and Answers

Should/can all AOC’s (LST, PMN/PMA, DEV) for the finished device be used when importing components? Does this improve the PREDICT score? CPT = Device Component This code should be used when importing a component of a device that requires further processing or inclusion into the finished device. This code is not to be used if the device component is classified by FDA as a finished device, e.g., wheelchair component.

What Is a Medical Device?
FFDCA section 201(h) The term "device" (except when used in paragraph (n) of this section and in sections 301(i), 403(f), 502(c), and 602(c)) means an instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent, or other similar or related article, including any component, part, or accessory, which is-- (1) recognized in the official National Formulary, or the United States Pharmacopeia, or any supplement to them, (2) intended for use in the diagnosis of disease or other conditions, or in the cure, mitigation, treatment, or prevention of disease, in man or other animals, or (3) intended to affect the structure or any function of the body of man or other animals, and which does not achieve its primary intended purposes through chemical action within or on the body of man or other animals and which is not dependent upon being metabolized for the achievement of its primary intended purposes. Emphasis added

Components and Accessories
21 CFR 820.3(c) Component means any raw material, substance, piece, part, software, firmware, labeling, or assembly which is intended to be included as part of the finished, packaged, and labeled device. 21 CFR 820.3(l) Finished device means any device or accessory to any device that is suitable for use or capable of functioning, whether or not it is packaged, labeled, or sterilized.

Component A of Cs If the component is being imported for further processing into a finished device, then the foreign manufacturer is not required to register and list under (a) Excludes certain wheelchair, cast, and exercise device components (see next slide) Use of the following Affirmation of Compliance codes and Data Elements will expedite the entry review process and increase the likelihood that your shipment may be processed based on import system screening: Component (CPT), no qualifier Device Initial Importer (DII) and qualifier (ACE Data Element) Device Listing (LST) and qualifier for the finished medical device PMN or PMA/PM# and qualifier, if applicable

Accessory A of Cs If the component/accessory is packaged or labeled for commercial distribution to an end user, then the foreign manufacturer is required to register and list Certain wheelchair, cast, and exercise device components are regulated as finished medical devices Use of the following Affirmation of Compliance codes will expedite the entry review process and increase the likelihood that your shipment may be processed based on import system screening: Device Foreign Manufacturer (DEV) or Device Foreign Exporter (DFE) and qualifier Device Listing (LST) and qualifier Device Initial Importer (DII) and qualifier PMN or PMA/PM# and qualifier, if applicable

Component vs. Accessory
For guidance on whether a specific product is a device, accessory, or component: Contact CDRH Import/Export Safety Staff

Device A of C: KIT KIT = Convenience Kit
The code KIT should be used for all individual devices within kits imported in the U.S. There is no associated qualifier See guidance:

Convenience Kits KIT DDM DEV/DFE
The code KIT should be used for all individual devices within kits imported in the U.S. There is no associated qualifier DDM The code DDM and qualifier should be the device registration number issued by CDRH for the U.S. firm manufacturing the individual finished device within the kit DDM should be used only in conjunction with KIT DEV/DFE DEV/DFE should be used for the foreign manufacturers or exporters of individual finished devices within the kits

Convenience Kits

Most Frequent Automated Lookup Failure Reasons – Devices
Registration: Registration number not provided Registration number not valid Registration number does not match other data provided Listing: Listing number not provided Listing number not valid No records match listing number provided

Unique Device Identifier (UDI)

What is UDI and are all devices, even Class I devices, required to have UDI labeling?
In 2013, the Food and Drug Administration (FDA) released a final rule establishing a unique device identification system designed to adequately identify devices through distribution and use. The final rule requires device labelers to include a unique device identifier (UDI) on device labels and packages, except where the rule provides for an exception or alternative.

Each UDI must be provided in a plain-text version and in a form that uses automatic identification and data capture (AIDC) technology. The UDI will also be required to be directly marked on a device that is intended for more than one use, and intended to be reprocessed before each use. All UDIs are to be issued under a system operated by an FDA-accredited issuing agency. The rule provides a process through which an applicant would seek FDA accreditation, specifies the information that the applicant must provide to FDA, and the criteria FDA will apply in evaluating applications.

A UDI consists of two parts:
a device identifier (DI), a mandatory, fixed portion of a UDI that identifies the labeler and the specific version or model of a device, and a production identifier (PI), a conditional, variable portion of a UDI that identifies one or more of the following when included on the label of a device: the lot or batch number within which a device was manufactured; the serial number of a specific device; the expiration date of a specific device; the date a specific device was manufactured; the distinct identification code required by § (c) for a human cell, tissue, or cellular and tissue-based product (HCT/P) regulated as a device.

Example of UDI

Implementation of UDI FDA is using a phased approach over a seven year timespan Highest risk devices have a compliance date starting as early as September 24, 2014 Other devices are phased in over the next six years based on Classification and other factors See timeline at:

UDI Exceptions, Alternatives and Time Extensions
The UDI rule provides a method for labelers to request exceptions, alternatives, and time extensions to UDI requirements. Online Request Form: A labeler of a device identified in § is not required to request an exception from FDA. 11 total exceptions including Class I medical devices, which are exempt from GMP requirements.

NEW Device A of C: DI Device Identifier
This affirmation and qualifier should be the Device Identifier portion of the Unique Device Identifier Example:

Special Issues to Consider During Importation process
Consider performing due diligence by verifying that firm is not on an FDA Import alert Filer audits and CBP referrals allow FDA to detect cases of improper disclaiming or incorrect declaration of FDA regulated products Supply chain safety is very important to FDA to prevent counterfeit products and illegal goods from entering the US If you suspect illegal activity on the part of your clients, please report it to FDA and CBP

Special Issues to Consider During Importation process
Import for Export (IFE) declaration can only be used for products undergoing further processing. It cannot be used for transshipment of finished devices through the United States It cannot be used to store in US warehouses finished devices intended solely for export Entries that raise issues with PREDICT and import entry process include: Entries from Foreign Trade Zones American Goods Returned Trade show entries Sample entries Any non-standard entry

Additional References
PREDICT

FDA Imports Program

Regulatory Procedures Manual, Chapter 9, Imports

Supervisory Investigator/Import Program Manager
Drug Entries George Jackson Supervisory Investigator/Import Program Manager FDA Atlanta District

Drug or Cosmetic? A cosmetic is a drug
Example: “Cosmetic” with anti‐aging, anti-wrinkle, scar reducing claims Both drug and cosmetic – antimicrobial soap and antiperspirant/deodorant These products must meet both the drug and cosmetic regulations. Cosmeceuticals?

Drug or Dietary Supplement
Dietary supplements must meet definition found at FDCA Section 201(ff)(1) Cannot be a dietary supplement if it is not ingested or when it is intended to treat, cure, prevent, mitigate disease Products that otherwise can be dietary supplements are drugs if they contain a drug that is the subject of an approval, i.e., steroid Nutraceuticals

Registration & Listing Requirements [510(j) & 21 CFR 207]
All foreign firms that manufacture, prepare, propagate, compound, or process a drug imported or offered for import into the U.S. are required to… Register their name and place of business List all drug products imported or offered for import into the U.S. (FDA form 2657) Designate a U.S. Agent

R & L Requirements Manufacturers: APIs & finished drug products
Repackers and relabelers Control laboratories: registration only Domestic manufactures that pack/repack, label/relabeled, etc. drugs under the Import for Export (IFE) requirements NDC #: FDA requests but not require that it appears on the product label or labeling If NDC # appears on the label it must comply with regulation [21 CFR (b)(3)] Registration & Listing does not indicate FDA’s approval of a firm or its products [21 CFR ]

R & L Requirements Registration must be renewed annually
Registration required before any application is approved Listing information must be updated: Every June and December or Discretion of the registrant or When any change occurs

Drug Listing Exemptions
Component of a drug (e.g. non-API intermediates used to synthesize APIs) Drugs not for importation into U.S. (i.e. FTZ) Drugs offered under Investigational New Drug (IND) [21 CFR 312] Research for own study only and not for research in humans (If distributed by someone and research is conducted by someone else then, not exempt)

R&L Affirmations of Compliance
REG – Drug Registration Number FDASIA amends current law relating to registration of domestic drug establishments to require facilities to register between October 1 and December 31 of each year and to provide additional information including a unique facility identifier (UFI) for each establishment and a point-of-contact address. Agency has specified DUNS DLS – Drug Listing Number NDC – National Drug Code

?? Previously Submitted Question ??
Please clarify the differences between DLS and NDC Affirmation of Compliance codes. Are they both needed on a drug entry regardless of importing quantity/size? Can the DLS be found on FDA’s website? Will the DLS and NDC ever be the exact same number? Is there a website that can be utilized for looking up the DLS?

Answer with ACE Submit information using DLS regardless if it is a bulk drug substance or a finished dosage product.

DLS = Drug Listing Number
Drug Listing Number issued by FDA/CDER for the BULK drug product identified in the FDA line. The drug listing number is provided on the application for drug listing, Form FDA 2657. The DLS affirmation is NOT used for finished drug products.

DLS = Drug Listing Number
Bulk drug substances are identified and reported using a unique, three-segment number. The first segment of numbers is the labeler code. This number identifies the manufacturer of the product. The second segment of numbers identifies the specific ingredient/strength/formulation manufactured by the firm. The last segment of numbers identifies a specific package code.

NDC = National Drug Code
Number assigned to final marketed drugs submitted to FDA in electronic listing files by labelers. A labeler may be either a manufacturer, including a firm that is performing repackaging or relabeling, or, for drugs subject to private labeling arrangements, the entity under whose own label or trade name the product will be distributed.

NDC’s Are NOT Assigned to:
Animal Drugs Blood Products Human drugs that are not in final marketed form, such as Active Pharmaceutical Ingredients(APIs) Drugs for further processing Drugs manufactured exclusively for a private label distributor Drugs that are marketed solely as part of a kit or combination product or inner layer of a multi-level packaged product not marketed individually.

National Drug Code Directory
NDC’s are searchable online Drug listing numbers are not National Drug Code Directory “Old” and “New” Directories available on this page

Other AoC’s for Drug Products
NDA=DA(ACE) – New Drug Application Number A new drug can not be commercially marketed in the U.S. unless it has been approved as safe and effective by the FDA based on a New Drug Application. The qualifier required is the NDA number assigned to the product by FDA. ANDA=DA(ACE) – Abbreviated New Drug Application Number The ANDA contains data that, when submitted to FDA's CDER, provides for the review and ultimate approval of a generic drug product. Generic drug applications are called "abbreviated" because they are generally not required to include preclinical (animal) and clinical (human) data to establish safety and effectiveness. Instead, a generic applicant must scientifically demonstrate that its product is bioequivalent (i.e., performs in the same manner as the innovator drug). Once approved, an applicant may manufacturer and market the generic drug product.

Other AoC’s for Drug Products
IND – Investigational New Drug Investigational drugs are new drugs intended solely for investigational use by experts qualified by scientific training and experience to investigate the safety and effectiveness of drugs. These drugs are not approved by FDA. The FFD&C Act requires that a drug be the subject of an approved marketing application before it is transported or distributed across state lines (including import). A sponsor who wants to ship the investigational drug to clinical investigators, must seek an exemption from that legal requirement. The IND is the means through which the sponsor obtains its exemption from the FDA. An active IND allows for the shipment of an investigational new drug.

NDA vs ANDA: The differences in the two are noted in red
(Brand Name Drug) NDA Requirements 1. Animal Studies* 2. Clinical Studies* 3. Bioavailability Studies* 4. Chemistry 5. Manufacturing 6. Controls 7. Labeling 8. Testing * See next slide for IND information (Generic Drug) ANDA Requirements 1. Bioequivalence 2. Chemistry 3. Manufacturing 4. Controls 5. Labeling 6. Testing

IND & NDA Process Animal Studies: (Takes 1-4 years)
Pre-IND, Pre-Clinical Testing or R&D studies on animals 2. Clinical Studies: IND Involves NIH and clinical trials can be viewed at 3. Bioavailability Studies: (Takes 2-10 years) Phases I, II, III 4. NDA (Brand Name Drug): (Takes 2 mos. – 4 years)

Format for NDA, AND and IND
The qualifier for BOTH is six digits. If less than six digits, preceding zeros may be used to make six digits. Examples: DA=NDA DA=AND IND

Active Pharmaceutical Ingredients (API’s) [21 CFR 201.122(a)]
Intended for use in a product approved in a NDA or ANDA Manufactured by the supplier approved in the new drug application Intended for use in approved prescription (Rx) and over-the-counter (OTC) drugs

API Labeling [21 CFR 201.122(a)] Labeling (Must):
“Caution: for manufacturing, processing, or repacking” “Rx only” - when most dosage forms in which the API may be used are subject to prescription [503(b)(1)] Meet 21 CFR labeling requirements

API Entries [21 CFR 201.122(a)] Useful Information*:
API product name and drug listing number Name and address of the API manufacturer Number of approved NDA/ANDA or supplement Finished dosage drug product name and NDC number * Useful Information that may demonstrate applicability of an exemption. Alternative information may also suffice.

API Use in Clinical Studies (a.k.a. IND) [21 CFR 201.122(b)]
Must be covered by an active IND Must be going to person(s) authorized in the IND Labeling (Must): “Caution: for manufacturing, processing, or repacking in the preparation of a new drug or new animal drug limited by federal law to investigational use” Meet 21 CFR labeling requirements Drugs for clinical studies may not be used for manufacturing.

API Use in Clinical Studies (a.k.a. IND) [21 CFR 201.122(b)]
Useful Information: IND number Sponsor’s name and address Name of the product

API Pending/Near NDA/ANDA (Rx & OTC) [21 CFR 201.122(c)]
Intended for use in a product subject to a pending/near NDA, ANDA, or supplement approval Manufactured by the supplier included in pending/near NDA, ANDA, or supplement approval Applies to both prescription (Rx) and over-the-counter (OTC) drugs

Labeling (Must): “Caution: for manufacturing, processing, or repacking” “Rx only”- when most dosage forms in which the API may be used are subject to prescription [503(b)(1)] Meet 21 CFR labeling requirements

Useful Information: API product name and NDC number Name and address of the API manufacturer Pending NDA/ANDA number or supplement Finished dosage drug product name and NDC number (if applicable) Written commitment that products manufactured with the API will not be introduced in commercial distribution until they are approved

APIs - Pre-Submission Batches (21 CFR 201.122(c))
Batches used to conduct the studies necessary to generate data required to submit an application and/or supplement Enforcement discretion Useful Information: Explanation that API is intended to generate data to submit an application/supplement Example: Bioequivalence and/or bioavailability batches.

APIs - Pre-Submission Batches (21 CFR 201.122(c))
Useful Information – Cont.: Written commitment that product manufactured with API will not be introduced in commercial distribution until approved API product name and NDC # Name and address of the API manufacturer Name and address of U.S. consignee Product must be labeled as per 21 CFR For supplements - may include NDA/ANDA number to be supplemented and NDC # of finished product

Drugs for teaching, law, research enforcement & analysis. [21 CFR 201
Includes both APIs and finished drug products Research cannot used on humans API product name and NDC number Name and address of the API manufacturer Name and address of U.S. Consignee Written commitment that the quantity offered for import is reasonable for the contemplated research, teaching, analysis, etc. * Make sure product is not manufactured in the U.S. , exported and being re-imported back into U.S.

API’s for OTC Products Pending & Final Monographs
Labeling (Must): - “Caution: for manufacturing, processing, or repacking” Useful Information: - Name and NDC # of product to be manufactured with the API - A statement justifying why an approval is not required for the finished drug product - API label content demonstrating compliance with 21 CFR

API’s for Pharmacy Compounding
Labeling (Must): - “For Prescription Compounding” - “Rx only” Useful Information: - API is a component of an FDA approved drug - API meets official compendial requirements when applicable (Example: Certificate of Analysis) - Drug has not been withdrawn or removed from the U.S. market for public health reasons (list in CPG )

APIs – Pharmacy Compounding
Useful Information: API product name and NDC # Name/address of API manufacturer and registration number A written commitment that the API will be sold and used solely for pharmacy compounding by a state licensed pharmacy or federal facility A written commitment that the drug has not been withdrawn or removed from the U.S. market for public health reasons

Filer Evaluations George Jackson Supervisory Investigator/Import Program Manager FDA Atlanta District

Filer Evaluations FDA conducts evaluations of filers to ensure they are transmitting accurate electronic data ATL-DO attempts to evaluate as many local filers as possible each year

Starting in FY12, Filer Evaluation Results Are Posted on the FDA website.
Updated monthly List sorted alphabetically Will list one of five evaluation outcomes for each filer

Filer Evaluation Outcomes
Paperless – Satisfactory evaluation result; FDA has determined that electronic filing is appropriate. Corrective Action Plan – Based on the filer’s error rate, FDA has determined that continued electronic filing is appropriate, but FDA has requested a corrective action plan.

Dual-Mode Filer – The filer has been returned to Dual Mode (electronic and paper submissions) after FDA found repeated failures to successfully execute a Corrective Action Plan for improving the quality of the data being submitted. •New Filer – FDA has insufficient information to determine whether electronic filing, alone, is sufficient; FDA requires both electronic and paper submissions.

Inactive – The most recent evaluation determined that the firm is either out of business or inactive in FDA commodities. FDA recognizes that the filer evaluation process currently does not distinguish between serious mistakes or omissions and typographical errors, and FDA is working to improve this process.

ACE CONTACTS ACE Support Center (24/7) Local FDA Offices
ACE Support Center (24/7) Toll Free: | Local/International: Areas of focus: Technical issues related to the FDA supplemental guide, required data elements, and general ACE submission questions, including entry submissions rejected by FDA Local FDA Offices Webpage: Areas of focus: Entry-specific questions working through the FDA entry admissibility process, once the entry is successfully transmitted to/accepted by FDA DIO FDA Imports Inquiry Phone: Areas of focus: General questions regarding FDA import operations and policy, including product classification (program, processing, product coding and FD flags associated with HTS codes) and entry declaration requirements Division of Food Defense Targeting Phone: Webpage: Areas of focus: General questions regarding Prior Notice for food shipments

Question and Answer Session

A Joint Collaboration Between FDA and AIFBA

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A Joint Collaboration Between FDA and AIFBA

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