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U.S. Department of Health and Human Services

Inspections, Compliance, Enforcement, and Criminal Investigations

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SUBCHAPTER 2.9 - REGULATORY SUBMISSIONS

2.9 - REGULATORY SUBMISSIONS
2.9.1 - CENTER FOR DRUG EVALUATION AND RESEARCH (CDER)
      2.9.1.1 - Registration and Listing
      2.9.1.2 - Investigational New Drug Application (IND)
      2.9.1.3 - New Drug Application (NDA)
      2.9.1.4 - Abbreviated New Drug Application (ANDA)
2.9.2 - CENTER FOR DEVICES AND RADIOLOGICAL HEALTH (CDRH)
      2.9.2.1 - Device Registration and ListingHighlighted to denote updated text
      2.9.2.2 - Investigational Device Exemption (IDE) Regulation
      2.9.2.3 - Premarket Notification - Section 510(k)
      2.9.2.4 - Premarket Approval
      2.9.2.5 - Classification of Devices
         2.9.2.5.1 - CLASS I
         2.9.2.5.2 - CLASS II
         2.9.2.5.3 - CLASS III
      2.9.2.6 - Requests for GMP Exemption and Variances
      2.9.2.7 - Medical Device Reporting
      2.9.2.8 - Radiation Reporting
2.9.3 - CENTER FOR BIOLOGICS EVALUATION AND RESEARCH (CBER)
      2.9.3.1 - Registration and Listing
         2.9.3.1.1 - HUMAN BLOOD AND BLOOD PRODUCTS
         2.9.3.1.2 - HUMAN CELLS, TISSUES, AND CEULLULAR AND TISSUE-BASED PRODUCTS (HCT/PS)
      2.9.3.2 - Biologic LicenseHighlighted to denote updated text
2.9.4 - CENTER FOR VETERINARY MEDICINE (CVM)
      2.9.4.1 - Registration and Listing
      2.9.4.2 - Medicated Feed Mill License (FML)
      2.9.4.3 - Abbreviated New Animal Drug Application (ANADA)
      2.9.4.4 - New Animal Drug Application (NADA)
2.9.5 - CENTER FOR FOOD SAFETY AND APPLIED NUTRITION (CFSAN)
      2.9.5.1 - Low Acid Canned Food (LACF) / Acidified Foods (AF) Food Canning Establishment (FCE) Registration
      2.9.5.2 - FCE Process Filing of LACF/AF Processors
      2.9.5.3 - CosmeticsHighlighted to denote updated text
      2.9.5.4 - Color Certification Program
      2.9.5.5 - Infant Formula
      2.9.5.6 - Interstate Certified Shellfish (Fresh and Frozen Oysters, Clams, and Mussels) Shippers
      2.9.5.7 - Interstate Milk Shippers (IMS)      
2.9.6 - CENTER FOR TABACCO PRODUCTSHighlighted to denote updated text
Highlighted to denote updated text

  2.9 - REGULATORY SUBMISSIONS

Subchapter 2.9 provides information on the procedures for obtaining information and filing applications with the agency. These will be covered by Center. The filing and registration requirements are directed by the FD&C Act and its implementing regulations. They are filed, in most cases, by industry (e.g.: drug registration, LACF registration and process filing, ANDA's, etc.).

 2.9.1 - CENTER FOR DRUG EVALUATION AND RESEARCH (CDER)

The FD&C Act and its regulations require the filing of certain forms by firms which produce human drugs and drug related products. The requirements and procedures for these are described below.

 2.9.1.1 - Registration and Listing

Owners or operators of all drug establishments not exempt under Section 510(g) of the FD&C Act [21 U.S.C. 360 (g)] or 21 CFR 207.10, that engage in the manufacture, preparation, propagation, compounding, or processing of a drug or drugs, including blood products, and biologicals, are required to register each such establishment and to submit a list of every drug in commercial distribution, whether or not the output of such establishment or any particular drug so listed enters interstate commerce. Begin Changed TextChanges in the Act, resulting from the FDA Amendments Act of 2007 (PL 110-85) require drug establishment registration and drug listing information be submitted electronically unless a waiver is granted, effective June 1, 2009. End Changed Text

Registration and Listing are required whether or not interstate commerce is involved.

Begin Changed TextThe guidance document on electronic submissions for drug establishments registration and drug product listing is available at: http://www.fda.gov/downloads/Drugs/
GuidanceComplianceRegulatoryInformation/guidances/ucm072339.pdf
.End Changed Text

General information and questions can be addressed by: Phone: 301-210-2840, or e-mail: DRLS@cder.fda.gov. See IOM Exhibit 5-12 for types for drug operations that require registration and listing.

 2.9.1.2 - Investigational New Drug Application (IND)

An application which a drug sponsor must submit to FDA before beginning tests of a new drug on humans. The IND contains the plan for the study and is supposed to give a complete picture of the drug, including its structural formula, animal test results, and manufacturing information. Detailed instructions for the submission of INDs can be found in 21 CFR 312.

 2.9.1.3 - New Drug Application (NDA)

A New Drug Application is an application requesting FDA approval to market interstate commerce a new drug for human use. The application must contain among other things, data from clinical studies needed for FDA review from specific technical viewpoints, including chemistry, pharmacology, biopharmaceutics, statistics, and anti-infectives, microbiology. Detailed instructions for the submission of NDAs can be found in 21 CFR 314.

 2.9.1.4 - Abbreviated New Drug Application (ANDA)

A simplified submission permitted for a duplicate of an already approved drug. ANDAs are for products with the same or very closely related active ingredients, dose form, strength, administration route, use, and labeling as a product already shown to be safe and effective. An ANDA includes all the information on chemistry and manufacturing controls found in a new drug application (NDA), but does not have to include data from studies in animals and humans. It must, however, contain evidence the duplicate drug is bioequivalent to the previously approved drug. Information concerning the submission of ANDAs can be found in 21 CFR 320.

 2.9.2 - CENTER FOR DEVICES AND RADIOLOGICAL HEALTH (CDRH)

The FD&C Act, its amendments, and the regulations promulgated under the Act, require the filing of certain forms and submission of certain data by those involved in the production (and in some cases the use) of medical devices and radiological products. Within the CDRH, the Division of Small Manufacturers, International and Consumer Assistance (HFZ-220) has been charged with responsibility for providing information and assistance to industry in complying with these requirements. The general requirements are discussed below, as are several issues unique to CDRH submissions.

 2.9.2.1 - Device Registration and Listing

Section 510 of the FD&C Act [21 U.S.C. 360] and 21 CFR 807 describe the establishment registration, device listing, and premarket notification requirements and specify conditions under which establishments are exempt from these requirements.

Manufacturers of finished devices (including device specification developers, reprocessors of single use devices), repackers and relabelers, foreign exporters and initial importers of medical devices, are required to register their establishments by submitting a form FDA 2891. After initial submission, annual registration is accomplished by use of the Center for Devices and Radiological Health (CDRH) computer generated FDA 2891(a). Component manufacturers are not required to register if the components are sold to registered device establishments for assembly into finished devices. Registration and listing is required, however, if the component is labeled for a health care purpose and sold to medical or clinical users. Optical laboratories, clinical laboratories, dental laboratories, orthotic and prosthetic appliance assemblers, hearing aid dispensers and others who, using previously manufactured devices, perform a service function for physicians, dentists, other licensed practitioners or their patients, are exempt from establishment registration if they are located in the United States. X-ray assemblers are exempt from establishment registration. An exemption from registration does not exempt an establishment from inspection under Section 704 of the FD&C Act [21 U.S.C. 374].

Each establishment, except initial importers of medical devices, required to register must list their devices. Device listing is accomplished using a form FDA-2892; the same form is used to update listing information.

All foreign manufacturers are required to notify FDA of the name, address, telephone and fax numbers, and e-mail address of their United States agent. The United States agent must reside or have a physical place of business in the United States. Post office boxes, answering services and machines are not allowed.

Establishments are required to register and list, even if interstate commerce is not involved. Foreign establishments must register, list and submit a United States agent notification prior to exporting to the United States. See IOM Exhibit 5-13 for types of medical device operations, which require registration and listing.

An establishment must initially register on the form FDA 2891, and list on form FDA 2892 which may be obtained from:

  1. FDA Internet site: http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/ HowtoMarketYourDevice/RegistrationandListing/default.htm.
  2. CDRH, Division of Small Manufacturers, International and Consumer Assistance (HFZ-220), 1350 Piccard Drive, Rockville, MD 20850, 800-638-2041. Please note this is an automated publications' request line. Caller must leave name, address, phone number and publications needed.

A sample United States agent notification letter may be obtained from:

  1. FDA Internet site: http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/ HowtoMarketYourDevice/RegistrationandListing/default.htm.
  2. CDRH, Division of Small Manufacturers, International and Consumer Assistance (HFZ-220), 1350 Piccard Drive, Rockville, MD 20850, 800-638-2041. Please note this is an automated publications' request line. Caller must leave name, address, phone number and publications needed.

General information and policy questions can be addressed by:

  1. Sending an e-mail message to device.reg@fda.hhs.govHighlighted to denote updated text.
  2. Writing to or calling Food and Drug Administration, Center for Devices and Radiological Health, Office of Compliance/Division of Enforcement Risk Management Operations, Regulatory Policy and Systems Branch, 10903 New Hampshire Ave, Bldg 66, Silver Spring, MD 20993, 301-796-7400.Highlighted to denote updated text

 2.9.2.2 - Investigational Device Exemption (IDE) Regulation

The IDE regulation in 21 CFR 812 contains requirements for sponsors, Institutional Review Boards (IRBs) and Clinical Investigators. Additional requirements are found in 21 CFR 50, Informed Consent, and 21 CFR 56, IRB's. All Sponsors of device clinical investigations must have an approved IDE, unless specifically exempted by the regulation. Sponsors who have an approved IDE are exempt from requirements on labeling, registration and listing, premarket notification, performance standards, premarket approval, GMPs except the design control provisions, banning of devices, restricted devices, and color additives.

Provisions for obtaining an IDE, and the sections of the regulations, with which sponsors, investigators, and IRBs must comply, differ according to the risks posed by the device. Sponsors of nonsignificant risk devices must obtain IRB approval, and are subject to a limited number of provisions; sponsors of significant risk (See 21 CFR 812.3(m)) investigations are subject to the entire regulation.

There are investigations, described in 21 CFR 812.2(c) that are exempt from the IDE regulation. Exempted investigations apply to devices and diagnostics, which meet the criteria in the regulation. These devices are, however, still subject to other regulatory requirements of the Act, such as labeling, premarket approval of Class III devices, and GMPs (as stated in the preamble to the IDE regulation).

A Sponsor who knows a new device is not "substantially equivalent" to a preamendment device, or who is not sure if a device is "substantially equivalent" without conducting a clinical investigation, must obtain an approved IDE to conduct the clinical investigation. After collecting clinical data, a sponsor who desires to market a device must either submit a premarket notification (510k) or premarket approval application to FDA. A premarket notification may be submitted if the sponsor believes the data supports a finding of substantial equivalence.

Certain radiation-emitting electronic devices that are investigational are also subject to radiological health regulations, 21 CFR 1000 through 1050.

Transitional devices, must have an approved IDE in order to be investigated.

Sponsors, Monitors, IRBs, Investigators, and Non-Clinical Toxicological Laboratories will be covered under the Bioresearch Monitoring Program. FDA has the authority to inspect and copy records relating to investigations. Records identifying patients by name will be copied only if there is reason to believe adequate informed consent was not obtained, or investigator records are incomplete, false, or misleading.

 2.9.2.3 - Premarket Notification - Section 510(k)

The Medical Device Amendments of 1976 require device manufacturers to notify the CDRH at least 90 days before commercially distributing a device. This is known as a "Premarket Notification" or a "510(k)" submission. "Commercial distribution", for practical purposes, means the device is held for sale. These 510(k) requirements do not apply to Class I devices unless the device is intended for a use which is of substantial importance in preventing impairment of human health, or to any Class I device that presents a potential unreasonable risk of illness or injury. See section 510(l) of the FD&C Act [21 U.S.C. 360(l)]

A manufacturer must submit a Premarket Notification to FDA in any of the following situations:

  1. Introducing a device into commercial distribution for the first time.
  2. Introducing for the first time, a new device or product line which may already be marketed by another firm.
  3. Introducing or reintroducing a device with significant changes or modifications affecting the safety or effectiveness of the device. Such changes or modifications could relate to design, material, chemical composition, energy source, manufacturing method, or intended use.

These requirements do not apply to "custom devices." A "custom device" is a device made exclusively for, and to meet the special needs of, an individual physician or health professional, or for use by an individual patient named in the order of a physician or dentist (such as specially designed orthopedic footwear). A "custom device" is not generally available in finished form for purchase; and is not offered through labeling or advertising for commercial distribution.

Refer to IOM Exhibit 5-13 for types of medical devices, which require 510(k) submissions. The investigator should document for CDRH review failures to submit required 510(k)s.

 2.9.2.4 - Premarket Approval

Class III devices are required to undergo premarket approval in accordance with the provisions of Section 515 of the FD & C Act [21 U.S.C. 360e]. Premarket approval for a device is initiated with the submission of an application to FDA. Prior to approval of a premarket approval application (PMA), or a supplemental PMA, FDA has the authority to inspect the applicant's facilities and those records pertinent to the PMA.

Compliance Program Guidance Manual 7383.001 contains specific guidance on performing PMA pre-approval and post-approval inspections.

Inspections of manufacturing facilities are usually required prior to approval of a Premarket Approval Application. A full GMP inspection may not be necessary if there has been a recent satisfactory inspection covering a device similar to the PMA device.

Requests for PMA inspections issue from HFZ-306. The assignments will request the firm be inspected for compliance with the GMP regulations, and with their commitments in the PMA.

 2.9.2.5 - Classification of Devices

All medical devices subject to the FD&C Act will be classified as either Class I, Class II, or Class III medical devices.

Manufacturers who have questions regarding the classification of a device can write CDRH under Section 513(g) of the FD&C Act [21 U.S.C. 360c (g)] and request an opinion as to the status of the device.

 2.9.2.5.1 - CLASS I

Class I - General - Devices for which general controls (i.e., the controls in Section 501, 502, 510, 516, 518, 519 and 520 of the FD&C Act [21 U.S.C. 351, 352, 360, 360f, 360h, 360i, and 360j]) provide reasonable assurance of safety and effectiveness.

 2.9.2.5.2 - CLASS II

Class II - Special Controls - Devices for which the general controls, by themselves, are insufficient to provide reasonable assurance of safety and effectiveness of the device, and for which there is sufficient information to promulgate special controls, necessary to provide such assurance.

 2.9.2.5.3 - CLASS III

Class III - Premarket Approval - Devices which:

  1. Cannot be placed into Class I or II because insufficient information exists to provide assurance of safety and effectiveness, and cannot be placed into Class II because too little data exists to support the promulgation of special controls, and
  2. Are purported or represented to be for use in supporting or sustaining human life, or for a use which is of substantial importance in preventing impairment of human health, or
  3. Presents a potentially unreasonable risk of illness or injury.

Unless they are determined substantially equivalent to devices distributed prior to the 1976 Medical Device Amendments, devices proposed for marketing after May 28, 1976, fall automatically into Class III. Class III medical devices marketed before May 28, 1976, and the substantially equivalent devices marketed after that date, remain subject to the premarket notification requirements until required to have an approved PMA. Petitioners can request to have such devices reclassified into Class I or II. Transitional devices, those regulated as new drugs before May 28, 1976, are automatically assigned to Class III.

 2.9.2.6 - Requests for GMP Exemption and Variances

Section 520f(2)(A) of the FD&C Act [21 U.S.C. 360j (f)(2)(A)] allows manufacturers, trade organizations, or other interested persons to petition for exemption or variance from all or part of the GMP. Filing a petition does not defer compliance with the GMP requirements, and petitions will not be processed while an investigation is ongoing, or while regulatory action is pending.

Some Class I devices have been exempted from the GMP through the classification process. Each classification panel was required to consider the Class I devices reviewed by that panel and recommend if they should be exempt from the GMP. Devices exempted from the GMP by the classification process are published in classification regulations in the Federal Register.

Devices labeled or otherwise represented as sterile are not eligible for exemption from the GMP regulation. A sterile device is subject to all GMP requirements pertinent to sterility and sterilization processes.

No exemptions will be granted from 21 CFR 820.198 - Complaint Files, which requires the device manufacturer to have an adequate system for complaint investigation and follow-up. This Policy extends to 820.180 - General Requirements, which gives authorized FDA employees access to complaint files, device related injury reports, and failure analysis records for review and copying. When FDA has granted a manufacturer an exemption from one or more GMP requirements, the manufacturer still has the responsibility to implement appropriate quality control measures to assure the finished device has the quality it purports to possess, as stated in Begin Changed TextSection 501(c) of the FD&C Act [21 U.S.C. 351 (c)]. A manufacturer who has been granted a GMP exemption is still subject to inspection under Section 704(a) of the FD&C Act [21 U.S.C. 374 (a)], and may be subject to regulatory action if devices are adulterated or misbranded.End Changed Text

 2.9.2.7 - Medical Device Reporting

The Medical Device Reporting (MDR) regulation and the changes mandated by the Safe Medical Devices Act of 1990 (SMDA) is a mandatory information reporting system. It requires manufacturers, importers, and users of medical devices to report to FDA certain adverse experiences caused or contributed to by their devices. This program is administered by the Center's Office of Surveillance and Biometrics. The regulation requires a report be submitted to FDA whenever a manufacturer or an importer becomes aware of information that its device:

  1. May have caused or contributed to a death or serious injury, or
  2. Has malfunctioned and, if the malfunction recurs, is likely to cause or contribute to a death or serious injury.

Under the Safe Medical Devices Act of 1990, user facilities must report device-related deaths to FDA and to the manufacturer, if known. User facilities must also report device-related serious illnesses and injuries to the manufacturer, or to FDA if the manufacturer is unknown. In addition, SMDA also requires user facilities to submit to FDA, on an annual basis, a summary of all reports submitted.

The CDRH Division of Small Manufacturers International and Consumer Assistance and the Office of Surveillance and Biometrics should be contacted for further guidance about the MDR regulation. Inspections for compliance with the MDR regulation are conducted following the guidance contained in the Compliance Program 7382.845 - Inspection of Medical Device Manufacturers. When reviewing the manufacturer's complaint files, look for complaints, which are reportable, and have not been reported by the manufacturer.

 2.9.2.8 - Radiation Reporting

Prior to introduction of products into commerce, manufacturers of radiation-emitting electronic products must submit radiation safety Product Reports if the product is listed and marked in Table 1 of 21 CFR 1002.1. (Non-medical radiation products have NO registration and listing requirements, but the same type of information is included in these reports.) These are premarket documents but there is no timeframe for review and manufacturers do not have to wait for clearance. However, these documents must be processed by CDRH, Office of Compliance to provide rapid import entry of electronic products. Radiation Product Reports provide technical specifications, how products comply with standards, and radiation testing and quality control programs to support the firm's (self)-certification of compliance of each product.

In addition, manufacturers must file annual reports (if specified in Table 1), defect or noncompliance reports when appropriate (similar to recall notices), and accidental radiation occurrence reports when appropriate (similar to, and sometimes replaced by, Medical Device Reports (MDRs)).

 2.9.3 - CENTER FOR BIOLOGICS EVALUATION AND RESEARCH (CBER)

The requirements for the registration and licensing of biological products fall under both the Public Health Service Act (PHS) and the FD&C Act.

 2.9.3.1 - Registration and Listing

See also IOM 5.7.3.

CBER provides industry with registration and listing forms, FDA 2830, Blood Establishment Registration and Product Listing, and FDA 3356, Establishment Registration and Listing for Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps). Instructions for completing these documents are on the reverse side of these forms along with establishment and product definitions. Registration forms are available through the district office and through CBER's Office of Communication, Training and Manufactures Assistance, and from the CBER website. Registration and listing is required whether or not interstate commerce is involved. (See IOM 5.7.3)

 2.9.3.1.1 - HUMAN BLOOD AND BLOOD PRODUCTS

Human Blood and Blood Products:

  1. Who must register - Section 510 of the FD&C Act and 21 CFR 607 delineate the requirements and exemptions relating to the registration of establishments engaged in the collection, manufacturing, preparation, or processing of human blood or blood products. Registration and listing are required whether or not interstate commerce is involved. Fixed blood collection sites that have supplies or equipment requiring quality control or have an expiration date, e.g., copper sulfate, centrifuges, etc., or are used to store donor records, must register. Temporary collection sites, to which all blood collection supplies are brought on the day of collection and are completely removed from the site at the end of the collecting period (except beds, tables, and chairs) and blood mobiles, are not required to register. All Military blood bank establishments are required to register. (MOU with Department of Defense [Federal Cooperative Agreements Manual] Regarding Licensure of Military Blood Banks.) Brokers, who take physical possession of blood products, such as in storage, pooling, labeling, or distribution, are required to register. Blood establishments located outside of the United States that import or offer for import blood products into the U.S. are required to register with FDA. They must also provide the name of the United States agent, the name of each importer, and each person who imports or offers for import these blood products.
  2. When to register - Establishments must register within five days after beginning operations and must submit a list of blood products they distribute commercially. They must register annually thereafter.
  3. How to register - Owners or operators of blood establishments register using the Form FDA 2830. Refer to Compliance Policy Guide (CPG) 230.110 for additional information on registration. These persons may complete and submit Form FDA 2830 on the Internet or may submit a paper form.
  4. Where to mail completed paper forms - Mail completed legible forms to: Food and Drug Administration, Center for Biologics Evaluation and Research, Division of Blood Applications (HFM-370), 1401 Rockville Pike, 200N, Rockville, MD 20852-1448.
  5. General Information and Questions:
    Phone: 301-827-3546
    Email: bloodregis@cber.fda.gov
    Mail: Food and Drug Administration, Center for Biologics Evaluation and Research, Division of Blood Applications, (HFM-370), 1401 Rockville Pike, 200N, Rockville, MD 20852-1448.

 2.9.3.1.2 - HUMAN CELLS, TISSUES, AND CELLULAR AND TISSUE-BASED PRODUCTS (HCT/PS)

Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps):

  1. Who must register - Establishment that manufacture HCT/Ps that are regulated solely under the authority of section 361 of the Publish Health Service Act (42USC264) (the PHS Act) must register and list with CBER whether or not the HCT/P enters into interstate commerce (21 CFR 1271.1). Establishments that manufacture HCT/Ps that are regulated as drugs, devices and/or biological products under section 351 of the PHS Act and/or the Federal Food, Drug and Cosmetic Act, must register and list with CBER following procedures in subpart B, 21 CFR 1271.21 thru 1271.37. Registration and listing are required if the establishment recovers, processes, stores, labels, packages, or distributes any human cell or tissue, or screens or tests the cell or tissue donor. Establishments exempted from registration are listed in 21 CFR 1271.15. Establishments that only have HCT/Ps under premarket review (IND/IDE/BLA/PMA) do not have to register and list until the HCT/P has been licensed, approved or cleared by FDA.
  2. When to register - Establishments must register within five days after beginning operations and must submit a list of each HCT/P manufactured.
  3. How to register - To register a Form FDA 3356 must be completed.
  4. Where to mail completed forms - Mail completed legible forms to: Food and Drug Administration, Center for Biologics Evaluation and Research, (HFM-775), 1401 Rockville Pike, 200N, Rockville, MD 20852-1448, Attention: Tissue Establishment Registration Coordinator. Or it may be submitted by FAX according to form instructions. Alternatively, establishments may now submit the information electronically via the Electronic Human Cell and Tissue Establishment Registration (eHCTERs) page.
  5. General Information and Questions:
    Phone: 301-827-6176 (Tissue Establishment Registration Coordinator) Email:
    tissuereg@cber.fda.gov Mail: Food and Drug Administration, Center for Biologics Evaluation and Research, HFM-775, 1401 Rockville Pike, 200N, Rockville, MD 20852-1448.

 2.9.3.2 - Biologic License

Section 351 of the Public Health Service Act requires individuals or companies who manufacture biological products for introduction into interstate commerce to hold a license for the products. Biologics licenses are issued by CBER and CDER (21 CFR 601.4).

What changes to an approved biologics license application are reportable - Applicants must inform the FDA about each change in the product, production process, quality controls, equipment, facilities, responsible personnel, or labeling established in the approved license application (21 CFR 601.12).

When to Report - Major changes require supplement submission and approval prior to distribution of products made using the change (21 CFR 601.12(b)). Certain changes require supplement submissions at least 30 days prior to distribution of the product made using the change, and other minor changes need only be described in an annual report (21 CFR 601.12(c) and (d)).

Where to send Reports - For licensed biological products regulated by CBER: Document Control Center (HFM-99), Center for Biologics Evaluation and Research, Food and Drug Administration, 1401 Rockville Pike, 200N, Rockville, MD 20852-1448. For licensed biological products regulated by CDER: Food and Drug Administration, Center for Drug Evaluation and Research, Office of New Drugs (Specify OND Review Division) 5901-B Ammendale Road, Beltsville, MD 20705-1266.Highlighted to denote updated text (21 CFR 600.2)

 2.9.4 - CENTER FOR VETERINARY MEDICINE (CVM)

Requirements for registration and filing of various applications by firms which manufacture animal drugs, feeds, and other veterinary products are required by the FD&C Act.

 2.9.4.1 - Registration and Listing

Owners or operators of all drug establishments, not exempt under section 510(g) of the FD&C Act [21 U.S.C. 360 (g)] or subpart D of 21 CFR 207, who engage in the manufacture, preparation, propagation, compounding, or processing of a drug or drugs are required to register. Also, they must submit a list of every drug in commercial distribution, except that listing information may be submitted by the parent, subsidiary, and/or affiliate company for all establishments when operations are conducted at more than one establishment, and there exists joint ownership and control among all the establishments. Registration of animal drug firms is handled by the Center for Drug Evaluation and Research (CDER). CVM maintains its own animal drug listing database.

Who must register - Owners and operators of establishments engaged in manufacture or processing of drug products must register and list their products.

When to register - The owner or operator of an establishment must register within 5 days after beginning of the operation and submit a list of every drug in commercial distribution at that time. Owners or operators of all establishments engaged in drug activities described in 21 CFR 207.3(a)(8) shall register annually. 

Begin Changed TextThe Guidance document on electronic submissions for drug establishment registration and drug product listing is available at: http://www.fda.gov/downloads/Drugs/
GuidanceComplianceRegulatoryInformation/Guidances/ucm072339.pdf
.End Changed Text

For information on registered animal drugHighlighted to denote updated text firms - CVM's Registration Monitor is Charise Kasser (HFV-212), 7519 Standish Place, Rockville, MD 20855 240-276-9069. You may make inquiries on registration status of individual firms through Ms. Kasser.

For information on animal drug listing - CVM maintains its own database for animal drug listing. You may make inquiries for information to 240-276-9300.
 

 2.9.4.2 - Medicated Feed Mill License (FML)

Who must register - The manufacture of a Type B or Type C medicated feed containing a Category II drug, from a Type A medicated article, must hold an approved license (FDA 3448). The mill must be registered with the Food and Drug Administration, Information Management Team, HFD-095, to obtain an FDA Registration Number and be operating in compliance with Good Manufacturing Practices as described in 21 CFR 225 by passing an inspection conducted by FDA or a designated party.

How to obtain a license application - Form FDA 3448 is available on the Center for Veterinary Medicine’s web page or from the Food and Drug Administration, Center for Veterinary Medicine, Division of Animal Feeds (HFV-220), 7500 Standish Place, Rockville, MD 20855. Where to mail completed forms - Mail completed legible form to the Division of Animal Feeds at the address above. Supplemental applications also go to the above address.

General Information and Questions:
Phone: 240-276-9300.
Mail: Food and Drug Administration, Center for Veterinary Medicine (HFV-220), 7500 Standish Place, Rockville, MD 20855.

 2.9.4.3 - Abbreviated New Animal Drug Application (ANADA)

The Generic Animal Drug and Patent Term Restoration Act amended the FD&C Act to provide for the approval of generic copies of previously approved animal drug products. The generic product may be approved by providing evidence it contains the same active ingredients, in the same concentration, as the approved article, and is bioequivalent. The information is submitted to the FDA in the form of an Abbreviated New Animal Drug Application or ANADA.

How to file - An ANADA must be submitted to FDA on the form FDA 356V. The format and content of the application must be in accordance with the policies and procedures established by FDA's Center for Veterinary Medicine. The application must be filled out completely in triplicate and submitted to the address below.

Where to obtain forms - ANADA’s also use the form FDA 356 which can be obtained from: Food and Drug Administration, Center for Veterinary Medicine (HFV-12), 7500 Standish Place, Rockville, MD 20855.

Where to mail completed forms - Completed legible applications should be mailed to: Food and Drug Administration, Center for Veterinary Medicine (HFV-199), 7500 Standish Place, Rockville, MD 20855.

General Information and Questions - Assistance and additional information can be obtained by calling 240-276-9300

 2.9.4.4 - New Animal Drug Application (NADA)

A new animal drug is any drug intended for use in animals other than man. Manufacturers of new animal drugs must complete a New Animal Drug Application (NADA), and receive approval prior to distribution.

How to file - Applications must be submitted on a form FDA 356. The applications must be signed by the applicant or by an authorized attorney, agent, or official. The application must be filled out completely, in triplicate, and submitted to the address below.

Where to obtain forms - NADAs use form FDA 356 which can be obtained from: Food and Drug Administration, Center for Veterinary Medicine (HFV-12), 7500 Standish Place, Rockville, MD 20855.

Where to mail completed forms - Completed NADAs should be mailed to: Food and Drug Administration, Center for Veterinary Medicine (HFV-199), 7500 Standish Place, Rockville, MD 20855.

General Information and Questions - General information or questions can be answered by calling 240-276-9300

 2.9.5 - CENTER FOR FOOD SAFETY AND APPLIED NUTRITION (CFSAN)

The FDA issued 21 CFR 1, an interim final regulation in FR Vol. 68 No. 197  pgs 58893-58974 on October 10, 2003 that requires affected domestic and foreign facilities that manufacture/process, pack or hold food for human or animal consumption in the United States to register with the FDA by December 12, 2003. The interim final rule implements the Public Health Security and Bioterrorism Preparedness and Response Act of 2002 (the Bioterrorism Act). For more information see the FDA/CFSAN website on food firm registration.

The FD&C Act and its regulations require certain firms to register and to file scheduled processes, while other firms are requested to do this voluntarily. CFSAN provides guidance and assistance as described below.

 2.9.5.1 - Low Acid Canned Food (LACF) / Acidified Foods (AF) Food Canning Establishment (FCE) Registration

Food Canning Establishments (FCE) (foreign and domestic) engaged in the manufacture of Low Acid Canned Food/Acidified Foods (LACF/AF) offering their products for interstate commerce within the United States are required by 21 CFR Parts 108, 113, and 114 to register their facility with the FDA as indicated below.

Who must register - All commercial processors of LACF and AF products located in the US, and all processors in other countries who export their LACF or AF into the US must register their processing plants with the FDA. Wholesalers, importers, distributors, brokers, shippers, etc. are not required to register and file scheduled process information. However, they must ensure the processing firms they represent comply with all registration and process filing requirements.

When to register - Commercial LACF and AF processors in the US must register with FDA not later than 10 days after first engaging in the manufacture, processing, or packing of AF or LACF. Processors in other countries must register before offering any such products for import into the US.

How to register - To register with FDA, processors must complete and submit the FCE Registration Form (FDA 2541) for each processing establishment location and file scheduled process information for their products using forms FDA 2541a, "Food Process Filing for All Methods Except Low-Acid Acid Aseptic Systems" or FDA 2541c, “Food Process Filing for Low-Acid Aseptic Systems” with Required Supplemental Information.

A copy of the FCE Registration form will be returned to the firm or its authorized representative upon assigning of the five-digit FCE number to the plant. For domestic plants, a copy of the FCE Registration Form will be forwarded to the Investigations Branch of the FDA District Office in which the plant is located.  The District Office sends a response notifying the LACF Registration Coordinator of the firm’s assigned FEI.

FCE registration information changes - Manufacturers must notify the FDA of any changes to their FCE registration information. These notifications should be made using form FDA 2541 for changes in firm name, ownership, street name and number, or preferred mailing address. It would be marked as a "Change of Registration Information" and the type of change requested. When the plant does not actually change location, but location is rezoned or to identify an authorized representative this can be accomplished through a letter.

Where to mail completed forms - Mail completed legible forms to: LACF Registration Coordinator, Center for Food Safety and Applied Nutrition, 5100 Paint Branch Parkway, College Park, MD 20740-3835.

General Information and Questions:
E-mail: LACF@fda.hhs.gov

 2.9.5.2 - FCE Process Filing of LACF/AF Processors

In addition to processors registering their establishments with the FDA, processors must also submit and file scheduled process information for their LACF/AF products with the FDA. That information must be submitted on forms FDA 2541a or FDA 2541c with Required Supplemental Information. Processes must be filed no later than 60 days after registration and prior to packing a new product or, in the case of firms in other countries, before importing their products into the United States.

It is the responsibility of the manufacturer and/or its authorized representative to ensure the design process used is safe from a standpoint of public health significance and will destroy or inhibit the growth of microorganisms. This is accomplished through the consultation of and recommendations by a process authority. Documentation that scheduled processes are delivered should be maintained through appropriate and accurate record keeping. Forms and documentation must be presented in English.

Process filing information consists of the following:

  1. FCE number to the plant,
  2. Submission Identifier (SID) number to identify a specific form submitted by the manufacturer,
  3. Governing regulation (LACF - 21 CFR 108.35/113 or AF - 21 CFR 108.25/114),
  4. Food name or description, which includes form or style of the product (whole, sliced, diced, etc.) and packing medium (in water, in brine, in tomato sauce, etc.),
  5. Container type,
  6. Process Establishment Source, and
  7. Container dimensions in inches and/or capacity.
  8. Scheduled process
  9. Other critical factors if applicable

 2.9.5.3 - Cosmetics

VOLUNTARY REGISTRATION OF COSMETIC PROD­UCT ESTABLISHMENTS (21 CFR 710)

Who should register - The owner or operator of a cosmetic product establishment, which is not exempt under 21 CFR 710.9, and engages in the manufacture or packaging of a cosmetic product, is asked to register each such establishment, whether or not the product enters interstate commerce. This request extends to any foreign cosmetic product establishment whose products are exported for sale in any State as defined in section 201(a)(1) of the FD&C Act [21 U.S.C. 321 (a)(1)]. No registration fee is required.

Time for registration - The owner or operator of an establishment entering into the manufacture or packaging of a cosmetic product should register the establishment within 30 days after the operation begins.

How and where to register - The FDA 2511 - Registration of Cosmetic Product Establishment is available from the FDA, CPK-2, Office of Cosmetics and Colors, Cosmetics Staff (HFS-125), 5100 Paint Branch Parkway, College Park, MD 20740-3835, or at any FDA district office. The completed form should be mailed to HFS-125. The form is also available online at VCRP Online Forms.  Establishments can also be registered online at VCRP Online Registrations.

Information requested - The FDA 2511 requests information on the name and address of the cosmetic product establishment, including post office ZIP code; all business trading names used by the establishment; and the type of business (manufacturer and/or packer). The information requested should be given separately for each establishment.

General information and questions - Call 240-402-1345, or e-mail at https://www.accessdata.fda.gov/scripts/ocacapp/client/vcrp/contact/Highlighted to denote updated text. Instructions are sent with the forms.

VOLUNTARY FILING OF COSMETIC PRODUCT IN­GREDIENT COMPOSITION STATEMENT (21 CFR 720)

Who should file - Either the manufacturer, packer, or distributor of a cosmetic product is requested to file a FDA-2512 Cosmetic Product Ingredient Statement, whether or not the product enters interstate commerce. The request extends to any foreign manufacturer, packer, or distributor of a cosmetic product exported for sale in any State as defined in section 201(a)(1) of the FD&C Act [21 U.S.C. 321 (a)(1)]. No filing fee is required.

Times for filing - The FDA 2512 should be filed for each cosmetic product being commercially distributed. The FDA-2512 should be filed within 60 days after the beginning of commercial distribution of any product.

How and where to file - The FDA 2512 and FDA 2514 - Discontinuance of Commercial Distribution of Cosmetic Product Formulation are obtainable on request from the FDA, CPK-2, Office of Cosmetics and Colors, Cosmetics Staff (HFS-125), 5100 Paint Branch Parkway, College Park, MD 20740-3835 or at any FDA district office. The forms are also available online at VCRP Online Forms. The completed form should be mailed or delivered according to instructions provided with the form to HFS-125. The FDA-2512 Cosmetic Product Ingredient Statement can also be filed online at VCRP Online Registrations.

General information and questions - Phone: 240-402-1257, or e-mail at https://www.accessdata.fda.gov/scripts/ocacapp/client/vcrp/contact/Highlighted to denote updated text.

 2.9.5.4 - Color Certification Program

Request for Certification - A request for certification of a batch of color additive (straight, repack, lake) should be submitted in duplicate. Formats for these requests are found in 21 CFR 80.21. The fee prescribed in 21 CFR 80.10 should accompany the request, unless the firm has established with the FDA an advanced deposit to be used for prepayment of such fees.

A sample accompanying a request for certification must be submitted under separate cover, and should be addressed to the Food and Drug Administration, Color Certification Branch (HFS-107), 5100 Paint Branch Parkway, College Park, MD 20740-3835.

Where to mail request - Mail or deliver the request to the Food and Drug Administration, Color Certification Branch (HFS-107), 5100 Paint Branch Parkway, College Park, MD 20740-3835.

General information and questions - Phone: 240-402-1136, or e-mail at Naomi.Richfield-Fratz@cfsan.fda.gov.

Contact the Food and Drug Administration, Color Certification Branch (HFS-107), 5100 Paint Branch Parkway, College Park, MD 20740-3835.

Costs - There is a fee for services provided (analytical work) which will vary based on type (straight, repack, lake), weight, number of batches, etc. See 21 CFR 80.10.

 2.9.5.5 - Infant Formula

Who should register - There are three types of notifications:

  1. First Notification - All manufacturers of infant formula sold in the US, and any manufacturer of a "new infant formula", must register with FDA no less than 90 days before it is introduced into interstate commerce.

    The first notification shall include:

    1. The quantitative formulation of the infant formula,
    2. A description of any reformulation of the formula or change in processing of the infant formula,
    3. Assurances the infant formula meets regulations and, as demonstrated by the testing required under regulations, and
    4. Assurances the processing of the infant formula complies with regulations.
  2. Second notification - This notification is given to FDA after the first production of an infant formula, and before it is introduced into interstate commerce. The manufacturer shall submit a written verification which summarizes test results and records demonstrating such formula complies with regulations.
  3. Third notification - This notification must be sent to FDA if the manufacturer determines a change in the formulation or processing of the formula may adversely affect the article.

Where to mail notifications - Notifications should be sent to: Food and Drug Administration, Office of Nutrition, Labeling and Dietary Supplements, Infant Formula and Medical Foods Staff, HFS-850, 5100 Paint Branch Parkway, College Park, MD 20740-3835.

General information and questions phone: 240-402-2373.

 2.9.5.6 - Interstate Certified Shellfish (Fresh and Frozen Oysters, Clams, and Mussels) Shippers

Persons interested in receiving general information about the National Shellfish Sanitation Program - Contact: Food and Drug Administration, Division of Seafood Safety, HFS-325, 5100 Paint Branch Parkway, College Park, MD 20740. Phone: 240-402-2300; FAX: 301-436-2601

Persons interested in technical assistance about the National Shellfish Sanitation Program - Contact: Food and Drug Administration, Retail Food & Cooperative Programs Coordination Staff (HFS-320), 5100 Paint Branch Parkway, College Park, MD 20740. Phone: 240-402-2149; FAX: 301-436-2672

Persons interested in receiving the Interstate Certified Shellfish Shippers List (ICSSL) - Contact: Charlotte V. Epps. Mail: Food and Drug Administration, Retail Food & Cooperative Programs Coordination Staff (HFS-320), 5100 Paint Branch Parkway, College Park, MD 20740. Phone: 240-402-2154; FAX: 301-436-2672

 2.9.5.7 - Interstate Milk Shippers (IMS)

Rules for inclusion in the IMS List - All Grade A milk shippers certified by State Milk Sanitation Rating authorities as having attained an acceptable sanitation compliance and enforcement rating are include in the IMS list. These ratings are based on compliance with the requirements of the "USPHS/FDA Grade A Pasteurized Milk Ordinance (PMO) and/or the Grade A Condensed and Dry Milk Products and Condensed and Dry Whey Ordinance (DMO)" and are made in accordance with the procedures set forth in "Methods of Making Sanitation Rating of Milk Shippers" and the "Procedures Governing the Cooperative State-Public Health Service/ Food and Drug Administration Program of the National Conference on Interstate Milk Shippers". The IMS List is published semi-annually and updated monthly on the FDA website.

To obtain a free copy of the IMS List contact:

Food and Drug Administration
Dairy and Egg Branch (HFS-316)
Division of Plant and Diary Food Safety
5100 Paint Branch Parkway
College Park, MD 20740

General Information and Questions.

Contact: Dairy and Egg Branch (HFS-316), Division of Plant and Diary Food Safety, Food and Drug Administration, 5100 Paint Branch Parkway, College Park, MD 20740. Phone: 240-402-1700.

2.9.6 - CENTER FOR TOBACCO PRODUCTSHighlighted to denote updated text

The FD&C Act and its amendment under the Family Smoking Prevention and Tobacco Control Act require manufacturers or importers to submit certain information to the FDA including: Tobacco Health Document Submission, Establishment Registration and Product Listing, and Listing of Ingredients in Tobacco Products.Highlighted to denote updated text

General information regarding industry submissions or the process can be found at http://www.fda.govlTobaccoProducts/ResourcesforYou/ForManufacturers/default.htm.Highlighted to denote updated text