51276 Federal Register / Vol. 71, No. 167 / Tuesday, August 29, 2006 / Proposed Rules 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

21 CFR Parts 20, 201, 207, 314, 330, 

514, 515, 601, 607, 610, and 1271 

[Docket No. 2005N–0403] 

RIN 0910–AA49 

Requirements for Foreign and 

Domestic Establishment Registration 

and Listing for Human Drugs, 

Including Drugs that are Regulated 

Under a Biologics License Application, 

and Animal Drugs 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Proposed rule. 

SUMMARY: The Food and Drug 

Administration (FDA) is proposing to 

amend its regulations governing drug 

establishment registration and drug 

listing. The proposed revisions would 

reorganize, consolidate, clarify, and 

modify current regulations concerning 

who must register establishments and 

list human drugs, human drugs that are 

also biological products (including 

vaccines and allergenic products), and/ 

or human cells, tissues, and cellular and 

tissue-based products (HCT/Ps), and 

animal drugs. The proposal describes 

when and how to register and list and 

what information must be submitted for 

registration and listing. In addition, the 

proposal would make certain changes to 

the National Drug Code (NDC) system 

and would require the appropriate NDC 

number to appear on the labels for drugs 

subject to the listing requirements. The 

proposed regulations generally would 

require the electronic submission of all 

registration and most listing 

information. We (FDA) rely on 

establishment registration and drug 

listing information for administering 

many of our programs, such as 

postmarketing surveillance (including 

FDA inspections), bioterrorism, drug 

shortages and availability, and user fee 

assessments. We are taking this action to 

use the latest technology to improve our 

registration and listing system, which 

would further our goal of protecting the 

public health. We also believe that the 

conversion to an electronic system 

would make the registration and listing 

processes more efficient and effective 

for industry and us. We are also taking 

this action to support the 

implementation of, for example, the 

electronic prescribing provisions of the 

Medicare Prescription Drug, 

Improvement, and Modernization Act, 

our rulemaking requiring a bar code on 

certain drug products, and the DailyMed 

initiative. 

DATES: Submit written or electronic 

comments by November 27, 2006. 

Submit written comments on the 

information collection requirements by 

September 28, 2006 to OMB (see 

ADDRESSES). See section IX of this 

document for the proposed effective 

date and section X for the proposed 

compliance dates of a final rule based 

on this document. 

ADDRESSES: You may submit comments, 

identified by Docket No. 2005N–0403 

and/RIN 0910–AA49, by any of the 

following methods: 

Electronic Submissions 

Submit electronic comments in the 

following ways: 

• Federal eRulemaking Portal: http:// 

www.regulations.gov. Follow the 

instructions for submitting comments. 

• Agency Web site: http:// 

www.fda.gov/dockets/ecomments. 

Follow the instructions for submitting 

comments on the agency Web site. 

Written Submissions 

Submit written submissions in the 

following ways: 

• FAX: 301–827–6870. 

• Mail/Hand delivery/Courier [For 

paper, disk, or CD-ROM submissions]: 

Division of Dockets Management (HFA– 

305), Food and Drug Administration, 

5630 Fishers Lane, rm. 1061, Rockville, 

MD 20852. 

To ensure more timely processing of 

comments, FDA is no longer accepting 

comments submitted to the agency by email. FDA encourages you to continue 

to submit electronic comments by using 

the Federal eRulemaking Portal or the 

agency Web site, as described in the 

Electronic Submissions portion of this 

paragraph. 

Instructions: All submissions received 

must include the agency name and 

Docket No(s). and Regulatory 

Information Number (RIN) (if a RIN 

number has been assigned) for this 

rulemaking. All comments received may 

be posted without change to http:// 

www.fda.gov/ohrms/dockets/ 

default.htm, including any personal 

information provided. For additional 

information on submitting comments, 

see the ‘‘Comments’’ heading of the 

SUPPLEMENTARY INFORMATION section of 

this document. 

Docket: For access to the docket to 

read background documents or 

comments received, go to http:// 

www.fda.gov/ohrms/dockets/ 

default.htm and insert the docket 

number(s), found in brackets in the 

heading of this document, into the 

‘‘Search’’ box and follow the prompts 

and/or go to the Division of Dockets 

Management, 5630 Fishers Lane, rm. 

1061, Rockville, MD 20852. 

Information Collection Provisions: 

Submit written comments on the 

information collection provisions to the 

Office of Information and Regulatory 

Affairs, Office of Management and 

Budget (OMB).To ensure that comments 

on the information collection are 

received, OMB recommends that written 

comments be faxed to the Office of 

Information and Regulatory Affairs, 

OMB, Attn: FDA Desk Officer, FAX: 

202-395-6974. 

FOR FURTHER INFORMATION CONTACT: For 

information concerning drugs regulated 

by the Center for Drug Evaluation and 

Research (CDER): Herbert Gerstenzang 

or John W. Gardner, Center for Drug 

Evaluation and Research (HFD–330), 

Food and Drug Administration, 5600 

Fishers Lane, Rockville, MD 20857, 

301–827–8920, 

herbert.gerstenzang@fda.hhs.gov or 

john.gardner@fda.hhs.gov. 

For information concerning products 

regulated by the Center for Biologics 

Evaluation and Research (CBER): 

Valerie A. Butler, Center for Biologics 

Evaluation and Research (HFM–17), 

Food and Drug Administration, 1401 

Rockville Pike, Rockville, MD 20852– 

1448, 301–827–6210, 

valerie.butler@fda.hhs.gov. 

For information concerning animal 

drugs: Lowell Fried (HFV–212) or Isabel 

W. Pocurull (HFV–226), Center for 

Veterinary Medicine (CVM), Food and 

Drug Administration, 7519 Standish Pl., 

Rockville, MD 20855, 301–827–7820 or 

240–453–6853, lowell.fried@fda.hhs.gov 

or isabel.pocurull@fda.hhs.gov. 

SUPPLEMENTARY INFORMATION: 

Table of Contents 

I. Background 

II. Summary of Current Registration and 

Listing Requirements 

A. Summary of Section 510 of the Act 

B. Summary of Current Registration and 

Listing Regulations 

1. Who Must Register and List Under 

Current Regulations? 

2. What Are the Current Registration 

Requirements? 

3. What Are the Current Listing 

Requirements? 

4. What Are the Current Requirements 

Associated With the Use of the NDC 

Number? 

5. Who Is Exempt from Registration and 

Listing Under Current Regulations and 

Who Is Not Covered by the Current 

Registration and Listing Requirements in 

21 CFR part 207? 

6. Do Current Regulations Permit the 

Disclosure of Registration and Listing 

Information? 

III. Highlights of the Proposed Rule 

A. Proposed Changes to the Current 

Registration and Listing Requirements 


jlentini on PROD1PC65 with PROPOSAL2
Federal Register / Vol. 71, No. 167 / Tuesday, August 29, 2006 / Proposed Rules 51277 

1 ‘‘Drug’’ or ‘‘drugs’’ refers to human drugs, 

including drugs that are regulated under a biologics 

license application, and animal drugs (including 

Type A medicated articles), unless otherwise 

specifically stated. ‘‘Drugs’’ is defined in proposed 

§ 207.1 and discussed in section IV.A.5 of this 

document. Biological products subject to proposed 

part 207 are described in proposed § 207.9(c). 

B. Promotion of Department of Health and 

Human Services Federal Health 

Information Technology Initiatives 

IV. Description of the Proposed Rule 

A. General 

1. What Is the Purpose of Proposed Part 

207? 

2. Who Would Part 207 Cover? 

3. Who Would Not Be Subject to Part 207? 

4. Who Would Be Exempt from 

Registration and Listing? 

5. What Definitions and Interpretations of 

Terms Would Apply to Part 207? 

B. Registration 

1. Who Would Be Required to Register? 

2. When Would Initial Registration 

Information Be Provided? 

3. What Information Would Be Required 

for Registration? 

4. What Are the Proposed Requirements for 

Reviewing and Updating Registration 

Information? 

C. The National Drug Code (NDC) Number: 

What is It? How is It Used? What 

Changes Are We Proposing? 

1. What Is the NDC Number? 

2. How Did NDC Numbers Originate? How 

Are They Used? 

3. What Changes Are We Proposing? 

4. How Do We Intend to Implement the 

NDC Number Changes? 

D. Listing 

1. Who Would Be Required to List Drugs? 

2. When Would Initial Listing Information 

Be Provided? 

3. What Listing Information Would Be 

Required? 

4. What Listing Information Would Be 

Required for Manufacturers? 

5. What Listing Information Would Be 

Required for Repackers and Relabelers? 

6. What Listing Information Would Be 

Required for Drug Product Salvagers 

Who are Not Repackers or Relabelers? 

7. What Additional Drug Listing 

Information May Be Required? 

8. What Are the Proposed Requirements for 

Reviewing and Updating Listing 

Information? 

E. Electronic Format 

1. How Would Registration and Listing 

Information Be Provided to FDA? 

2. What Was the Electronic Submission 

Pilot Project? 

3. How Would the Electronic Registration 

and Listing System Work? 

4. What Are the Proposed Requirements for 

the Submission of Content of Labeling in 

Electronic Format? 

5. Would the Proposal Require Electronic 

Submission of Advertisements and Other 

Labeling? 

6. What Guidance Documents Do We 

Intend To Issue on Providing 

Registration and Listing Information 

Electronically? 

7. How Would 21 CFR Part 11 Apply to the 

Electronic Submission of Registration 

and Listing Information? 

8. What Language Would Be Used to 

Provide Registration and Listing 

Information? 

9. Could the Electronic Format 

Requirements Be Waived? 

F. Miscellaneous 

1. What Are the Proposed Requirements for 

an Official Contact and a United States 

Agent? 

2. What Legal Status Is Conferred by 

Registration and Listing? 

3. What Registration and Listing 

Information Would Be Made Available 

for Public Disclosure? 

G. Conforming Actions 

1. Withdrawal from Sale of Drugs with 

Approved Marketing Applications 

2. Proposed Revisions to Other Regulations 

3. Compliance Verification Reports 

V. Legal Authority 

VI. Analysis of Economic Impacts 

VII. Paperwork Reduction Act of 1995 

VIII. Environmental Impact 

IX. Proposed Effective Date 

X. Proposed Compliance Dates 

XI. Federalism 

XII. Request for Comments 

XIII. References 

I. Background 

We originally published 

establishment registration regulations 

for human drugs, certain biological 

products, and animal drugs in the 

Federal Register of February 14, 1963 

(28 FR 1457) (proposed rule) and April 

3, 1963 (28 FR 3195) (final rule), and 

listing regulations for these drugs in the 

Federal Register of December 12, 1972 

(37 FR 26431) (proposed rule) and 

March 7, 1973 (38 FR 6258) (final rule). 

We currently maintain a database 

containing the establishment 

registration and drug listing information 

submitted on paper to us. We rely on 

complete and accurate registration and 

listing information to accomplish a 

number of our statutory and regulatory 

objectives. For example, we use 

registration and listing information to: 

• Identify the manufacturers, 

repackers, relabelers, and drug product 

salvagers of marketed drugs;1

• Identify the manufacturers, 

repackers, or relabelers of a specific 

drug or ingredient when that drug or 

ingredient is in short supply or is 

needed for a national emergency. This 

information helps us facilitate prompt 

drug shipment to the place where it is 

needed. For example, during a 

bioterrorism incident, we could use 

drug listing information to identify 

manufacturers, repackers, and relabelers 

of drugs that would be helpful in 

preventing or counteracting the deadly 

effects of biological weapons. With this 

information, we could facilitate prompt 

shipment of the drugs as needed; 

• Facilitate the recall of drugs 

marketed by manufacturers, repackers, 

and relabelers; 

• Identify and catalogue marketed 

drugs; 

• Administer our postmarketing 

surveillance programs for drugs, 

including the drug surveillance 

sampling program that monitors the 

quality of the national drug supply; 

• Identify drugs marketed in violation 

of the law; 

• Schedule and plan inspections of 

registered establishments pursuant to 

section 704 of the Federal Food, Drug, 

and Cosmetic Act (the act) (21 U.S.C. 

374); and 

• Determine which marketed drugs 

are identical, related, or similar to drugs 

reviewed for effectiveness under the 

Drug Efficacy Study Implementation 

(DESI) program. 

We also rely on registration and 

listing information to help us comply 

with several other statutory provisions. 

We use the information to: 

• Determine which entities are 

subject to establishment and product 

user fees under the prescription drug 

user fee program and the animal drug 

user fee program (21 U.S.C.379h and 

379). 

• Generate accurate estimates of the 

number of manufacturers, repackers, 

relabelers, and drug product salvagers 

and drugs that are affected by our 

rulemaking. These estimates help us 

assess the impact of our regulations on 

the regulated industry, which we are 

required to do under the Regulatory 

Flexibility Act (5 U.S.C. 601–612), as 

amended by the Small Business 

Regulatory Enforcement Fairness Act 

(Public Law 104–121), the Unfunded 

Mandates Reform Act of 1995 (2 U.S.C. 

1501 et seq.), the Paperwork Reduction 

Act of 1995 (44 U.S.C. 3501–3520), 

Executive Order 12866 (September 30, 

1993), and the Congressional Review 

Act (section 251 of Public Law 104–

121). 

Registration and listing information 

will continue to be used for all of the 

important public health purposes 

outlined above. Moreover, recent 

technological advances would allow us 

to enhance the usefulness of registration 

and listing information. Specifically, we 

are proposing that registration and 

listing information be submitted to us 

by using the electronic drug registration 

and listing system that we intend to 

develop. In addition to making the 

registration and listing process more 

efficient for industry, the electronic 

submission of registration and listing 

information would allow us to review 

and use such information more quickly 

and effectively in carrying out all of the 


jlentini on PROD1PC65 with PROPOSAL2
51278 Federal Register / Vol. 71, No. 167 / Tuesday, August 29, 2006 / Proposed Rules 

2‘‘Drug or drugs’’ includes drugs regulated under 

a BLA. For a description of biological products 

covered under proposed part 207, see proposed 

§ 207.9(c). 

activities described above. Electronic 

submission of this information would 

also allow us to fully support the 

implementation of the provisions of the 

Medicare Prescription Drug, 

Improvement, and Modernization Act 

(Public Law 108–173) (Medicare 

Modernization Act), specifically the 

electronic prescribing provisions. In 

addition, electronic submission of 

registration and listing information 

would further the purpose of several 

statutes: 

• The Public Health Security and 

Bioterrorism Preparedness and 

Response Act of 2002 (Public Law 107–

188) (Bioterrorism Act) amended section 

510(i) of the act (21 U.S.C. 360(i)) to 

require that foreign establishments 

submit, among other things, registration 

information electronically. 

• The Medical Device User Fee and 

Modernization Act of 2002 (Public Law 

107–250) also amended section 510 of 

the act (at section 510(p)) to explicitly 

give the Secretary of Health and Human 

Services (the Secretary) discretion to 

require the electronic submission of 

registration information, upon a finding 

that electronic receipt of such 

registration information is feasible, 

unless the Secretary grants a request for 

a waiver. 

• The Government Paperwork 

Elimination Act of 1998 (Public Law 

105–277, Title XVII) (GPEA) requires 

Federal agencies to give persons who 

are required to maintain, submit, or 

disclose information the option of doing 

so electronically when practicable as a 

substitute for paper, and to use 

electronic authentication (electronic 

signature) methods to verify the identity 

of the sender and the integrity of the 

electronic content. 

We believe that conversion to the 

electronic submission of registration 

and listing information will further the 

purpose of these laws and make the 

registration and listing processes more 

efficient and effective for industry and 

us. 

II. Summary of Current Registration 

and Listing Requirements 

A. Summary of Section 510 of the Act 

Section 510(c) of the act requires 

every person upon first engaging in the 

‘‘manufacture, preparation, propagation, 

compounding, or processing’’ of a drug 

in any establishment that he owns or 

operates in any State to immediately 

register his name and place of business 

and such establishment. Under section 

510(a)(1) of the act, the term 

‘‘manufacture, preparation, propagation, 

compounding, or processing’’ must 

include ‘‘repackaging or otherwise 

changing the container, wrapper, or 

labeling of any drug package * * * in 

furtherance of the distribution of the 

drug * * * from the original place of 

manufacture to the person who makes 

final delivery or sale to the ultimate 

consumer or user.’’ Section 510(a)(2) of 

the act mandates that the term ‘‘name’’

include, among other things, the name 

of each partner of a partnership, and the 

name of each corporate officer and 

director of a corporation. An owner or 

operator of a registered establishment 

must also immediately register any 

additional establishment that he owns 

or operates in any State and in which he 

begins the ‘‘manufacture, preparation, 

propagation, compounding, or 

processing’’ of a drug (section 510(d) of 

the act). An owner or operator of any 

establishment that engages in these 

activities must register its establishment 

on or before December 31 of each year 

(section 510(b) of the act). Section 510(i) 

of the act contains certain registration 

requirements pertaining to foreign 

establishments (e.g., submission of the 

name of each importer of a drug in the 

United States that is known to the 

establishment, submission of the name 

of each person who imports or offers for 

import a drug into the United States for 

purposes of importation). Section 510(g) 

of the act provides for certain 

exemptions from the registration 

requirements. In addition, section 

510(p) of the act gives the Secretary 

discretion to require the electronic 

submission of registration information, 

upon a finding that electronic receipt of 

such registration information is feasible, 

unless the Secretary grants a request for 

a waiver. 

Section 510(j)(1) of the act requires 

that every person, at the time of 

registration, submit a list of all drugs 

that are being manufactured, prepared, 

propagated, compounded, or processed 

by him for commercial distribution and 

that have not been previously listed by 

him. This information must be 

submitted in the form and manner 

prescribed by the Secretary (section 

510(j)(1) of the act). This listing 

information must be accompanied by, 

among other things, a copy of certain 

labeling and, in some cases, advertising 

for certain categories of drugs. Section 

510(j)(2) of the act requires certain 

changes in listing information to be 

reported every June and December, 

including any material changes in 

information previously submitted under 

the listing provisions. 

Section 510(e) of the act permits the 

Secretary to assign a registration number 

to any person or any establishments 

registered under section 510 and a 

listing number to each drug or class of 

drugs listed under section 510(j) as long 

as the listing number is the same as that 

assigned pursuant to the National Drug 

Code. The disclosure provision in 

section 510(f) of the act requires the 

Secretary to make available for 

inspection any registration filed under 

section 510. Section 510(f) also provides 

that certain listing information must be 

exempt from disclosure unless the 

Secretary finds that such exemption 

would be inconsistent with protection 

of the public health. 

B. Summary of Current Registration and 

Listing Regulations 

1. Who Must Register and List Under 

Current Regulations? 

Under current part 207 (21 CFR part 

207), with certain exceptions, owners or 

operators of establishments that engage 

in the manufacturing or processing of a 

drug or drugs must, in addition to other 

requirements, register their 

establishments and submit listing 

information for each of their drugs in 

commercial distribution.2

Notwithstanding certain exceptions, 

foreign drug establishments that 

manufacture, repack, or relabel a drug 

that is imported or offered for import 

into the United States must also comply 

with the registration and listing 

requirements. As explained in section 

IV.E of this document, all registration 

and listing information must currently 

be submitted to us using paper forms 

specified by us. 

2. What Are the Current Registration 

Requirements? 

Current requirements for registration 

include, among other things, the 

following provisions: 

• Owners or operators of 

establishments entering into the 

manufacturing or processing of a drug or 

drugs must register their establishments 

within 5 days after beginning the 

manufacturing or processing of drugs at 

the establishments (§ 207.21(a)). 

• If owners or operators of the 

establishments have not previously 

entered into such operations, then those 

owners or operators must register within 

5 days after the submission of a new 

drug application (NDA), abbreviated 

new drug application (ANDA), new 

animal drug application (NADA), 

abbreviated new animal drug 

application (ANADA), medicated feed 

mill license application, or biologics 

license application (BLA) (§ 207.21(a)). 


jlentini on PROD1PC65 with PROPOSAL2
Federal Register / Vol. 71, No. 167 / Tuesday, August 29, 2006 / Proposed Rules 51279 

• Owners or operators of 

establishments that are required to 

register must renew their registration 

annually in accordance with the 

specified schedule (§ 207.21(a)). 

Changes in individual ownership, 

corporate or partnership structure, 

location, or drug-handling activity must 

be submitted as amendments to 

registration within 5 days of such 

changes (§ 207.26). 

• We assign a permanent registration 

number to each registered establishment 

(§ 207.35). 

• Private label distributors that do not 

otherwise manufacture or process drugs 

are not required to register; however, 

they must submit specified information 

to us to obtain a labeler code 

(§ 207.20(b)). Private label distributors 

are owners or operators of 

establishments not otherwise required 

to register under section 510 of the act 

that distribute under their own label or 

trade name a drug manufactured or 

processed by a registered establishment. 

3. What Are the Current Listing 

Requirements? 

Current requirements for listing 

include, among other things, the 

following provisions: 

• Owners or operators of 

establishments must, at the time of 

registration, submit a list of every drug 

being manufactured or processed in 

commercial distribution at that time 

(§ 207.21(a)). 

• Private label distributors that do not 

otherwise manufacture or process drugs 

are not required to list, but may elect to 

submit listing information directly to us 

(§ 207.20(b)). Currently, private label 

distributors that elect to submit listing 

information directly to us assume full 

responsibility for compliance with the 

requirements of part 207 (§ 207.20(b)). 

Owners or operators of establishments 

that are required to register and list 

must submit listing information to us on 

behalf of private label distributors that 

do not elect to submit listing 

information directly to us (§ 207.20(b)). 

• Drugs that may be subject to current 

listing requirements include bulk drug 

substances; finished dosage forms, 

whether prescription or over-thecounter (OTC) drugs; and Type A 

medicated articles (§ 207.25(b)). 

• The required listing information 

submitted to us includes, but is not 

limited to: 

—The application number, if 

applicable, 

—Copies of current labeling as 

specified in current § 207.25(b) and, in 

some cases, a representative sampling of 

advertisements, 

—A quantitative listing of the active 

ingredient(s) (in some cases), 

—The NDC number, and 

—Any imprinting information 

(§ 207.25(b)). 

• Owners or operators of 

establishments that are required to 

register must update their listing 

information every June and December 

or, at the discretion of the owner or 

operator, when the change occurs. 

Updated information must include, but 

is not limited to: 

—A list of each drug introduced by 

the registrant for commercial 

distribution that has not been included 

in any previously submitted list, 

—A list of all previously listed drugs 

for which commercial distribution has 

been discontinued, 

—A list of all drugs for which a notice 

of discontinuance was submitted and 

for which commercial distribution has 

resumed, and 

—Any material change, as defined 

under current § 207.3(a)(3), in any 

information previously submitted 

(§ 207.30(a)). 

4. What Are the Current Requirements 

Associated With the Use of the NDC 

Number? 

The NDC system is used, among other 

things, to assign a drug listing number 

to each drug or class of drugs. 

• The NDC number currently consists 

of the labeler code, product code, and 

package code. We assign the labeler 

code, and, as stated in current 

regulations, ‘‘establishments’’ assign the 

product code and package code within 

certain parameters specified by us 

(§ 207.35). 

• Currently, we request, but not 

require, that the NDC number appear on 

all drug labels and labeling (§ 201.2 (21 

CFR 201.2), § 207.35(b)(3)). However, 

drug products described in current 

§ 201.25(b) (21 CFR 201.25(b)) must 

have on the label a bar code that 

contains, at a minimum, the appropriate 

NDC number in a linear bar code that 

meets specified standards (§ 201.25). 

• The current regulations specify both 

format and placement of the NDC 

number if the NDC number is included 

on drug labels and labeling 

(§ 207.35(b)(3)). 

5. Who Is Exempt From Registration and 

Listing Under Current Regulations and 

Who Is Not Covered by the Current 

Registration and Listing Requirements 

in 21 CFR Part 207? 

Under current regulations, certain 

establishments are exempt from the 

registration and listing requirements. 

For example, practitioners who are 

licensed by law to prescribe or 

administer drugs and who manufacture 

or process drugs solely for use in their 

professional practice, and persons who 

manufacture or process drugs not for 

sale but solely for use in research, 

teaching, or chemical analysis are 

exempt from registration and listing 

requirements. Many of the exemptions 

in current § 207.10 are also listed in 

section 510(g) of the act. 

The current regulations also describe 

those establishments that are not 

covered under part 207. Owners and 

operators of human blood and blood 

product establishments must register 

and list their products in accordance 

with part 607 (21 CFR part 607). 

However, such owners and operators 

who also manufacture or process other 

drug products at the same establishment 

must also register and list those drugs in 

accordance with part 207 (§ 207.7). 

Owners and operators of establishments 

that solely engage in the manufacture or 

processing of medical devices are not 

covered under part 207. However, such 

owners and operators must register and 

list their products in accordance with 

part 807. 

6. Do Current Regulations Permit the 

Disclosure of Registration and Listing 

Information? 

The current regulations specify the 

registration and listing information 

submitted to us that is available for 

public disclosure (§ 207.37). 

III. Highlights of the Proposed Rule 

This proposal would reorganize, 

consolidate, and modify the current 

registration and listing requirements. It 

would also assist us in promoting other 

important electronic health initiatives. 

A. Proposed Changes to the Current 

Registration and Listing Requirements 

We are proposing many changes to 

the current registration and listing 

requirements. In section IV of this 

document, we discuss in detail these 

changes and the reasons for the changes. 

The most significant proposed changes 

to the current requirements are as 

follows: 

• All registration information and 

most listing information would be 

provided to us electronically using the 

electronic drug registration and listing 

system that we intend to develop. 

(Currently, the information is submitted 

to us on paper forms.) 

• The appropriate NDC number 

would be required, with certain 

exceptions, to appear on drug labels. 

The appropriate NDC number is the 

NDC number belonging to the 

manufacturer, repacker, or relabeler, 

that corresponds to the particular drug; 


jlentini on PROD1PC65 with PROPOSAL2
51280 Federal Register / Vol. 71, No. 167 / Tuesday, August 29, 2006 / Proposed Rules 

a repacker or relabeler would not be 

permitted to place an NDC number that 

corresponds to an original manufacturer 

on a repackaged or relabeled drug. 

Although the NDC number would not be 

required to appear on other drug 

labeling (that is, the prescription drug 

labeling or the package insert), the NDC 

number would need to accompany the 

submission of the other drug labeling. 

(Currently, we only request that the 

NDC number appear on drug labels and 

labeling. However, certain drug 

products must have on the label a bar 

code that contains, at a minimum, the 

appropriate NDC number (see § 201.25).) 

• All three sections of the NDC 

number—that is, the labeler code, 

product code, and package code—would 

be assigned prospectively by us to drugs 

that have not previously been assigned 

NDC numbers by a manufacturer, 

repacker, or relabeler. (Currently, we 

assign the labeler code, and the 

registered establishment or private label 

distributor assigns the product code and 

package code within certain parameters 

specified by us.) The labeler code 

assigned prospectively by us would be 

the same as the labeler code (or one of 

the labeler codes) used by the 

manufacturer, repacker, or relabeler on 

its currently marketed drugs. 

• The NDC numbers currently 

assigned to drugs prior to the effective 

date of the rule would remain 

unchanged, provided those NDC 

numbers comply with the new 

regulations as finalized. FDA intends to 

validate that current NDC numbers 

comply with the new regulations as 

finalized. Manufacturers, repackers, and 

relabelers should review the 

information that they submitted to our 

registration and listing database to 

obtain an NDC number and update the 

information if necessary. They should 

complete their reviews and updates 

within 9 months after a final rule’s 

effective date. If, after the effective date 

of the final rule, there is a change in a 

drug (in accordance with proposed 

§ 207.33(f)), we would assign a new 

product code and package code to the 

newly changed drug, but the drug 

would keep the labeler code. If, after the 

effective date of the final rule, there is 

a change in a drug’s packaging, we 

would assign a new package code to the 

drug, but the drug would keep the 

labeler code and the product code. 

(Currently, the registered establishment 

or private label distributor may assign 

the product and package codes within 

certain parameters specified by us.) 

• Private label distributors would not 

be permitted to register or list under the 

proposed rule. (Currently, private label 

distributors submit certain information 

to request a labeler code and may list 

drugs. If the private label distributor 

elects not to submit drug listing 

information directly to us and to obtain 

a labeler code, the registered 

establishment must submit the drug 

listing information.) Manufacturers, 

repackers, relabelers, or drug product 

salvagers must submit drug listing 

information for those drugs they 

manufacture, repack, relabel, or salvage 

for a private label distributor. 

• Drug product salvagers would, in 

addition to registering, be required to 

list the drugs they salvage, even if they 

do not repack or relabel the drugs. 

(Currently, drug product salvagers are 

required to register but not list.) 

• The ‘‘content of labeling’’ as 

defined in proposed § 207.1 would be 

electronically submitted at the time of 

listing in a format that we can process, 

review, and archive. (Currently, all 

labeling required for listing is submitted 

in paper form.) 

B. Promotion of the Department of 

Health and Human Services (DHHS) 

Federal Health Information Technology 

Initiatives 

The proposal would allow us to 

provide important support for the full 

implementation of the electronic 

prescription provisions of the Medicare 

Modernization Act. The proposal would 

also support other initiatives, described 

in section IV.C.2 of this document, 

including DHHS Federal Health 

Information Technology initiatives. The 

proposal would result in an up-to-date 

NDC number system, in which we 

assign the NDC number, providing for 

accurate, unique, and unambiguous 

NDC numbers for each drug. This would 

allow electronic systems to reliably and 

consistently link the NDC number to the 

appropriate drug labeling through 

another DHHS health information 

technology initiative, Structured 

Product Labeling (SPL). The drug 

labeling would supply the drug 

ingredient and other information 

necessary to support the development of 

the standards for medication 

terminology necessary for electronic 

prescribing. Other initiatives supported 

by this proposal, including bar coding 

for drugs, are discussed in section 

IV.C.2 of this document. 

IV. Description of the Proposed Rule 

We are proposing to reorganize, 

consolidate, clarify, and modify the 

regulations in part 207. As a result, we 

have revised and recodified some 

provisions, added new provisions, and 

eliminated others. The following 

description of the proposed rule 

describes both new provisions and 

changes to existing regulations. 

A. General 

1. What Is the Purpose of Proposed Part 

207? 

We are proposing to add new § 207.5 

to explicitly state the purpose of part 

207, as set forth in the legislative history 

of the Drug Amendments of 1962 and 

the Drug Listing Act of 1972. 

• Establishment registration 

information helps us to identify who is 

manufacturing, repacking, relabeling, or 

salvaging drugs and where those 

operations are being performed. As 

explained in Senate Report No. 1744, 

‘‘drugs should not be on the market 

unless [FDA] knows who is making 

them, and where they are being made. 

This will help stop illicit and 

substandard manufacturers who do not 

follow the methods or establish the 

controls called for by good 

manufacturing practice’’ (1962 

U.S.C.C.A.N. 2884, 2889). Knowing 

where drugs are being made is even 

more important today because it would 

increase the Nation’s ability to prepare 

for and respond effectively to 

bioterrorism and other public health 

emergencies. 

• Drug listing information gives us a 

current inventory of marketed drugs. As 

stated in Senate Report No. 92–924, 

‘‘[t]he effective enforcement of the drug 

provisions of the [a]ct requires the ready 

availability of a current inventory of all 

marketed drugs’’ (1972 U.S.C.C.A.N. 

2963, 2964). Moreover, the intent of 

drug listing is to provide us ‘‘with an 

effective means of surveillance’’ (Id. at 

2965). Both establishment registration 

and drug listing information facilitate 

our implementation and enforcement of 

the act and are used for many important 

public health purposes. In addition, this 

information will help us better respond 

to emergencies (for example, we will be 

in a better position to effectively 

facilitate recalls should there be such a 

need). 

2. Who Would Part 207 Cover? 

We are proposing to add new § 207.9 

to explain that part 207 would apply to 

the following. 

• Domestic manufacturers, domestic 

repackers, domestic relabelers, and 

domestic drug product salvagers, unless 

they are exempt under section 510(g) of 

the act or proposed § 207.13. The terms 

‘‘domestic manufacturers,’’ ‘‘domestic 

repackers,’’ ‘‘domestic relabelers,’’ and 

‘‘domestic drug product salvagers’’ are 

defined in proposed § 207.1 and are 

explained in section IV.A.5 of this 

document. Proposed § 207.9 does not 


jlentini on PROD1PC65 with PROPOSAL2
Federal Register / Vol. 71, No. 167 / Tuesday, August 29, 2006 / Proposed Rules 51281 

3See footnote 1 of section 510 of the act. 

change the scope of current part 207. 

Domestic manufacturers, domestic 

repackers, domestic relabelers, and 

domestic drug product salvagers would 

be covered under proposed part 207 

whether or not the drugs they 

manufacture, repack, relabel, or salvage 

enter interstate commerce. Section 

510(b) and (c) of the act refer to an 

establishment ‘‘in any State.’’ Congress’s 

intention for section 510 of the act to 

apply to drugs both in interstate and 

intrastate commerce is stated in section 

301 of Public Law 82–781, in part, as 

follows: ‘‘[T]he products of all 

[establishments in which drugs are 

manufactured, prepared, propagated, 

compounded, or processed] are likely to 

enter the channels of interstate 

commerce and directly affect such 

commerce; and * * * the regulation of 

interstate commerce in drugs without 

provision for registration and inspection 

of establishments that may be engaged 

only in intrastate commerce in such 

drugs would discriminate against and 

depress interstate commerce in such 

drugs, and adversely burden, obstruct, 

and affect such interstate commerce.’’3

Accordingly, we are proposing to add to 

proposed § 207.9 the clause ‘‘regardless 

of whether their drugs enter interstate 

commerce’’ to reflect this congressional 

finding. The phrase ‘‘Drug products 

* * * must be listed whether or not the 

output of such establishments or any 

particular drug so listed enters interstate 

commerce’’ is already included in 

current § 207.20(a). 

• Foreign manufacturers, foreign 

repackers, foreign relabelers, and foreign 

drug product salvagers, unless they are 

exempt under proposed § 207.13(c) 

through (h). Foreign manufacturers, 

foreign repackers, foreign relabelers, and 

foreign drug product salvagers are 

currently required to register, and 

foreign manufacturers, foreign 

repackers, and foreign relabelers are 

currently required to submit listing 

information in accordance with section 

510 of the act and § 207.40. The terms 

‘‘foreign manufacturers,’’ ‘‘foreign 

repackers,’’ ‘‘foreign relabelers,’’ and 

‘‘foreign drug product salvagers’’ are 

defined in proposed § 207.1 and 

explained in section IV.A.5 of this 

document. 

An increased number of foreign 

manufacturers, foreign repackers, 

foreign relabelers, and foreign drug 

product salvagers may be required to 

comply with registration and/or listing 

requirements because we are proposing, 

as explained in section IV.A.4 of this 

document, to revoke certain provisions 

of current § 207.40(a) and (b). We are 

proposing to revoke the exemption in 

current § 207.40(a) relating to foreign 

establishments whose drugs enter a 

foreign trade zone and are re-exported 

from the foreign trade zone without 

having entered U.S. commerce. We are 

also proposing to revoke, in part, 

current § 207.40(b), which allows for a 

component of a drug imported under 

section 801(d)(3) of the act (21 U.S.C. 

381(d)(3)) to be imported or offered for 

import into the United States even if the 

component is not listed and 

manufactured, prepared, propagated, 

compounded, or processed at a 

registered foreign establishment. We are 

proposing to eliminate these two 

exemptions in current § 207.40(a) and 

(b) from the registration and listing 

requirements in light of certain statutory 

changes that have occurred since the 

publication of the final rule on foreign 

establishment registration and listing. 

Those changes include enactment of the 

Bioterrorism Act, which reflects 

Congress’ desire to increase the Nation’s 

ability to prepare for and respond 

effectively to bioterrorism and other 

public health emergencies. 

• Manufacturers of drugs regulated 

under a BLA, as follows: 

Manufacturers of drugs regulated 

under a BLA including, but not limited 

to: (1) Plasma derivatives such as 

albumin, Immune Globulin, Factor VIII 

and Factor IX, and recombinant versions 

of plasma derivatives or animal derived 

plasma derivatives; (2) vaccines; (3) 

allergenic products; (4) bulk product 

substances such as fractionation 

intermediates or pastes; and (5) 

therapeutic biological products. 

Establishments solely engaged in the 

manufacture, as defined in § 1271.3(e) 

(21 CFR 1271.3(e)), of HCT/Ps, as 

defined in § 1271.3(d), that, under 

§ 1271.20, are also drugs regulated 

under section 351 of the Public Health 

Service Act (PHS Act) or section 505 of 

the act. Proposed § 207.9(c)(2) would 

direct these establishments to register 

and list those HCT/Ps with CBER by 

following the procedures described in 

subpart B of part 1271 (21 CFR part 

1271) instead of the procedures for 

registration and listing described in part 

207. Proposed § 207.9(c)(2) is similar to 

current § 207.20(f), which we propose to 

revoke and replace with proposed 

§ 207.9(c)(2). 

We are also explaining the 

relationship between the requirements 

for HCT/Ps in part 207 and part 1271 of 

this chapter. We have implemented, in 

part 1271, a comprehensive, risk-based 

regulatory approach for HCT/Ps. Under 

this approach, some HCT/Ps are 

regulated solely under section 361 of the 

PHS Act (42 U.S.C. 264) and the 

regulations in part 1271; other HCT/Ps 

are also subject to regulation as drugs or 

devices under the act and to premarket 

application or notification requirements 

(submissions may include BLAs, NDAs, 

or device PMAs, product development 

protocols, or 510(k) applications). 

Current § 207.20(f) also states that the 

additional listing information 

requirements in current § 207.31 are 

applicable to HCT/Ps registered in 

accordance with the procedures in part 

1271, subpart B if they are also drugs 

regulated under a BLA and/or the act. 

We are proposing to revoke current 

§ 207.31 and move several of its 

requirements to other sections of the 

proposed rule (see discussion in 

sections IV.C and IV.D of this 

document). Consistent with the 

provisions in current § 207.20(f), the 

requirements will continue to apply to 

HCT/Ps that, under § 1271.20, are also 

drugs regulated under a BLA or section 

505 of the act. 

In addition, proposed § 207.9(c)(2) 

would require the submission of 

information not currently required for 

HCT/Ps under part 207, although the 

submission of such information has 

been required for drug products that are 

not HCT/Ps. For example, proposed 

§ 207.9(c)(2) would require 

establishments to submit the NDC 

number, as described in proposed 

§§ 207.49(a), 207.53(a), and 207.54(b)(1), 

and the route of administration, as 

described in proposed § 207.49(b). 

Under these provisions, such HCT/P 

establishments would not be required to 

register and list with both CBER and 

CDER. Rather, we envision that 

establishments will register with CBER, 

and then will be asked to provide 

additional information as required 

under part 207. We will manage our 

databases so that both CBER and CDER 

have use of the registration and listing 

information provided. The concept is 

that there will be a link in place when 

the establishment electronically 

accesses the electronic registration and 

listing system at http://www.fda.gov/ 

cber/tissue/tisreg.htm for tissue 

registration. This will allow access to 

the drug database fields to fill in the 

additional information such as the NDC 

number. If the establishment enters that 

it manufactures a licensed biologic, this 

will trigger the link. At the current time, 

there is only one such product. 

3. Who Would Not Be Subject to Part 

207? 

Proposed § 207.9 also describes two 

categories of establishments that would 

not be subject to part 207: 

• Owners and operators of human 

blood and blood product 


jlentini on PROD1PC65 with PROPOSAL2
51282 Federal Register / Vol. 71, No. 167 / Tuesday, August 29, 2006 / Proposed Rules 

establishments. This proposed rule does 

not apply to owners and operators of 

human blood and blood product 

establishments unless they manufacture 

any of the products listed in proposed 

§ 207.9(c)(1)(i) and (c)(1)(iv). If the 

owners and operators of human blood 

and blood product establishments 

manufacture any of those products, then 

they must register and list under part 

207. Establishments that collect or 

process whole blood and blood products 

as well as establishments involved in 

the testing of whole blood and blood 

products would register and list under 

part 607. For purposes of this proposal, 

blood and blood products consist of 

human whole blood, plasma, or serum 

or any product derived from human 

whole blood, plasma, or serum, and the 

term includes biological products 

regulated as licensed devices. 

Manufacturers of licensed devices and 

manufacturers of licensed biological 

components used in a licensed device 

would register and list under part 607. 

This exclusion is consistent with 

current § 207.7(a) and would not apply 

to owners and operators of human blood 

and blood product establishments who 

also manufacture other drugs. 

• Establishments that solely 

manufacture, prepare, propagate, 

compound, assemble, or process 

medical devices. Establishment 

registration and device listing 

regulations for such establishments and 

initial importers of devices, including in 

vitro diagnostic products, are codified 

in part 807. Establishments that 

manufacture, prepare, propagate, 

compound, assemble, or process 

medical devices, and also manufacture, 

prepare, propagate, compound, or 

process drugs, are subject to part 207 for 

drugs and part 807 for devices. 

As a result of these proposed 

revisions clarifying the scope of part 

207, proposed § 207.9 includes the 

provisions in current § 207.7 that 

explain the applicability of part 207 to 

human blood and blood products and 

medical devices. We are also proposing 

to revoke related provisions that set 

forth addresses in the Center for Devices 

and Radiological Health (CDRH) and 

CBER for submitting registration and 

listing information, and provisions that 

specify the appropriate forms for 

submitting such information. 

4. Who Would Be Exempt From 

Registration and Listing? 

Section 510(g) of the act and current 

§ 207.10 provide for exemptions from 

registration and drug listing 

requirements. Proposed § 207.13 

contains certain changes to some of the 

exemptions in current § 207.10, as 

discussed in the first part of this section. 

Proposed § 207.13 also incorporates 

without change some exemptions from 

current § 207.10, as discussed at the end 

of this section. 

The introductory paragraph of 

proposed § 207.13, largely consistent 

with current § 207.10, states that, except 

as provided in proposed § 207.13(i), the 

classes of persons listed in proposed 

§ 207.13 are exempt from registration 

and drug listing under section 510(g) of 

the act, or because we have found, 

under section 510(g)(5) of the act, that 

their registration is not necessary for the 

protection of the public health. We are 

proposing to add the phrase ‘‘except as 

provided in proposed § 207.13(i)’’ to 

indicate that even though the classes of 

persons identified in paragraphs (a) 

through (h) are exempt from registration 

and drug listing, if such persons engage 

in activities as set forth in paragraph (i), 

the exemption does not apply and they 

are required nonetheless to register and 

list. We are also proposing to include in 

the introductory paragraph a sentence 

clarifying that the exemption under 

proposed § 207.13 would not provide 

exemptions from other provisions of the 

act or regulations. For example, persons 

that do not have to register 

establishments and list drugs are still 

subject to the adulteration and 

misbranding provisions under sections 

501 and 502 of the act (21 U.S.C. 351 

and 352) and also may be subject to the 

new drug approval requirements under 

section 505 of the act (21 U.S.C. 355) or 

new animal drug approval requirements 

under section 512 of the act (21 U.S.C. 

360b). We may inspect their 

establishments in accordance with 

section 704 of the act and the current 

good manufacturing practice 

requirements. We are proposing to add 

the clarifying sentence because in the 

past some manufacturers, repackers, 

relabelers, and drug product salvagers 

that were exempt from registration and 

listing requirements incorrectly believed 

these provisions provided exemptions 

from other provisions of the act and 

regulations. Accordingly, we are 

proposing to add this sentence to 

remedy any confusion on this point. 

a. Pharmacies—The current 

exemption for pharmacies is codified at 

§ 207.10(a). The proposed rule would 

revise and clarify the exemption, and 

would move it to § 207.13(a). Except as 

noted in the discussion below, proposed 

§ 207.13(a) is generally consistent with 

current § 207.10(a). 

Under proposed § 207.13(a), 

pharmacies would be exempt from the 

registration and listing requirements if 

they: Operate in conformance with all 

applicable local laws regulating the 

practice of pharmacy, including all 

applicable local laws regulating the 

dispensing of prescription drugs; 

regularly engage in dispensing 

prescription drugs upon prescription of 

practitioners licensed by law to 

administer these drugs to patients under 

their professional care; and do not 

manufacture (as defined in proposed 

§ 207.1), repack, or relabel drugs for sale 

other than in the regular course of the 

practice of pharmacy, including 

dispensing and selling drugs at retail. 

Additional language has been added 

to proposed § 207.13(a)(1)(i) and 

(a)(1)(ii) to more closely track the 

language in section 510(g)(1) of the act. 

In addition, proposed § 207.13(a) does 

not include language that is in current 

§ 207.10(a) that provides that the 

supplying of prescription drugs to a 

practitioner licensed to administer the 

drugs for use in the course of the 

practitioner’s professional practice or to 

other pharmacies to meet temporary 

inventory shortages are not acts that 

require pharmacies to register. We are 

deleting this language because it is not 

necessary. Pharmacies that engage in 

such activities would be exempt from 

registration if they fulfill the following 

requirements: Operate in conformance 

with all applicable local laws regulating 

the practice of pharmacy, including all 

applicable local laws regulating 

dispensing of prescription drugs 

(proposed § 207.13(a)(1)(i)); regularly 

engage in dispensing prescription drugs 

upon prescription of practitioners 

licensed by law to administer these 

drugs to patients under their 

professional care (proposed 

§ 207.13(a)(1)(ii)); and do not 

manufacture (as defined in § 207.1), 

repack, or relabel drugs for sale other 

than in the regular course of the practice 

of pharmacy, including dispensing and 

selling drugs at retail (proposed 

§ 207.13(a)(1)(iii)). 

Proposed § 207.13(a)(2) clarifies that 

pharmacies may potentially qualify for 

the exemption in proposed § 207.13(a) 

only if they are located in any State as 

defined in section 201(a)(l) of the act (21 

U.S.C. 321) (that is, any State or 

Territory of the United States, the 

District of Columbia, and the 

Commonwealth of Puerto Rico). This 

proposed provision is currently located 

in the introductory paragraph in current 

§ 207.10. We believe it would be more 

clear to place this provision in proposed 

§ 207.13(a)(2). This aspect of the 

proposed provision is consistent with 

current §§ 207.10 and 207.40. 

b. Hospitals, clinics, other health care 

entities, and public health agencies—

The current exemption for hospitals, 

clinics, and public health agencies is 


jlentini on PROD1PC65 with PROPOSAL2
Federal Register / Vol. 71, No. 167 / Tuesday, August 29, 2006 / Proposed Rules 51283 

codified at § 207.10(b). The proposed 

exemption is generally consistent with 

current § 207.10(b), except for the 

addition of ‘‘other health care entities’’

and other mostly minor revisions and 

clarifications, as described below. The 

proposed exemption would move to 

§ 207.13(b). 

Hospitals, clinics, other health care 

entities, and public health agencies are 

exempt, under proposed § 207.13(b), 

from the registration and listing 

requirements if they: Operate 

establishments in conformance with all 

applicable local laws regulating the 

practice of pharmacy and medicine, 

including all applicable local laws 

regulating the dispensing of prescription 

drugs; regularly engage in dispensing 

prescription drugs, other than human 

blood or blood products, upon 

prescription of practitioners licensed by 

law to administer these drugs to patients 

under their professional care; and do 

not manufacture (as defined in proposed 

§ 207.1), repack, or relabel drugs other 

than in the regular course of the practice 

of pharmacy, including dispensing. 

The exemption in proposed 

§ 207.13(b) would be limited to 

hospitals, clinics, other health care 

entities, and public health agencies 

located in any State as defined in 

section 201(a)(1) of the act. The 

proposed provision requiring that such 

facilities be located in any State is 

currently located in the introductory 

paragraph in current § 207.10. We 

believe it would be more clear to place 

this provision in proposed 

§ 207.13(b)(2). This proposed provision 

(except with respect to BLA holders and 

the clarification with respect to positron 

emission tomography (PET) drugs) is 

generally consistent with current 

§§ 207.10 and 207.40. 

We are proposing to add ‘‘other health 

care entities’’ to this exemption because 

we are aware that other health care 

entities besides hospitals, clinics, and 

public health agencies (such as skilled 

nursing facilities) lawfully provide 

medical care and dispense drugs and 

logically are similarly situated to 

hospitals, clinics, and public health 

agencies for purposes of exempting 

them from registration and listing, if 

they meet the statutory and regulatory 

requirements. 

We are also proposing to add language 

to proposed § 207.13(b) to make the 

exemption more consistent with the 

pharmacy exemption in proposed 

§ 207.13(a). For example, we are 

proposing to add language to proposed 

§ 207.13(b)(1)(i) so that this exemption 

also specifically requires compliance 

with all applicable laws regulating 

dispensing of prescription drugs, as is 

required by proposed § 207.13(a)(1)(i). 

We are similarly proposing to add 

§ 207.13(b)(1)(iii) to be consistent with 

proposed § 207.13(a)(1)(iii), although in 

proposed § 207.13(b)(1)(iii) we have not 

included the terms ‘‘for sale’’ or ‘‘selling 

drugs at retail’’ since this language is 

appropriate for retail pharmacies relying 

on the exemption provided by proposed 

§ 207.13(a), but not for hospitals, clinics, 

other health care entities, and public 

health agencies relying on the 

exemption provided by proposed 

§ 207.13(b). 

We believe that the exemption for 

hospitals, clinics, other health care 

entities, and public health agencies 

provided in proposed § 207.13(b)(2) 

should be relied upon by pharmacies 

within these health care entities that 

dispense drugs to patients receiving care 

in the health care entities and that meet 

the requirements of the exemption, but 

should not be relied upon by retail 

pharmacies located within these health 

care entities. Retail pharmacies should 

rely upon the exemption in proposed 

§ 207.13(a) if they meet the 

requirements of that proposed 

provision. 

c. Persons who manufacture, repack, 

relabel, or salvage certain medicated 

feeds—Although we are proposing to 

reorganize and clarify the exemption for 

persons who manufacture, repack, 

relabel, or salvage certain medicated 

feeds, we are not proposing to change 

the substance of the exemption. Under 

proposed § 207.13(f), persons who 

manufacture, repack, relabel, or salvage 

Type B or Type C medicated feeds, 

except for manufacturers, repackers, 

relabelers, or drug product salvagers of 

Type B or Type C medicated feeds made 

from Category II, Type A medicated 

articles, are exempt from registration. 

This exemption would not apply to 

persons who would otherwise be 

required to register (such as 

manufacturers, repackers, relabelers, or 

drug product salvagers of certain freechoice feeds, as defined in 21 CFR 

510.455, or certain liquid feeds, as 

defined in 21 CFR 558.5, where the 

specifications and/or formulas are not 

published and a feed mill license is 

required). Proposed § 207.13(f) also 

clarifies that all manufacturers, 

repackers, relabelers, or drug product 

salvagers of Type B or Type C 

medicated feeds would be exempt from 

listing. 

d. The current exemptions for foreign 

trade zones and drugs imported under 

section 801(d)(3) of the act would be 

revoked—In 2001, we issued a final rule 

on foreign establishment registration 

and listing (66 FR 59138, November 27, 

2001). The regulation created two 

exemptions in § 207.40: 

• Under current § 207.40(a), a foreign 

establishment is not required to comply 

with the registration and listing 

requirements if its drug enters a foreign 

trade zone and is re-exported from that 

foreign trade zone without having 

entered U.S. commerce. We created this 

exemption as part of the final rule on 

foreign establishment registration and 

listing because registering such foreign 

establishments or listing drugs that were 

confined to a foreign trade zone—and 

were therefore not introduced into 

domestic commerce—was not 

considered necessary for the protection 

of the public health (see 66 FR 59138 at 

59139 and 59140). 

• Current § 207.40(b), which states 

that no drug may be imported or offered 

for import into the United States unless 

the drug is listed and manufactured, 

prepared, propagated, compounded, or 

processed at a registered foreign 

establishment, also states that this 

prohibition does not apply to 

components of drugs imported under 

section 801(d)(3) of the act. Section 

801(d)(3) of the act, as it existed before 

June 2002, allowed persons to import 

unapproved or otherwise noncompliant 

articles (such as drug components) 

provided that the imported articles were 

further processed or incorporated into 

products and exported or, if not used, 

the imported articles were destroyed or 

exported. The provision in § 207.40(b) 

reflected the fact that, at the time, 

section 801(d)(3) of the act imposed 

very few restrictions on the admission 

of drug components that are imported 

into the United States for further 

processing or incorporation into a 

product that will be exported from the 

United States (66 FR 59138 at 59148). 

Given the additional level of import 

restrictions imposed by the Bioterrorism 

Act, and the underlying security 

concerns that led to the Bioterrorism 

Act’s adoption, we are proposing to 

eliminate these two exemptions in 

current § 207.40(a) and (b) from the 

registration and listing requirements. In 

particular, sections 321 and 322 of the 

Bioterrorism Act, which affected foreign 

establishment registration by amending 

sections 510 and 801 (among other 

provisions) of the act, suggest that 

Congress intended the information 

requirements for foreign establishments 

and imported products to be 

comprehensive, and that Congress 

regarded the information it was 

requiring to be important to its goal in 

increasing the Nation’s ability to 

prepare for and respond effectively to 

bioterrorism and other public health 

emergencies. This, in turn, suggests to 


jlentini on PROD1PC65 with PROPOSAL2
51284 Federal Register / Vol. 71, No. 167 / Tuesday, August 29, 2006 / Proposed Rules 

FDA that the exceptions from the 

registration and listing requirements are 

therefore no longer appropriate. 

The Bioterrorism Act affected foreign 

establishment registration, in relevant 

part, by amending sections 510(i) and 

801 of the act: 

• To require, as part of an 

establishment’s registration, the name of 

each importer of the drug that is known 

to the establishment and the name of 

each person who imports or offers to 

import the drug into the United States; 

and 

• To provide that we may refuse 

admission of a product and, if the 

product is refused admission, that the 

product shall be held at the port of entry 

until a statement regarding the foreign 

establishment’s registration is submitted 

to us. 

The amendment to section 510(i) of 

the act reflects a determination on the 

part of Congress that a foreign 

establishment shipping drugs to the 

United States should provide additional 

information in its registration (that is, 

information about importers and 

persons who import or offer for import). 

FDA is concerned that if a foreign 

establishment is not subject to this 

establishment registration 

requirement—either by virtue of 

importing into a foreign trade zone or by 

importing components under section 

801(d)(3) of the act—it would allow 

some importers and persons who import 

or offer for import to go undetected, 

thereby creating an unnecessary 

vulnerability in Congress’ system of 

requiring this information. 

The amendment to section 801(o) of 

the act reflects a determination that 

establishment registration and drug 

listing information is important enough 

that, if it is lacking at the time the article 

is offered for import, the article may be 

refused admission (and, if refused, shall 

be held at the port of entry). FDA is 

concerned that if a foreign 

establishment is exempt from the 

registration and listing requirements—

either by virtue of importing into a 

foreign trade zone or by importing 

components under section 801(d)(3) of 

the act—FDA would be unable to rely 

on amended sections 510(i) and 801 of 

the act to require that imported products 

be held at the port of entry to the United 

States or to prevent such product’s 

delivery to the importer or consignee. 

This situation would stand in the way 

of implementing Congress’ apparent 

intent that this information be a 

prerequisite for entry of the imported 

product into the United States. 

We believe that removing the 

exception to the registration and listing 

requirements for products entering 

foreign trade zones and for products 

imported under section 801(d)(3) of the 

act is consistent with Congress’ desire to 

increase the Nation’s ability to prepare 

for and respond effectively to 

bioterrorism and other public health 

emergencies by requiring foreign 

establishments to provide more, rather 

than less, information for imported 

products. 

The Bioterrorism Act also revised 

section 801(d)(3) of the act, in part, by: 

• Requiring importers to identify the 

manufacturers of the imported drug 

component, and each processor, packer, 

distributor, or other entity that had 

possession of the article from the 

manufacturer to the importer; 

• Requiring certificates of analysis to 

accompany most imported articles; and 

• Giving us the ability to refuse 

admission to the United States if we 

determine there is credible evidence or 

information indicating that the article is 

not intended to be further processed by 

the initial owner or consignee, or 

incorporated by the initial owner or 

consignee into a drug, biological 

product, or other product specified in 

section 801(d)(3) of the act that will be 

exported from the United States. 

These statutory changes also indicate 

a congressional desire to know more, 

rather than less, about the articles 

entering the United States under section 

801(d)(3) of the act and to prevent 

potentially dangerous articles from 

entering the United States. The 

legislative history supports this belief, 

as the conference report for the 

Bioterrorism Act explained: ‘‘Refusal of 

entry should not involve shipments 

between known shippers and known 

recipients unless the Secretary has 

received credible evidence or 

information that suggests such 

shipments may not be legitimate. The 

Managers intend to permit the Secretary 

to refuse admission of articles if the 

Secretary determines there is credible 

evidence or information that the articles 

may be used as instruments of terror. 

Such evidence might include highly 

toxic or otherwise exceptionally 

dangerous products going to recipients 

unknown to the Secretary or to 

recipients believed to lack the capability 

to further process such dangerous 

articles * * *.’’ (See H. Rept. 107–481, 

l07th Cong. (2002), ‘‘Joint Explanatory 

Statement of the Committee of 

Conference,’’ ‘‘Subtitle B—Protection of 

Drug Supply’’ (discussing section 322).) 

The legislative history’s references to 

‘‘known’’ shippers, ‘‘known’’ recipients, 

and recipients who may lack the ability 

to further process an article, combined 

with the new statutory provision on 

refusing admission even if the article is 

imported under section 801(d)(3) of the 

act, strongly support our proposal to 

require that all drugs imported or 

offered for import into the United States 

be listed and manufactured at a 

registered foreign establishment. Failure 

to register such foreign establishments 

could compromise our ability to refuse 

admission of a dangerous article. 

Therefore, the proposed rule would 

eliminate the exemption from the 

establishment registration and drug 

listing requirements for foreign 

establishments whose drugs enter a 

foreign trade zone and are re-exported 

from that foreign trade zone without 

having entered U.S. commerce. In 

addition, the proposal would require 

that all drugs imported or offered for 

import into the United States be listed 

and manufactured at a registered foreign 

drug establishment, even if the drug is 

imported under section 801(d)(3) of the 

act. 

e. Other exemptions—As described in 

current § 207.10, the following remain 

exempt from registration and drug 

listing (proposed § 207.13): 

• Practitioners who are licensed by 

law to prescribe or administer drugs and 

who manufacture, repack, relabel, or 

salvage drugs solely for use in their 

professional practice (current 

§ 207.10(c); proposed § 207.13(c)). 

• Manufacturers, repackers, 

relabelers, or drug product salvagers of 

drugs solely for use in research, 

teaching, or chemical analysis and not 

for sale (current § 207.10(d); proposed 

§ 207.13(d)). Under proposed 

§ 207.13(d), manufacturers, repackers, 

relabelers, or drug product salvagers 

who manufacture, repack, relabel, or 

salvage drugs solely for use in research, 

teaching, or chemical analysis and not 

for sale are exempt from registration 

requirements. Proposed § 207.13(d) 

would be consistent with the exemption 

in section 510(g)(3) of the act, except the 

language would be modified to take into 

account the proposed rule’s uses of the 

terms ‘‘manufacturer,’’ ‘‘repacker,’’

‘‘relabeler,’’ ‘‘drug product salvager,’’

‘‘manufacture,’’ ‘‘repack,’’ ‘‘relabel,’’ and 

‘‘salvage.’’ We want to take the 

opportunity to remind interested 

persons that while the exemption from 

registration would apply to a sponsor 

that manufactures its own drug for use 

in its clinical trial of the drug, the 

exemption would not apply, for 

example, to a firm that manufactures a 

drug with the purpose of selling the 

drug to a sponsor for use in a clinical 

trial. In the latter situation, the 

manufacturer of the drug would be 

required to register. 

• Manufacturers, repackers, 

relabelers, and drug product salvagers of 


jlentini on PROD1PC65 with PROPOSAL2
Federal Register / Vol. 71, No. 167 / Tuesday, August 29, 2006 / Proposed Rules 51285 

4The term ‘‘manufacture’’ is defined in proposed 

§ 207.1 and is used here for brevity to refer to the 

activities that trigger registration requirements (that 

is, ‘‘manufacture, preparation, propagation, 

compounding, or processing’’ of drugs). Although 

many PET facilities do not consider themselves to 

be ‘‘manufacturing’’ drugs, but rather preparing or 

compounding drugs, we are nonetheless using the 

term ‘‘manufacture’’ for brevity. 

harmless inactive ingredients (current 

§ 207.10(e); proposed § 207.13(e)). We 

considered proposing to revoke this 

exemption because of concerns related 

to potential contamination of those 

inactive ingredients. However, we 

concluded that submitting and 

maintaining in the database all 

excipients, colorings, flavorings, 

emulsifiers, lubricants, preservatives, or 

solvents that become components of 

drugs could be burdensome for 

industry. In proposing to maintain this 

exemption, we note that current 

regulations governing the manufacture 

of finished drug products require all 

manufacturers to perform quality 

control testing to ensure that 

components meet established 

specifications (see generally, part 211 

(21 CFR part 211)). 

• Manufacturers, repackers, 

relabelers, and drug product salvagers of 

animal viruses, serums, toxins, or 

analogous products (current § 207.10(g); 

proposed § 207.13(g)). 

• Carriers (current § 207.10(h); 

proposed § 207.13(h)). 

f. Limits on exemptions—Proposed 

§ 207.13(i) would clarify that any of the 

persons who otherwise would qualify 

for an exemption under § 207.13(a) 

through (h) are not exempt from 

registration or listing if they: (1) 

Manufacture (as defined in proposed 

§ 207.1),4 repack, relabel, or salvage 

compounded positron emission 

tomography (PET) drugs as defined in 

section 201(ii) of the act; (2) 

manufacture (as defined in § 600.3(u)) a 

biological product subject to licensing 

under section 351 of the Public Health 

Service (PHS) Act; (3) manufacture (as 

defined in § 1271.3(e)) an HCT/P that, 

under § 1271.20, are also drugs 

regulated under section 351 of the PHS 

Act or section 505 of the act; or (4) 

engage in activities that would 

otherwise require them to register under 

this part. 

Thus, any person identified in 

proposed § 207.13(a) through (h), such 

as pharmacies, hospitals, clinics, other 

health care entities, public health 

agencies, or practitioners, if they 

manufacture, repack, relabel, or salvage 

compounded PET drugs, as defined in 

section 201(ii) of the act (21 U.S.C. 

321(ii)), would fall outside the scope of 

the exemptions provided in proposed 

§ 207.13(a) through (h). Manufacturers, 

repackers, relabelers, or drug product 

salvagers of compounded PET drugs are 

not included among the persons that are 

exempt from registration under 

proposed § 207.13 because exempting 

manufacturers of compounded PET 

drugs from registration would be 

inconsistent with section 121 of the 

Food and Drug Administration 

Modernization Act of 1997 (the 

Modernization Act) (Public Law 105–

115), which addresses the regulation of 

PET drug products. Section 121 of the 

Modernization Act directs us to develop 

appropriate procedures for the approval 

of PET drugs under section 505 of the 

act and appropriate CGMP requirements 

for such drugs. It also requires the 

submission of NDAs or ANDAs for PET 

drugs either 4 years after the date of 

enactment or 2 years after the date on 

which we establish approval procedures 

and CGMPs, whichever is longer. We 

published proposed CGMPs for PET 

drugs on September 20, 2005 (70 FR 

55038). If Congress had intended to 

exempt manufacturers, repackers, 

relabelers, or drug product salvagers of 

PET drugs from registration 

requirements, it would have done so. 

Given that PET manufacturers will be 

expected to comply with CGMP 

requirements and FDA will need to 

inspect them to determine compliance, 

it is reasonable to require PET 

manufacturers, repackers, relabelers, or 

drug product salvagers to register so we 

can identify PET manufacturers, 

repackers, relabelers, or drug product 

salvagers and the drugs they 

manufacture, repack, relabel, or salvage 

for inspection purposes. Therefore, the 

proposed rule would require 

compounded PET drug manufacturers, 

repackers, relabelers, or drug product 

salvagers to register with us and list 

their drugs in accordance with section 

510(j) of the act and proposed part 207. 

Likewise, any person identified in 

§ 207.13(a) through (h) who would 

otherwise qualify for an exemption 

would not qualify for an exemption if it 

manufactures (as defined in § 600.3(u)) 

a biological product subject to licensing 

under section 351 of the PHS Act. 

We note that to the extent a person 

manufactures, repacks, relabels, or 

salvages PET drugs as set forth in 

proposed § 207.13(i)(1) or manufactures 

a biological product subject to licensing 

as set forth in proposed § 207.13(i)(2), 

the obligation to register and list would 

only apply to the extent that that person 

engages in the activities identified in 

proposed § 207.13(i)(1) or (i)(2). For 

example, a hospital dispensing and 

administering drugs and that also 

manufactures compounded PET drugs 

would list only the PET drugs it 

manufactures, assuming none of its 

other activities would subject it to 

registration or listing requirements. 

Likewise, a public health agency 

dispensing and administering drugs that 

holds a biologics license application 

would list only the biological drugs it 

manufactures, assuming none of its 

other activities would subject it to 

registration or listing requirements. 

Proposed paragraph (i) also states that 

the exemptions provided in proposed 

§ 207.13(a) through (h) do not apply to 

such persons if they engage in activities 

that would otherwise require them to 

register. This concept appeared in 

current § 207.10(e). We are proposing to 

apply this concept to all the exemptions 

in proposed § 207.13 to reiterate that if 

a person qualifies for an exemption from 

the activities stated in proposed 

§ 207.13(a) through (h), that person may 

still need to register if that person 

engaged in activities that would 

otherwise require registration. 

5. What Definitions and Interpretations 

of Terms Would Apply to Part 207? 

In proposed § 207.1, we set forth new 

definitions and interpretations of terms 

for part 207 and revise or revoke certain 

definitions in current § 207.3(a). 

Current § 207.3(b) states that the 

definitions and interpretations of terms 

in sections 201, 502(e), and 510 of the 

act apply to the terms used in part 207. 

We are proposing to revoke this 

sentence because it is unnecessary and 

has caused confusion in the past. For 

purposes of proposed part 207, the 

following definitions and 

interpretations of terms would apply to 

proposed part 207: 

Act. This term, as used in proposed 

§ 207.1, remains the same as current 

§ 207.3(a)(1). ‘‘Act’’ means the Federal 

Food, Drug, and Cosmetic Act (52 Stat. 

1040 et seq., as amended (21 U.S.C. 301 

et seq.)), except as otherwise provided. 

Active pharmaceutical ingredient. We 

are proposing to replace the term ‘‘bulk 

drug substance,’’ as defined in current 

§ 207.3(a)(4), with the term ‘‘active 

pharmaceutical ingredient.’’ We believe 

that the term ‘‘bulk drug substance’’

may be confused with the term ‘‘bulk 

drug.’’ The term ‘‘bulk drug,’’ as 

commonly used in the pharmaceutical 

industry, means an active ingredient, 

inactive ingredient, or finished dosage 

form, packaged in a large container (for 

example, a drum). To prevent 

confusion, we are proposing to replace 

the term ‘‘bulk drug substance’’ with the 

more descriptive term ‘‘active 

pharmaceutical ingredient.’’

We are also proposing to revise the 

definition of the current term ‘‘bulk 


jlentini on PROD1PC65 with PROPOSAL2
51286 Federal Register / Vol. 71, No. 167 / Tuesday, August 29, 2006 / Proposed Rules 

5The use of the language ‘‘that the manufacturer 

regards as subject to section 505 of the act or section 

351 of the PHS Act,’’ is explained in detail in 

section IV.D.7 of this document. 

6For additional information, also see the guidance 

‘‘Providing Regulatory Submissions in Electronic 

Format—Content of Labeling’’ (April 2005) 

(available at http://www.fda.gov/cder/guidance/ 

index.htm), which discusses issues related to the 

submission of the content of labeling in electronic 

format in marketing applications for human drug 

and biological products. This guidance reflects our 

current thinking on providing in electronic format 

the content of labeling required in 21 CFR parts 314 

and 601. 

drug substance’’ (changed to ‘‘active 

pharmaceutical ingredient’’ in the 

proposal) to make it consistent with the 

definition of ‘‘drug substance’’ in 

current § 314.3 (21 CFR 314.3). Current 

§ 207.3(a)(4) states, in part, that a ‘‘bulk 

drug substance * * * becomes an active 

ingredient,’’ but does not explain what 

it means for an ingredient to be 

‘‘active.’’ We believe that the definition 

of ‘‘drug substance’’ in current § 314.3 is 

more descriptive; that definition 

explains, in part, that ‘‘drug substance 

means an active ingredient that is 

intended to furnish pharmacological 

activity or other direct effect in the 

diagnosis, cure, mitigation, treatment, or 

prevention of disease or to affect the 

structure or any function of the * * * 

body.’’ Consistent with the language of 

current § 314.3, we are proposing to 

define ‘‘active pharmaceutical 

ingredient’’ in proposed § 207.1 as any 

substance that is intended to furnish 

pharmacological activity or other direct 

effect in the diagnosis, cure, mitigation, 

treatment, or prevention of disease, or to 

affect the structure or any function of 

the body. Consistent with both current 

§ 314.3 and current § 207.3(a)(4), the 

term would not include intermediates 

used in the synthesis of the substance. 

As proposed, the term would include 

both an active pharmaceutical 

ingredient marketed alone and as part of 

a finished dosage form. 

Advertising and labeling. We are 

proposing to delete current § 207.3(a)(2), 

which explains that the terms 

‘‘advertising’’ and ‘‘labeling,’’ as used in 

current part 207, include the 

promotional material described in 

current § 202.1(l)(1) and (l)(2) (21 CFR 

202.1(l)(1) and (l)(2)), respectively. We 

believe that this information is more 

appropriately included in the 

definitions of ‘‘representative sampling 

of advertisements’’ and ‘‘representative 

sampling of any other labeling.’’ As a 

result, we are proposing to revise the 

definitions of those terms accordingly 

and delete current § 207.3(a)(2). 

Commercial distribution. We are not 

proposing to substantively change the 

definition of ‘‘commercial distribution’’

from that set forth in current 

§ 207.3(a)(5). The term would still mean 

any distribution of a human drug, 

except for investigational use under 21 

CFR part 312, and any distribution of an 

animal drug or an animal feed bearing 

or containing an animal drug for noninvestigational uses. The term would 

not include internal or interplant 

transfer of an active pharmaceutical 

ingredient between registered 

establishments within the same parent, 

subsidiary, and/or affiliate company. 

For foreign manufacturers, foreign 

repackers, foreign relabelers, foreign 

drug product salvagers, foreign private 

label distributors, and foreign 

establishments, the term ‘‘commercial 

distribution’’ would have the same 

meaning except that it does not include 

distribution of any drug that is neither 

imported nor offered for import by it 

into the United States. We are proposing 

to change the term ‘‘bulk drug 

substance’’ in the current definition to 

‘‘active pharmaceutical ingredient’’

because the proposal replaces the 

definition of ‘‘bulk drug substance’’

with the definition of ‘‘active 

pharmaceutical ingredient.’’ Defining 

‘‘commercial distribution’’ is important 

because, under proposed part 207, 

listing information must be provided to 

us for any drug that is being 

manufactured, repacked, relabeled, or 

salvaged for commercial distribution. 

Content of labeling. We are proposing 

to add a new term, ‘‘content of 

labeling,’’ to part 207. The proposed 

definition of the term describes the 

labeling material that would be required 

to be electronically submitted at the 

time of listing under proposed 

§§ 207.49(g) and 207.61(a)(2). The 

proposed requirement to electronically 

submit the ‘‘content of labeling’’ would 

be in addition to the current listing 

requirement that formatted copies of 

certain labeling be submitted. We are 

proposing to define ‘‘content of 

labeling’’ because, as explained in 

section IV.E.4 of this document, the 

electronic submission of the ‘‘content of 

labeling’’ would be required for drug 

listing to permit us to electronically 

review, compare, and extract data from 

the labeling. 

• For human prescription drugs that 

the manufacturer regards as subject to 

section 505 of the act or section 351 of 

the PHS Act, we are proposing to define 

‘‘content of labeling’’ as the content of 

the prescription drug labeling, as 

specified in §§ 201.56, 201.57, and 

201.80 (21 CFR 201.56, 201.57, and 

201.80), including all text, tables, and 

figures.5

This proposed definition is consistent 

with how the term ‘‘content of labeling’’

is used in the final rule entitled 

‘‘Requirements for Submission of 

Labeling for Human Prescription Drugs 

and Biologics in Electronic Format,’’

(electronic labeling final rule), which 

published in the Federal Register of 

December 11, 2003 (68 FR 69009). 

Under the electronic labeling final rule, 

applicants are required to electronically 

submit, in a format that we can process, 

review, and archive, the ‘‘content of 

labeling’’ for human prescription drugs 

in NDAs, certain BLAs, ANDAs, 

supplements, and annual reports.6 The 

electronic labeling final rule, including 

the use of the term ‘‘content of 

labeling,’’ only applies to this subset of 

drugs. Under the proposal, however, as 

set forth in proposed § 207.49(g), the 

‘‘content of labeling’’ would be provided 

for drugs subject to the listing 

requirements of proposed part 207. 

Proposed part 207 would also differ in 

one other respect from the way ‘‘content 

of labeling’’ is used in the electronic 

labeling final rule. The electronic 

labeling final rule states that the 

‘‘content of labeling’’ that must be 

submitted electronically is commonly 

referred to as the content of the package 

insert or professional labeling. We are 

proposing to use the term ‘‘prescription 

drug labeling’’ instead of the term 

package insert or professional labeling. 

‘‘Prescription drug labeling’’ is used in 

the final rule entitled ‘‘Requirements on 

Content and Format of Labeling for 

Human Prescription Drug and Biological 

Products,’’ published in the Federal 

Register of January 24, 2006 (71 FR 

3922). In that final rule, ‘‘prescription 

drug labeling’’ is used to mean labeling 

for approved prescription drug products 

described in §§ 201.56, 201.57, and 

201.80, which is commonly described 

using a variety of terms including 

‘‘professional labeling,’’ ‘‘package 

insert,’’ ‘‘direction circular,’’ or 

‘‘package circular.’’ We are proposing 

that the term ‘‘content of labeling’’ for 

human prescription drugs, as defined in 

proposed § 207.1 and required under 

proposed § 207.49(g), would be the 

content of the ‘‘prescription drug 

labeling.’’

• For human prescription drugs that 

the manufacturer regards as not subject 

to section 505 of the act or section 351 

of the PHS Act, we are proposing to 

define ‘‘content of labeling’’ as the 

labeling equivalent to the content of the 

prescription drug labeling, as specified 

in §§ 201.56, 201.57, and 201.80, 

including all text, tables, and figures. 

• For human OTC drugs, we are 

proposing to define ‘‘content of 

labeling’’ as the content of the drug facts 

labeling required by § 201.66 (21 CFR 


jlentini on PROD1PC65 with PROPOSAL2
Federal Register / Vol. 71, No. 167 / Tuesday, August 29, 2006 / Proposed Rules 51287 

201.66) (format and content 

requirements for OTC drug product 

labeling), including all text, tables, and 

figures. Under § 201.66(b)(10), drug facts 

labeling means the title, headings, 

subheadings, and information required 

under or described in § 201.66(c) 

(content requirements). 

• For animal drugs (including, but 

not limited to, drugs that the 

manufacturer regards as subject to 

section 512 of the act), we are proposing 

to define ‘‘content of labeling’’ as the 

content of the labeling that accompanies 

the drug that is necessary to enable safe 

and proper administration of the drug 

(for example, the labeling specified in 

§§ 201.1 and 201.5 (21 CFR 201.1 and 

201.5)), including all text, tables, and 

figures. 

Domestic. For the purposes of 

registration and listing under this 

proposal, and when used to modify the 

term ‘‘manufacturer,’’ ‘‘repacker,’’

‘‘relabeler,’’ ‘‘drug product salvager,’’

‘‘private label distributor,’’ or 

‘‘establishment,’’ we are proposing to 

use the term ‘‘domestic’’ to refer to a 

manufacturer, repacker, relabeler, drug 

product salvager, private label 

distributor, or establishment within any 

State or Territory of the United States, 

the District of Columbia, or the 

Commonwealth of Puerto Rico. The 

terms ‘‘manufacturer,’’ ‘‘repacker,’’

‘‘relabeler,’’ ‘‘drug product salvager,’’

‘‘private label distributor,’’ and 

‘‘establishment’’ are defined in 

proposed § 207.1, and these definitions 

are discussed elsewhere in this section 

of the preamble. We are proposing to 

define the term ‘‘domestic’’ separately 

rather than repeat the meaning of the 

term under separate definitions for 

domestic manufacturer, domestic 

repacker, domestic relabeler, domestic 

drug product salvager, domestic private 

label distributor, and domestic 

establishment. The definition of 

‘‘foreign,’’ as it would modify 

manufacturer, repacker, relabeler, drug 

product salvager, private label 

distributor, and establishment, is 

discussed elsewhere in this section of 

the preamble. 

Drug(s). We are proposing to use the 

term ‘‘drug(s),’’ for purposes of 

proposed part 207, to mean the same as 

the definition of ‘‘drug’’ in section 

201(g)(1) of the act. Section 201(g)(1) of 

the act defines ‘‘drug’’ to include, 

among other things, articles intended for 

use in the diagnosis, cure, mitigation, 

treatment, or prevention of disease in 

man or other animals, and articles (other 

than food) intended to affect the 

structure or any function of the body of 

man or other animals. ‘‘Drug(s)’’ under 

proposed § 207.1 would include drugs 

intended for use in humans, including 

the biologics described in proposed 

§ 207.9(c), and animal drugs, including 

Type A medicated articles, and also 

includes articles ‘‘intended for use as a 

component’’ of any drug. The proposed 

term includes active pharmaceutical 

ingredients and finished dosage forms 

(prescription and OTC). 

Drug product salvager, drug product 

salvaging. We are proposing to use the 

term ‘‘drug product salvaging’’ to mean 

applying manufacturing controls such 

as those required by current good 

manufacturing practice in parts 210 (21 

CFR part 210) and part 211 to drug 

products and segregating out those drug 

products that may have been subjected 

to improper storage conditions (such as 

extremes in temperature, humidity, 

smoke, fumes, pressure, age, or 

radiation) for the purpose of returning 

the products to the marketplace. We 

note, however, that drug product 

salvaging, like all manufacturing, must 

be conducted in accordance with 

current good manufacturing practice. 

We are proposing to use the term ‘‘drug 

product salvager’’ to mean a person who 

owns or operates an establishment that 

engages in drug product salvaging. 

When not modified by ‘‘domestic’’ or 

‘‘foreign,’’ as defined in proposed 

§ 207.1 and discussed in section IV.A.5 

of this document, the term would 

include both domestic drug product 

salvagers and foreign drug product 

salvagers. 

Under current § 207.3(a)(6), drug 

product salvaging means the act of 

segregating drug products that may have 

been subjected to improper storage 

conditions, such as extremes in 

temperature, humidity, smoke, fumes, 

pressure, age, or radiation, for the 

purpose of returning some or all of the 

products to the marketplace. We are 

proposing to revise the current 

definition of drug product salvaging to 

include ‘‘applying manufacturing 

controls such as those required by 

current good manufacturing practice in 

part 210 and part 211 to drug products.’’

We are not proposing to change the 

meaning of drug product salvaging but 

to clarify the current definition by 

explaining that the term also includes 

applying manufacturing controls to drug 

products. Drug product salvagers apply 

manufacturing controls to drug products 

so that they can determine whether the 

drug products may have been subjected 

to improper storage conditions. As 

discussed further in sections IV.B.1 and 

IV.D.1 of this document, ‘‘applying 

manufacturing controls to drug products 

and segregating drug products’’ would 

be covered under the scope of 

manufacturing, preparing, propagating, 

compounding, or processing, and 

repackaging or otherwise changing the 

container, wrapper, or labeling of any 

drug package in furtherance of the 

distribution of the drug from the 

original place of manufacture to the 

person who makes the final delivery or 

sale to the ultimate consumer or user 

(section 510(a)(1) of the act). This 

activity would trigger the requirement to 

register under the act. In addition, under 

the proposal, drug product salvagers 

would also be subject to the drug listing 

requirements in section 510(j)(1) of the 

act because their activities involve 

conducting one of the aforementioned 

activities with respect to a given drug 

for the purpose of commercial 

distribution. As discussed in section 

IV.D.1 of this document, we are 

requesting comments specifically on 

whether drug product salvagers should 

be subject to the drug listing 

requirements because the drug products 

are being salvaged for commercial 

distribution. 

Establishment. We are proposing to 

revise the definition of ‘‘establishment’’

at current § 207.3(a)(7) to mean, for 

purposes of registration and drug listing, 

a place of business under one 

management at one geographic location. 

Under the proposed definition, one 

geographic location may include 

separate buildings within the same city 

if their activities are closely related to 

the same business enterprise and are 

under the supervision of the same local 

management. When not modified by 

‘‘domestic’’ or ‘‘foreign,’’ as defined in 

proposed § 207.1 and discussed in 

section IV.A.5 of this document, the 

term would include both domestic 

establishments and foreign 

establishments. We are proposing to 

define the term ‘‘establishment’’

because, under proposed part 207, 

manufacturers, repackers, relabelers, 

and drug product salvagers must register 

each establishment, providing to us 

such information as the name and 

address of the establishment and type of 

operation performed at the 

establishment. 

The proposed definition of 

‘‘establishment’’ would clarify the 

phrase ‘‘at one general physical 

location’’ in the current definition by 

revising the phrase to read ‘‘one 

geographic location’’ and stating that 

this may include separate buildings 

within the same city if their activities 

are closely related to the same business 

enterprise and are under the supervision 

of the same local management. 

The proposed definition of 

‘‘establishment’’ is intended to simplify 

the current definition. The current 

definition defines establishment as a 


jlentini on PROD1PC65 with PROPOSAL2
51288 Federal Register / Vol. 71, No. 167 / Tuesday, August 29, 2006 / Proposed Rules 

place of business under one 

management at one general physical 

location, and includes, among others, 

independent laboratories that engage in 

control activities for a registered drug 

establishment (for example, consulting 

laboratories), manufacturers of 

medicated feeds and vitamin products 

that are drugs in accordance with 

section 201(g) of the act, human blood 

donor centers, animal facilities used for 

the production or control testing of 

licensed biologics, and establishments 

engaged in drug product salvaging. For 

brevity, the proposed definition of 

establishment does not restate the 

examples of establishments stated in the 

current definition. Some of these 

establishments would be covered under 

other definitions set forth in proposed 

§ 207.1 and explained in section IV.A.5 

of this document. For example, 

‘‘independent laboratories that engage 

in control activities for a registered drug 

establishment’’ would be covered under 

the proposed definition of 

‘‘manufacturer.’’ ‘‘Establishments 

engaged in drug product salvaging’’

would be covered under the proposed 

definition of ‘‘drug product salvager.’’

Establishment registration number. 

We are proposing to define 

‘‘establishment registration number’’ as 

the number assigned by FDA to the 

establishment during the establishment 

registration process required in this 

part. The establishment registration 

number is assigned to each 

establishment of each manufacturer, 

repacker, relabeler, or drug product 

salvager inspected by our district office. 

The establishment registration number 

is assigned when the manufacturer, 

repacker, relabeler, or drug product 

salvager begins manufacturing, 

repacking, relabeling, or salvaging drugs 

subject to part 207. The establishment 

registration number would identify, 

among other things, where the drug is 

manufactured, repacked, relabeled, or 

salvaged. Currently, the FDA 

Establishment Identifier (FEI) will be 

the number we assign as the 

establishment registration number. In 

the future, however, we may use a 

different number as the establishment 

registration number. 

Foreign. For the purposes of 

registration and listing under this 

proposal, and when used to modify the 

term ‘‘manufacturer,’’ ‘‘repacker,’’

‘‘relabeler,’’ ‘‘drug product salvager,’’ or 

‘‘private label distributor,’’ we are 

proposing to use the term ‘‘foreign’’ to 

refer to a manufacturer, repacker, 

relabeler, drug product salvager, or 

private label distributor who is located 

in a foreign country and who 

manufactures, repacks, relabels, 

salvages, or distributes a drug that is 

imported or offered for import into the 

United States. When used to modify the 

term ‘‘establishment,’’ we are proposing 

to use the term ‘‘foreign’’ to refer to an 

establishment that is located in a foreign 

country and is the site where a drug that 

is imported or offered for import into 

the United States was manufactured, 

repacked, relabeled, salvaged or 

distributed. The terms ‘‘manufacturer,’’

‘‘repacker,’’ ‘‘relabeler,’’ ‘‘drug product 

salvager,’’ ‘‘private label distributor,’’

and ‘‘establishment’’ are defined in 

proposed § 207.1, and these definitions 

are discussed elsewhere in this section 

of the preamble. We are proposing to 

define the term ‘‘foreign’’ separately 

rather than repeat the meaning of the 

term under separate definitions for 

foreign manufacturer, foreign repacker, 

foreign relabeler, foreign drug product 

salvager, foreign private label 

distributor, and foreign establishment. 

The definition of ‘‘domestic,’’ as it 

would modify manufacturer, repacker, 

relabeler, drug product salvager, private 

label distributor, and establishment, is 

discussed elsewhere in this section of 

the preamble. 

Importer. We are proposing to define 

‘‘importer’’ to mean a company or 

individual in the United States that is 

an owner, consignee, or recipient of the 

foreign establishment’s drug that is 

imported into the United States. We 

recognize that a foreign establishment 

may have more than one ‘‘importer’’ and 

we are proposing to include in this term 

any owner, consignee, or recipient, even 

if not the initial owner, consignee, or 

recipient, of the foreign establishment’s 

drug that is imported into the United 

States. Under this proposal, the 

recipient of the drug would not include 

the consumer or patient who ultimately 

purchases, receives, or is administered 

the drug, unless the foreign 

establishment ships the drug directly to 

the consumer or patient. As described in 

section IV.B.3 of this document, this 

proposal would require foreign 

establishments to provide, for drugs 

manufactured, repacked, relabeled, or 

salvaged at the establishment, the name 

of each importer known to the 

establishment of such drug into the 

United States. Therefore, the 

establishment would need to provide 

the name of each owner, consignee, or 

recipient of the foreign establishment’s 

drug imported into the United States 

that was known to the establishment. 

We describe more fully what we mean 

by ‘‘known to the establishment’’ in 

section IV.B.3 of this document. We 

invite comments on our definition of 

importer, including the scope of the 

entities included in the definition. 

Manufacture, manufacturer. We are 

proposing to use the term 

‘‘manufacture’’ for purposes of this part 

to mean each step in the manufacture, 

preparation, propagation, compounding, 

or processing of a drug. Manufacture 

includes the making by chemical, 

physical, biological, or other procedures 

or manipulations of a drug, including 

control procedures applied to the final 

product or to any part of the process. 

Manufacture includes manipulation, 

sampling, testing, or control procedures 

applied to the final product or to any 

part of the process, including, for 

example, analytical testing of drugs, for 

another registered establishment’s drug. 

We are proposing to use the term 

‘‘manufacturer’’ for purposes of this part 

to mean a person who owns or operates 

an establishment that manufactures a 

drug. When not modified by ‘‘domestic’’

or ‘‘foreign,’’ as defined in proposed 

§ 207.1 and discussed in section IV.A.5 

of this document, ‘‘manufacturer’’

would include both domestic 

manufacturers and foreign 

manufacturers. 

Under section 510(a)(1) of the act, the 

term ‘‘manufacture, preparation, 

propagation, compounding, or 

processing’’ includes repackaging or 

otherwise changing the container, 

wrapper, or labeling of any drug 

package in furtherance of the 

distribution of the drug from the 

original place of manufacture to the 

person who makes final delivery or sale 

to the ultimate consumer or user. 

Accordingly, section 510(a)(1) of the act 

sets up a shorthand way of referring to 

all the activities that trigger registration 

requirements by using the specified 

phrase ‘‘manufacture, preparation, 

propagation, compounding, or 

processing’’ throughout section 510 of 

the act. However, for purposes of 

proposed part 207, the term 

‘‘manufacture’’ would refer to the 

manufacture, preparation, propagation, 

compounding, or processing of a drug, 

as set forth in the proposed definition. 

The term ‘‘manufacturer’’ would 

include, among others, control 

laboratories, contract laboratories, 

contract manufacturers, contract 

packers, contract labelers, and other 

entities that manufacture a drug, as 

defined in proposed § 207.1 and 

discussed in section IV.A.5 of this 

document. A ‘‘control laboratory’’ and a 

‘‘contract laboratory’’ include 

independent establishments that 

manipulate, sample, test, or perform 

other quality control functions for 

another registered establishment’s drug, 

including, for example, analytical 


jlentini on PROD1PC65 with PROPOSAL2
Federal Register / Vol. 71, No. 167 / Tuesday, August 29, 2006 / Proposed Rules 51289 

testing of drugs. A ‘‘contract 

manufacturer’’ is sometimes employed 

by other manufacturers to manufacture 

the drug. Similarly, a manufacturer may 

sometimes subcontract part of the 

manufacturing process such as packing 

or labeling to a ‘‘contract packer’’ or a 

‘‘contract labeler.’’ The term 

‘‘manufacturer’’ would include control 

laboratories, contract laboratories, 

contract manufacturers, and other 

entities that manufacture a drug because 

their activities include the making of 

drugs by chemical, physical, biological, 

or other procedures, including the 

manipulation, sampling, testing, or 

control procedures applied to the final 

drug product or to a part of the process. 

Such activities would fall under the 

scope of activities (that is, manufacture, 

prepare, propagate, compound, or 

process) in section 510(a)(1) of the act 

that trigger registration requirements. 

The proposed definition of 

‘‘manufacture’’ also explains that, for 

purposes of proposed part 207, the term 

manufacture is defined and used 

separately from the terms relabel, 

repack, and drug product salvage. 

Although we explain that repacking, 

relabeling, and drug product salvaging 

are activities that trigger registration 

(because the term ‘‘manufacture, 

preparation, propagation, compounding, 

or processing,’’ under section 510 of the 

act includes repackaging or otherwise 

changing the container, wrapper, or 

labeling of any drug package in 

furtherance of the distribution of the 

drug from the original place of 

manufacture to the person who makes 

the final delivery or sale to the ultimate 

consumer or user), we believe that it is 

clearer to use four separate terms for the 

different activities for purposes of 

proposed part 207. We use separate 

terms so that we can clarify and 

differentiate the responsibilities of the 

four types of parties engaged in the 

separate activities of: ((1) Manufacturing 

that does not include repacking, 

relabeling, or drug product salvaging; (2) 

repacking; (3) relabeling; and (4) drug 

product salvaging). 

Similarly, the proposed definition of 

‘‘manufacturer’’ explains that the term 

manufacturer is defined and used 

separately from the terms relabeler, 

repacker, and drug product salvager. We 

explain that repackers, relabelers, and 

drug product salvagers are 

‘‘manufacturers’’ (as that entity is 

contemplated in section 510 of the act), 

but we believe that, for purposes of 

proposed part 207, it is clearer to use 

four separate terms for the different 

entities: (1) Manufacturers (that are not 

also repackers, relabelers, or drug 

product salvagers); (2) repackers; (3) 

relabelers; and (4) drug product 

salvagers. Repackers, relabelers, and 

drug product salvagers would be subject 

to the provisions of part 207 that are 

applicable to repackers, relabelers, and 

drug product salvagers, respectively, but 

would not be subject to the provisions 

of part 207 that are applicable to 

‘‘manufacturers,’’ as that term is defined 

in this proposal. For example, if a 

repacker, relabeler, or a drug product 

salvager supplies us with the 

manufacturer’s NDC number, we would 

not require the repacker, relabeler, or 

drug product salvager to provide all of 

the information that the manufacturer 

provides to list a drug or, for the 

repacker or relabeler, to obtain an NDC 

number. We would already have much 

of the information in the database 

linked to the manufacturer’s NDC 

number, and it would be an unnecessary 

burden to require that the information 

be provided again. 

We are proposing to delete the 

definition of ‘‘manufacturing or 

processing’’ at current § 207.3(a)(8) and 

incorporate parts of the definition 

elsewhere in the proposed definitions. 

For example, the phrase ‘‘control 

procedures applied to the final product 

or to any part of the process’’ in the 

proposed definition of ‘‘manufacture’’ is 

part of the current definition of 

‘‘manufacturing or processing.’’

Material change. We are proposing to 

revise the definition of ‘‘any material 

change’’ in current § 207.3(a)(3). The 

current definition includes, but is not 

limited to: (1) Any change in the name 

of the drug; (2) any change in the 

identity or quantity of the active 

ingredient(s); (3) any change in the 

identity or quantity of the inactive 

ingredient(s) where quantitative listing 

of all ingredients is required by current 

§ 207.31(a)(2); (4) any significant change 

in the labeling of a prescription drug; 

and (5) any significant change in the 

label or package insert of an OTC drug. 

Changes that are not significant 

currently include changes in 

arrangement or printing or changes of an 

editorial nature. The proposed 

definition would continue to exclude 

labeling changes in arrangement or 

printing or labeling changes of an 

editorial nature. The inclusion of a bar 

code or NDC number on the label would 

not be considered a material change 

because it would be too burdensome to 

require the resubmission of labeling if 

the only change was to include a bar 

code or an NDC number. We are, 

however, proposing to rename the term 

‘‘material change’’ and to more precisely 

identify all of the changes that would be 

considered ‘‘material’’ in the current 

definition. With respect to 

manufacturers, repackers, and 

relabelers, and drug product salvagers, a 

change in any information provided 

under proposed §§ 207.49, 207.53, 

207.54, 207.55, or 207.57 would be 

considered a material change. 

All listing information required under 

the proposal is needed to identify the 

drug. Under the broader definition of 

material change, as proposed, we would 

be better informed of changes to 

marketed drugs. This would result in 

more accurate and up-to-date drug 

listing information. Under proposed 

§ 207.57 and section 510(j)(2)(D) of the 

act, the June and December updates of 

listing information must include reports 

of ‘‘material changes’’ in listing 

information previously submitted. The 

proposed definition of ‘‘material 

change’’ has been revised to more 

precisely identify which changes must 

be reported under proposed § 207.57. 

Person who imports or offers for 

import. We are proposing to define a 

‘‘person who imports or offers for 

import’’ as an agent, broker, or other 

entity that the foreign establishment 

uses to facilitate the import of its drug 

into the United States. As described in 

section IV.B.3 of this document, this 

proposal would require foreign 

establishments to provide, for drugs 

manufactured, repacked, relabeled, or 

salvaged at the establishment, the name 

of each person known to the 

establishment who imports or offers for 

import such drug into the United States. 

Therefore, the establishment would 

need to provide the name of each agent, 

broker, or other entity that the foreign 

registrant uses to facilitate the import of 

its drug into the United States. We 

describe more fully what we mean by 

‘‘known to the establishment’’ in section 

IV.B.3 of this document. The term 

‘‘person who imports or offers to 

import’’ would not include carriers, 

consistent with the legislative history of 

the Bioterrorism Act. The legislative 

history shows that although the House 

provision originally would have 

required registration information for 

importers and carriers, the conference 

substitute changed the language. The 

conference substitute deleted the term 

‘‘carriers,’’ replacing it with ‘‘persons 

who import or offer for import,’’

clarifying that foreign manufacturers are 

not required to include information on 

carriers with annual registration. (See H. 

Rept. 107–481, 107th Cong., 2d sess., p. 

140, 2002, Conf. Rept. to accompany 

H.R. 3448) We invite comments on our 

proposed definition of ‘‘persons who 

import or offer for import.’’

We also invite comment on our use of 

the word ‘‘facilitate’’ in the proposed 

definition. We recognize that the term 


jlentini on PROD1PC65 with PROPOSAL2
51290 Federal Register / Vol. 71, No. 167 / Tuesday, August 29, 2006 / Proposed Rules 

could be interpreted to include 

middlemen or other entities that may be 

viewed as assisting with or promoting 

the importation of a drug into the 

United States. For example, we are 

aware that ‘‘buyer’s clubs’’ could be 

captured in the definition if ‘‘facilitate’’

were to be interpreted broadly. Buyer’s 

clubs are groups that consolidate orders 

for drugs purchased from foreign 

establishments and then, once those 

drugs are imported into the United 

States, send them to the individuals or 

other entities who ordered the drugs 

through the clubs. It is also possible that 

‘‘facilitate’’ could be interpreted to 

include organizations that may promote 

the awareness and sale of products 

through advertisements on the internet, 

for example. We recognize that, under 

this proposal, foreign establishments 

would only be required to give us 

information for persons who import or 

offer for import that are known to the 

establishments. Although the 

knowledge requirement in this proposed 

rule would include information that the 

foreign establishment, and persons in 

the foreign establishment, has reason to 

know of, we believe it is likely that 

foreign establishments generally would 

not know about most of the 

‘‘middlemen’’ described previously. 

Therefore, even though the term 

‘‘facilitate’’ in the proposed definition 

would be interpreted broadly to include 

middlemen, if the foreign establishment 

did not know of, or have reason to know 

of, the middlemen, the foreign 

establishment would not be required to 

report information about the middlemen 

under this proposal. 

We also note that the terms ‘‘broker’’

or ‘‘agent’’ include ‘‘customhouse 

brokers’’ who facilitate importation by 

filing documents with the U.S. Customs 

Service, as well as FDA and other 

Federal agencies responsible for the 

regulation of imported products. We 

specifically invite comment on our use 

of the term ‘‘facilitate’’ in this proposal. 

We invite comment on whether we 

should interpret the term ‘‘facilitate’’

broadly to include middlemen as 

described previously. We also invite 

comment on whether foreign 

establishments would know about such 

middlemen and, if so, what effect a 

requirement to report information about 

those middlemen would have on foreign 

establishments. We also invite comment 

on whether there are benefits associated 

with such a reporting requirement, and, 

if so, what they are. 

Private label distributor. We are 

proposing to define ‘‘private label 

distributor’’ to mean a person who owns 

or operates an establishment that 

commercially distributes, under its own 

label or trade name, any drug 

manufactured, repacked, relabeled, or 

salvaged by a registered establishment. 

When not modified by ‘‘domestic’’ or 

‘‘foreign,’’ as defined in proposed 

§ 207.1 and discussed in section IV.A.5 

of this document, the term would 

include both domestic private label 

distributors and foreign private label 

distributors. 

Private label distributors are not 

considered to be manufacturers, 

repackers, relabelers, or drug product 

salvagers because they do not conduct 

any of the activities covered in section 

510(a)(1) of the act with respect to the 

products they commercially distribute. 

Private label distributors only distribute 

drugs under their own label or trade 

name. The proposed definition is 

consistent with current § 207.20(b) and 

the description of private label 

distributors set forth in the 1973 final 

rule on drug listing requirements (38 FR 

6258 at 6259). We are proposing to 

define this term to clarify its meaning 

and to distinguish private label 

distributors from manufacturers, 

repackers, relabelers, and drug product 

salvagers. Under the proposed 

definition, a private label distributor 

does not engage in any activities 

performed by a manufacturer, repacker, 

relabeler, or drug product salvager for 

the drug it distributes. As discussed in 

section IV.D.1 of this document, private 

label distributors currently may elect to 

submit listing information to us for the 

drugs they distribute. Under the 

proposal, private label distributors 

would not be permitted to list, and 

manufacturers, repackers, relabelers, 

and drug product salvagers would be 

required to provide listing information 

to us for drugs being manufactured, 

repacked, relabeled, or salvaged for 

private label distributors. However, if a 

private label distributor is a 

manufacturer with respect to a 

particular drug or drugs, for example, 

the private label distributor is subject to 

the registration and listing requirements 

for manufacturers in proposed part 207 

with respect to that drug or drugs. 

Relabel, relabeler. We are proposing 

to use the term ‘‘relabel’’ to mean 

changing the label or labels on a drug or 

drug package, or adding to the labeling 

for a drug or drug package, without 

repacking the drug or drug package. We 

remind interested persons that those 

activities must be conducted in 

accordance with the act and FDA 

regulations. We are proposing to use the 

term ‘‘relabeler’’ to mean a person who 

owns or operates an establishment that 

relabels a drug. When not modified by 

‘‘domestic’’ or ‘‘foreign,’’ as defined in 

proposed § 207.1 and discussed in 

section IV.A.5 of this document, the 

term would include both domestic 

relabelers and foreign relabelers. 

Under the proposal, relabelers must 

provide registration and listing 

information. Under section 510(a)(1) of 

the act, the term ‘‘manufacture, 

preparation, propagation, compounding, 

or processing’’ includes repackaging or 

otherwise changing the container, 

wrapper, or labeling of any drug 

package in furtherance of the 

distribution of the drug from the 

original place of manufacture to the 

person who makes final delivery or sale 

to the ultimate consumer or user. As 

discussed previously, we use the term 

‘‘relabeler’’ separately from the term 

‘‘manufacturer’’ because, although the 

relabeler’s registration and listing 

responsibilities in general are the same 

as those for manufacturers under the 

act, the proposal would modify some of 

these requirements. For example, as 

described under the definition of 

‘‘manufacturer’’ in section IV.A.5 of this 

document, if a relabeler supplies us 

with the manufacturer’s NDC number, 

we would not require the relabeler to 

provide all of the information that the 

manufacturer provides to obtain an NDC 

number and to list a drug. We would 

already have much of the information in 

the database linked to the 

manufacturer’s NDC number, and it 

would be an unnecessary burden to 

require that the information be provided 

again. Under the proposed definition, a 

relabeler does not engage in any other 

activity performed by a manufacturer for 

the drugs they relabel. 

Repack, repacker. We are proposing 

to use the term ‘‘repack’’ to mean repack 

or repackage or otherwise change the 

container or wrapper of a drug or drug 

package. We are proposing to use both 

the terms ‘‘repack’’ and ‘‘repackage’’ in 

the definition because these terms are 

often used interchangeably with respect 

to drugs and, whether such activities are 

characterized as repacking or 

repackaging, they are subject to the 

requirements of this part. Although the 

term ‘‘repackaging’’ is used in section 

510(a)(1) of the act, the terms 

‘‘repacking,’’ ‘‘repack,’’ and ‘‘repacker’’

are more commonly used by industry 

when referring to this activity, and, 

therefore, we are using these terms 

throughout the proposal. We are 

proposing to use the term ‘‘repacker’’ to 

mean a person who owns or operates an 

establishment that repacks a drug or 

drug package. When not modified by 

‘‘domestic’’ or ‘‘foreign,’’ as defined in 

proposed § 207.1 and discussed in 

section IV.A.5 of this document, the 

term would include both domestic 

repackers and foreign repackers. 


jlentini on PROD1PC65 with PROPOSAL2
Federal Register / Vol. 71, No. 167 / Tuesday, August 29, 2006 / Proposed Rules 51291 

Under the proposal, repackers must 

provide registration and listing 

information. Under section 510(a)(1) of 

the act, the term ‘‘manufacture, 

preparation, propagation, compounding, 

or processing’’ includes repackaging or 

otherwise changing the container, 

wrapper, or labeling of any drug 

package in furtherance of the 

distribution of the drug from the 

original place of manufacture to the 

person who makes final delivery or sale 

to the ultimate consumer or user. We 

use the term ‘‘repacker’’ separately from 

the term ‘‘manufacturer’’ because, 

although the repacker’s registration and 

listing responsibilities in general are the 

same as those for manufacturers under 

the act, the proposal would modify 

some of these requirements. For 

example, as described under the 

definition of ‘‘manufacturer’’ in section 

IV.A.5 of this document, if a repacker 

supplies us with the manufacturer’s 

NDC number, we would not require the 

repacker to provide all of the 

information that the manufacturer 

provides to obtain an NDC number and 

to list a drug. We would already have 

much of the information in the database 

linked to the manufacturer’s NDC 

number, and it would be an unnecessary 

burden to require that the information 

be provided again. Under the proposed 

definition, a repacker does not engage in 

any other activity performed by a 

manufacturer for the drugs they repack. 

Representative sampling of 

advertisements. We are proposing to 

revise the definition of ‘‘representative 

sampling of advertisements.’’ Currently, 

§ 207.3(a)(2) explains that the term 

‘‘advertising’’ as used in part 207 

includes the promotional material 

described in § 202.1(l). However, 

current § 207.3(a)(9) expressly excludes 

such material from the definition of 

‘‘representative sampling of 

advertisements.’’ We believe that the 

inconsistency between the two 

provisions was an unintended result of 

certain editorial amendments made to 

part 207. We are proposing to revise the 

definition of ‘‘representative sampling 

of advertisements’’ to resolve the 

inconsistency. Specifically, we believe 

that the content of current § 207.3(a)(2) 

should be incorporated into the 

definition of ‘‘representative sampling 

of advertisements’’ to clarify that the 

term includes the promotional material 

described in § 202.1(l)(1). 

We are proposing to define 

‘‘representative sampling of 

advertisements’’ as typical advertising 

material (including the promotional 

material described in § 202.1(l)(1), but 

excluding labeling as determined in 

§ 202.1(l)(2)), that gives a balanced 

picture of the promotional claims used 

for the drug. In addition to resolving the 

inconsistency described previously, the 

proposed definition would delete the 

example currently provided in 

§ 207.3(a)(9) (that is, if more than one 

medical journal advertisement is used 

but the promotional content is 

essentially identical, only one needs to 

be submitted). We believe that this 

example is unnecessary and are 

proposing to simplify the definition by 

deleting it. 

Representative sampling of any other 

labeling. We are proposing to revise the 

definition of ‘‘representative sampling 

of any other labeling.’’ We are proposing 

to delete current § 207.3(a)(2), which 

explains that the term ‘‘labeling’’ as 

used in part 207 includes the 

promotional material described in 

§ 202.1(l)(2). We believe that this 

information would be more 

appropriately included in the definition 

of ‘‘representative sampling of any other 

labeling.’’

We are proposing to define 

‘‘representative sampling of any other 

labeling’’ as typical labeling material 

(including the promotional material 

described in § 202.1(l)(2), but excluding 

labels and package inserts) that gives a 

balanced picture of the promotional 

claims used for the drug. In addition to 

incorporating the relevant content of 

current § 207.3(a)(2), the proposed 

definition would delete the example 

currently provided in current 

§ 207.3(a)(10) (that is, if more than one 

brochure is used but the promotional 

content is essentially identical, only one 

needs to be submitted). We believe that 

this example is unnecessary and are 

proposing to simplify the definition by 

deleting it. 

United States agent. We are proposing 

to remove the definition of ‘‘United 

States agent’’ in current § 207.3(a)(11). 

Proposed § 207.69 would incorporate 

many of the provisions of the current 

definition of United States agent and 

current § 207.40 (registration and listing 

requirements for foreign 

establishments). The same requirements 

in the current definition appear at 

proposed § 207.69(b)(1), (b)(2), and 

(b)(3). 

B. Registration 

1. Who Would Be Required to Register? 

Proposed § 207.17(a) would require 

manufacturers, repackers, relabelers, 

and drug product salvagers to register 

each establishment. This provision 

would replace the requirement at 

current § 207.20(a) that owners or 

operators of all drug establishments that 

engage in the manufacture, preparation, 

propagation, compounding, or 

processing of a drug must register. The 

terms ‘‘manufacturer,’’ ‘‘repacker,’’

‘‘relabeler,’’ and ‘‘drug product 

salvager,’’ as defined in proposed 

§ 207.1 and discussed in section IV.A.5 

of this document, more clearly indicate 

who must register. 

Manufacturers, repackers, relabelers, 

and drug product salvagers would be 

required to register because the 

activities they perform fall within the 

scope of activities that trigger 

registration requirements in section 

510(a)(1) of the act. Section 510(a)(1) 

states that the phrase ‘‘manufacture, 

preparation, propagation, compounding, 

or processing’’ includes repacking or 

otherwise changing the container, 

wrapper, or labeling of any drug 

package in furtherance of the 

distribution of the drug from the 

original place of manufacture to the 

person who makes final delivery or sale 

to the ultimate consumer or user. 

We are proposing to use the terms 

‘‘repacker,’’ ‘‘relabeler,’’ and ‘‘drug 

product salvager’’ separately from the 

term ‘‘manufacturer’’ in the proposal 

because, although the repacker, 

relabeler, and drug product salvager’s 

listing responsibilities in general are 

similar to those for manufacturers under 

the act, the proposal would modify 

some of these requirements. In 

particular, if a repacker, relabeler, or 

drug product salvager supplies us with 

the manufacturer’s NDC number, we 

would not require the repacker, 

relabeler, or drug product salvager to 

provide all of the information that the 

manufacturer provides to list a drug. 

Similarly, we would not require 

repackers and relabelers to submit all of 

the information that the manufacturer 

submits to obtain an NDC number. 

Proposed § 207.17(a) would enable us 

to identify who is making drugs and 

where they are being made. Being able 

to accurately identify who makes drugs 

and where they are made is very 

important. Certain marketed drugs may 

need to be quickly identified and used 

to help counteract the effects of a 

bioterrorism attack. Registration 

information also assists us in scheduling 

and planning inspections of registered 

establishments pursuant to section 704 

of the act. 

Proposed § 207.17(a) also provides 

that registration 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. This provision would 

also apply when operations are 


jlentini on PROD1PC65 with PROPOSAL2
51292 Federal Register / Vol. 71, No. 167 / Tuesday, August 29, 2006 / Proposed Rules 

conducted at both domestic and foreign 

establishments and there exists joint 

ownership and control among all the 

establishments. This provision is 

consistent with current § 207.20(a). 

We are proposing to revoke the 

requirement in current § 207.20(a) that 

no owner or operator may register an 

establishment if any part of that 

establishment is registered by another 

owner or operator. The requirement has 

caused uncertainty about who must 

register and which establishment must 

be registered. Under proposed 

§ 207.17(a), manufacturers, repackers, 

relabelers, and drug product salvagers 

must register each establishment unless 

they are otherwise exempt under section 

510(g) of the act or proposed § 207.13. 

Under proposed § 207.17(b), private 

label distributors would not register 

with us unless they also manufacture, 

repack, relabel, or salvage drugs and are 

required to register under the act or 

proposed § 207.17(a). Private label 

distributors are not considered to be 

manufacturers, repackers, relabelers, or 

drug product salvagers because they do 

not conduct any of the activities covered 

under section 510(a)(1) of the act with 

respect to the drugs they commercially 

distribute. Private label distributors only 

distribute drugs under their own label 

or trade name. Proposed § 207.17(b) 

would revise the provision in current 

§ 207.20(b) that owners or operators of 

establishments that distribute under 

their own label or trade name a drug 

manufactured or processed (as defined 

in current § 207.3(a)(8)) by a registered 

establishment may elect to obtain a 

labeler code from us and submit listing 

information directly to us. Under 

current regulations, if a private label 

distributor does not elect to submit drug 

listing information to us, the registered 

establishment must submit the drug 

listing information. As explained in 

section IV.D.1 of this document, we are 

proposing to revise current § 207.20(b) 

and not permit private label distributors 

to register or list. Manufacturers, 

repackers, relabelers, and drug product 

salvagers must submit drug listing 

information for those drugs they 

manufacture, repack, relabel, or salvage 

for commercial distribution for a private 

label distributor. 

2. When Would Initial Registration 

Information Be Provided? 

Under proposed § 207.21, a domestic 

manufacturer, domestic repacker, 

domestic relabeler, and domestic drug 

product salvager must register each 

establishment no later than 5 calendar 

days after beginning to manufacture, 

repack, relabel, or salvage a drug. The 

proposed timeframe ‘‘no later than 5 

calendar days’’ is consistent with 

current § 207.21(a) in that the current 

registration requirement also provides 

for a 5-day registration timeframe for 

owners or operators of establishments 

entering into the ‘‘manufacturing or 

processing’’ of a drug (as defined in 

current § 207.3(a)(8)). The proposed 

timeframe is also consistent with the 

requirement in section 510(c) of the act 

to register each establishment 

‘‘immediately’’ and ‘‘upon first engaging 

in the manufacture, preparation, 

propagation, compounding, or 

processing’’ of a drug. 

Under proposed § 207.21, a foreign 

manufacturer, foreign repacker, foreign 

relabeler, and foreign drug product 

salvager must register each 

establishment before a drug 

manufactured, repacked, relabeled, or 

salvaged at the establishment is 

imported or offered for import into the 

United States. This is consistent with 

current § 207.40(b), which states that no 

drug may be imported or offered for 

import into the United States unless it 

is listed and manufactured, prepared, 

propagated, compounded, or processed 

at a registered foreign drug 

establishment. In addition, section 

510(i) of the act states that any 

establishment within any foreign 

country engaged in the manufacture, 

preparation, propagation, compounding, 

or processing of a drug or device that is 

imported or offered for import into the 

United States shall register with the 

Secretary. 

Proposed § 207.21 uses the term ‘‘each 

establishment’’ to emphasize that the 

requirement to register would apply 

even if the manufacturer, repacker, 

relabeler, or drug product salvager has 

previously registered one or more other 

establishments. This proposed 

requirement is consistent with two 

provisions of section 510 of the act. 

Section 510(d) of the act requires 

registration of any additional 

establishment immediately upon 

beginning the manufacture, preparation, 

propagation, compounding, or 

processing of a drug at that 

establishment. Section 510(i)(1) of the 

act states that any establishment within 

any foreign country engaged in the 

manufacture, preparation, propagation, 

compounding, or processing of a drug or 

a device that is imported or offered for 

import into the United States must 

register with the Secretary. 

We are proposing to specify 

‘‘calendar’’ days to be consistent with 

the terminology and timeframes used in 

the international pharmaceutical 

regulatory guidances of the International 

Conference on the Harmonisation of 

Technical Requirements for Registration 

of Pharmaceuticals for Human Use (ICH) 

(http://www.ich.org) and the World 

Health Organization’s Council for 

International Organizations of Medical 

Sciences (CIOMS) (http:// 

www.cioms.ch). 

We are proposing to revoke the 

requirement in current § 207.21(a) to 

register within 5 days after submitting 

certain marketing applications if the 

owner or operator has not previously 

entered into the manufacture or 

processing of a drug (as defined in 

current § 207.3(a)(8)). We are also 

proposing to revoke the requirement in 

current § 207.20(c) that, before 

beginning the manufacture or 

processing of a drug subject to certain 

marketing applications, an owner or 

operator of an establishment must 

register before the application is 

approved. We are proposing to revoke 

these requirements because, under 

proposed § 207.21 and consistent with 

section 510(c) and (d) of the act, 

registration of each establishment must 

occur no later than 5 calendar days after 

beginning to manufacture, repack, 

relabel, or salvage a drug at the 

establishment. This provision would 

govern when to register an 

establishment rather than the date a 

marketing application is submitted or 

approved. We believe that this proposed 

requirement would provide us with 

sufficient notice as to who is 

manufacturing, repacking, relabeling, or 

salvaging drugs and where those 

activities are taking place. In addition, 

marketing application approval is 

linked to registration elsewhere in our 

regulations. Under current 

§ 314.125(b)(11) (21 CFR 

314.125(b)(11)), we may refuse to 

approve an application if the drug will 

be manufactured or processed in an 

establishment that is not registered. For 

consistency with current 

§ 314.125(b)(11), we are proposing to 

revise § 514.111(a)(12) (21 CFR 

514.111(a)(12)) for NADAs to state that 

we will refuse to approve an application 

if ‘‘the drug will be manufactured in 

whole or in part in an establishment 

that is not registered and not exempt 

from registration under section 510 of 

the act and part 207.’’ For licensed 

human biological products, current 21 

CFR 601.4(b) includes a provision that 

we must deny a BLA if the 

establishment or product does not meet 

‘‘requirements established in Title 21, 

Chapter I’’ (this would include the 

registration and listing provisions). 

3. What Information Would Be Required 

for Registration? 

Under proposed § 207.25, all 

manufacturers, repackers, relabelers, 


jlentini on PROD1PC65 with PROPOSAL2
Federal Register / Vol. 71, No. 167 / Tuesday, August 29, 2006 / Proposed Rules 51293 

and drug product salvagers must 

provide the following information to 

register each of their establishments: 

• Name of the owner or operator of 

each establishment; if a partnership, the 

name of each partner would be 

submitted; if a corporation, the name of 

each corporate officer and director and 

the place of incorporation would be 

submitted (proposed § 207.25(a)). This 

provision is consistent with section 

510(a)(2) of the act, which states that 

‘‘the term ’name’ shall include in the 

case of a partnership the name of each 

partner and, in the case of a corporation, 

the name of each corporate officer and 

director, and the State of 

incorporation.’’ The proposal would 

replace ‘‘State of incorporation’’ with 

‘‘place of incorporation’’ to include 

foreign corporations. Proposed 

§ 207.25(a) is also consistent with 

section 510(c) of the act, which states 

that ‘‘Every person * * * shall 

immediately register with the Secretary 

his name, place of business, and such 

establishment.’’ The proposal would use 

‘‘owner or operator’’ for consistency 

with current § 207.25(a), which provides 

that the information required for 

registration includes the name of the 

owner or operator of the establishment. 

Current § 207.25(a) provides that the 

term ‘‘name of the owner or operator’’

includes, in the case of a partnership, 

the name of each partner and, in the 

case of a corporation, the name and title 

of each corporate officer and director 

and the name of the State of 

incorporation. The proposal would 

revoke the requirement to include the 

title of each corporate officer and 

director because we have determined 

that it is not necessary for registration 

purposes. Current § 207.25(a) also 

requires the submission of the ‘‘kind of 

ownership or operation (that is, 

individually owned, partnership, or 

corporation).’’ The proposal would 

replace this requirement because the 

kind of ownership or operation would 

be captured under the requirement to 

provide, if applicable, the name of each 

partner, and corporate officer and 

director, and the place of incorporation 

in proposed § 207.25(a). 

• Name, trade name(s), and address of 

each establishment (proposed 

§ 207.25(b), (c), and (d)). This provision 

is consistent with section 510(c) of the 

act and current § 207.25(a). The 

proposal would continue the 

requirement in current § 207.25(a) to 

submit all trade names used by the 

establishment, but rephrase current 

§ 207.25(a) to clarify that, for purposes 

of this subsection, we want the trade 

name(s) of the establishment, names 

under which the establishment 

conducts business, and additional 

names by which the establishment is 

known. We are not seeking under this 

section the trade name(s) of the drugs of 

the establishment. Although we are 

interested in the trade names of the 

drugs, we can obtain that information 

through the drug listing requirements. 

• Registration number of each 

establishment, if previously assigned to 

the establishment by us (proposed 

§ 207.25(e)). If not previously assigned 

by us, we would assign a registration 

number after we receive the registration 

information (proposed § 207.25(e)). 

Under section 510(e) of the act, we may 

assign a registration number to any 

person or establishment registered and, 

under current § 207.35(a), we will assign 

a permanent registration number to each 

establishment that registers. The 

‘‘establishment registration number’’ is 

defined in proposed § 207.1 to mean the 

number assigned by FDA to the 

establishment during the establishment 

registration process. (Currently, the FEI 

will be the number we assign as the 

establishment registration number.) We 

are proposing to require the submission 

of the registration number because each 

establishment is identified by its 

registration number for registration and 

inspection purposes and to enable us to 

identify all registered establishments. 

The registration number is currently 

submitted on Form FDA 2656. 

• Type of operations(s) performed at 

each establishment—for example, 

manufacturing, repacking, relabeling, or 

salvaging (proposed §207.25(f)). We are 

proposing to require this information 

because it is important for identifying, 

prior to an inspection, which operation 

the establishment engages in so that our 

investigators can be better prepared 

before inspection. Currently, the 

‘‘business type’’ (for example, 

manufacturer, repacker, relabeler) must 

be submitted on Form FDA 2656. 

• Name, address, telephone and fax 

numbers, and e-mail address of the 

official contact, as provided in proposed 

§ 207.69(a), for each establishment 

(proposed § 207.25(g)). We are 

proposing to require this information 

because we need a contact person to 

facilitate discussion with the 

manufacturer, repacker, relabeler, and 

drug product salvager. This information 

needs to be current and, under proposed 

§ 207.29(a)(3), any change in this 

information must be provided to us 

within 30 calendar days. This 

information is not required under 

current part 207. The requirements for 

the official contact are discussed in 

section IV.F.1 of this document. 

• Information for foreign 

establishments only (proposed 

§ 207.25(h)). With respect to foreign 

establishments only, for drugs 

manufactured, repacked, relabeled, or 

salvaged at the establishment, the name, 

address, telephone and fax numbers, 

and e-mail address must also be 

provided for: (1) The United States 

agent, as provided in proposed 

§ 207.69(b), (2) each importer of such 

drug in the United States that is known 

to the establishment, and (3) each 

person who imports or offers for import 

such drug to the United States. The 

requirements for the United States agent 

are discussed in section IV.F.1 of this 

document. The name, address, and 

phone number of the United States 

agent is required to be submitted under 

current § 207.40(c). The information on 

importers and persons who import is 

not required to be submitted under 

current part 207. We are proposing to 

require the submission of the 

information on importers and persons 

who import because the Bioterrorism 

Act requires foreign establishments to 

submit, among other things, the name of 

each importer of each drug that is 

known to the manufacturer, repacker, 

relabeler, and drug product salvager and 

the name of each person who imports or 

offers for import each drug to the United 

States for purposes of importation. We 

want to make clear that the term 

‘‘known to’’ would include any importer 

that is known to the foreign 

establishment as well as any importer 

that the foreign establishment has 

reason to know of. We therefore expect 

that the person responsible for 

completing the required registration 

forms on behalf of the foreign 

establishment would undertake 

appropriate due diligence in completing 

those forms, including to find out and 

report importers that others in his or her 

establishment know of or have reason to 

know of. In addition to the name, the 

proposal would require that the address, 

telephone and fax numbers, and e-mail 

address of each importer and of each 

person who imports or offers for import 

be provided to enable us to contact 

these persons. 

All information required under 

proposed § 207.25 must be submitted for 

the establishment to be considered 

registered. As explained in section 

IV.B.l of this document, establishment 

registration would enable us to identify 

who is making drugs and where they are 

being made. Being able to accurately 

identify who makes drugs and where 

they are made is very important for 

protecting the public health. Among 

other things, registration information 

would enable us to become aware of and 

take action to stop manufacturers, 


jlentini on PROD1PC65 with PROPOSAL2
51294 Federal Register / Vol. 71, No. 167 / Tuesday, August 29, 2006 / Proposed Rules 

repackers, relabelers, and drug product 

salvagers who do not follow the 

requirements set forth in the act and in 

our regulations. 

4. What Are the Proposed Requirements 

for Reviewing and Updating 

Registration Information? 

The proposal would modify and 

streamline the requirements associated 

with updating registration information. 

Currently, manufacturers, repackers, 

relabelers, and drug product salvagers 

must enter new or revised registration 

information on Form FDA 2656 and 

return the form to us annually. Under 

the proposal, manufacturers, repackers, 

relabelers, and drug product salvagers 

would access the electronic drug 

registration and listing system and 

review their current registration 

information online, making any changes 

where needed. Updating registration 

information would be less time 

consuming under the proposal because 

the manufacturer’s, repacker’s, 

relabeler’s, and drug product salvager’s 

information would be easily accessible 

at any time and only changes to the 

information already in the system 

would need to be entered in the fields 

provided. 

The following sections provide a 

description of the proposed 

requirements for reviewing and 

updating registration information and 

how they modify or reduce the burden 

of the current requirements. 

a. Expedited updates of registration 

information. Manufacturers, repackers, 

relabelers, and drug product salvagers 

would report, under proposed 

§ 207.29(a), the following changes as 

expedited updates no later than 30 

calendar days after the change: 

• The close or sale of an 

establishment; 

• Any change in the name or address 

of an establishment; and 

• Any change in the name, address, 

telephone and fax numbers, or e-mail 

address of the official contact or the 

United States agent. 

We are proposing to require that these 

changes be reported as expedited 

updates because we need to know as 

soon as possible when a business has 

closed or has been sold and when the 

establishment’s name or address has 

changed. This information is especially 

important for scheduling inspections. 

We also need current information for 

contacting the official contact or United 

States agent. As previously mentioned, 

it is increasingly important for us to be 

able to identify where drugs are being 

made and when drugs are no longer 

available. The expedited receipt of this 

information will help promote the 

efficient enforcement of the act. 

Manufacturers, repackers, relabelers, 

and drug product salvagers are 

encouraged to provide expedited 

updates as soon as possible but no later 

than 30 calendar days after the change 

occurs. Our electronic drug registration 

and listing system will be easily 

accessible all the time to make changes. 

The close or sale of an establishment, 

and a change in the name or address of 

an establishment, are currently reported 

annually on Form FDA 2656. 

Proposed § 207.29(a) would revise 

current §§ 207.26 and 207.40(c)(3). 

Current § 207.26 requires the 

submission of certain amendments to 

registration information within 5 days of 

the change, and as noted previously, 

§ 207.40(c)(3) requires the submission of 

any changes to the United States agent’s 

name, address, or phone number within 

10 business days of the change. As 

explained below, the proposal would 

lengthen the time period for reporting 

the changes in current § 207.40(c)(3). 

The proposal also would lengthen the 

time period for reporting some of the 

changes in current § 207.26 and revoke 

some of the reporting requirements in 

current § 207.26: 

• A change in location would no 

longer be submitted as an amendment to 

registration within 5 days of the change, 

but would be reported under proposed 

§ 207.29(a)(2) as an expedited update no 

later than 30 calendar days after the 

change (‘‘address’’ of an establishment 

is used in the proposal instead of 

location). We have determined that 

notification no later than 30 calendar 

days would be sufficient and would be 

consistent with the proposed timeframe 

for the other expedited updates. 

• A change in ‘‘drug-handling 

activity’’ would no longer be submitted 

as an amendment to registration within 

5 days of the change. A change in this 

information would only be reported 

during the annual review and update 

under proposed § 207.29(b). (The term 

‘‘type of operations’’ is used in proposed 

§ 207.25(f) instead of ‘‘drug-handling 

activity.’’) We have determined that 

annual notification of this change would 

be sufficient. 

• Changes in ‘‘individual ownership’’

and ‘‘corporate or partnership 

structure,’’ in current § 207.26, would 

no longer be reported as amendments to 

registration because the proposal would 

revoke the corresponding provision for 

registration in current § 207.25(a) (the 

‘‘kind of ownership or operation (that is, 

individually owned, partnership or 

corporation)’’). As explained in section 

IV.B.3 of this document, the kind of 

ownership or operation would no longer 

be submitted for registration because the 

information would be captured under 

the requirement to provide, if 

applicable, the name of the partner, 

corporate officer and director, and the 

place of incorporation in proposed 

§ 207.25(a). This information would be 

reviewed and updated annually under 

proposed § 207.29(b). This proposed 

requirement is consistent with current 

§ 207.26, which specifies that changes 

in the names of officers and directors of 

the corporation do not require an 

amendment and must be submitted at 

the time of annual registration. 

• Under current § 207.26, a change in 

a registered establishment’s firm name 

within 6 months of the registration of 

the establishment must be supported by 

a signed statement of the 

establishment’s owner or operator that 

the change was not made for the 

purpose of changing the name of the 

manufacturer of a drug product under 

current § 201.1. This verification would 

no longer be required to be submitted as 

an amendment to registration. A change 

in the name of an establishment would 

be reported under proposed 

§ 207.29(a)(2) no later than 30 calendar 

days after the change. 

Proposed § 207.29(a)(3) would revise 

current § 207.40(c)(3), which provides 

that a foreign drug establishment or 

United States agent must report to us, 

within 10 business days, any changes to 

the United States agent’s name, address, 

or phone number. The proposal would 

make the following revisions: 

• The changes to the information 

about the United States agent would be 

revised to include not only the name, 

address, and telephone number, but also 

the fax number and e-mail address. This 

provision would be consistent with the 

information required to be submitted for 

the United States agent for registration 

under proposed § 207.25(h). 

• The time period for reporting the 

changes would be lengthened to no later 

than 30 calendar days for consistency 

with the time period for the other 

expedited reports in proposed 

§ 207.29(a). 

• Changes in the name, address, 

telephone and fax numbers, and e-mail 

address of the official contact would 

also be reported under proposed 

§ 207.29(a)(3) within 30 calendar days. 

This provision would be consistent with 

the information required to be 

submitted for the official contact for 

registration under proposed § 207.25(g). 

• Under proposed § 207.29(a)(3), the 

manufacturer, repacker, relabeler, and 

drug product salvager, official contact, 

or United States agent may notify us 

about a change of information for the 

designated official contact or United 


jlentini on PROD1PC65 with PROPOSAL2
Federal Register / Vol. 71, No. 167 / Tuesday, August 29, 2006 / Proposed Rules 51295 

States agent. This provision would make 

the updates easier than the requirement 

in current § 207.40(c)(3) because it 

would enable the official contact and 

the United States agent (in addition to 

the manufacturer, repacker, relabeler, 

and drug product salvager) to update 

their own or each other’s registration 

information. 

• Under proposed § 207.29(a)(3), only 

a manufacturer, repacker, relabeler, or 

drug product salvager may designate a 

new official contact or United States 

agent. This proposed requirement is 

necessary because the manufacturer, 

repacker, relabeler, and drug product 

salvager is ultimately responsible for the 

actions of the official contact and the 

United States agent. 

The requirements for the official 

contact and the United States agent are 

discussed in section IV.F.1 of this 

document. 

b. Annual review and update of 

registration information. Proposed 

§ 207.29(b) would require that the 

registration information provided under 

proposed § 207.25 be reviewed and 

updated annually. This timeframe is 

consistent with the requirement in 

section 510(b) of the act that owners or 

operators register on or before December 

31 of each year and with the 

requirement in current § 207.21(a) that 

owners or operators renew their 

registration information annually. 

Proposed § 207.29(b) uses the term 

‘‘review and update’’ to stress the 

importance of first reviewing all 

registration information to determine if 

any changes have occurred and then 

updating the information where needed. 

Proposed § 207.29(b)(1) specifies that 

the first review and update must occur 

no later than 1 year after the date of the 

initial registration of each establishment 

and that subsequent reviews and 

updates must occur no later than 

annually thereafter from the date of 

initial registration. Proposed 

§ 207.29(b)(2) provides that the updates 

must reflect all changes that have 

occurred since the last annual review 

and update. 

The proposal would add a new 

requirement for updating registration 

information. Under proposed 

§ 207.29(b)(3), if none of the registration 

information has changed since the last 

annual registration (accomplished 

through the review and update of 

registration information), 

manufacturers, repackers, relabelers, 

and drug product salvagers must certify 

electronically that no changes have 

occurred. This is consistent with section 

510(b) of the act, which requires 

manufacturers to register on or before 

December 31 of each year. If 

manufacturers, repackers, relabelers, 

and drug product salvagers certify that 

no changes have occurred, this 

certification would be the equivalent of 

resubmitting registration information, 

thereby satisfying the annual 

registration requirement. We are 

proposing to require that manufacturers, 

repackers, relabelers, and drug product 

salvagers certify annually that no 

changes have occurred because many 

manufacturers, repackers, relabelers, 

and drug product salvagers have not 

reviewed or updated this information on 

a regular basis. It has been difficult for 

us to determine whether failure to 

register annually is the result of no 

changes in information or 

noncompliance. The proposed 

requirement is intended to reduce these 

instances and improve the accuracy of 

our registration database. To increase 

the nation’s ability to prepare for and 

respond effectively to bioterrorism and 

other public health emergencies, it is 

increasingly important for 

manufacturers, repackers, relabelers, 

and drug product salvagers to comply 

with registration requirements. With 

accurate information, we can identify 

where drugs are being made and better 

ensure that drugs are promptly available 

when needed. Furthermore, taking steps 

to increase compliance is consistent 

with section 301(p) of the act (21 U.S.C 

331(p)), which makes it a prohibited act 

to fail to register under section 510 of 

act. 

C. The National Drug Code (NDC) 

Number: What is It? How is It Used? 

What Changes Are We Proposing? 

1. What Is the NDC Number? 

The NDC number is a widely used 

identifier for drugs. It is a unique 10- 

digit number consisting of 3 segments: 

The labeler code, the product code, and 

the package code. Currently, the labeler 

code consists of four or five digits, the 

product code consists of either three or 

four digits, and the package code 

consists of either one or two digits. We 

assign the labeler code to the 

manufacturer, repacker, or relabeler 

after it has registered with us. For 

private label distributors, currently we 

provide a labeler code to the private 

label distributor if the private label 

distributor submits the required 

information to us. Alternatively, we 

provide a labeler code for a private label 

distributor to the manufacturer, 

repacker, or relabeler who is 

manufacturing, repacking, or relabeling 

the drug for the private label distributor 

after the manufacturer, repacker, or 

relabeler provides the required 

registration information pertaining to 

the private label distributor. The 

manufacturer, repacker, relabeler, or 

private label distributor then assigns the 

product code and package code to each 

drug within certain parameters that we 

have established. 

2. How Did NDC Numbers Originate? 

How Are They Used? 

Created in 1969, NDC numbers were 

originally intended to ‘‘provide an 

identification system in computer 

language to permit automated 

processing of drug data by Government 

agencies, drug manufacturers and 

distributors, hospitals, and insurance 

companies’’ (see 34 FR 11157, July 2, 

1969). Participation in the NDC system 

was voluntary initially, and the program 

covered ‘‘firms which manufacture and 

label or which repackage and label 

drugs’’ (id.). In 1971, the NDC system 

expanded to include ‘‘distributors who 

are marketing drug products in 

interstate commerce, under their own 

name (label), and through multiple 

wholesale outlets and/or five or more 

retail outlets’’ (see 36 FR 27, January 1, 

1971). 

The enactment of the Drug Listing Act 

of 1972 (Public Law 92–387, 86 Stat. 

559) changed the NDC number system 

even further. The Drug Listing Act 

required registered establishments to list 

all drugs that the establishment 

manufactures, prepares, propagates, 

compounds, or processes for 

commercial distribution and authorized 

us to assign a ‘‘listing number’’ to each 

drug or class of drugs that was listed. 

The Drug Listing Act declared that, 

‘‘Any number assigned * * * shall be 

the same as that assigned pursuant to 

the National Drug Code.’’ Thus, by 

linking drug listings to the NDC 

numbers, the Drug Listing Act, in 

essence, authorized us to make 

participation in the NDC number system 

mandatory. In addition, by referring to 

the word, ‘‘drug,’’ the Drug Listing Act 

extended the NDC number system to 

over-the-counter drugs and animal 

drugs (because both are ‘‘drugs’’ under 

the act and are listed under section 

510(j) of the act). 

Today, NDC numbers continue to be 

an important, standardized, 

identification system for drug products 

used in data or claims processing, as 

well as in applications other than data 

or claims processing. For example, 

consumers may use NDC numbers to 

identify drugs that are the subject of a 

recall. Health care professionals 

submitting MedWatch reports 

(concerning possible adverse drug 

events) use NDC numbers to identify the 

drug at issue. Our investigators 

sometimes use NDC numbers to 


jlentini on PROD1PC65 with PROPOSAL2
51296 Federal Register / Vol. 71, No. 167 / Tuesday, August 29, 2006 / Proposed Rules 

determine a drug’s compliance status by 

linking the NDC number to our 

registration and listing database to 

verify whether the manufacturer has 

registered and listed a particular drug. 

We compile the NDC numbers in the 

National Drug Code Directory, and the 

directory is accessible online at http:// 

www.fda.gov/cder/ndc/database. 

In addition, several new or future 

public health programs or initiatives 

rely or will rely on NDC numbers. For 

example: 

• On February 26, 2004 (69 FR 9120), 

we published in the Federal Register a 

final rule to require certain human drug 

and biological products to have bar 

codes (see 69 FR 9120). The bar code 

must contain, at a minimum, the drug’s 

NDC number. This rule is designed to 

reduce the number of medication errors 

in hospitals and other health care 

settings by allowing health care 

professionals to use bar code scanning 

equipment to verify that the right drug 

(in the right dose and right route of 

administration) is being administered to 

the right patient at the right time. 

• The electronic prescription drug 

program established by the Medicare 

Modernization Act promotes uniform 

standards that permit (among other 

things) electronic exchange of drug 

labeling and drug listing information 

maintained by us and by the National 

Library of Medicine (see 42 U.S.C. 

1860D–4(e)(3)(C)(iii)). The goal behind 

the program is to reduce transcription 

and dispensing errors (which, in turn, 

lead to medication errors) and to 

prevent adverse drug interactions. As 

we stated previously in this document, 

drug listing numbers are, under the 

Drug Listing Act of 1972, to be the same 

as NDC numbers. 

• The Health Insurance Portability 

and Accountability Act (Public Law 

104–191) required, among other things, 

adoption of code set standards to 

facilitate electronic transactions. The 

standard code set for drugs is the NDC 

(see final rule on ‘‘Health Insurance 

Reform: Standards for Electronic 

Transactions’’ (65 FR 50312, August 17, 

2000), 45 CFR 162.1002(c); amended 

February 20, 2003: ‘‘Health Insurance 

Reform: Modifications to Electronic 

Data Transaction Standards and Code 

Sets’’ (68 FR 8381), 45 CFR 

162.1002(a)(3) and (b)(2)). 

• We are working with the National 

Library of Medicine, manufacturers, 

repackers, relabelers, and health care 

information suppliers to improve 

patient safety by better access to 

medication information through the 

DailyMed initiative. The DailyMed is an 

up-to-date, computerized repository of 

medication information including 

product labeling. The changes we are 

proposing to the NDC number would 

complement the DailyMed initiative by 

providing a link to product labeling 

made available through the DailyMed. 

The product labeling in this repository 

would be in the form of SPL. SPL is a 

standardized computer readable product 

labeling that links the NDC number to 

the product information. 

To illustrate how this would work, 

someone could simply scan a bar code 

encoded with the NDC number or type 

into the DailyMed search program the 

NDC number on the carton label to 

access the most current information in 

the product labeling available from the 

DailyMed. This capability would enable 

DailyMed users to have the most up-todate information for a drug, which 

could be an important public health 

benefit for consumers and health care 

professionals. For example, assume that 

a manufacturer modified its labeling to 

reflect a new adverse drug experience. 

If a consumer, pharmacist, or health 

care provider received a drug whose 

labeling had been printed earlier, the 

consumer, pharmacist, or health care 

provider would not be alerted to the 

new adverse drug experience. By using 

the DailyMed, the consumer, 

pharmacist, or health care provider 

would be able to access the new drug 

labeling and would, therefore, learn 

about the new adverse drug experience 

and possibly be able to avoid it. The 

consumer, pharmacist, or health care 

provider would also be better able to 

assess the risks and benefits of the drug 

and, therefore, would be able to make 

more informed decisions about using 

the drug. The DailyMed would be a 

publicly accessible repository of drug 

information that could be used in many 

ways by various parties, such as by 

those who could add value to the 

information, such as pricing 

information, and make it available to 

other parties. 

Unfortunately, despite the widespread 

and growing use and reliance on NDC 

numbers, the existing NDC number 

system has several shortcomings. For 

example, manufacturers, repackers, and 

relabelers can assign NDC numbers, and 

the current regulations at 

§ 207.35(b)(4)(ii) permit them to re-use 

the product codes under certain 

circumstances (such as taking the NDC 

number assigned to drug X and then, 

after drug X has been discontinued, later 

assign the same NDC number to drug Z). 

Also, under current regulations, it is 

difficult for FDA to control the practice 

of a manufacturer, repacker, or relabeler 

making changes to a drug but 

continuing to use the same NDC number 

despite those changes. 

The manufacturer, repacker, and 

relabeler’s ability to assign the product 

code and package code themselves has 

also resulted in problems that affect the 

National Drug Code Directory and its 

reliability. Product and package codes 

are not always assigned appropriately, 

and industry practices for assigning 

codes are inconsistent. In addition, 

manufacturers, repackers, and relabelers 

currently do not tell us what codes they 

have assigned until they list drugs with 

us; this means that the National Drug 

Code Directory is not always complete 

or comprehensive. Moreover, 

manufacturers, repackers, and relabelers 

may never list a product or may 

sometimes omit information or submit 

incorrect information to us; this often 

prevents us from including the correct 

information in the National Drug Code 

Directory and forces us to devote 

resources to obtaining, sometimes 

unsuccessfully, the correct information. 

Furthermore, because NDC code 

segments can vary in length (such as a 

NDC having a four-digit labeler code, a 

four-digit product code, and a two-digit 

package code while another NDC has a 

five-digit labeler code, a three-digit 

product code, and a two-digit package 

code), electronic systems that view the 

NDC as a single number might interpret 

two different NDC numbers as being the 

same number. For example, one 

manufacturer, repacker, or relabeler’s 

drug might have a NDC number that 

reads as 12345–678–90 while another 

could have a drug whose NDC number 

reads as 1234–5678–90. If a database 

omits the hyphens, the result would be 

a misleading impression that both drugs 

have identical NDC numbers (i.e., 

1234567890), although they are made by 

different manufacturers and may be 

entirely different products. 

We have also found that some 

manufacturers, repackers, and relabelers 

have assigned NDC numbers to products 

that are not drugs, such as dietary 

supplements and medical devices; such 

actions can confuse drug databases or 

lead to inappropriate reimbursements. 

Consequently, to address these 

shortcomings and to create an accurate, 

up-to-date NDC number system, we 

propose to revise the NDC number 

system. In brief, we believe that to 

ensure that the numbers are unique and 

unambiguous, we need to take on the 

responsibility of assigning the NDC 

numbers prospectively to drugs that 

have not previously been assigned NDC 

numbers by a manufacturer, repacker, or 

relabeler. The NDC numbers currently 

assigned to drugs prior to the effective 

date of the rule would remain 

unchanged, provided those NDC 

numbers comply with the new 


jlentini on PROD1PC65 with PROPOSAL2
Federal Register / Vol. 71, No. 167 / Tuesday, August 29, 2006 / Proposed Rules 51297 

regulations as finalized. FDA intends to 

validate that current NDC numbers 

comply with the new regulations as 

finalized. We believe that the NDC 

number structure can remain very 

similar to what exists today, as we 

describe below, and still allow for 

unique and unambiguous NDC numbers 

if we assign the NDC numbers. 

The proposal would also delete 

obsolete or unnecessary requirements. 

For example, current § 207.35 refers to 

the National Health Related Items Code 

(NHRIC) system as another code system; 

the proposal would omit references to 

the NHRIC system because we no longer 

maintain the NHRIC database (see 42 FR 

52808 at 52810, September 30, 1977)). 

We describe the proposed changes in 

more detail in the next section. 

3. What Changes Are We Proposing? 

a. Proposed § 201.2—Drugs; National 

Drug Code (NDC) Number. Currently, 

§ 201.2 states that NDC numbers are 

requested, but not required, to appear 

on all drug labels and in all drug 

labeling, ‘‘including the label of any 

prescription drug container furnished to 

a consumer.’’ Section 201.2 also states 

that if the NDC number appears on the 

drug label, it must be displayed as 

required by current § 207.35(b)(3). 

The proposal would revise § 201.2 to 

explain: 

• What drugs must have an NDC 

number, in human-readable form, on the 

label; 

• What an appropriate NDC number 

is; 

• Whether any other NDC number 

may appear on a label; 

• What prefix must be used to 

identify the NDC number on the label; 

and 

• Where the NDC number goes on the 

label. 

Specifically, proposed § 201.2(a) 

would require the appropriate NDC 

number, in human-readable form, to 

appear on the labels of drugs subject to 

the drug listing requirements. In this 

case, the word ‘‘drugs’’ should be 

interpreted in light of proposed § 207.1 

and encompasses human drugs, 

including the drugs regulated under a 

BLA, as described in proposed 

§ 207.9(c), and animal drugs, including 

Type A medicated articles. These drugs 

may be active pharmaceutical 

ingredients or finished dosage forms, 

whether prescription or OTC. The drugs 

regulated under a BLA, as described in 

proposed § 207.9(c) include, but are not 

limited to: (1) Plasma derivatives such 

as albumin, Immune Globulin, Factor 

VIII and Factor IX, and recombinant 

versions of plasma derivatives or animal 

derived plasma derivatives; (2) 

Vaccines; (3) Allergenic products; (4) 

Bulk product substances such as 

fractionation intermediates or pastes; 

and (5) Therapeutic biological products. 

We propose to require humanreadable NDC numbers to appear on 

drug labels because various individuals 

and databases use and rely on NDC 

numbers, and those individuals or 

databases might not have the technology 

or means to read an automatic 

identification technology such as a bar 

code that is required under § 201.25. In 

addition, for those who are able to read 

bar codes, a human-readable NDC 

number may serve as a ‘‘backup’’ in case 

the bar code is damaged, cannot be read, 

or is otherwise illegible. 

Proposed § 201.2(b) would explain 

that an ‘‘appropriate NDC number’’ is 

the NDC number that we have assigned 

(under proposed §§ 207.33 or 207.37, 

which we discuss later in this part) to 

the last manufacturer, repacker or 

relabeler (including a drug product 

salvager who repacks or relabels the 

drug), or private label distributor 

responsible for the drug immediately 

before it is received by the wholesaler 

or retailer. For example, assume that a 

manufacturer makes a drug and sells 

that drug to a wholesaler or retailer. 

Under proposed § 201.2(b), the 

manufacturer is the last person 

responsible for the drug immediately 

before it reached the wholesaler or 

retailer, so the appropriate NDC number 

would be the manufacturer’s NDC 

number that we have assigned to that 

drug. If, however, the manufacturer sold 

the drug to a repacker, who then 

repackages the drug and sells the 

repackaged drug to a retailer, the 

repacker is the last person responsible 

for the drug immediately before it 

reached the retailer, so the appropriate 

NDC number would be the repacker’s 

NDC number that we have assigned and 

not the manufacturer’s NDC number. 

Identifying the last person responsible 

for a drug may be important in 

situations where the drug’s quality, 

purity, labeling, or packaging may be at 

issue; for example, if a drug appeared to 

be contaminated, knowing who the last 

person was who manufactured, 

repacked, or relabeled the drug could 

help focus an investigation to determine 

how the contamination occurred. It also 

allows linking to the correct product 

information in the DailyMed. In 

addition, requiring the NDC number of 

the last manufacturer, repacker, 

relabeler, or private label distributor 

responsible for the drug immediately 

before it is received by the wholesaler 

or retailer would enable us to accurately 

and quickly identify the original 

manufacturer by connecting the NDC 

number on the label to the information 

in the electronic drug registration and 

listing system. 

The proposed approach of assigning 

NDC numbers would mean that 

repackers, for example, would have to 

use their own NDC number, rather than 

using the manufacturer’s NDC number 

on drug labels. We recognize that some, 

but not all, repackers have been using 

the manufacturer’s NDC number rather 

than their own on drug labels. We are 

aware that some repackers’ practice of 

using the manufacturers’ NDC numbers 

has led to some confusion among FDA, 

the Centers for Medicare & Medicaid 

Services (CMS), other Federal agencies, 

State agencies, and private insurance 

organizations that rely on NDC numbers 

for many purposes, including to identify 

a drug and a drug’s source and for 

purposes of reimbursement and 

dispensing systems. It also has led to 

some confusion by practitioners and 

patients. There may be other reasons 

that this practice has posed difficulties 

or is cause for concern. 

We are aware that the use of 

manufacturer’s NDC numbers by some 

repackers may lead to inaccurate or 

improper reimbursement by Medicaid, 

Medicare, and private insurers. It also 

may result in misunderstanding as to 

which rebate agreement a particular 

drug is covered by or whether a 

particular drug is covered by any rebate 

agreement at all. 

We are also aware that the use of 

manufacturer’s NDC numbers by 

repackers may not always be accurate or 

consistent. For example, a repacker 

might use a manufacturer’s NDC 

number for a particular drug and then 

continue to use that manufacturer’s 

NDC number for generic equivalents to 

that drug. This may lead to confusion 

for caregivers and patients who may be 

dispensed medication based on the 

original manufacturer’s NDC number, 

but receive a drug that is different in 

size, shape and/or color than the drug 

they are accustomed to using. 

Additionally, there could be 

reimbursement differences between one 

firm’s product and another firm’s 

product. Further, the NDC number of 

the wrong manufacturer on the drug’s 

label (even if the drugs of both 

manufacturers are generic equivalents) 

may also be a problem when pharmacies 

rely on verification systems that include 

exact color images of drugs based on 

NDC numbers. 

Recently, the National Association of 

Chain Drug Stores (NACDS) and the 

Healthcare Distribution Management 

Association (HDMA) asked us to 

exercise enforcement discretion 

concerning our recent bar code rule (see 


jlentini on PROD1PC65 with PROPOSAL2
51298 Federal Register / Vol. 71, No. 167 / Tuesday, August 29, 2006 / Proposed Rules 

21 CFR 201.25 (69 FR 9170, February 

26, 2004)) so that repackers could 

continue using manufacturers’ NDC 

numbers on retail-based repackaged 

drug products (Ref. 1). In brief, NACDS 

and HDMA assert that FDA has 

‘‘historically allowed the use of original 

manufacturer NDC numbers by 

repackagers on the product labels of 

retail-based repackaged drug products’’

and that this practice is standard among 

repackers (Ref. 1, p. 2). NACDS and 

HDMA also stated that use of the 

repackers’ NDC numbers ‘‘is not 

necessary or desirable’’ because 

repackers identify themselves on the 

drug labels and that procedures exist to 

allow recall of particular lots of 

repacked drugs (rather than all drugs 

made by a manufacturer). They also 

stated that mandatory use of the 

repackers’ NDC numbers might affect 

patient safety adversely and create 

additional, excessive costs to patients, 

health care providers, and payers 

because databases use the 

manufacturers’ NDC numbers and 

cannot be modified to accommodate 

repackers’ NDC numbers (Ref. 1, pp. 4 

through 9). For example, NACDS and 

HDMA said that requiring repackers to 

use their own NDC numbers could 

‘‘greatly increase the potential for 

medication errors’’ because pharmacists 

would: ‘‘be required to inefficiently and 

manually choose between multiple 

options of the same product, e.g., Motrin 

800mg by [one manufacturer] or Motrin 

800mg repackaged by 5 different 

repackagers. The more NDC numbers in 

use for the same product across the 

country, the greater the chance that data 

entry errors will occur across the many 

pharmacies that use repackaged 

products.’’ (Ref. 1, p. 7.) In addition, 

NACDS and HDMA said that requiring 

repackers to use their own NDC 

numbers would oblige them to pay 

substantial rebate fees under Medicaid 

when Congress intended drug 

manufacturers, not repackers, to pay 

those rebates and would complicate 

Medicaid billing; they further stated that 

requiring repackers to use their own 

NDC numbers would lead to a ‘‘sharp 

reduction or elimination of this type of 

repackaging’’ (Ref. 1, p. 8). 

On March 28, 2005, we issued a 

response to the letter from NACDS and 

HDMA. The response stated, among 

other things, that we intend to 

temporarily exercise our enforcement 

discretion and permit repackers to use 

manufacturers’ NDC numbers in bar 

codes placed on their products. We said 

that there will be an opportunity to 

directly consider this issue when we 

issue our proposed rule on 

establishment registration and drug 

listing. The response stated that we will 

consider all information provided that 

documents the impact on repackers. 

We lack sufficient information to 

assess whether requiring repackers to 

use their own NDC numbers would be 

as problematic and expensive as NACDS 

and HDMA suggest. We also do not 

know the extent to which databases that 

use NDC numbers cannot be modified to 

accommodate repackers’ NDC numbers 

or to associate more than one NDC 

number with drugs made by the same 

manufacturer. Moreover, although 

repackers currently assign their own 

NDC numbers and report those numbers 

to us, we do not know whether 

databases ignore or omit repackers’ NDC 

numbers that we make available through 

the National Drug Code Directory. 

We believe that allowing repackers to 

use the manufacturers’ NDC numbers 

would be contrary to the proposal’s goal 

of making the NDC number unique and 

the system more accurate and reliable. 

We are requesting additional 

information on this issue. We 

specifically invite comments on the 

proposed approach of requiring on the 

drug’s label the NDC number of the last 

manufacturer, repacker or relabeler 

(including the drug product salvager 

who repacks or relabels the drug), or 

private label distributor responsible for 

the drug immediately before it is 

received by the wholesaler or retailer, 

which would result in prohibiting the 

use of manufacturer’s NDC numbers by 

repackers. We are especially interested 

in: (1) Examples and discussions of 

dispensing errors or difficulties, 

confusion, reimbursement problems, or 

other difficulties that may have been 

caused or contributed to by the practice 

of some repackers using the 

manufacturer’s NDC number; (2) The 

magnitude of the problems that may be 

attributed to the use of manufacturer’s 

NDC numbers by repackers and of the 

problems that NACDS and HDMA have 

articulated that may result from 

mandating the use of repacker’s NDC 

numbers by repackers; (3) the extent to 

which such problems do or are likely to 

occur; and (4) whether there are 

technological (that is, software) 

solutions or alternatives that could 

address the issues presented in the 

NACDS and HDMA letter, other issues 

identified in this preamble, or those 

raised in comments to this proposed 

rule. 

By inviting comment, we are 

specifically giving NACDS and HDMA, 

and any other interested parties, the 

opportunity to comment on whether 

repackers should be able to use the 

manufacturers’ NDC numbers on the 

repacked drugs’ label. 

Proposed § 201.2(c) states that only 

the appropriate NDC number required 

by proposed § 201.2(b) may appear on 

the label. This provision would 

complement proposed § 201.2(b) by 

requiring the drug’s label to bear the 

appropriate NDC number. 

Proposed § 201.2(d) would require the 

human-readable NDC number to be 

immediately preceded by the letters 

‘‘NDC.’’ This provision would modify 

the current requirement at 

§ 207.35(b)(3)(ii), which states that the 

NDC number must be preceded by the 

prefix ‘‘NDC’’ or ‘‘N’’ when used on a 

label or labeling. We decided to limit 

the prefix to ‘‘NDC’’ because, when 

compared to ‘‘N’’ alone, ‘‘NDC’’ is a 

clearer signal that the number following 

‘‘NDC’’ is the NDC number. 

Proposed § 201.2(e) would require 

that the appropriate NDC number 

appear clearly on the drug’s label as 

defined by section 201(k) of the act. 

Section 201(k) of the act defines ‘‘label’’

as ‘‘a display of written, printed, or 

graphic matter upon the immediate 

container of any article.’’ Section 201(k) 

also states that ‘‘a requirement made by 

or under authority of this Act that any 

word, statement, or other information 

appear on the label shall not be 

considered to be complied with unless 

such word, statement, or other 

information also appears on the outside 

container or wrapper, if any there be, of 

the retail package of such article, or is 

easily legible through the outside 

container or wrapper.’’ This proposed 

requirement would be a change from 

current § 207.35(b)(3)(i), which requires 

the NDC number to appear 

‘‘prominently in the top third of the 

principal display panel.’’ We decided to 

remove the restriction on the NDC 

number’s location because our bar code 

rule, which requires the bar code to 

encode the drug’s NDC number, allows 

the bar code to appear anywhere on the 

drug’s label. Consequently, some 

establishments may wish to place the 

human-readable NDC number next to 

the bar code, so we have decided against 

specifying the location of the humanreadable NDC number. 

We are also proposing to revise 

current § 201.25 because, as discussed 

in section IV.A.5 of this document 

(definition of ‘‘drug(s)’’) and in the 

February 26, 2004, bar code final rule, 

certain drugs that would be subject to 

proposed part 207 are not subject to 

current § 201.25. Under proposed 

§ 201.25(e), a drug product that is 

subject to the drug listing requirements 

of proposed part 207 but is not subject 

to current § 201.25 may display a bar 


jlentini on PROD1PC65 with PROPOSAL2
Federal Register / Vol. 71, No. 167 / Tuesday, August 29, 2006 / Proposed Rules 51299 

code on the label only if the bar code 

meets the requirements of § 201.25(c). 

We are proposing this revision to help 

ensure consistency in the appearance, 

content, and placement of bar codes on 

drug labels. We are also proposing to 

revise current § 201.25 to further clarify 

what ‘‘appropriate’’ NDC number must 

appear in the bar code. Current 

§ 201.25(c)(1) states that each drug 

product subject to current § 201.25 must 

have a bar code that contains, at a 

minimum, the appropriate NDC 

number. To clarify this requirement, we 

are proposing to amend current 

§ 201.25(c)(1) to state that the 

‘‘appropriate NDC number,’’ as used in 

current § 201.25(c)(1), is described in 

proposed § 201.2(b). 

We note that when there is a change 

in the NDC number on a drug product 

label, or when an NDC number is added 

to a label, application holders must 

submit revised labeling to us with their 

annual reports under § 314.81(b)(2) for 

human drugs, § 514.80(b)(4) for animal 

drugs (‘‘periodic reports’’ are required 

instead of ‘‘annual reports’’), and 

§ 601.12(f)(3) for biological drugs. 

b. Proposed § 207.33—What is the 

National Drug Code Number, who must 

obtain it, and what information must be 

submitted? Proposed § 207.33 would 

describe the NDC number and the 

process for obtaining NDC numbers. The 

proposal would differ from the preexisting NDC number system by having 

us assign the NDC number for newly 

listed drugs, by describing the changes 

that would require a manufacturer, 

repacker, or relabeler to obtain a new 

NDC number, and by describing when 

information must be submitted to us to 

obtain an NDC number. Under the 

proposal, all three sections of the NDC 

number would be assigned 

prospectively by us to drugs that have 

not previously been assigned NDC 

numbers by a manufacturer, repacker, or 

relabeler. The NDC numbers currently 

assigned to drugs prior to the effective 

date of the rule would remain 

unchanged, provided those NDC 

numbers comply with the new 

regulations as finalized. FDA intends to 

validate that current NDC numbers 

comply with the new regulations as 

finalized. 

Currently, § 207.35(a) states that we 

will provide a validated copy of an 

establishment’s registration form and 

assign a permanent registration number 

to each drug establishment in 

accordance with our regulations. 

Current § 207.35(b)(1) and (b)(2) state 

that we will assign a drug listing 

number to each drug or class of drugs 

and that the number of characters in 

that number may differ depending on 

whether the drug is already listed in the 

NDC system or the NHRIC system. For 

example, current § 207.35(b)(1) states 

that if a drug is already listed in the 

NDC system or NHRIC system, the drug 

listing number is the same as that 

assigned under those codes and that we 

will add a lead zero to the first three 

characters to create a four-character 

labeler code. Current § 207.35(b)(1) also 

states that manufacturers or distributors 

may retain alphanumeric characters that 

they already use in the product and 

package code segments and must inform 

us if they convert those code segments 

into numeric digits. Current 

§ 207.35(b)(2) also explains how many 

characters may be in a labeler code, 

product code, and package code. 

Given that this proposal would 

designate the responsibility of assigning 

the NDC number to FDA, the proposal 

would eliminate many of the provisions 

in current § 207.35, such as our need to 

provide to sponsors validated copies of 

registration forms as well as information 

on how to assign the product code and 

package code. Proposed § 207.33(a) 

explains that the NDC number is a 

unique 10-digit number composed of a 

labeler code, product code, and package 

code. Proposed § 207.33(a) also states 

that we would assign the complete NDC 

number (that would include the existing 

labeler code, if any) to each drug that is 

subject to the listing requirements in 

part 207. We would use the same 

configuration when assigning each 

segment of the NDC number: The labeler 

code would be either five or four digits, 

the product code would be either four 

or three digits, and the package code 

would be either two digits or one digit. 

When we assign a NDC number to a 

drug, we intend to leave a space 

between the segments of the NDC 

number so that the separate codes are 

distinguishable. Manufacturers, 

repackers, and relabelers may add 

symbols, such as hyphens or asterisks, 

between the segments of the humanreadable NDC number if they want to 

visually distinguish the codes in such a 

manner. Under the proposal, 

manufacturers, repackers, and relabelers 

would keep the same labeler code that 

they use for currently marketed drugs. 

However, if more than one labeler code 

is currently used by a manufacturer, 

repacker, or relabeler, only one labeler 

code would be used for any new NDC 

numbers that we would assign under 

this rule prospectively. Also, as 

described below, the proposal would 

allow currently marketed drugs to keep 

the same NDC numbers in most cases. 

Proposed § 207.33(b)(1) and (b)(2) 

would require that manufacturers, 

repackers, relabelers, and, in certain 

circumstances, drug product salvagers, 

obtain NDC numbers from us for each 

drug that is subject to the drug listing 

requirements. In the case of drug 

product salvagers, they would obtain an 

NDC number for each drug that is 

subject to the drug listing requirements 

only if they repack or relabel the 

salvaged drug. For private label 

distributors, proposed § 207.33(b)(3) 

states that the manufacturer, repacker, 

or relabeler who manufactures, repacks, 

or relabels the drug for the private label 

distributor is responsible for obtaining 

the NDC number from us for each drug 

that is subject to the drug listing 

requirements. 

Proposed § 207.33(b) is intended to 

clarify who must obtain NDC numbers. 

For example, drug product salvagers 

ordinarily would not need to obtain 

NDC numbers because they merely 

salvage drugs. If a drug product salvager 

simply recovers the drug and sells it 

without repacking or relabeling the 

product, the drug product salvager 

would not need to obtain an NDC 

number for the salvaged drug. However, 

if the drug product salvager repacks or 

relabels the salvaged drug, then the drug 

product salvager is similar to a repacker 

or relabeler, and proposed § 207.33(b) 

would require the drug product salvager 

to obtain an NDC number from us for 

the repacked or relabeled drug. As 

another example, under the proposal, 

private label distributors would not be 

permitted to register or list and, 

consequently, they would not obtain 

NDC numbers for the drugs they 

distribute. Instead, the manufacturer, 

repacker, or relabeler who 

manufactures, repacks, or relabels the 

drug for the private label distributor 

would be responsible for obtaining the 

NDC number, including a labeler code 

appropriate for the private label 

distributor. This change ensures that 

more accurate information is provided 

to FDA about the drug distributed by the 

private label distributor because the 

manufacturer supplies the necessary 

drug information to FDA. 

Under current § 207.35, 

manufacturers, repackers, and relabelers 

assign NDC numbers to the drugs they 

manufacture, repack, or relabel, and 

private label distributors assign NDC 

numbers to the drugs they distribute if 

they opt to list the drugs themselves. 

Drug product salvagers currently do not 

receive NDC numbers for the drugs they 

salvage, and under current § 207.20(a), 

they are not required to list the drugs 

they salvage. 

As noted previously, even though we 

would assign NDC numbers under the 

proposal, an establishment’s labeler 

code would remain the same in most 


jlentini on PROD1PC65 with PROPOSAL2
51300 Federal Register / Vol. 71, No. 167 / Tuesday, August 29, 2006 / Proposed Rules 

cases. For example, if a manufacturer’s 

labeler code were 12345, we would 

assign NDC numbers for the 

manufacturer’s drugs and still use 12345 

as the manufacturer’s labeler code. 

However, under the proposal, if a 

manufacturer, repacker, or relabeler 

uses more than one labeler code, we 

would prospectively assign NDC 

numbers that use only one labeler code 

for that manufacturer, repacker, or 

relabeler. 

Note, too, that other components in an 

NDC number may remain unchanged 

under the proposal. For example, 

assume that a drug is already listed in 

the National Drug Code Directory and 

its manufacturer later decides to change 

its package size. In this situation, the 

labeler code and the product code 

would ordinarily remain the same, and, 

generally, we would assign a new 

package code for the changed drug. 

Furthermore, if a drug already has an 

NDC number at the time of the effective 

date of a final rule, the drug would 

retain that NDC number provided that 

the manufacturer, repacker, or relabeler, 

within 9 months after the effective date 

of a final rule, reviews and updates, in 

accordance with proposed §§ 201.2, 

207.33, 207.37, 610.60, and 610.61, the 

information in our database for the NDC 

number (see sections IV.C.4, IX, and X 

of this document for information on the 

proposed implementation and effective 

and compliance dates of this 

rulemaking). We also will work with 

manufacturers, repackers, and relabelers 

to address any problems with existing 

NDC numbers (such as duplicate or 

potentially duplicate NDC numbers) 

that might arise after a final rule 

becomes effective. 

Using a 5-digit labeler code, we 

estimate that we have the capacity for 

NDC numbers for up to 100,000 

registered establishments, each having a 

capacity for up to 100,000 product/ 

package size combinations (using the 5 

remaining digits). If a registered 

establishment requires more than 

100,000 product/package size codes, we 

could issue that establishment an 

additional labeler code. We currently 

have about 25,000 active establishments 

in our registration database, utilizing 

less than half of the 5-digit labeler code 

capacity. We currently issue about 1,000 

new labeler codes annually. If we reach 

NDC number capacity (possibly in 30 to 

50 years), we could propose to either 

add alphanumeric capability or expand 

the number of numeric digits to 11 or 

12 (current § 207.35(b)(2)(i) states that 

FDA will go from a 5- to 6-digit labeler 

code if needed). This change in NDC 

numbers will necessitate advances in 

current UPC technology (due to the 

need for bar code reading), which we 

anticipate will likely occur prior to our 

reaching the 10-digit NDC numeric 

capacity. 

The proposal would also omit the 

references to Form FDA–2656 in current 

§ 207.35(a) and (b)(2) because the 

proposal’s electronic submission of 

registration and listing information 

would make it unnecessary for us to 

provide validated copies of forms. In 

addition, because we would assign NDC 

numbers, the proposal would eliminate 

the provision in current § 207.35(b)(1) 

that allows manufacturers and 

distributors to convert alphanumeric 

product codes and package codes they 

may have and report such changes to us. 

(If any establishment still has 

alphanumeric product or package codes 

for a drug, we will work with them to 

assign new NDC numbers.) The 

proposal would also omit references in 

current § 207.35(b)(1) and (b)(2) to the 

NHRIC system because we do not 

maintain a NHRIC database (see 42 FR 

52808 at 52810). 

Proposed § 207.33(c) and (d) describes 

the information that a manufacturer, 

repacker, or relabeler would be required 

to submit before we assign an NDC 

number to a drug. As discussed earlier 

in this section, if a drug product 

salvager simply recovers the drug and 

sells it without repacking or relabeling 

the drug, the drug product salvager 

would not need to obtain an NDC 

number for the salvaged drug. However, 

if the drug product salvager repacks or 

relabels the salvaged drug, then the drug 

product salvager is similar to a repacker 

or relabeler, and proposed § 207.33(b) 

would require the drug product salvager 

to obtain an NDC number from us for 

the repacked or relabeled drug. The 

following table illustrates the proposed 

requirements. 

TABLE 1.—INFORMATION TO BE SUBMITTED TO OBTAIN AN NDC NUMBER, ARRANGED BY MANUFACTURER, REPACKER, OR

RELABELER AND DRUG

Proposed Section Type of Drug Information to be Submitted 

§ 207.33(c)(1) 

(Manufacturer) 

Active pharmaceutical ingredient • Manufacturer’s name, address, telephone number, fax number, e-mail address, and labeler code 

• Drug’s established name and proprietary name (if any) 

• Package size and type 

• Drug Master File number or Veterinary Master File number, if any, assigned to the active pharmaceutical ingredient 

§ 207.33(c)(2) 

(Manufacturer) 

Drug other than an active 

pharmaceutical ingredient 

• Manufacturer’s name, address, telephone number, fax number, e-mail address, and labeler code 

• Drug’s established name and proprietary name (if any) 

• Name and quantity of each active pharmaceutical ingredient or the approved U.S. application number 

• Name of each inactive ingredient (or approved U.S. application number) for certain 

drugs, and whether you consider the name of the inactive ingredient to fall under 

§ 20.61 (21 CFR 20.61) of this chapter or to be otherwise prohibited from disclosure 

and, if so, why 

• Dosage form 

• Package size and type, including immediate unit-of-use container 

• Marketing status (e.g., prescription or OTC) 

• Drug or drug product type (human drug or animal drug) 

• Imprinting information 


jlentini on PROD1PC65 with PROPOSAL2
Federal Register / Vol. 71, No. 167 / Tuesday, August 29, 2006 / Proposed Rules 51301 

TABLE 1.—INFORMATION TO BE SUBMITTED TO OBTAIN AN NDC NUMBER, ARRANGED BY MANUFACTURER, REPACKER, OR

RELABELER AND DRUG—Continued 

Proposed Section Type of Drug Information to be Submitted 

§ 207.33(c)(3) 

(Manufacturer) 

Active pharmaceutical ingredient for a private label distributor • Manufacturer’s name, address, telephone number, fax number, e-mail address, and labeler code 

• Drug’s established name and proprietary name (if any) 

• Package size and type 

• Drug Master File number or Veterinary Master File number, if any, assigned to the active pharmaceutical ingredient 

• Private label distributor’s name, address, telephone number, fax number, e-mail address, labeler code 

• Drug’s proprietary name (if any) as assigned by the private label distributor 

§ 207.33(c)(3) 

(Manufacturer) 

Drug other than an active 

pharmaceutical ingredient 

for a private label distributor 

• Manufacturer’s name, address, telephone number, fax number, e-mail address, and labeler code 

• Drug’s established name and proprietary name (if any) 

• Name and quantity of each active pharmaceutical ingredient or the approved U.S. application number 

• Name of each inactive ingredient (or approved U.S. application number) for certain 

drugs, and whether you consider the name of the inactive ingredient to fall under 

§ 20.61 of this chapter or to be otherwise prohibited from disclosure and, if so, why 

• Dosage form 

• Package size and type, including immediate unit-of-use container 

• Marketing status (e.g., prescription or OTC) 

• Drug or drug product type (human drug or animal drug) 

• Imprinting information 

• Private label distributor’s name, address, telephone number, fax number, e-mail address, and labeler code 

• Drug’s proprietary name (if any) as assigned by the private label distributor 

§ 207.33(d)(1) 

(Repacker or 

relabeler) 

Drug that is repacked or relabeled • Repacker’s or relabeler’s name, address, telephone number, fax number, e-mail address, and labeler code 

• NDC number assigned to the drug immediately before its receipt by the repacker or relabeler 

• Type of operation performed for the drug (repacking or relabeling) 

• Drug’s established name and proprietary name (if any) 

• Package size and type, including immediate unit-of-use container, if any (required for 

repackers only) 

§ 207.33(d)(2) 

(Repacker or 

relabeler) 

Drug that is repacked or relabeled for a private label 

distributor 

• Repacker’s or relabeler’s name, address, telephone number, fax number, e-mail address, and labeler code 

• NDC number assigned to the drug immediately before its receipt by the repacker or relabeler 

• Type of operation performed for the drug (repacking or relabeling) 

• Drug’s established name and proprietary name (if any) 

• Package size and type, including immediate unit-of-use container, if any (required for 

repackers only) 

• Private label distributor’s name, address, telephone number, fax number, e-mail address, and labeler code 

• Drug’s proprietary name (if any) assigned by the private label distributor 

Proposed § 207.33(c) and (d) are 

intended to accomplish several goals: 

1. The proposal would reduce 

redundant data submission and improve 

the accuracy of information that we 

receive. For example, under the current 

system, a manufacturer and a repacker 

may submit the same drug listing 

information for the same type of drug. 

However, the repacker might not have 

adequate information from the 

manufacturer or might describe the drug 

differently than the manufacturer; this 

would lead to data discrepancies and 

omissions. So, by requiring only 

manufacturers to provide descriptive 

information about the drugs they make, 

we would eliminate potential duplicate 

submissions, data discrepancies, and 

data omissions. Instead, the repacker, 

under the proposal, would simply tell 

us the NDC number of the drug that the 

repacker receives, and we could use the 

NDC number to link the drug back to its 

manufacturer. 

2. By having manufacturers, 

repackers, relabelers, and drug product 

salvagers submit information on behalf 

of private label distributors, the 

proposal would eliminate the potential 

for redundant, incomplete, or 

inconsistent submissions by private 

label distributors. For example, under 

the current system, some manufacturers 

have submitted information for drugs 

that they manufactured for private label 

distributors, and the private label 

distributors also submitted information 

for the same drugs; if the manufacturers 

and private label distributors described 

the drugs differently to us, we then had 

different information for the same drugs. 

3. By linking a repacker’s or 

relabeler’s drug to an NDC number, the 

proposal would eliminate a problem 

that some repackers and relabelers have 

encountered in the past. Under the 

current listing system, repackers and 

relabelers have sometimes found it 

difficult to obtain necessary information 

from manufacturers. This difficulty has 


jlentini on PROD1PC65 with PROPOSAL2
51302 Federal Register / Vol. 71, No. 167 / Tuesday, August 29, 2006 / Proposed Rules 

resulted in data errors and omissions 

and an incomplete or inaccurate 

National Drug Code Directory. 

4. By separating the NDC number 

process from drug listing and creating 

an electronic drug registration and 

listing system, the proposal should 

make it easier for manufacturers, 

repackers, and relabelers (and drug 

product salvagers who obtain NDC 

numbers for private label distributors) to 

obtain their NDC numbers quickly and, 

as a result, prepare product labels and 

marketing plans earlier. 

5. Under the proposal, the 

information submitted about the drug to 

obtain an NDC number would be 

retained in the electronic drug 

registration and listing system. Thus, 

when the manufacturer, repacker, or 

relabeler later lists the drug, they would 

need to provide only the additional 

information required for listing. 

6. By assigning a unique NDC number 

to each drug, the proposal would ensure 

that the drug has an accurate identifier, 

allowing us to support the 

implementation of the electronic 

prescribing provisions of the Medicare 

Modernization Act. We would link the 

accurate NDC number to the product 

labeling that would be made available 

through the DailyMed initiative. 

i. Information to be submitted to 

receive an NDC number. We describe 

the information that proposed 

§ 207.33(c) and (d) would require and 

our reasons for proposing to require the 

information, as follows: 

• Name, address, telephone and fax 

numbers, e-mail address, and labeler 

code. Proposed § 207.33(c) and (d) 

would require manufacturers, repackers, 

and relabelers to provide this 

information to enable us to identify and 

contact (if necessary) the appropriate 

manufacturer, repacker, or relabeler and 

identify their labeler code. In situations 

where a manufacturer, repacker, or 

relabeler manufactures, repacks, or 

relabels a drug for a private label 

distributor, the proposal would also 

require the manufacturer, repacker, or 

relabeler to provide comparable 

information for the private label 

distributor. This information would 

enable us to associate the 

manufacturer’s, repacker’s, or relabeler’s 

drugs with a particular private label 

distributor and to contact that private 

label distributor if necessary. 

• The drug’s or active pharmaceutical 

ingredient’s established name and 

proprietary name (if any). The 

established name (sometimes referred to 

as generic name) is ordinarily either the 

drug’s compendial name or, if there is 

no compendial name, the drug’s 

common or usual name. The proprietary 

name (sometimes referred to as trade 

name) is generally the drug’s marketed 

or advertised name as designated by the 

manufacturer, repacker, relabeler, or 

private label distributor. Most 

consumers recognize a drug by its 

proprietary name rather than its 

established name. Proposed § 207.33(c) 

and (d) would require submission of 

these names because knowing a drug’s 

established name would let us 

determine, for example, which 

companies market identical drugs and 

which drugs can be substituted in the 

event of drug shortages or recalls. 

Knowing a drug’s proprietary name 

would enable us to identify a drug to the 

public during a recall or consumer alert. 

This information is currently required 

under § 207.25(b)(1) and is submitted on 

Form FDA 2657. 

• The Drug Master File (DMF) 

number or Veterinary Master File (VMF) 

number, if any, assigned to the active 

pharmaceutical ingredient. Under 

proposed § 207.33(c)(1)(iv) (and, if 

applicable, proposed § 207.33(c)(3)), if a 

DMF number or VMF number is 

assigned to the active pharmaceutical 

ingredient, the manufacturer would 

identify for us the DMF number or the 

VMF number. The DMF or VMF may 

contain additional information about 

the active pharmaceutical ingredient 

that our electronic drug registration and 

listing system could associate with the 

active pharmaceutical ingredient at 

other points in the registration and 

listing process. This could reduce the 

burden on the manufacturer of 

submitting to us the information already 

contained in the DMF or VMF. This 

information is not currently provided to 

us under current part 207 or Form FDA 

2657 or Form FDA 2658. 

• Name and quantity of each active 

pharmaceutical ingredient in a drug. 

Proposed § 207.33(c)(2) and, if 

applicable, proposed § 207.33(c)(3), 

would require manufacturers to submit 

this information to us (unless the 

approved U.S. application number is 

provided). Knowing the name and 

quantity of a drug’s active 

pharmaceutical ingredients would help 

us assign unique product codes and 

help ensure that the assigned NDC 

numbers are unique to different 

products. For example, assume that a 

manufacturer makes a drug in two 

different strengths, 100 milligrams (mg) 

and 500 mg. If we only required the 

manufacturer to identify the active 

pharmaceutical ingredient, we might 

assume, incorrectly, that the 

manufacturer made two versions of the 

same drug in the same strength and then 

assign the same product code to both 

drugs. Instead, by proposing to require 

information about the quantity of the 

drug’s active pharmaceutical ingredient, 

we would be able to assign one product 

code to the 100 mg product and a 

different product code to the 500 mg 

product. As an alternative to providing 

the name and quantity of the drug’s 

active pharmaceutical ingredient, 

proposed § 207.33(c)(2) would allow a 

manufacturer to give us the drug’s 

approved U.S. application number; the 

approved U.S. application number 

would allow us to link the drug to a 

particular application and determine the 

name and quantity of the active 

pharmaceutical ingredients in that drug. 

The proposed requirement is similar 

to the requirement regarding 

quantitative listing of active ingredients 

in current § 207.25(b). Current 

§ 207.25(b)(6) requires a quantitative 

listing of a drug’s active ingredient(s) for 

drugs that a registrant regards as not 

being subject to sections 505 or 512 of 

the act or section 351 of the PHS Act. 

Current 207.25(b)(2) requires, for each 

drug listed that the registrant regards as 

subject to section 505 or 512 of the act, 

the application number. The act, for 

purposes of certain drug listing 

requirements, appears to treat drugs 

differently depending on whether those 

drugs are subject to sections 505 or 512 

of the act or not. Section 510(j)(1)(A) of 

the act mandates that the drug list be 

prepared in the form and manner 

prescribed by us. That drug list, for 

drugs subject to sections 505 or 512 of 

the act, must be accompanied by ‘‘the 

authority for the marketing of such 

drug’’. In contrast, section 510(j)(1)(C) of 

the act states that the drug list, for drugs 

that are not subject to either section 505 

or 512 of the act, must be accompanied 

by a ‘‘quantitative listing’’ of the drug’s 

active ingredient or ingredients and that 

we may require a quantitative listing of 

all ingredients with respect to a 

particular product if we find such 

submission is necessary to carry out the 

act’s purposes. 

We believe that these provisions, and 

others, give us sufficient authority to 

require the submission of active 

ingredient information for all drugs as 

part of the NDC number assignment 

process. We already have such 

information for drugs approved under 

sections 505 and 512 of the act because 

information concerning active 

ingredients is an essential part of the 

drug’s marketing application. Thus, 

when a manufacturer gives us the 

approved U.S. application number (as 

proposed § 207.33(c)(2)(i) would require 

and as current § 207.25(b)(2) (pertaining 

to required drug listing information) 

requires), the manufacturer is, in 

essence, giving us a link to information 


jlentini on PROD1PC65 with PROPOSAL2
Federal Register / Vol. 71, No. 167 / Tuesday, August 29, 2006 / Proposed Rules 51303 

about the drug’s active ingredients. As 

noted previously, section 510(j)(1)(A) of 

the act, for drugs subject to sections 505 

or 512 of the act, requires the ‘‘reference 

to the authority for the marketing of 

such drug.’’ This reference would be the 

approved U.S. application number. The 

act, for drugs not subject to section 505 

or 512, explicitly requires a quantitative 

listing of active ingredients. Proposed 

§ 207.33(c)(2)(i) would, therefore, enable 

us to input the active ingredient 

information into an electronic database. 

This would enable us to link to certain 

information in the application, and 

would be more efficient than having to 

review individual marketing 

applications, identify each drug’s active 

ingredients, and then enter that data 

into the database ourselves. 

• Name of the inactive ingredient(s). 

Proposed § 207.33(c)(2), and, if 

applicable, (c)(3) would require 

manufacturers to give us the drug’s 

approved U.S. application number or, in 

the alternative, the name of each 

inactive ingredient for each human and 

animal drug that the manufacturer 

regards as subject to section 505 or 

section 512 of the act or section 351 of 

the PHS Act, and for each human OTC 

drug that the manufacturer regards as 

not subject to section 505 of the act, and 

whether the name of an inactive 

ingredient falls under § 20.61 or is 

otherwise prohibited from disclosure 

and, if so, why. Proposed § 207.33(c)(3) 

describes the requirements of the 

manufacturer who is manufacturing a 

drug for a private label distributor. Such 

manufacturers would be required to give 

us the name of each inactive ingredient 

for certain drugs, as described 

previously, or the drug’s U.S. approved 

application number for the drug it 

manufactures for a private label 

distributor. Proposed § 207.33(c)(2) and 

(c)(3) are authorized under section 510 

of the act as well as other provisions. 

We are considering whether to require 

the name of each inactive ingredient to 

be submitted for other categories of 

drugs as well. 

• Dosage form. Proposed 

§ 207.33(c)(2) and (c)(3) would require 

manufacturers to identify a drug’s 

dosage form. This information will also 

help us distinguish between drug 

products that contain the same active 

ingredient and, consequently, assign 

unique product codes to such drugs. For 

example, assume that a manufacturer 

makes drug X, in a 100 mg strength, in 

a tablet form and also in a gelatin 

capsule. If we did not know there were 

two dosage forms of drug X, we might 

mistakenly assign the same product 

code to the tablet and gelatin capsule. 

Thus, information about dosage forms 

will help us create an NDC system that 

ties unique NDC numbers to unique 

products. The drug’s dosage form is 

currently submitted on Form FDA 2657. 

• Package size and type. Proposed 

§ 207.33(c)(1), (c)(2), (c)(3) (if 

applicable), (d)(1), and (d)(2) would 

require manufacturers and repackers 

respectively to provide information 

about package size and type. This 

information would obviously be 

relevant in helping us assign package 

codes to a particular drug. For example, 

a drug packaged in a glass container 

would have a different NDC number 

from the same drug packaged in a 

plastic container. The proposal would 

require that information about the 

drug’s package size and type be 

provided for each package, including 

the immediate unit-of-use container. For 

example, a drug packaged in a box 

containing a card of 12 unit-of-use 

blisters would have a different NDC 

number than each individual blister 

(unit-of-use). In the latter example, the 

different NDC numbers would have a 

practical impact with respect to our bar 

code requirements. A database system 

computer reading the bar code for the 

individual unit-of-use blister would see 

that the health care professional is 

administering a single dose of a 

particular drug to a patient; if the NDC 

number for the box were the same as 

that used for each unit-of-use blister, 

then the computer might mistakenly 

believe that the health care professional 

was administering 12 doses to the 

patient. In these scenarios, distinct NDC 

numbers for each package level would 

enhance the bar code’s accuracy and 

value. The drug’s package size and type 

is currently submitted on Form FDA 

2657. 

• Marketing status. Proposed 

§ 207.33(c)(2) and, if applicable, (c)(3), 

would require manufacturers to tell us 

whether the drug is available only by 

prescription or is available OTC. Having 

such information in our electronic 

database would enable us to determine 

quickly which drugs are available by 

prescription and which are OTC. In 

addition, some entities that rely on NDC 

numbers, such as CMS and health care 

insurance companies, might treat 

prescription drugs differently from OTC 

drugs. For example, an insurer might 

reimburse consumers for prescription 

drug expenses, but not for OTC drug 

expenses. The drug’s marketing status—

whether prescription or OTC—is 

currently submitted on Form FDA 2657. 

• Drug or drug product type. Under 

proposed § 207.33(c)(2) and, if 

applicable, (c)(3), manufacturers would 

identify whether a drug is a human drug 

or animal drug. This information would 

enable us to refine our databases to 

distinguish quickly between human and 

animal drugs. Having such information 

readily available could help us 

determine the regulatory obligations for 

a particular drug. For example, the bar 

code requirement applies to human 

drugs only. Thus, if we could 

differentiate quickly between human 

and animal drugs based on NDC 

numbers alone and we received a report 

that a particular drug failed to have a 

bar code on its label, we would be able 

to determine, based on the NDC number 

alone, whether that drug was subject to 

the bar code requirement. This 

information is currently submitted 

under ‘‘product type’’ on Form FDA 

2657. 

• Imprinting information. For each 

drug product subject to the listing 

requirements and covered under 

§ 206.1, including products that are 

exempted under § 206.7(b), 

manufacturers must provide the size, 

shape, color, and code imprint (if any) 

(proposed § 207.33(c)(2)(vii) and, if 

applicable, proposed § 207.33(c)(3)). 

This provision is similar to current 

§ 207.25(c), except the current provision 

also requires that the name of the drug 

product, its active ingredient(s), dosage 

strength, NDC number, and the name of 

its manufacturer or distributor be 

submitted. Under the proposal, the 

name of the drug product, its active 

ingredient(s) (proposed § 207.33(c)(2) 

uses the term ‘‘active pharmaceutical 

ingredient’’), and dosage strength 

(proposed § 207.33(c)(2) uses the term 

‘‘dosage form’’) would be submitted to 

us under proposed § 207.33(c) along 

with the imprinting information. The 

NDC number would be submitted under 

proposed § 207.49 for listing, the name 

of the private label distributor would be 

submitted under proposed §§ 207.33 

and 207.49 for listing, and the name of 

the manufacturer would be submitted 

under proposed § 207.25 for registration. 

All of this information would be 

accessible via our electronic drug 

registration and listing system. The 

proposal would also delete the 

requirement in current § 207.25(c) that 

‘‘any other characteristic that identifies 

the drug product as unique’’ must be 

submitted. We need to know the drug’s 

size, shape, color, and code imprint, as 

well as the other information required 

under proposed § 207.33(c), to assign an 

NDC number to the manufacturer’s 

drug. Imprinting information would 

enable us to investigate reports of 

medication errors and counterfeiting 

and to assist poison control centers in 

identifying drugs in overdose and 

accidental poisoning situations. 


jlentini on PROD1PC65 with PROPOSAL2
51304 Federal Register / Vol. 71, No. 167 / Tuesday, August 29, 2006 / Proposed Rules 

• NDC number assigned to the drug 

immediately before the repacker or 

relabeler received that drug. Proposed 

§ 207.33(d) would require repackers and 

relabelers to give us the NDC number of 

the drug that they receive. This 

information would enable us to link that 

drug to a particular source and, as we 

said earlier in this part, eliminate the 

need for repackers and relabelers to 

obtain certain drug information from 

those sources to obtain an NDC number. 

For example, assume that relabeler 

Alpha received drug X from 

manufacturer Beta. If Alpha gives us the 

NDC number for drug X, we will then 

be able to link Alpha’s relabeled drug to 

Beta. We would also eliminate any need 

for Alpha to ask Beta for information 

about drug X for purposes of getting an 

NDC number and eliminate the 

possibility that Alpha might report 

incorrect or contradictory information 

about drug X compared to the 

information given to us by Beta. 

• Type of operation. Proposed 

§ 207.33(d) would require repackers and 

relabelers to report the type of operation 

(that is, repacking or relabeling) 

performed for a drug. This information 

is comparable to the information we 

currently receive about an 

establishment’s ‘‘type of business’’ on 

Form FDA 2657, except that proposed 

§ 207.33(d) is limited to repackers and 

relabelers. 

• Information regarding private label 

distributors. Proposed § 207.33(c)(3) and 

207.33(d)(2) would require 

manufacturers, repackers, and relabelers 

who manufacture, repack, or relabel 

drugs for a private label distributor to 

tell us the private label distributor’s 

name, address, telephone number, fax 

number, e-mail address, labeler code, 

and any proprietary name assigned by 

the private label distributor to the drug. 

This information will help us link the 

manufacturer’s, repacker’s, or relabeler’s 

drug to a particular private label 

distributor and, as we stated earlier in 

this part, eliminate potential data 

duplication, omissions, and 

inaccuracies that would otherwise result 

if private label distributors were able to 

seek NDC numbers from us. 

Manufacturers, repackers, and relabelers 

should be able to obtain the necessary 

information from private label 

distributors. Listing information for 

private label distributors is currently 

submitted on Form FDA 2658. 

ii. How the information would be 

submitted. Proposed § 207.33(e) would 

require manufacturers, repackers, and 

relabelers to submit information to us 

electronically, in accordance with 

proposed § 207.61 unless we grant a 

waiver under proposed § 207.65. We 

discuss proposed §§ 207.61 and 207.65 

later in this document. 

iii. Types of changes that would 

require a new NDC number. Proposed 

§ 207.33(f) would describe the types of 

changes in information that would 

require a new NDC number. In brief, 

proposed § 207.33(f)(1) would require a 

new NDC number for any change of 

information that would be required 

under proposed § 207.33(c) and (d), 

except for the following contact 

information: Name; address; telephone 

and fax numbers; and e-mail address for 

the manufacturer, repacker, relabeler, or 

private label distributor. In addition, 

§ 207.33(f)(2) requires manufacturers to 

obtain a new NDC number when there 

is a change in an inactive ingredient for 

each human prescription drug that the 

manufacturer regards as not subject to 

section 505 of the act and for each 

animal drug that the manufacturer 

regards as not subject to section 512 of 

the act. Although we are not proposing 

to require, at this time, that 

manufacturers submit the name of each 

inactive ingredient to us when they 

obtain an NDC number for these drugs, 

we are proposing to require that 

manufacturers notify us only of the fact 

that there has been a change in an 

inactive ingredient for these drugs. This 

would ensure that a unique NDC 

number is assigned to these drugs when 

the drug’s inactive ingredient(s) has 

changed. It is important that marketed 

drugs have unique NDC numbers that 

are accurate because, as discussed in 

section IV.C.2 of this document, NDC 

numbers are an important, standardized, 

identification system for drug products 

and are used for many purposes. In 

addition, identifying marketed drugs in 

our electronic database for which 

inactive ingredients have changed 

would help us investigate, as discussed 

in section IV.C.3 of this document, 

incidents of allergic reactions in 

patients as well as possible drug 

contamination, counterfeiting, or 

adulteration. Although we are not 

proposing it at this time, we are 

considering requiring in the future that 

manufacturers submit the name of each 

inactive ingredient to obtain an NDC 

number for categories of drugs beyond 

those referenced in proposed 

§ 207.33(c)(2)(ii) and 207.33(c)(3). We 

are specifically requesting comments on 

the feasibility of submitting these 

inactive ingredients. The proposed rule 

would be similar to current 

§ 207.35(b)(4)(i), which requires a 

registrant to assign a new NDC number 

if any change occurs in a product’s 

characteristics that clearly distinguishes 

one drug product version from another. 

However, proposed § 207.33(f) would 

differ from the current requirement in 

several important respects. First, 

proposed § 207.33(f) would require 

changes to be reported to us in 

accordance with proposed § 207.33(e) 

(which would require electronic 

submission of information) and 

§ 207.33(g) (which describes timing 

requirements discussed later in this 

part). The current regulation has no 

comparable electronic reporting 

requirement. Second, proposed 

§ 207.33(f) would not require us to 

publish a notice in the Federal Register 

announcing our determination as to 

whether a change requires assignment of 

a new product code. Because the 

proposed rule would create an 

electronic drug registration and listing 

system and have us assign NDC 

numbers quickly that would be 

accessible in the registration and listing 

database, we find it unnecessary and 

impractical to publish Federal Register 

notices regarding product code changes. 

Third, although current § 207.35(b)(4)(i) 

allows registrants to assign their own 

package codes for changes involving 

trade packages, proposed § 207.33(f) 

would eliminate this provision because 

we would assign the new NDC number 

ourselves to ensure that the NDC 

number is unique and that our NDC 

number database is accurate and up-todate. Fourth, proposed § 207.33(f), in 

conjunction with proposed § 207.33(c) 

and (d), gives a more complete 

description of which changes would 

require a new NDC number, compared 

with current § 207.25(b)(4)(i) (which 

currently lists examples of changes). 

Because manufacturers, repackers, and 

relabelers currently have different 

practices with respect to assigning NDC 

numbers, this change would eliminate 

inconsistency and would introduce an 

element of certainty with respect to the 

assignment of new NDC numbers. 

iv. When the information would be 

provided. Proposed § 207.33(g) would 

explain when a manufacturer, repacker, 

or relabeler must provide the 

information to obtain an NDC number. 

In brief, the proposal would require a 

manufacturer, repacker, or relabeler to 

provide the information described in 

proposed § 207.33(c), (d), and (f) either 

before or at the time drug listing 

information is required under proposed 

§§ 207.45 or 207.57. (We discuss 

proposed §§ 207.45 and 207.57 later in 

this document.) The proposed 

requirement differs slightly from current 

§§ 207.21(b), 207.22(b), and 

207.25(b)(8), which allows 

manufacturers, repackers, and relabelers 

to give us NDC numbers as part of their 


jlentini on PROD1PC65 with PROPOSAL2
Federal Register / Vol. 71, No. 167 / Tuesday, August 29, 2006 / Proposed Rules 51305 

drug listing information, because the 

proposal would allow companies to give 

us information earlier than the drug 

listing process would be completed. 

This ability to seek NDC numbers 

throughout the year should help us keep 

the National Drug Code Directory 

current and, as a result, provide more 

accurate and useful NDC number 

information to entities that rely on or 

use NDC numbers. In addition, the 

proposed scheme would give 

manufacturers, repackers, and relabelers 

more flexibility to obtain an NDC 

number earlier for their own planning 

purposes. Furthermore, we will know 

which NDC number corresponds to a 

drug immediately because we will 

assign it, rather than the current system 

where manufacturers, repackers, and 

relabelers assign their own NDC 

numbers and only report those numbers 

to us as part of their drug listing 

information. 

We considered assigning the NDC 

number as part of the drug listing 

process, but believe that allowing for 

earlier assignment would provide 

optimal flexibility for manufacturers, 

repackers, and relabelers. We note that 

the information submitted to have an 

NDC number assigned is a subset of the 

information submitted to list a drug. 

Therefore, if a manufacturer, repacker, 

or relabeler provides us the information 

early to get an NDC number, they will 

only need to provide the additional 

information needed when they later list 

the drug. 

c. Proposed § 207.37—What 

restrictions pertain to the use of NDC 

numbers? Proposed § 207.37 would 

establish four restrictions on the use of 

NDC numbers insofar as FDA-regulated 

products or activities are concerned. 

The proposed restrictions reflect 

practical problems or difficulties that 

we have encountered when 

manufacturers, repackers, or relabelers 

assign their own NDC numbers. 

Proposed § 207.37(a) would state that 

an NDC number must not be used to 

represent a different drug than the drug 

to which it was assigned. This 

restriction would prevent 

manufacturers, for example, from using 

the same NDC number for different 

drugs and thus prevent potential 

discrepancies among databases that rely 

on or use NDC numbers to distinguish 

between drugs. The restriction would 

prevent two different drugs from having 

the same NDC number and avoid 

medication errors that could result if the 

NDC number encoded in a bar code 

represented more than one drug. Use of 

an NDC number not assigned to a drug 

would also cause a drug to be 

misbranded under section 502(a) of the 

act because the drug’s label would be 

misleading. 

Proposed § 207.37(b) would state that 

a different NDC number must not be 

used if marketing is resumed for a drug 

that was discontinued earlier. If 

marketing is resumed for a drug, and no 

changes have been made to the drug that 

would require a new NDC number 

under § 207.33(f), the drug must have 

the same NDC number that was assigned 

to it earlier before marketing was 

discontinued. This would prevent two 

NDC numbers from being assigned to or 

used for the same drug. Consistent with 

this rationale, proposed § 207.37(b) 

would revoke current § 207.35(b)(4)(ii), 

which states that the product code of a 

discontinued product may be reassigned 

to another product 5 years after the 

expiration date of the discontinued 

product or, if there is no expiration date, 

5 years after the last shipment of the 

discontinued product into commercial 

distribution. 

Proposed § 207.37(c) would state that 

NDC numbers must not be used to 

denote FDA approval. This is similar to 

current § 207.39, which states, in part, 

that assignment of an NDC number does 

not in any way denote approval of a 

product. For drugs subject to sections 

505 or 512 of the act, those drugs must 

be shown to be safe and effective for 

their intended uses to obtain FDA 

approval. Mere assignment of an NDC 

number by us is not equivalent to our 

determining whether a drug is safe and 

effective for its intended uses. 

Proposed § 207.37(d) would state that 

NDC numbers must not be used on 

products that are not subject to the drug 

listing requirements of part 207, such as 

dietary supplements and medical 

devices. We are proposing this 

requirement because the fundamental 

purpose behind NDC numbers was to 

establish an identification system to 

help in the automated processing of 

drug data and claims. Use of NDC 

numbers on non-drug products could 

introduce misleading information in 

databases, lead to inappropriate claims 

processing, and undermine the accuracy 

and reliability of an NDC system. For 

example, some human dietary 

supplements bear an NDC number on 

their labels. FDA considers a human 

dietary supplement that bears an NDC 

number misbranded under 21 U.S.C. 

343(a)(1), which provides that a food is 

misbranded if its labeling is false or 

misleading in any particular. A product 

labeled and marketed as a human 

dietary supplement is not a drug listed 

with FDA; thus, the presence of an NDC 

number on the label is a false 

representation about the nature of the 

product. 

d. Proposed §§ 610.60(a)(2) and 

610.61(b)—Where would the NDC 

number be required for biological 

products? Under proposed § 201.2(a), all 

drugs, including human biological 

drugs, subject to the drug listing 

requirements of part 207 must have 

labels that bear the appropriate NDC 

number in human-readable form, in 

accordance with the provisions in 

proposed § 201.2. Current § 610.60(a) 

(21 CFR 610.60(a)) specifies which 

items must appear on the label affixed 

to each container of a biological product 

capable of bearing a full label and 

current § 610.61 specifies which items 

must appear on the label affixed to each 

package containing a biological product. 

We are proposing to amend 

§§ 610.60(a)(2) and 610.61(b) (21 CFR 

610.60(b)) to require that the NDC 

number appear, in accordance with 

proposed part 207, on these biological 

product labels. Many individuals and 

companies use NDC numbers and they 

may not have the technology or ability 

to read an automatic identification 

technology such as a bar code that is 

required under current § 207.25 or 

§ 610.67. In addition, a human-readable 

NDC number may serve as a ‘‘backup’’

in case the bar code is damaged, cannot 

be read, or is otherwise illegible. 

4. How Do We Intend to Implement the 

NDC Number Changes? 

a. When would we expect compliance 

with the NDC number requirements? We 

are proposing that our electronic drug 

registration and listing system be used 

to enter and update all NDC number 

information, as well as all registration 

and listing information, no later than 9 

months after the effective date of a final 

rule. If a drug already has an NDC 

number at the time of the effective date 

of a final rule, the drug would retain 

that NDC number provided that the 

manufacturer, repacker, or relabeler, 

within 9 months after the effective date 

of a final rule, reviews and updates, in 

accordance with proposed §§ 201.2, 

207.33, 207.37, 610.60, and 610.61, the 

information in our database for the NDC 

number. To retain the NDC number, 

new information about the drug’s 

characteristics may need to be provided 

to us. We will, if necessary, assign a 

new product code and/or package code, 

creating a new NDC number for the 

drug. If a manufacturer, repacker, or 

relabeler does not review or update its 

information within 9 months after a 

final rule’s effective date, we may assign 

a new NDC number to the drug or take 

other appropriate steps. 

As discussed in section IV.E.6 of this 

document, we intend to make available 

guidance on how to provide to us in 


jlentini on PROD1PC65 with PROPOSAL2
51306 Federal Register / Vol. 71, No. 167 / Tuesday, August 29, 2006 / Proposed Rules 

electronic format information required 

to receive an NDC number, as well as 

registration and listing information. We 

can assist manufacturers, repackers, and 

relabelers in determining whether their 

NDC numbers are accurate and address 

any problems with existing NDC 

numbers (such as duplicate or 

potentially duplicate NDC numbers). 

We are available to work with 

manufacturers, repackers, and relabelers 

to resolve issues that might arise after a 

final rule becomes effective. Information 

on how to contact us for assistance will 

be specified in the guidance. 

b. When would we expect NDC 

numbers to appear on drug labels? 

Although current regulations do not 

require NDC numbers on drug labels 

(other than NDC numbers encoded in a 

bar code, where such bar codes are 

required under current § 201.25), almost 

all human and animal prescription 

drugs already have NDC numbers on 

their labels because government 

agencies and third-party payers rely on 

NDC numbers for reimbursement and 

other purposes. Thus, when we issue a 

final rule requiring NDC numbers to 

appear on drug labels, such a 

requirement should have little impact 

on human and animal prescription drug 

labels. 

We intend to phase-in the 

requirements for NDC number 

placement and appearance on human 

and animal prescription drug labels over 

a 3-year period, starting from the 

effective date of a final rule. This 

implementation scheme should lessen 

the impact on prescription drug labels 

(which might stem from changing the 

NDC number on the label or adding an 

NDC number, for example, for unit-ofuse blisters). 

As for human and animal OTC drugs, 

we estimate that approximately 30 

percent of these drug labels currently 

have NDC numbers. (We discuss this 

issue further in section VI of this 

document.) We intend to phase-in the 

requirements for NDC number 

placement and appearance on OTC drug 

labels over a 7-year period, starting from 

the effective date of a final rule. 

We are considering shortening the 

compliance dates by which the 

appropriate NDC number must appear 

on drug labels to 2 years after the 

effective date of a final rule for 

prescription drugs and 5 years after the 

effective date of a final rule for OTC 

drugs. We discuss this issue further in 

section VI of this document. We invite 

comment on whether a shorter 

implementation period would be 

preferable. 

These implementation periods would 

permit manufacturers, repackers, and 

relabelers to incorporate the appropriate 

NDC number at minimal additional cost 

when redesigning their labels in the 

course of the normal relabeling cycle. 

We should note, however, that 

manufacturers, repackers, relabelers, 

and private label distributors who are 

subject to the bar code requirements at 

current § 201.25 might find it easier to 

put human-readable NDC numbers on 

their labels when they revise those 

labels to accommodate the bar code. We 

remind readers that the bar code 

requirement became effective on April 

26, 2004, and the compliance dates 

varied depending on when we approved 

a drug relative to the April 26, 2004, 

date. For example, for drugs approved 

on or after April 26, 2004, we expected 

compliance within 60 days of the drug’s 

approval date. For drugs approved 

before April 26, 2004, we expect 

compliance within 2 years. So, for 

example, a manufacturer whose 

prescription drug is subject to the bar 

code requirement might find it easier to 

redesign its label once to add a humanreadable NDC number and a bar code, 

rather than redesign its label twice. 

We invite comments on the 

implementation scheme described here. 

D. Listing 

1. Who Would Be Required To List 

Drugs? 

Proposed § 207.41(a) would require 

manufacturers, repackers, relabelers, 

and drug product salvagers who are 

subject to the registration requirements 

under proposed § 207.17 (and not 

exempt under proposed § 207.13) to list 

drugs being manufactured, repacked, 

relabeled, or salvaged by them for 

commercial distribution. Proposed 

§ 207.41(a) is consistent with current 

§ 207.20(a), which states that owners or 

operators of all drug establishments, not 

exempt under section 510(g) of the act 

or current § 207.10, that engage in the 

manufacture, preparation, propagation, 

compounding, or processing of a drug 

submit a list of every drug in 

commercial distribution. Section 

510(j)(1) of the act requires, among other 

things, that every person who registers 

with the Secretary must list drugs that 

are being manufactured, prepared, 

propagated, compounded, or processed 

for commercial distribution. 

Under current § 207.20(a), such drugs 

must be listed whether or not they enter 

interstate commerce. This is consistent 

with Congress’s intention for section 

510 of the act to apply to drugs both in 

interstate and intrastate commerce as 

stated in section 301 of Public Law 82–

781, in part, as follows: ‘‘[T]he products 

of all [establishments in which drugs are 

manufactured, prepared, propagated, 

compounded, or processed] are likely to 

enter the channels of interstate 

commerce and directly affect such 

commerce; and * * * the regulation of 

interstate commerce in drugs without 

provision for registration and inspection 

of establishments that may be engaged 

only in intrastate commerce in such 

drugs would discriminate against and 

depress interstate commerce in such 

drugs, and adversely burden, obstruct, 

and affect such interstate commerce.’’

Proposed § 207.41(a) also provides 

that when operations are conducted at 

more than one establishment and there 

exists joint ownership and control 

among all the establishments, listing 

information may be submitted by the 

parent, subsidiary, and/or affiliate 

company for drugs at all establishments. 

This provision would also apply when 

operations are conducted at both 

domestic and foreign establishments 

and there exists joint ownership and 

control among all the establishments. 

This provision is consistent with 

current § 207.20(a). 

Under proposed § 207.41(a), drug 

product salvagers would be required to 

list. As discussed in sections IV.A.5 and 

IV.B.1 of this document, and consistent 

with current § 207.20(a), drug product 

salvagers would continue to be required 

to register because their activities 

include applying manufacturing 

controls to drug products and 

segregating drug products. This activity 

would be covered under the scope of 

manufacturing, preparing, propagating, 

compounding, or processing, and would 

trigger the requirement to register under 

the act. Because drug product salvagers 

are conducting one of these activities 

with respect to a given drug for the 

purpose of commercial distribution, this 

activity would also trigger the 

requirement to list under the act 

(section 510(j)(1) of the act). (Drug 

product salvagers sometimes repack/ 

relabel drug products and would also 

have to register because of those 

activities.) Under current § 207.20(a), 

drug product salvagers are not required 

to list. Because drug product salvagers 

place the salvaged drug in commercial 

distribution, we are proposing to require 

that drug product salvagers submit 

listing information to us. We 

specifically invite comments on the 

scope of activities of drug product 

salvagers, that is, whether drug product 

salvagers salvage drug products for 

commercial distribution and whether 

these activities should trigger listing 

under the act. 

Under proposed § 207.41(b), 

manufacturers, repackers, relabelers, 

and drug product salvagers who engage 


jlentini on PROD1PC65 with PROPOSAL2
Federal Register / Vol. 71, No. 167 / Tuesday, August 29, 2006 / Proposed Rules 51307 

in more than one activity for drugs 

would list each drug in accordance with 

the requirements for the activity 

engaged in for that drug. An example of 

a company that engages in more than 

one activity for drugs would be a 

company that manufactures Drug X and 

relabels Drug Y. The company would 

provide the listing information 

described in proposed § 207.49 for Drug 

X and the listing information described 

in proposed § 207.53 for Drug Y. We are 

proposing this requirement to clarify 

which listing information would be 

provided by manufacturers, repackers, 

relabelers, and drug product salvagers 

who engage in more than one activity 

for drugs. As discussed below, 

manufacturers, repackers and relabelers, 

and drug product salvagers would 

provide similar listing information to us 

(although some information would be 

provided by reference). 

Under proposed § 207.41(c), 

manufacturers, repackers, relabelers, 

and drug product salvagers would, in 

addition to listing their own drugs, 

provide all listing information to us for 

drugs they manufacture, repack, relabel, 

or salvage for private label distributors. 

In general, private label distributors 

would not list drugs with us. However, 

private label distributors would be 

required to list a drug with us if they 

manufacture, repack, relabel, or salvage 

the drug for commercial distribution. 

Proposed § 207.41(c) would revise 

current § 207.20(b), which states that 

owners or operators of establishments, 

not otherwise required to register, that 

distribute under their own label or trade 

name a drug manufactured or processed 

(as defined in current § 207.3(a)(8)) by a 

registered establishment may elect to 

submit listing information directly to us 

and obtain a labeler code. Under current 

part 207, if a private label distributor 

does not elect to submit drug listing 

information to us, the registered 

establishment must submit the drug 

listing information. Currently, private 

label distributors that elect to submit 

listing information must include the 

registration number of the establishment 

that manufactured or processed (as 

defined in current § 207.3(a)(8)) each 

drug listed and must assume full 

responsibility for compliance with all 

the requirements of part 207. Private 

label distributors must currently certify 

to the registered establishment that the 

submission has been made by providing 

a signed copy of Form FDA 2656 to the 

registered establishment. Private label 

distributors must submit to us the 

original Form FDA 2656 showing this 

certification. A list showing the NDC 

number assigned to each drug must 

accompany the certification. 

We are proposing to alter the 

arrangement permitted under current 

§ 207.20(b). Although we recognize that 

this proposed shift in responsibility may 

alter current business practices, we 

believe that proposed § 207.41(c) will 

help to ensure that listing information is 

more accurate and complete. The 

current scheme has caused confusion 

and resulted in inaccurate and 

incomplete listing information. Some 

private label distributors that have 

elected to list their drugs have not had 

access to all the information needed to 

list the drugs accurately. Some private 

label distributors have claimed that 

manufacturers, repackers, and relabelers 

have been reluctant to provide certain 

information to them. In addition, in 

some instances, the parties have been 

uncertain about who is responsible for 

listing. 

As discussed in section IV.B.1 of this 

document and previously, 

manufacturers, repackers, relabelers, 

and drug product salvagers would be 

required to register and list the drugs 

they manufacture, repack, relabel, or 

salvage. They would be required to do 

so even if they conduct such activities 

on behalf of private label distributors. 

This proposed requirement would be 

consistent with section 510(j)(1) of the 

act which requires every person who 

registers to submit listing information 

for drugs ‘‘which are being 

manufactured, prepared, propagated, 

compounded, or processed by him for 

commercial distribution’’ (emphasis 

added). In addition, private label 

distributors would not be required (nor 

permitted) to register because their 

activities are not covered under the 

scope of manufacturing, preparing, 

propagating, compounding, or 

processing. Nor do private label 

distributors conduct one of these 

activities with respect to a given drug 

for the purpose of commercial 

distribution and, thus, would not be 

required (nor permitted) to list. Private 

label distributors only commercially 

distribute drugs under their own label 

or trade name. Manufacturers, 

repackers, relabelers, and drug product 

salvagers often manufacture, repack, 

relabel, or salvage drugs that are 

distributed by a private label distributor, 

and they have all the information about 

the drug that is necessary to list the drug 

distributed by the private label 

distributor. Under the proposal, to list a 

drug that is manufactured, repacked, 

relabeled, or salvaged for a private label 

distributor, manufacturers, repackers, 

relabelers, and drug product salvagers 

would have to obtain any existing NDC 

number from the private label 

distributor or would have to obtain the 

NDC number from FDA for a drug 

distributed by a private label distributor. 

Manufacturers, repackers, relabelers, 

and drug product salvagers would have 

to place the NDC number assigned to 

the private label distributor’s drug on 

the label. We specifically invite 

comments on this proposed change in 

the listing responsibilities of 

manufacturers, repackers, relabelers, 

drug product salvagers, and private 

label distributors and its potential effect 

on business practices. 

2. When Would Initial Listing 

Information Be Provided? 

Under proposed § 207.45, 

manufacturers, repackers, relabelers, 

and drug product salvagers would list, 

at the time of initial registration of an 

establishment, any drug being 

manufactured, repacked, relabeled, or 

salvaged for commercial distribution at 

that establishment. This provision is 

consistent with section 510(j)(1) of the 

act, which requires, among other things, 

that every person who registers with the 

Secretary under sections 510(b), (c), (d), 

or (i) of the act must list drugs that are 

being manufactured, prepared, 

propagated, compounded, or processed 

for commercial distribution. Proposed 

§ 207.45 pertains to the submission of 

listing information for drugs at the time 

of the initial registration of an 

establishment. Reviewing and updating 

information for drugs already listed and 

providing listing information for drugs 

not previously listed are covered under 

proposed § 207.57. Proposed § 207.57 is 

discussed in section IV.D.8 of this 

document. 

3. What Listing Information Would Be 

Required? 

To list a drug, manufacturers would 

be required to provide the information 

in proposed § 207.49, repackers and 

relabelers would be required to provide 

the information in proposed § 207.53, 

and drug product salvagers who are not 

repackers or relabelers would be 

required to provide the information in 

proposed § 207.54. We are proposing 

different listing requirements for 

manufacturers, repackers and relabelers, 

and drug product salvagers because 

much of the information about a drug is 

submitted to us by the manufacturer to 

obtain an NDC number and to list the 

drug. When the repacker, relabeler, and 

drug product salvager provide, during 

listing, the required NDC number for the 

drug, we can incorporate by reference 

the information already submitted about 

the drug by the manufacturer. The 

information required to obtain an NDC 


jlentini on PROD1PC65 with PROPOSAL2
51308 Federal Register / Vol. 71, No. 167 / Tuesday, August 29, 2006 / Proposed Rules 

7The drug product salvager (that does not repack 

or relabel) would submit the NDC number assigned 

to the drug immediately before the drug is received 

by the drug product salvager; the manufacturer, 

repacker, and relabeler (and the drug product 

salvager that repacks or relabels) would submit the 

NDC number assigned to their drug under proposed 

§ 207.33(c) and (d). 

8Human drugs are approved by FDA under an 

NDA, ANDA, or a BLA. Part 314 (21 CFR part 314) 

for human drugs and part 601 (21 CFR part 601) for 

biologics set forth the approval requirements. 

number is explained in section IV.C of 

this document, and the requirements for 

providing the NDC number during 

listing are explained in section IV.D.4.a 

of this document. 

The following paragraphs summarize 

the information that would be required 

for listing from manufacturers, 

repackers, relabelers, and drug product 

salvagers. These summaries are 

followed by descriptions of each of the 

listing requirements (see section IV.D.4 

of this document). 

a. Summary of proposed listing 

information for manufacturers. 

Manufacturers would be required to 

submit to us the following listing 

information (if applicable to the drug 

being listed) under proposed § 207.49: 

• NDC number; 

• Route of administration; 

• Approved U.S. application number 

or approved U.S. BLA number, if any; 

• Registration number of each 

establishment where the manufacturing 

is performed for the drug; 

• Schedule of the drug under section 

202 of the Controlled Substances Act 

(21 U.S.C. 812); 

• With respect to foreign 

establishments only, the name and 

contact information of each importer of 

the drug and of each person who 

imports or offers for import the drug; 

• Labeling; 

• Advertisements; and 

• Information about the private label 

distributor, if any. 

b. Summary of proposed listing 

information for repackers and 

relabelers. Repackers and relabelers 

would be required to submit to us the 

following listing information (if 

applicable to the drug being listed) 

under proposed § 207.53: 

• NDC number; 

• Registration number of each 

establishment where the repacking or 

relabeling is performed for the drug; 

• With respect to foreign 

establishments only, the name and 

contact information of each importer of 

the drug and of each person who 

imports or offers for import the drug; 

• Labeling; 

• Advertisements; and 

• Information about the private label 

distributor, if any. 

c. Summary of proposed listing 

information for drug product salvagers 

who are not repackers or relabelers. 

Drug product salvagers who do not 

otherwise repack or relabel the drugs 

they salvage would be required to 

submit to us the following listing 

information (if applicable to the drug 

being listed) under proposed § 207.54: 

• NDC number assigned to the drug 

immediately before the drug is received 

by the drug product salvager; 

• Lot number and expiration date of 

the salvaged drug; 

• Registration number of each 

establishment where the drug product 

salvager salvages the drug; 

• With respect to foreign 

establishments only, the name and 

contact information of each importer 

and of each person who imports or 

offers for import the drug; and 

• Information about the private label 

distributor, if any. 

4. What Listing Information Would Be 

Required for Manufacturers? 

Under proposed § 207.49, 

manufacturers would be required to 

provide to us the following listing 

information for each drug they list, 

including a drug manufactured for a 

private label distributor. 

a. NDC number. For a drug to be 

considered listed, manufacturers and, as 

discussed below, repackers, relabelers, 

and drug product salvagers, must 

submit the NDC number for the drug as 

part of the drug’s listing information.7

The NDC number, including the 

information that would be submitted to 

us to obtain an NDC number, is 

explained under proposed § 207.33. 

Knowing the NDC number of the drug 

would enable us to incorporate by 

reference information about the drug 

submitted by the manufacturer, 

repacker, or relabeler to obtain an NDC 

number under proposed § 207.33(c) and 

(d), as well as information submitted by 

the manufacturer, repacker, or relabeler 

to list the drug. This would reduce the 

amount of information that must be 

provided to us by manufacturers, 

repackers, relabelers, and drug product 

salvagers for listing. Current 

§ 207.25(b)(8) requires the submission of 

the NDC number for each drug listed, 

and this information is currently 

submitted on Form FDA 2657. 

b. Route of administration. The route 

of administration would enable us to 

identify a specific formulation of a drug. 

For example, drugs having the same 

active ingredient may have different 

routes of administration. The route of 

administration is currently submitted on 

Form FDA 2657. 

c. Approved U.S. application number. 

The approved U.S. application number 

or the approved U.S. BLA number,8 if 

any, would enable us to link to the 

information about the drug that was 

already submitted to us for marketing 

approval. Section 510(j)(1)(A) of the act 

requires the submission of a reference to 

the authority for marketing a drug 

subject to section 505 or 512 of the act. 

In addition, current § 207.25(b)(2) 

requires the submission of the 

application number for each drug listed 

that the registrant regards as subject to 

section 505 or 512 of the act. The drug’s 

application number is currently 

submitted on Form FDA 2657. As 

discussed in section IV.D.4.g of this 

document, if the approved U.S. 

application number is provided to us 

when a human prescription or OTC 

drug is listed, the manufacturer would 

not be required to re-submit the labeling 

for the approved drug. The application 

number would incorporate by reference 

the labeling for approved drugs. This 

would eliminate unnecessary 

duplication of effort and cost to 

industry. The application number may 

have already been provided under 

§ 207.33(c)(2)(i) and (c)(2)(ii) instead of 

providing the names of the active 

pharmaceutical ingredient and the 

inactive ingredient. If so, it will already 

be in our database and would not need 

to be resubmitted. 

d. Registration number of each 

establishment. The registration number 

of each establishment where the 

manufacturing is performed for the drug 

would enable us to identify the 

establishment where the drug is 

manufactured. This would help our 

investigators better prepare for 

inspections and collect postmarketing 

surveillance samples. Although this 

information would already be submitted 

for registration under proposed 

§ 207.25(e), submitting it at listing 

would enable us to link this information 

to the drug being listed. Current 

§ 207.25(b)(7) requires, for each drug 

listed, the submission of the registration 

number of each drug establishment at 

which the drug is manufactured or 

processed (within the meaning of 

current § 207.3(a)(8)). Current 

§ 207.25(b)(3) requires the submission of 

the license number of the manufacturer 

of drugs subject to section 351 of the 

PHS Act. The ‘‘establishment 

registration number’’ is defined in 

proposed § 207.1 to mean the number 

assigned by FDA to the establishment 

during the establishment registration 

process. Currently, we plan to assign the 

FEI number as the establishment 

registration number. In the future, 

however, we may use a different 


jlentini on PROD1PC65 with PROPOSAL2
Federal Register / Vol. 71, No. 167 / Tuesday, August 29, 2006 / Proposed Rules 51309 

number as the establishment registration 

number. The establishment registration 

number is currently submitted on Form 

FDA 2657. 

e. Schedule of the drug. The schedule 

of the drug under section 202 of the 

Controlled Substances Act would enable 

us to provide yearly estimates of 

medical, scientific, and reserve stock 

needs for Schedule I and II substances 

(21 CFR part 1303, 21 U.S.C. 826). 

Under section 302(a) of the PHS Act (42 

U.S.C. 242(a)), the Secretary is 

responsible for providing to the Drug 

Enforcement Administration estimates 

of the quantities of controlled 

substances for which production quotas 

must be established that will be 

required to meet the legitimate medical, 

scientific, and reserve stock needs of the 

United States for the following calendar 

year. The schedule of the drug is 

currently submitted on Form FDA 2657. 

f. Information about each importer of 

the drug and each person who imports 

or offers for import the drug to the 

United States. Foreign establishments 

only must provide the name, address, 

telephone and fax numbers, and e-mail 

address of each importer of such drug in 

the United States that is known to the 

establishment, and of each person who 

imports or offers for import such drug 

to the United States. As discussed under 

section IV.B.3 of this document, the 

term ‘‘known to’’ would mean any 

importer that is known to the foreign 

establishment as well as any importer 

that the foreign establishment has 

reason to know of. We therefore expect 

that the person responsible for 

completing the required registration 

forms on behalf of the foreign 

establishment would undertake 

appropriate due diligence in completing 

those forms, including to find out and 

report importers that others in his or her 

establishment know of or have reason to 

know of. Foreign establishments would 

provide this information for listing 

unless previously provided under 

proposed § 207.25(h) for registration. 

The Bioterrorism Act requires foreign 

establishments to submit, among other 

things, the name of each importer of 

each drug that is known to the 

establishment, and the name of each 

person who imports or offers for import 

each drug to the United States for 

purposes of importation. The 

Bioterrorism Act requires submission of 

such information as part of registration 

information and also specifically 

requires listing information to be 

submitted for each drug being 

manufactured for commercial 

distribution (see section IV.A.4.d of this 

document). We are proposing, under 

this part, to make the submission of 

information concerning importers of 

drugs and persons who import or offer 

for import drugs to the United States 

both a registration and a listing 

requirement. However, if the 

information has been previously 

provided by the foreign establishment at 

registration, the foreign establishment 

would not be required to re-enter that 

information into the database at listing. 

Our listing database will be populated 

automatically with the required 

information. This would reduce the 

amount of information that must be 

provided to us by the foreign 

establishment at listing. The 

information about each importer of the 

establishment’s drug that is known to 

the establishment and each person who 

imports or offers for import the drug to 

the United States is not currently 

required to be submitted under current 

part 207 or on Form FDA 2656 or Form 

FDA 2657. 

g. Labeling. Under proposed 

§ 207.49(g), the following labeling 

would be provided to us for each drug 

listed: 

• Human prescription drugs. If the 

manufacturer has not provided the 

drug’s approved U.S. application 

number as part of the listing information 

under proposed § 207.49(c), the 

manufacturer would submit a copy of 

all current labeling, including the 

content of labeling, for each human 

prescription drug (proposed 

§ 207.49(g)(1)). 

Under proposed § 207.49(g)(1) and, as 

discussed below under proposed 

§§ 207.49(g)(2) and 207.49(g)(3), only 

one representative container or carton 

label would be submitted where 

differences exist only in the quantity of 

contents statement or the bar code. This 

proposed provision is consistent with 

current § 207.25(b)(2), although the 

proposal would add differences in the 

bar code to the provision. This 

provision would reduce the number of 

labels that must be submitted to us by 

the manufacturer. 

If the manufacturer provides the 

drug’s approved U.S. application 

number as part of the drug’s listing 

information, the labeling required under 

proposed § 207.49(g)(1) and, as 

discussed below under proposed 

§ 207.49(g)(2), would be deemed to 

accompany the listing information. 

Incorporating the labeling, including the 

content of labeling, by reference to the 

application number would eliminate 

unnecessary duplication of effort and 

cost to industry. This proposed 

exception would not apply to animal 

drugs approved under section 512 of the 

act because currently these application 

holders are not required to provide the 

content of labeling electronically with 

the application for those drugs. 

The ‘‘content of labeling’’ would be 

provided to FDA under proposed 

§ 207.49(g)(1) and, as discussed below, 

under proposed § 207.49(g)(2) and (g)(3). 

The ‘‘content of labeling’’ is defined in 

proposed § 207.1 and discussed in 

sections IV.A.5 and IV.E.4 of this 

document and would mean, for human 

prescription drugs that the manufacturer 

regards as subject to section 505 of the 

act or section 351 of the PHS Act, the 

content of the prescription drug 

labeling, including all text, tables, and 

figures. For human prescription drugs 

that the manufacturer regards as not 

subject to section 505 of the act or 

section 351 of the PHS Act, the ‘‘content 

of labeling’’ would mean the labeling 

equivalent to the content of the 

prescription drug labeling, including all 

text, tables, and figures. For human OTC 

drugs, the ‘‘content of labeling’’ would 

mean the content of the drug facts 

labeling required by § 201.66, including 

all text, tables, and figures. For animal 

drugs, the ‘‘content of labeling’’ would 

mean the content of the labeling that 

accompanies the drug that is necessary 

to enable the safe and proper 

administration of the drug, including all 

text, tables, and figures. 

The labeling submission requirements 

in proposed § 207.49(g) are almost 

identical in substance to the labeling 

submission requirements of current 

§ 207.25(b)(2) through (b)(5), except that 

manufacturers would also be required, 

as discussed previously, to submit 

electronically the ‘‘content of labeling.’’

In addition, the labeling submission 

requirements in proposed § 207.49(g) 

conform to the statutory requirements of 

section 510(j) of the act. The proposed 

requirement to submit labeling, 

including the content of labeling, for 

human prescription drugs and, as 

discussed below, for human OTC drugs 

and animal drugs, whether or not the 

drugs are subject to the pre-approval 

provisions of the act or the PHS Act, is 

consistent with the statutory 

requirements of section 510(j)(1)(A), 

510(j)(1)(B)(i), and 510(j)(1)(B)(ii) of the 

act. Section 510(j)(1)(A) of the act 

requires, among other things, the 

submission of a copy of all labeling for 

drugs subject to section 505 or 512 of 

the act. Section 510(j)(1)(B)(i) requires, 

among other things, the submission of a 

copy of all labeling for prescription 

drugs not subject to section 505 or 512 

of the act, and section 510(j)(1)(B)(ii) 

requires, among other things, the 

submission of the label, package insert, 

and representative sampling of any 

other labeling for OTC drugs not subject 

to section 505 or 512 of the act. We also 


jlentini on PROD1PC65 with PROPOSAL2
51310 Federal Register / Vol. 71, No. 167 / Tuesday, August 29, 2006 / Proposed Rules 

have the authority to require that 

labeling be submitted in this format 

under other sections of the act (e.g., 

sections 201, 301, 501, 502, 503, 505, 

506, 506A, 506B, 506C, 513–516, 518–

520, 701, 704, 721, 801 of the act) and 

the PHS Act. 

• Human OTC drugs that 

manufacturers regard as subject to 

section 505 of the act or section 351 of 

the PHS Act. If the manufacturer has not 

provided the drug’s approved U.S. 

application number as part of the listing 

information under proposed § 207.49(c), 

the manufacturer would submit a copy 

of all current labeling, including the 

content of labeling, for each human OTC 

drug that the manufacturer regards as 

subject to section 505 of the act or 

section 351 of the PHS Act (proposed 

§ 207.49(g)(2)(i)). 

Drugs subject to section 505 of the act 

or section 351 of the PHS Act must be 

approved by FDA under an NDA, 

ANDA, or a BLA. Part 314 for human 

drugs and part 601 for biological 

products set forth the approval 

requirements. 

• Human OTC drugs that 

manufacturers regard as not subject to 

section 505 of the act or section 351 of 

the PHS Act. The manufacturer would 

submit a copy of the current label, the 

content of labeling, the package insert (if 

any), and a representative sampling of 

any other labeling for each human OTC 

drug that the manufacturer regards as 

not subject to section 505 of the act or 

section 351 of the PHS Act (proposed 

§ 207.49(g)(2)(ii)). 

The term ‘‘label’’ means the container 

label as defined at section 201(k) of the 

act. ‘‘Content of labeling’’ is defined at 

proposed § 207.1 (as discussed in 

section IV.A.5 of this document) and for 

OTC drugs refers to the content of the 

drug facts labeling as specified at 

§ 201.66. Most OTC drugs do not have 

a package insert. However, for those that 

do, it is currently required to be 

submitted for drug listing under section 

510(j)(1)(A) and (j)(1)(B)(ii) of the act 

and current § 207.25(b)(4) and (b)(5). We 

are proposing to retain that requirement 

in proposed § 207.49(g)(2)(i) and 

(g)(2)(ii). For OTC drugs marketed 

pursuant to an approved application, 

any package insert would be included 

within the requirement to submit ‘‘all 

current labeling.’’ The term 

‘‘representative sampling of any other 

labeling,’’ as used in proposed 

§ 207.49(g)(2)(ii) and, as discussed 

below, in proposed § 207.49(g)(3)(ii), is 

defined in proposed § 207.1 and 

discussed in section IV.A.5 of this 

document. Examples of OTC drugs that 

a manufacturer may regard as not 

subject to section 505 of the act or 

section 351 of the PHS Act would 

include human OTC drugs marketed 

under an OTC monograph and deemed 

generally recognized as safe and 

effective (see part 330 (21 CFR part 

330)). 

• Animal drugs that manufacturers 

regard as subject to section 512 of the 

act. The manufacturer would submit a 

copy of all current labeling, including 

the content of labeling, for each animal 

drug that the manufacturer regards as 

subject to section 512 of the act 

(proposed § 207.49(g)(3)(i)). 

• Animal drugs that manufacturers 

regard as not subject to section 512 of 

the act. For all other animal drugs, the 

manufacturer would submit a copy of 

the current label, the package insert, the 

content of labeling, and a representative 

sampling of any other labeling, for each 

animal drug that the manufacturer 

regards as not subject to section 512 of 

the act (proposed § 207.49(g)(3)(ii)). 

h. Advertisements. Under proposed 

§ 207.49(h), and in accordance with 

section 505(j)(1)(B)(i) of the act, the 

following advertisements would be 

provided by the manufacturer for each 

drug listed: 

• A representative sampling of 

advertisements for human prescription 

drugs that the manufacturer regards as 

not subject to section 505 of the act or 

section 351 of the PHS Act. Proposed 

§ 207.49(h)(1) is consistent with section 

510(j)(1)(B)(i) of the act and current 

§ 207.25(b)(4). The term ‘‘representative 

sampling of advertisements’’ is defined 

in proposed § 207.1 and discussed in 

section IV.A.5 of this document. 

• If we request it, for good cause, a 

copy of all advertisements for human 

prescription drugs that the manufacturer 

regards as not subject to section 505 of 

the act or section 351 of the PHS Act, 

including those advertisements 

described in § 202.1(l)(1), would be 

required to be submitted to FDA within 

30 calendar days after our request. 

Proposed § 207.49(h)(2) is consistent 

with section 510(j)(1)(B)(i) of the act and 

current § 207.31(a)(1). Section 

510(j)(1)(B)(i) of the act requires, among 

other things, the submission of a 

representative sampling of 

advertisements and, upon request for 

good cause, a copy of all advertisements 

for prescription drugs not subject to 

section 505 of the act. Current 

§ 207.31(a)(1) requires, upon request, 

the submission of a copy of all 

advertisements for prescription drugs 

that the manufacturer regards as not 

subject to section 505 of the act. 

i. Private label distributor. If the drug 

is manufactured for a private label 

distributor, the manufacturer would 

submit the name, address, labeler code, 

telephone and fax numbers, and e-mail 

address of the private label distributor. 

The manufacturer may obtain this 

information from the private label 

distributor or other sources. This 

information would indicate whose drug 

(the manufacturer’s or the private label 

distributor’s) is being listed and would 

identify and enable us, if needed, to 

contact the private label distributor. The 

information for a private label 

distributor is currently submitted on 

Form FDA 2658. 

5. What Listing Information Would Be 

Required for Repackers and Relabelers? 

Under proposed § 207.53, repackers 

and relabelers would be required to 

provide to us all of the following listing 

information for each drug they list, 

including a drug repacked or relabeled 

for a private label distributor. 

a. NDC number. For a drug to be 

considered listed, repackers and 

relabelers would submit the NDC 

number for the drug being repacked or 

relabeled as part of the drug’s listing 

information. This requirement is 

explained in section IV.D.4.a of this 

document. 

b. Registration number of each 

establishment. The registration number 

of each establishment where the 

repacking or relabeling is performed for 

the drug would enable us to identify the 

establishment where the drug is 

repacked or relabeled. This requirement 

is explained in section IV.D.4.d of this 

document. 

c. Information about each importer of 

the drug and each person who imports, 

or offers for import, the drug to the 

United States. This requirement is 

explained in section IV.D.4.f of this 

document. 

d. Labeling. Under proposed 

§ 207.53(d), the following labeling must 

be provided for each drug listed: 

• Human prescription drugs. If the 

repacker or relabeler makes any change 

in the labeling of the drug repacked or 

relabeled, the repacker or relabeler 

would submit a copy of all changed 

labeling for each human prescription 

drug that is repacked or relabeled 

(proposed § 207.53(d)(1)). We would 

already have, as required under 

proposed § 207.49(g), the labeling for 

the drug provided by the manufacturer 

during listing, and the repacker or 

relabeler would not need to resubmit it 

to us unless they make changes to the 

labeling. Proposed § 207.53(d)(1) is 

consistent with section 510(j)(1)(A) and 

(j)(1)(B)(i) of the act and current 

§ 207.25(b)(2) and (b)(4), except that 

repackers and relabelers would not need 

to resubmit labeling when no changes 

have been made. 


jlentini on PROD1PC65 with PROPOSAL2
Federal Register / Vol. 71, No. 167 / Tuesday, August 29, 2006 / Proposed Rules 51311 

• Human OTC drugs that 

manufacturers regard as subject to 

section 505 of the act or section 351 of 

the PHS Act. If the repacker or relabeler 

makes any changes, in accordance with 

the act and FDA regulations, in the 

labeling of the drug repacked or 

relabeled, the repacker or relabeler 

would submit a copy of all changed 

labeling for each human OTC drug that 

the manufacturer of the drug regards as 

subject to section 505 of the act or 

section 351 of the PHS Act (proposed 

§ 207.53(d)(2)(i)). As stated previously, 

we would not need a copy of the 

unchanged labeling because we would 

already have the labeling for the drug 

provided by the manufacturer during 

listing. Proposed § 207.53(d)(2)(i) is 

consistent with section 510(j)(1)(B)(i) of 

the act and current § 207.25(b)(2), 

except that some of the information 

required under current § 207.25(b)(2) 

would not need to be provided by the 

repacker or relabeler under proposed 

§ 207.53(d)(2)(i) if the repacker or 

relabeler provides the manufacturer’s 

NDC number. The NDC number would 

provide a link to that information. 

• Human OTC drugs that 

manufacturers regard as not subject to 

section 505 of the act or section 351 of 

the PHS Act. The repacker or relabeler 

would submit a copy of the current 

label, a copy of any changes made to the 

package insert, if there is one, and a 

representative sampling of any other 

labeling for each human OTC drug that 

the manufacturer of the drug regards as 

not subject to section 505 of the act or 

section 351 of the PHS Act (proposed 

§ 207.53(d)(2)(ii)). The term 

‘‘representative sampling of any other 

labeling,’’ as used in proposed 

§ 207.53(d)(2)(ii) and, as discussed 

below, in § 207.53(d)(3), is defined in 

proposed § 207.1 and discussed in 

section IV.A.5 of this document. 

Examples of OTC drugs that a 

manufacturer may regard as not subject 

to section 505 of the act or section 351 

of the PHS Act would include human 

OTC drugs marketed under an OTC 

monograph and deemed generally 

recognized as safe and effective (see part 

330). Proposed § 207.53(d)(2)(ii) is 

consistent with section 510(j)(1)(B)(ii) of 

the act and current § 207.25(b)(5), 

except redundant information would 

not be submitted. 

• Animal drugs. The repacker or 

relabeler would submit a copy of the 

current label, a copy of any changes 

made to each animal drug labeling, and 

a representative sampling of any other 

labeling for each animal drug (proposed 

§§ 207.53(d)(3)). Proposed § 207.53(d)(3) 

is consistent with section 510(j)(1)(B)(ii) 

of the act and current § 207.25(b)(2) and 

(b)(5), except redundant information 

would not be submitted. 

e. Advertisements. Under proposed 

§ 207.53(e), and in accordance with 

section 505(j)(1)(B)(i) of the act, the 

following advertisements would be 

provided by the repacker or relabeler for 

each drug listed: 

• A representative sampling of 

advertisements for human prescription 

drugs that the repacker or relabeler 

regards as not subject to section 505 of 

the act or section 351 of the PHS Act. 

Proposed § 207.53(e)(1) is consistent 

with section 510(j)(1)(B)(i) of the act and 

current § 207.25(b)(4). 

• If we request it, for good cause, a 

copy of all advertisements for human 

prescription drugs that the repacker or 

relabeler regards as not subject to 

section 505 of the act or section 351 of 

the PHS Act, including those 

advertisements described in 

§ 202.1(l)(1), would be required within 

30 calendar days after our request. 

Proposed § 207.53(e)(2) is consistent 

with section 510(j)(1)(B)(i) of the act and 

current § 207.31(a)(1). 

f. Private label distributor. If the drug 

is repacked or relabeled for a private 

label distributor, the repacker or 

relabeler would submit the name, 

address, labeler code, telephone and fax 

numbers, and e-mail address of the 

private label distributor. The repacker or 

relabeler may obtain this information 

from the private label distributor or 

other sources. This information would 

indicate whose drug (the repacker’s, 

relabeler’s, or private label distributor’s) 

is being listed and would identify and 

enable us, if needed, to contact the 

private label distributor. The 

information for a private label 

distributor is currently submitted on 

Form FDA 2658. 

6. What Listing Information Would Be 

Required for Drug Product Salvagers 

Who Are Not Repackers or Relabelers? 

Drug product salvagers who do not 

otherwise repack or relabel the drugs 

they salvage would be required to 

provide all of the following listing 

information to us for each drug they list, 

including a drug salvaged for a private 

label distributor. Drug product salvagers 

who also repack and relabel the drugs 

they salvage must list those drugs as a 

repacker or relabeler in accordance with 

§ 207.53. 

a. NDC number. For a drug to be 

considered listed, the drug product 

salvager would be required to provide 

the NDC number assigned to the drug 

immediately before the drug is received 

by the drug product salvager. Under the 

proposal, we would assign an NDC 

number to a manufacturer’s, repacker’s, 

or relabeler’s drug (or to a drug 

manufactured, repacked, or relabeled for 

a private label distributor) after the 

information required under proposed 

§ 207.33(c) or (d) is provided (see 

discussion in section IV.D.4.a of this 

document). The drug product salvager 

who is not also a repacker or a relabeler 

for the drug would provide to us the 

NDC number that is already on the 

salvaged drug’s label (that is, the NDC 

number of the manufacturer, repacker, 

relabeler, or private label distributor). 

Knowing the NDC number of the drug 

would enable us to incorporate by 

reference information about the drug 

submitted by the manufacturer, 

repacker, or relabeler to obtain an NDC 

number under proposed § 207.33(c) and 

(d), as well as information submitted by 

the manufacturer, repacker, or relabeler 

to list the drug. 

b. Lot number and expiration date. 

We need to know the lot number and 

expiration date to properly identify the 

drug because the drug product salvager 

who is not a repacker or relabeler for the 

drug would not be assigned an NDC 

number for the drug. The salvaged 

drug’s lot number would enable us to 

specifically identify the salvaged drug 

and determine which batch of a 

manufacturer’s drug has been processed 

by the drug product salvager. Lot 

number (or control number or batch 

number) is defined at current 

§ 210.3(b)(11) as any distinctive 

combination of letters, numbers, or 

symbols, or any combination of them, 

from which the complete history of the 

manufacture, processing, packing, 

holding, and distribution of a batch or 

lot of drug product or other material can 

be determined. Knowing the drug’s 

expiration date would indicate 

approximately how long the salvaged 

drug may be available for use by 

consumers. The expiration date would 

also allow us to identify the 

approximate date that the salvaged drug 

would no longer be marketed. 

c. Registration number of each 

establishment. The registration number 

of each establishment where the drug 

product salvager salvages the drug 

would enable us to connect the 

salvaging activity to a particular drug 

and identify the specific location where 

the drug product salvaging is performed 

for the drug. This information would 

also be used in conducting our 

establishment inspections and for 

collecting postmarketing surveillance 

samples. Current § 207.25(b)(7) requires, 

for each drug listed, the submission of 

the registration number of each drug 

establishment at which the drug is 

manufactured or processed (within the 

meaning of current § 207.3(a)(8)), and 


jlentini on PROD1PC65 with PROPOSAL2
51312 Federal Register / Vol. 71, No. 167 / Tuesday, August 29, 2006 / Proposed Rules 

current § 207.25(b)(3) requires the 

submission of the license number of the 

manufacturer of drugs subject to section 

351 of the PHS Act. The establishment 

registration number is currently 

submitted on Form FDA 2657. 

d. Information about each importer of 

the drug and each person who imports, 

or offers for import, the drug to the 

United States. This requirement is 

explained under section IV.D.4.f of this 

document. 

e. Private label distributor. If the drug 

is salvaged for a private label 

distributor, the drug product salvager 

would be required to submit the name, 

address, labeler code, telephone and fax 

numbers, and e-mail address of the 

private label distributor. The drug 

product salvager may obtain this 

information from the private label 

distributor or other sources. This 

information would identify the private 

label distributor and enable us, if 

needed, to contact the private label 

distributor. The information for a 

private label distributor is currently 

submitted on Form FDA 2658. 

7. What Additional Drug Listing 

Information May Be Required? 

Under proposed § 207.55, if we 

request it, the manufacturer, repacker, 

relabeler, or drug product salvager 

would be required to briefly state the 

basis for its belief that a particular drug 

product is not subject to section 505 or 

512 of the act or section 351 of the PHS 

Act. This proposed provision, which is 

consistent with section 510(j)(1)(D) of 

the act and current § 207.31(a)(3), is 

needed because some manufacturers, 

repackers, and relabelers have 

mistakenly considered a drug not to be 

subject to section 505 or 512 of the act 

or section 351 of the PHS Act. Although 

in some cases manufacturers, repackers, 

and relabelers have correctly concluded 

that a drug is not subject to section 505 

or 512 of the act or section 351 of the 

PHS Act, in other cases we may 

consider the drug to be subject to 

section 505 or 512 despite that 

conclusion. 

The brief statement that would be 

requested under proposed § 207.55 may 

include, for example, the Federal 

Register citation for the applicable OTC 

monograph. We anticipate that our 

electronic drug registration and listing 

system will provide some options for 

brief statements, including Federal 

Register citations as described in the 

example above, from which 

manufacturers, repackers, relabelers, 

and drug product salvagers may select 

as the basis for their belief that a 

particular drug product is not subject to 

section 505 or 512 of the act or section 

351 of the PHS Act. 

We are also considering whether to 

require establishments to provide the 

number of batches and batch size for 

each drug subject to the listing 

requirements that they manufactured, 

repacked, or relabeled since the 

establishment last provided listing 

information. Typically, this information 

would be provided every 6 months, 

based on the obligation to review and 

update listing information in June and 

December of each year. We would 

consider ‘‘batch size’’ to mean, as a 

general matter, the batch size included 

in the master production and control 

records for each drug, as required by the 

regulations governing current good 

manufacturing practice for finished 

pharmaceuticals in part 211, including 

§ 211.186(a) (master production and 

control records). Typically, ‘‘batch size’’

would be the number of unit dosage 

forms (such as for tablets) or, if the unit 

dosage form is not defined before 

primary packaging (such as for liquids), 

the total batch weight or volume before 

primary packaging. 

We are considering this requirement 

because it would provide us with 

important data regarding a product’s 

volume in the U.S. marketplace to 

assess the potential impact the product 

has on the public health, which, in turn, 

will enable us to use our limited 

resources more efficiently, particularly 

with regard to inspectional oversight. 

For example, we currently use data 

collected as a surrogate for production 

volume, among many other factors, in 

our risk-based model to prioritize 

routine inspections. This model is a 

systematic, objective, data-driven 

method to prioritize inspections. (See 

‘‘Risk-Based Method for Prioritizing 

CGMP Inspections of Pharmaceutical 

Manufacturing Sites—A Pilot Risk 

Ranking Model’’ at http://www.fda.gov/ 

cder/gmp/gmp2004/ 

risk_based_method.htm.) However, 

better estimates of manufacturing 

volume would improve our ability to 

implement a more risk-based approach 

to manufacturing quality oversight 

activities. By requiring establishments 

to provide the number of batches and 

batch size for each drug subject to the 

listing requirements, we would have 

objective data regarding production 

volume and be better able to find and 

address CGMP violations that may have 

the most impact on public health. 

Actual production data would also give 

us the ability to more efficiently allocate 

our resources in other areas. 

We specifically invite comments on 

whether we should require 

manufacturers, repackers, relabelers, 

and drug product salvagers to provide 

the number of batches and batch size for 

each drug subject to the listing 

requirements. 

8. What Are the Proposed Requirements 

for Reviewing and Updating Listing 

Information? 

Currently, manufacturers, repackers, 

and relabelers must enter new or revised 

listing information on Form FDA 2657 

(Form FDA 2658 is used when 

manufacturers, repackers, and relabelers 

enter new or revised information for a 

private label distributor’s drug) and 

return the form to FDA. Under the 

proposal, manufacturers, repackers, 

relabelers, and drug product salvagers 

would access our electronic drug 

registration and listing system and 

review their current listing information 

online, making any changes where 

needed. Updating listing information 

would be less time consuming under the 

proposal because the manufacturer, 

repacker, relabeler, and drug product 

salvager would be able to easily access 

their information at any time, and only 

changes to the information already in 

the system would need to be entered in 

the fields provided. 

Under proposed § 207.57, 

manufacturers who are required to list 

under proposed § 207.41 would review 

and update all listing information 

provided under proposed §§ 207.49, 

207.55, and 207.57; repackers and 

relabelers (including drug product 

salvagers who repack and/or relabel) 

who are required to list under proposed 

§ 207.41 would review and update all 

listing information provided under 

proposed §§ 207.53, 207.55, and 207.57; 

and drug product salvagers (who are not 

repackers and/or relabelers) who are 

required to list under proposed § 207.41 

would review and update all listing 

information provided under proposed 

§§ 207.54, 207.55, and 207.57. Proposed 

§ 207.57 uses the term ‘‘review and 

update’’ to stress the importance of first 

reviewing all listing information to 

determine if any changes have occurred 

and then updating the information. 

Under proposed § 207.57(a), during 

the annual review and update of 

registration information, manufacturers, 

repackers, relabelers, and drug product 

salvagers would provide listing 

information for any drug that has not 

been previously listed. Proposed 

§ 207.57(a) is consistent with section 

510(j)(1) of the act, which requires, 

among other things, that a list of all 

drugs must be provided at the time of 

annual registration. 

Under proposed § 207.57(b), 

manufacturers, repackers, relabelers, 

and drug product salvagers would 


jlentini on PROD1PC65 with PROPOSAL2
Federal Register / Vol. 71, No. 167 / Tuesday, August 29, 2006 / Proposed Rules 51313 

review and update their listing 

information each June and December of 

every year. Proposed § 207.57(b) is 

consistent with the timeframes set forth 

in section 510(j)(2) of the act, which 

requires, among other things, that each 

person who registers must report certain 

listing information ‘‘once during the 

month of June of each year and once 

during the month of December of each 

year.’’ Under current § 207.21(b), an 

update of listing information must occur 

each June and December. 

Under proposed § 207.57(b)(1) 

through (b)(5), manufacturers, 

repackers, relabelers, and drug product 

salvagers would, during the review and 

update, submit the following 

information: 

• Listing information would be 

provided for any drug manufactured, 

repacked, relabeled, or salvaged for 

commercial distribution that has not 

been previously listed (proposed 

§ 207.57(b)(1)). The information would 

be provided in accordance with 

proposed §§ 207.49, 207.53, 207.54, and 

207.55. This information is currently 

required under section 510(j)(2)(A) of 

the act and current § 207.30(a)(1). 

• The date that the manufacture, 

repacking, relabeling, or salvaging for 

commercial distribution of a listed drug 

has been discontinued would be 

provided (proposed § 207.57(b)(2)). The 

date of discontinuation is currently 

required under section 510(j)(2)(B) of 

the act and current § 207.30(a)(2). 

Section 510(j)(2)(B) of the act requires 

submission of a ‘‘notice of 

discontinuance.’’ We are proposing to 

also require that the expiration date of 

the last lot manufactured, repacked, 

relabeled, or salvaged be part of 

proposed § 207.57(b)(2). This 

information would enable us to know 

when a drug is no longer marketed and 

approximately how long the 

discontinued drug may be available for 

use by consumers. 

We recognize that because of their 

business practices, drug product 

salvagers may discontinue commercial 

distribution of a listed drug almost 

immediately after they salvage the drug. 

Drug product salvagers may salvage a 

drug, put the drug into commercial 

distribution by selling it to a retailer or 

other party, and then discontinue 

salvaging the drug. In that case, we 

intend to minimize the reporting burden 

on drug product salvagers by allowing 

the drug product salvager to provide 

notice of discontinuation of the drug at 

the same time the drug product salvager 

lists the drug. We would not expect 

under proposed § 207.57(b)(2) that the 

drug product salvager inform us again, 

during the review and update of listing 

information in either June or December 

of the year, that the salvaged drug is 

discontinued. Under this proposal, we 

expect that our electronic drug 

registration and listing system would 

provide the opportunity for drug 

product salvagers to first list a drug, as 

required by proposed § 207.54, and then 

indicate that they are discontinuing the 

drug, as required by proposed 

§ 207.57(b)(2). Because the drug product 

salvager would have provided the lot 

number and expiration date for the drug 

under proposed § 207.54(b)(2), we 

would not require that same information 

be submitted again under proposed 

§ 207.57(b)(2). 

• The date that the manufacture, 

repacking, or relabeling for commercial 

distribution of a previously 

discontinued drug has resumed and any 

other listing information not previously 

required or submitted for the drug 

would be provided (proposed 

§ 207.57(b)(3)). This proposed provision 

is consistent with section 510(j)(2)(C) of 

the act, which requires, among other 

things, that if a registrant has resumed 

the manufacture, preparation, 

propagation, compounding, or 

processing of a discontinued drug for 

commercial distribution, the registrant 

must provide notice and the date of 

such resumption, the established name 

and proprietary name of the drug, and 

other listing information required under 

section 510(j)(1) of the act not 

previously provided. The established 

name and proprietary name would have 

previously been submitted at the time of 

listing. Because we would be able to 

reference that information in our listing 

database, manufacturers, repackers, and 

relabelers would not need to resubmit 

the established name and proprietary 

name. Current § 207.30(a)(3) requires, in 

addition to the date of resumption of 

commercial distribution, that the NDC 

number, the established name and 

proprietary name, and any other listing 

information not previously submitted 

must be provided. Under the proposal, 

this information would not need to be 

provided at this time because we would 

have access to it from the listing 

database. 

We anticipate that drug product 

salvagers would not report information 

under proposed § 207.57(b)(3) because 

we are unaware of instances when drug 

product salvagers resume salvaging a 

drug that they have already salvaged 

and returned to the marketplace. Drug 

product salvagers salvage a drug and 

then put the drug into commercial 

distribution by selling it to a retailer or 

other party. This activity ends the drug 

product salvager’s association with that 

drug. In contrast, manufacturers, 

repackers, and relabelers may resume 

the manufacture, repacking, or 

relabeling of a drug (usually a different 

lot of the drug) that they had previously 

listed but are currently not 

manufacturing, repacking, or relabeling. 

Thus, we anticipate that proposed 

§ 207.57(b)(3) would not be applicable 

to drug product salvagers. We invite 

comment on whether drug product 

salvagers resume salvaging a drug that 

they have already salvaged and returned 

to the marketplace. 

• The June and December review and 

update of listing information would 

include the submission of all material 

changes in any information previously 

submitted under § 207.49, § 207.53, 

§ 207.54, § 207.55, or § 207.57 (proposed 

§ 207.57(b)(4)). Current § 207.30(a)(4) 

requires that any material change in any 

information previously submitted must 

be reported every June and December or, 

at the discretion of the registrant, when 

the change occurs. Material changes are 

listed in the definition of ‘‘any material 

change’’ in current § 207.3(a)(3). As 

discussed in section IV.A.5 of this 

document, we are proposing to broaden 

this definition to mean any change in 

any listing information provided under 

proposed §§ 207.49, 207.53, 207.54, 

207.55, and 207.57 (except for labeling 

changes in arrangement or printing or of 

an editorial nature, or the inclusion of 

a bar code or NDC number on the label). 

Under the proposed definition of 

‘‘material change,’’ the number of 

changes in listing information that are 

considered ‘‘material’’ would include 

more than the five types of changes 

considered ‘‘material’’ in the current 

definition. We are proposing a broader 

definition of material change because, 

for the reasons explained in section IV.D 

of this document, the accuracy of all 

listing information is essential for us to 

maintain a reliable and current drug 

listing database. Proposed § 207.57(b)(4) 

is consistent with section 510(j)(2)(D) of 

the act, which requires that each person 

who registers shall report once during 

the month of June of each year and once 

during the month of December of each 

year any material change in any 

information previously submitted 

pursuant to section 510(j)(1) or section 

510(j)(2) of the act. Section 510 of the 

act does not define ‘‘material change.’’

• If no changes have occurred since 

the last review and update of listing 

information, manufacturers, repackers, 

relabelers, and drug product salvagers 

would certify that no changes have 

occurred (proposed § 207.57(b)(5)). 

Proposed § 207.57(b)(5) also provides 

that if a drug is discontinued and we 

have received the information required 

under proposed § 207.57(b)(2) 


jlentini on PROD1PC65 with PROPOSAL2
51314 Federal Register / Vol. 71, No. 167 / Tuesday, August 29, 2006 / Proposed Rules 

9As explained in section IV.E.4 of this document, 

the NDC number may accompany the content of 

labeling; it does not need to be in the content of 

labeling. 

10See footnote 9. 

concerning the discontinuation of a 

listed drug, no further certifications 

would be necessary for the discontinued 

drug. We are proposing to revoke 

current § 207.30(b), which states that no 

report is required when no changes have 

occurred since the previously submitted 

list. 

FDA is proposing this certification to 

ensure that manufacturers, repackers, 

relabelers, and drug product salvagers 

have reviewed their listing information 

and have determined that there have 

been no changes. There have been many 

instances where manufacturers, 

repackers, and relabelers have not 

updated their listing information on a 

regular basis. It has been difficult for us 

to determine whether failure to update 

listing information is the result of no 

changes in information or 

noncompliance. The proposed 

requirement is intended to reduce these 

instances and improve the accuracy of 

our drug listing database. Furthermore, 

under section 301(p) of the act, it is a 

prohibited act to fail to submit drug 

listing information under section 510(j) 

of the act. Failure to submit drug listing 

information would also render a drug 

misbranded under section 502(o) of the 

act. In addition, the proposed 

requirement to certify is supported by 

the statutory provision in section 701(a) 

of the act (21 U.S.C. 371(a)) that the 

Secretary has the authority to 

promulgate regulations for the efficient 

enforcement of the act. 

We specifically request comment on 

any burden that may result from this 

proposed requirement that 

manufacturers, repackers, relabelers, 

and drug product salvagers certify that 

no changes have occurred. 

Current § 207.30(a) provides that the 

updates to listing information must be 

submitted during each June and 

December or, at the discretion of the 

registrant, when the change occurs. 

Although proposed § 207.57(b) would 

require that listing information be 

reviewed and updated only every June 

and December, we are requesting that 

manufacturers, repackers, relabelers, 

and drug product salvagers provide all 

updates to listing information within 30 

calendar days of a change. We are 

requesting that this information be 

provided on an expedited basis because 

our listing database will be more 

accurate if listing information is 

submitted sooner. 

E. Electronic Format 

1. How Would Registration and Listing 

Information Be Provided To FDA? 

Under proposed § 207.61(a)(1), the 

following information required under 

proposed part 207 would be provided to 

us using our electronic drug registration 

and listing system: 

• Establishment registration 

information required in proposed 

§§ 207.25 and 207.29 (proposed 

§ 207.61(a)(1)(i)); 

• Information required for an NDC 

number in proposed § 207.33 (proposed 

§ 207.61(a)(1)(ii)); and 

• Drug listing information required in 

proposed § 207.49 (except for labeling 

and advertising information in proposed 

§ 207.49(g) and (h)), 207.53 (except 

proposed §§ 207.53(d) and (e)), 207.54, 

207.55, and 207.57 (proposed 

§ 207.61(a)(1)(iii)). As explained in 

section IV.E.7 of this document, the 

submission of establishment registration 

and drug listing information and 

information required for an NDC 

number would be made in accordance 

with 21 CFR part 11, except for the 

requirements under § 11.10(b), (c), and 

(e), and the corresponding requirements 

in § 11.30. 

Proposed § 207.61(a)(2) would require 

that the content of labeling defined in 

proposed § 207.1 and required under 

proposed § 207.49(g)(1) through (g)(3) be 

provided to us in electronic format. The 

NDC number would also be provided 

with9 the content of labeling for each 

drug. As explained in section IV.E.7 of 

this document, the submission of the 

content of labeling would be made in 

accordance with 21 CFR part 11, except 

for the requirements under § 11.10(a), 

(c) through (h), and (k), and the 

corresponding requirements under 

§ 11.30. As explained in section IV.E.4 

of this document and stated in proposed 

§ 207.49(g), the labeling, including the 

content of labeling, would not be 

required if the approved U.S. 

application number is provided by the 

manufacturer when the drug is listed. 

In addition to the electronic 

submission of information under 

proposed § 207.61(a)(1)(i), (a)(1)(ii), 

(a)(1)(iii), and (a)(2)), advertisements 

and labeling (other than the content of 

labeling) required under §§ 207.49(g) 

and (h) and 207.53(d) and (e) would be 

provided to us in either paper or 

electronic format (proposed 

§ 207.61(a)(3)). The NDC number would 

also be provided with10 the 

advertisements and labeling. As 

explained in section IV.E.7 of this 

document, the electronic submission of 

advertisements and labeling, other than 

the content of labeling, would be made 

in accordance with part 11 (21 CFR part 

11), except for the requirements under 

§ 11.10(a), (c) through (h), and (k), and 

the corresponding requirements under 

§ 11.30. 

Under proposed § 207.61(a)(4), 

electronic format submissions must be 

in a form that we can process, review, 

and archive. As explained in section 

IV.E.6 of this document, we may 

periodically issue guidance on how to 

provide registration and listing 

information in electronic format (for 

example, method of transmission, 

media, file formats, preparation and 

organization of files). 

The electronic submission of the 

information covered under proposed 

§ 207.61(a) would provide a number of 

advantages over the current submission 

of FDA paper forms: 

• We would receive a greater quantity 

of accurate information in less time than 

it takes to receive information from 

paper submissions. The information 

received would also be more accurate 

because our electronic drug registration 

and listing system would eliminate 

errors associated with inputting paperbased data into an electronic system. 

• The electronic transmission of the 

information would be easier and more 

efficient for both industry and us than 

the current use of paper forms. For 

example, you would receive on-screen 

feedback if the information submitted 

was not complete, reducing errors and 

the time and cost of communicating 

with us. Similarly, electronic 

transmission of the information would 

reduce significantly the time and cost 

associated with our processing paper 

forms and communicating with industry 

concerning errors on those forms. 

• Information search and retrieval 

time would be reduced, allowing 

quicker access to the information in the 

database. 

The requirement to provide listing 

information to us electronically is 

consistent with the requirement to list 

in section 510(j)(1) of the act: ‘‘Every 

person who registers with the Secretary 

* * * shall * * * file with the 

Secretary a list of all drugs * * *. Such 

list shall be prepared in such form and 

manner as the Secretary may prescribe 

* * *.’’ The requirement to provide 

registration information to us 

electronically is consistent with section 

510(p) of the act: ‘‘Registrations * * * 

(including the submission of updated 

information) shall be submitted to the 

Secretary by electronic means, upon a 

finding by the Secretary that the 

electronic receipt of such registrations is 

feasible * * *.’’ Persons who register 

are also required to list drugs which are 

being manufactured, prepared, 


jlentini on PROD1PC65 with PROPOSAL2
Federal Register / Vol. 71, No. 167 / Tuesday, August 29, 2006 / Proposed Rules 51315 

propagated, compounded, or processed 

for commercial distribution (21 U.S.C. 

510(j)(1)). 

2. What Was the Electronic Submission 

Pilot Project? 

In the Federal Register of January 9, 

2001 (66 FR 1684), we requested 

volunteers to participate in a pilot 

project involving the electronic 

submission of registration and listing 

information. In a September 2001 

meeting/teleconference with the pilot 

project volunteers, we provided 

information on the major functions of 

the electronic drug registration and 

listing system, including instructions on 

the installation, setup, and testing of the 

systems. The pilot test was held from 

October 19, 2001, through November 9, 

2001, and approximately 28 industry 

representatives voluntarily participated. 

As mentioned previously, our 

electronic drug registration and listing 

system is expected to be a Web-enabled, 

integrated system that provides 

controlled database access for you to 

register establishments and list drugs. A 

separate capability—an extranet—could 

be used that authenticates external users 

and controls their access to the our 

online registration and listing database. 

This system would allow you to create 

user accounts and manage additional 

users. 

Industry representatives accessed the 

pilot test through our extranet to 

perform the following functions: (l) 

Initial company setup and 

establishment registration; (2) 

registration of additional 

establishments; (3) drug listing; (4) 

updates; and (5) system access, logoff, 

and exit. The pilot test included 

installation, setup, and operational 

testing of our electronic drug 

registration and listing system. 

The pilot test was intended to get 

direct input from the pilot participants 

about the usability and functionality of 

the system. The pilot test provided 

feedback to us on: 

• The pilot participants’ experience 

in submitting and preparing registration 

and listing data. 

• Web browsers used. 

• Acceptability of proposed normal 

operating hours. 

• Page layout and design. 

• Ease of navigation within pages and 

between functions. 

• Whether error messages provide 

sufficient information to resolve the 

error. 

• The appropriateness of the style, 

content, and depth of detail of the 

onpage help. 

The comments we received on our 

electronic drug registration and listing 

system were generally positive. Those 

who volunteered to participate in the 

pilot test were able to successfully 

access the system, set up a company 

account within the system, register 

establishments, and list drugs. Pilot 

participants encountered a few one-time 

difficulties that we will address, 

including minor password problems 

and difficulties completing the initial 

company setup and establishment 

registration process. 

We are using information from the 

pilot program to develop our electronic 

system. 

3. How Would the Electronic Drug 

Registration and Listing System Work? 

Electronic format submissions of 

registration and listing information, as 

well as information required for an NDC 

number, would consist of the electronic 

transmission via the Internet of the 

required information from 

manufacturers, repackers, relabelers, 

and drug product salvagers into our 

electronic drug registration and listing 

system. 

Our electronic drug registration and 

listing system would be made available 

using an Internet-based data collection 

system accessed through our FDA 

Internet site. 

• To use the Web site, you would 

need access to the Internet using a 

browser. 

• You could arrange for Internet 

access through one of many available 

Internet Service Providers (ISPs). 

• You would need an e-mail address 

so we can send you confirmation of 

submissions and other related 

information. 

• This e-mail service could be 

provided by the ISP or by other sources. 

Prior to accepting registration and 

listing information from this online 

system, we would authenticate the 

source (that is, the manufacturer, 

repacker, relabeler, or drug product 

salvager) providing the data. 

• We could, for example, authenticate 

entry into the electronic drug 

registration and listing system by 

establishing user accounts based on 

current registration information. 

• We anticipate that we may contact 

manufacturers, repackers, relabelers, 

and drug product salvagers to obtain 

contact information to establish an 

administration account. 

To register and list electronically, to 

provide updated registration and listing 

information, and to provide information 

to obtain an NDC number, you would go 

to our Web site and follow the prompts. 

• You could sign onto the system by 

entering the account number, user 

name, and password obtained by 

following the procedures in the 

guidance we intend to issue on our 

electronic drug registration and listing 

system, as discussed in section IV.E.6 of 

this document. 

• You would then be prompted to 

provide general information about your 

company and then specific information 

about each establishment and drug as 

required in proposed part 207. 

• When all of the required 

information is provided, your official 

contact would receive confirmation 

electronically that the information has 

been received by us. 

• If you provide information to obtain 

an NDC number, the number could be 

issued electronically. 

4. What Are the Proposed Requirements 

for the Submission of Content of 

Labeling in Electronic Format? 

Under proposed § 207.61(a)(2), the 

content of labeling would be provided 

to us in an electronic format. The 

electronic submission of the content of 

labeling would permit us to 

electronically review, compare, and 

extract data from the labeling. 

The content of labeling would be 

submitted in electronic format for the 

following drugs: 

• Human prescription drugs; 

• Human OTC drugs, including those 

that the manufacturer regards as subject 

to section 505 of the act or section 351 

of the Public Health Service Act as well 

as those regarded as not subject to 

sections 505 or 351; and 

• Animal drugs, including those that 

the manufacturer regards as subject to 

section 512 of the act as well as those 

regarded as not subject to section 512. 

The ‘‘content of labeling’’ is defined 

in proposed § 207.1 (and discussed in 

section IV.A.5 of this document) to 

mean: 

• For human prescription drugs that 

the manufacturer regards as subject to 

section 505 of the act or section 351 of 

the Public Health Service Act: The 

content of the prescription drug labeling 

(as specified in §§ 201.56, 201.57, and 

201.80 of this chapter), including all 

text, tables, and figures. 

• For human prescription drugs that 

the manufacturer regards as not subject 

to section 505 of the act or section 351 

of the Public Health Service Act: The 

labeling equivalent to the content of the 

prescription drug labeling (as specified 

in §§ 201.56, 201.57, and 201.80 of this 

chapter), including all text, tables, and 

figures. 

• For human OTC drugs: The content 

of the drug facts labeling required by 

§ 201.66 of this chapter, including all 

text, tables, and figures. 


jlentini on PROD1PC65 with PROPOSAL2
51316 Federal Register / Vol. 71, No. 167 / Tuesday, August 29, 2006 / Proposed Rules 

11This docket may be accessed on the Internet at 

http://www.fda.gov/ohrms/dockets. 

• For animal drugs (including, but 

not limited to, drugs that the 

manufacturer regards as subject to 

section 512 of the act): The content of 

the labeling that accompanies the drug 

that is necessary to enable the safe and 

proper administration of the drug (e.g., 

the labeling specified in §§ 201.1 and 

201.5 of this chapter), including all text, 

tables, and figures. 

The proposed requirement to provide 

the content of labeling electronically is 

consistent with (among other things) 

that part of the listing requirement in 

section 510(j)(1) of the act which states 

that ‘‘Such list shall be prepared in such 

form and manner as the Secretary may 

prescribe.’’ The proposed requirement 

to submit the content of labeling for 

human prescription drugs, human OTC 

drugs, and animal drugs is consistent 

with the statutory requirements of 

section 510(j)(1)(A), (j)(1)(B)(i), and 

(j)(1)(B)(ii) of the act. Section 

510(j)(1)(A) of the act requires, among 

other things, the submission of a copy 

of all labeling for drugs subject to 

sections 505 or 512 of the act. Section 

510(j)(1)(B)(i) requires, among other 

things, the submission of a copy of all 

labeling for prescription drugs not 

subject to section 505 or 512 of the act. 

Section 510(j)(1)(B)(ii) requires, among 

other things, the submission of the label, 

package insert, and representative 

sampling of any other labeling for OTC 

drugs not subject to section 505 or 512 

of the act. 

We are proposing that manufacturers 

provide the NDC number electronically 

with the content of labeling during 

listing so that we can more easily link 

the content of labeling to the listed drug 

and, thus, expedite the listing process. 

The NDC number may accompany the 

content of labeling by being referenced, 

for example, in the transmittal message 

to us that contains the content of 

labeling. The NDC number does not 

need to be on the content of labeling. 

As discussed in greater detail in 

section IV.D.4 of this document, we are 

proposing that you need not submit the 

content of labeling for human 

prescription or OTC drugs approved 

under section 505 of the act or section 

351 of the PHS Act if you provide the 

application number when listing the 

drug or requesting an NDC number for 

the drug. Incorporating the content of 

labeling by reference to the application 

number would eliminate unnecessary 

duplication of effort and cost to 

industry. 

The submission of the content of 

labeling in an electronic format would 

assist us in several ways: 

• The use of computer technology to 

identify changes in different versions of 

the labeling would greatly enhance our 

accuracy and efficiency in updating our 

listing database. 

• Our ability to protect the public 

health would be enhanced because 

electronic review and comparison of 

labeling files would provide a higher 

degree of certainty that all portions of 

the labeling are consistent and up to 

date. 

• Our ability to protect the public 

health would be enhanced because we 

could provide and make easily 

accessible up-to-date product labeling 

through the DailyMed initiative, as 

described in section IV.C.2 of this 

document. 

• Our ability to protect the public 

health would be enhanced by 

supporting the implementation of the 

electronic prescribing provisions of the 

Medicare Modernization Act. The 

product labeling information we would 

make available through DailyMed 

would be associated with the unique 

NDC number for each drug, supporting 

electronic prescribing. 

• In the future, the electronic 

submission of the content of labeling 

would enable us to receive much of the 

drug listing information through the 

labeling, thus improving efficiency in 

the drug registration and listing system. 

Industry would be able to satisfy many 

drug listing requirements through the 

submission of the content of labeling. 

The proposed requirement to provide 

the content of labeling would not 

significantly burden industry because 

labeling is maintained in electronic 

format by most manufacturers. In 

addition, our proposal seeks to limit 

industry costs by avoiding unnecessary 

duplication of effort—for example, as 

mentioned previously, if the content of 

labeling has already been submitted in 

an approved application, supplement, 

or annual report, the manufacturer 

would only have to reference the 

application number to comply with this 

listing requirement. In addition, only 

the manufacturer would be required to 

submit the content of labeling. 

We would require, under proposed 

207.61(a)(4), that the information in 

electronic format be submitted in a form 

we can process, review, and archive. We 

are prepared at this time to receive the 

content of labeling as a portable 

document format (PDF) file that is 

searchable. Using commercially 

available software, an electronic source 

document created by any number of 

programs (for example, word processors 

and desktop publishing programs) can 

be converted to a PDF file, preserving 

the fonts, formatting, and graphics of the 

source document, regardless of the 

application and platform used to create 

it. The PDF file can be copied onto a 

disk or CD–ROM and shared with other 

users who can use PDF reading software 

to view, navigate through, and print the 

document, as well as view, search, and 

print the file, and copy text, tables, and 

figures from the file. 

However, to be responsive to 

technological advances, we may 

recommend in the future that new file 

formats such as extensible markup 

language and software applications be 

used to submit labeling electronically. 

The language in proposed § 207.61(a)(4), 

that electronic format submissions must 

be in a form that we can process, 

review, and archive, will provide us 

with the flexibility to recommend file 

formats or software other than PDF, if 

appropriate, such as SPL (described 

earlier in sections III.B and IV.C.2 of this 

document). We will provide advance 

notice, in accordance with FDA’s good 

guidance practice regulations under 

§ 10.115 (21 CFR 10.115), so that 

affected parties will have adequate time 

to convert to any new format or 

software. In addition, we expect that 

such format or software will be widely 

available before we switch to a new 

technology. Changes in format and/or 

software will be identified in public 

docket number 92S–0251.11 During any 

such transition, we will accept 

submissions using either file format or 

software. 

5. Would the Proposal Require 

Electronic Submission of 

Advertisements and Other Labeling? 

Under proposed § 207.61(a)(3), 

advertisements and labeling, other than 

the content of labeling, required under 

proposed §§ 207.49(g) and (h) and 

207.53(d) and (e) would be provided to 

us in paper or electronic format. 

Information on how and where to send 

labeling and advertisements that are not 

provided electronically will be 

described in the guidance document we 

intend to develop, as discussed in 

section IV.E.6 of this document. 

Although we are proposing to require 

that only registration and listing 

information, information submitted to 

receive an NDC number, and the content 

of labeling need be submitted in 

electronic format, we expect to identify 

in public docket number 92S–0251 

copies and samples of labeling and 

advertisements as types of documents 

we accept in electronic format. Under 

the proposal, you would have the option 

of submitting advertisements and 

labeling either electronically or in 

paper. 


jlentini on PROD1PC65 with PROPOSAL2
Federal Register / Vol. 71, No. 167 / Tuesday, August 29, 2006 / Proposed Rules 51317 

The proposed requirement to submit 

advertisements is consistent with 

section 510(j)(1)(B)(i) of the act, which 

requires, among other things, the 

submission of a representative sampling 

of advertisements and, upon request, a 

copy of all advertisements for 

prescription drugs not subject to section 

505 of the act. The proposed 

requirement to submit labeling is, as 

explained previously, consistent with 

the statutory requirements of section 

510(j)(1)(A), (j)(1)(B)(i), and (j)(1)(B)(ii) 

of the act. 

6. What Guidance Documents Do We 

Intend To Issue on Providing 

Registration and Listing Information 

Electronically? 

We plan to publish draft guidance and 

technical specifications on the 

electronic submission of registration 

and listing information through our 

electronic drug registration and listing 

system (the draft guidance). The draft 

guidance and technical specifications 

will explain the electronic process for 

providing registration and listing 

information and for providing the 

information that would be required to 

obtain an NDC number, including stepby-step instructions on entering 

information required under proposed 

part 207. We are also planning to issue 

guidance on providing registration and 

listing information in electronic format 

(concerning the method of transmission, 

media, file formats, and preparation and 

organization of files), and this guidance 

will be updated regularly to reflect the 

evolving nature of the technology. 

In addition to the draft guidance and 

the guidance on providing registration 

and listing information in electronic 

format under development, we have 

issued other guidances that explain the 

process for submitting information to us 

in electronic format. These guidance 

documents are available at FDA’s Web 

site http://www.fda.gov/cder/guidance/ 

index.htm under the heading 

‘‘Electronic Submissions.’’

7. How Would Part 11 Apply to the 

Electronic Submission of Registration 

and Listing Information? 

Under proposed § 207.61(a)(1), the 

submission of registration and listing 

information (except for the content of 

labeling and advertisements and 

labeling) and the information required 

to receive an NDC number would be 

made in accordance with part 11, except 

for the requirements under § 11.10(b), 

(c), and (e) and the corresponding 

requirements under § 11.30. Under 

proposed § 207.61(a)(2) and (a)(3), the 

submission of the content of labeling, 

and advertisements and other labeling 

in electronic format, would be made in 

accordance with part 11, except for the 

requirements under § 11.10(a), (c) 

through (h), and (k), and the 

corresponding requirements under 

§ 11.30. In the Federal Register of 

March 20, 1997 (62 FR 13430), we 

published regulations on electronic 

records and electronic signatures (part 

11). Part 11 regulations, among other 

things, set forth the criteria under which 

records submitted to us may be 

submitted in electronic format in lieu of 

paper records. Section 11.2(b) states 

that, for records submitted to us, 

persons may use electronic records in 

lieu of paper records, in whole or part, 

provided the requirements of part 11 are 

met and the documents or parts of 

documents to be submitted have been 

identified by us in public docket 

number 92S–0251 as being the type of 

submission we are prepared to accept in 

electronic format. 

Part 11 permits the widest possible 

use of electronic technology, compatible 

with our responsibility to promote and 

protect the public health (62 FR 13430). 

Part 11 helps to ensure the authenticity, 

integrity, and, when appropriate, the 

confidentiality of electronic records. 

Part 11 also helps to safeguard against 

the possible repudiation of those 

records. The controls in subpart B of 

part 11 are intended to further this 

purpose. 

We recently announced in the Federal 

Register our current thinking on part 11. 

In the Federal Register of September 5, 

2003 (68 FR 52779), we announced the 

availability of a guidance for industry 

entitled ‘‘Part 11, Electronic Records; 

Electronic Signatures—Scope and 

Application’’ (the part 11 guidance). 

The part 11 guidance explains our 

current thinking regarding the 

requirements and application of part 11 

and states that we intend to exercise 

enforcement discretion in the manner 

specified in the guidance with respect to 

the validation (§ 11.10 (a)), audit trail 

(§§ 11.10(e) and (k)(2)), record retention 

(§ 11.10(c)), and copies of records 

(§ 11.10(b)) requirements of part 11, and 

any corresponding requirements in 

§ 11.30. In addition, we announced that 

we intend to exercise enforcement 

discretion and do not intend to take (or 

recommend) action to enforce any part 

11 requirements with regard to systems 

that were operational before August 20, 

1997, the effective date of part 11 

(commonly known as legacy systems) 

under the circumstances described in 

section III.C.3 of the part 11 guidance. 

Although we explain the relationship 

between the part 11 guidance and this 

proposal, as discussed below, you 

should refer to the guidance we intend 

to issue on electronic registration and 

listing for information on complying 

with part 11 when providing 

registration and listing information 

electronically. The part 11 requirements 

from which we propose exemptions in 

this proposal differ from the part 11 

requirements for which we intend to 

exercise enforcement discretion, as 

described in the part 11 guidance. They 

differ because the proposed exemptions 

in this rule are specific to the electronic 

submission of registration and listing 

information, including information that 

must be submitted to receive an NDC 

number and the content of labeling, for 

drugs that would be covered under 

proposed part 207, whereas the part 11 

draft guidance applies to the 

maintenance of all electronic records 

and to all electronic submissions subject 

to part 11. 

With respect to the electronic 

submission of registration and listing 

information, including the information 

required to receive an NDC number but 

not including the content of labeling 

and advertisements and other labeling, 

as previously noted, we believe, as 

provided in proposed § 207.61(a)(1), 

that several of the requirements in 

subpart B of part 11 are not necessary 

to further the goals of part 11. Because 

we control the electronic drug 

registration and listing system, certain 

controls for systems would not apply to 

the submission of registration and 

listing information, such as: 

• The ability to generate accurate and 

complete copies of records in both 

human readable and electronic form 

suitable for inspection, review, and 

copying by the agency (§ 11.10(b)); 

• The protection of records to enable 

their accurate and ready retrieval 

throughout the records retention period 

(§ 11.10(c)); 

• The use of secure, computergenerated, time-stamped audit trails to 

independently record the date and time 

of operator entries and actions that 

create, modify, or delete electronic 

records (§ 11.10(e)); and 

• The corresponding controls of 

§ 11.30. 

You would be exempt from these 

subpart B controls because our 

registration and listing database is 

designed to ensure the authenticity, 

integrity, and confidentiality of this 

information in several ways. For 

example, we would control the 

database, and you would only be able to 

enter and/or revise information in your 

own account. In addition, the database 

would contain records of registration 

and listing information, and we could 

generate accurate and complete copies 

of records. 


jlentini on PROD1PC65 with PROPOSAL2
51318 Federal Register / Vol. 71, No. 167 / Tuesday, August 29, 2006 / Proposed Rules 

With respect to the electronic 

submission of the content of labeling 

and advertisements and other labeling, 

as previously noted, we believe, as 

provided in proposed § 207.61(a)(2) and 

(a)(3), that several of the requirements in 

subpart B of part 11 are not necessary 

to further the goals of part 11. For the 

reasons described below, certain 

controls for systems would not apply to 

the submission of the content of labeling 

and advertisements and other labeling, 

such as: 

• The validation of systems to ensure 

accuracy, reliability, consistent 

intended performance, and the ability to 

discern invalid or altered records 

(§ 11.10(a)); 

• The protection of records to enable 

their accurate and ready retrieval 

throughout the records retention period 

(§ 11.10(c)); 

• Limiting system access to 

authorized individuals(§ 11.10(d)); 

• The use of secure, computergenerated, time-stamped audit trails to 

independently record the date and time 

of operator entries and actions that 

create, modify, or delete electronic 

records (§ 11.10(e)); 

• The use of operational system 

checks to enforce permitted sequencing 

of steps and events, as appropriate 

(§ 11.10(f)); 

• The use of authority checks to 

ensure that only authorized individuals 

can use the system, electronically sign 

a record, access the operation or 

computer system input or output 

device, alter a record, or perform the 

operation at hand (§ 11.10(g)); 

• The use of device checks to 

determine, as appropriate, the validity 

of the source of data input or 

operational instruction (§ 11.10(h)); 

• The use of appropriate controls over 

certain systems documentation 

(§ 11.10(k));and 

• The corresponding controls of 

§ 11.30. 

We are proposing to exempt the 

submission of electronic content of 

labeling from certain part 11 

requirements because we believe these 

part 11 requirements are not critical to 

ensure the quality of the content of 

labeling that would be submitted under 

this proposed rule and we do not think 

it is necessary for industry to expend 

resources on controls that are not 

necessary to further the goals of part 11. 

For example, validation for the system 

used to generate the labeling record is 

not necessary because the 

manufacturer’s verification that the 

information in the labeling record is 

accurate serves the same objective. Our 

review of the content of labeling is 

based on the version of the labeling 

record submitted to us. Earlier versions 

of the record, as well as changes made 

to the earlier versions, are not relevant 

to our analysis. In addition, our 

registration and listing database is 

designed to ensure the authenticity, 

integrity, and confidentiality of this 

information. As mentioned, we would 

control the database, you would only be 

able to enter and/or revise information 

in your own account, and the database 

would contain records of the 

information from which we could 

generate accurate and complete copies. 

Thus, controls related to the creation, 

modification, and maintenance of the 

content of labeling are not needed. 

For the content of labeling and 

advertisements and other labeling, we 

recognize that there are some 

differences with respect to the 

exemptions from part 11 requirements 

provided in this proposal (that is, 

§ 11.10(a), (c) through (h), and (k), and 

the corresponding requirements of 

§ 11.30), and the part 11 requirements 

set forth in the part 11 guidance for 

which we intend to exercise 

enforcement discretion (that is, 

§ 11.10(a) through (c), (e), and (k)(2), 

and any other corresponding 

requirements in § 11.30)). Although the 

proposal does not provide an exemption 

from § 11.10(b) for the content of 

labeling and advertisements and other 

labeling, the part 11 guidance 

announces that we intend to exercise 

enforcement discretion with respect to 

that section in the manner described in 

the guidance. 

If this proposed rule is finalized, we 

intend to identify in docket number 

92S–0251 the registration and listing 

information and the content of labeling 

specified previously as the types of 

records that we are prepared to accept 

in electronic format. 

8. What Language Would Be Used to 

Provide Registration and Listing 

Information? 

Under proposed § 207.61(b), we 

would require that all registration and 

listing information be submitted in the 

English language. We are also proposing 

that labeling be submitted in the English 

language except, as provided under 

current 21 CFR 201.15(c), when drugs 

are distributed solely in the 

Commonwealth of Puerto Rico or in a 

Territory where the predominant 

language is one other than English. In 

those instances, the predominant 

language may be substituted for English. 

We are proposing § 207.61(b) because 

providing information in languages 

other than English would lead to 

problems using the registration and 

listing computerized database and 

problems with our review of registration 

and listing information and the content 

of labeling. Foreign establishments are 

currently required to submit all 

registration and listing information in 

the English language under current 

§ 207.40(b). Because all domestic 

manufacturers, repackers, relabelers, 

and drug product salvagers currently 

submit this information in English, and 

because foreign establishments are 

already subject to this requirement, we 

do not believe the proposed requirement 

would increase the burden on industry. 

9. Could the Electronic Format 

Requirements Be Waived? 

Under proposed § 207.65, 

manufacturers, repackers, relabelers, 

and drug product salvagers may request 

a waiver from the proposed requirement 

in § 207.61(a) that information be 

provided to us in electronic format. This 

proposed waiver provision is consistent 

with the Medical Device User Fee and 

Modernization Act of 2002 (Public Law 

107–250) which amended section 510 of 

the act to add section 510(p) to 

explicitly give the Secretary discretion 

to require the electronic submission of 

registration information upon a finding 

that electronic receipt of such 

registration information is feasible, 

unless the Secretary grants a request for 

a waiver because the use of electronic 

means is not reasonable for the person 

requesting the waiver. Under proposed 

§ 207.65, we may grant a waiver request 

if the manufacturer, repacker, relabeler, 

or drug product salvager does not have 

an e-mail address and access to a 

computer and an ISP that can access our 

Web-based registration and listing 

database and communicate with us. The 

request must include a telephone 

number and/or mailing address where 

we can contact the person making the 

request. We intend to provide the 

mailing address for submitting a waiver 

request in the draft guidance and 

technical specifications on the 

electronic submission of registration 

and listing information. 

We do not anticipate many waiver 

requests because the expenses 

associated with owning a personal 

computer, obtaining an e-mail address, 

and subscribing to Internet access are 

low. If owning a computer is not 

possible, however, only access to a 

computer and an ISP as well as having 

an e-mail address would be needed to 

input information electronically in 

accordance with the registration and 

listing requirements under this part, 

including the requirements for obtaining 

an NDC number. There would be no 

need for you to maintain data files on 

disks or other formats; all data would be 


jlentini on PROD1PC65 with PROPOSAL2
Federal Register / Vol. 71, No. 167 / Tuesday, August 29, 2006 / Proposed Rules 51319 

maintained in our database and 

accessed electronically via the Internet. 

We would control the database and the 

information contained in it, and you 

would only enter new information and/ 

or revise your own previously submitted 

information. 

In those instances when we grant a 

request for a waiver, we would provide 

information on how to submit 

registration and/or listing information. 

One option may be to make available a 

paper form for submitting the required 

registration and listing information 

(including the information required to 

obtain an NDC number). 

F. Miscellaneous 

1. What Are the Proposed Requirements 

for an Official Contact and a United 

States agent? 

Under proposed § 207.69(a), 

manufacturers, repackers, relabelers, 

and drug product salvagers that are 

subject to the registration requirements 

in proposed part 207 would designate 

an official contact for each 

establishment. The official contact 

would be responsible for: 

• Ensuring the accuracy of 

registration and listing information; and 

• Reviewing, disseminating, routing, 

and responding to communications 

from us. 

We are proposing to require an official 

contact to facilitate communications 

between you and us and to help ensure 

compliance with the registration and 

listing requirements. On numerous 

occasions, we have found it difficult to 

contact certain manufacturers, 

repackers, relabelers, and drug product 

salvagers to discuss registration and 

listing issues. 

In addition to the proposed 

requirement to designate an official 

contact, each foreign manufacturer, 

foreign repacker, foreign relabeler, and 

foreign drug product salvager would be 

required, under proposed § 207.69(b), to 

designate a single United States agent. 

The United States agent would be 

responsible for: 

• Helping us communicate with the 

foreign manufacturer, foreign repacker, 

foreign relabeler, and foreign drug 

product salvager; 

• Responding to questions concerning 

those drugs that are imported or offered 

for import to the United States; and 

• Helping us schedule inspections. 

We would not object if the same 

individual serves as both the United 

States agent and the official contact for 

a foreign manufacturer, foreign 

repacker, foreign relabeler, or foreign 

drug product salvager, or if the same 

individual serves as the United States 

agent for more than one foreign 

manufacturer, foreign repacker, foreign 

relabeler, or foreign drug product 

salvager. 

We are proposing that each foreign 

manufacturer, foreign repacker, foreign 

relabeler, and foreign drug product 

salvager designate a single United States 

agent. (We note, however, the United 

States agent may be a company 

comprised of more than one person). As 

we explained in the final rule entitled 

‘‘Foreign Establishment Registration and 

Listing’’ (66 FR 59138 at 59140), we 

interpret section 510(i) of the act as 

allowing only one United States agent 

for each foreign establishment because 

section 510(i) of the act refers to the 

United States agent in singular, rather 

than plural, terms. We also explained in 

that final rule (66 FR 59138 at 59141) 

that we interpret section 510(i) of the act 

as requiring that the United States agent 

must be in the United States. These 

proposed provisions are also consistent 

with the use of ‘‘U.S. agent’’ in the 

interim final rule entitled ‘‘Registration 

of Food Facilities Under the Public 

Health Security and Bioterrorism 

Preparedness Act of 2002’’ (68 FR 58894 

at 58915, October 10, 2003). 

Currently, the provisions concerning a 

United States agent, as well as other 

requirements for foreign manufacturers, 

foreign repackers, foreign relabelers, or 

foreign drug product salvagers, are set 

forth under § 207.40. In addition, 

current § 207.3(a)(11) defines United 

States agent as a person residing or 

maintaining a place of business in the 

United States whom a foreign 

establishment designates as its agent. 

The definition states that ‘‘United States 

agent’’ excludes mailboxes, answering 

machines or services, or other places 

where an individual acting as the 

foreign establishment’s agent is not 

physically present. We are proposing to 

revoke current §§ 207.3(a)(11) and 

207.40 and include these requirements 

(as revised), for example, under 

proposed §§ 207.1, 207.9, 207.13, 

207.17, 207.33, 207.41, 207.61, and 

207.69. 

Under proposed § 207.69(b)(2) 

through (b)(4), the United States agent 

would be required to reside or maintain 

a place of business in the United States. 

A United States agent may not be a 

mailbox, answering machine or service, 

or other place where a person acting as 

the United States agent is not physically 

present. If we are unable to contact the 

foreign manufacturer, foreign repacker, 

foreign relabeler, or foreign drug 

product salvager directly or 

expeditiously, we may provide 

information or documents to the United 

States agent, which we would consider 

equivalent to providing the same 

information or documents to the foreign 

manufacturer, foreign repacker, foreign 

relabeler, or foreign drug product 

salvager. 

We are proposing the requirements for 

a United States agent to facilitate 

communications between you and us 

and to help ensure compliance with the 

registration and listing requirements. On 

numerous occasions, we have found it 

difficult to contact certain foreign 

manufacturers, foreign repackers, 

foreign relabelers, and foreign drug 

product salvagers, resulting in their 

drugs being detained because certain 

registration and/or listing issues have 

not been resolved. 

2. What Legal Status Is Conferred by 

Registration and Listing? 

Under proposed § 207.77(a), 

registration of an establishment or 

listing of a drug does not denote 

approval of the establishment, the drug, 

or other drugs of the establishment, nor 

does it mean that a product may be 

legally marketed. Any representation 

that creates an impression of official 

approval or that a drug is approved or 

is legally marketable because of 

registration or listing would be 

misleading and would constitute 

misbranding under section 502 of the 

act. To clarify and consolidate current 

regulations, we are proposing to revise 

and move a similar provision in current 

§ 207.39 to proposed §§ 207.77(a) and 

207.37. Current § 207.39 states that 

registration of a drug establishment or 

drug wholesaler, assignment of a 

registration number, or assignment of an 

NDC number does not in any way 

denote approval of the firm or its 

products. Any representation that 

creates an impression of official 

approval because of registration or 

possession of a registration number or 

NDC number is misleading and 

constitutes misbranding. The 

registration provisions in current 

§ 207.39 would be included in proposed 

§ 207.77(a), and the NDC number 

provisions in current § 207.39 would be 

included in proposed § 207.37. 

Proposed § 207.37(c) states that the NDC 

number must not be used to denote FDA 

approval of that drug. We are proposing 

to include in proposed § 207.77(a) that 

listing a drug would not denote 

approval of the drug and that any such 

representation would be misleading and 

constitute misbranding. 

Under proposed § 207.77(b), 

assignment of an establishment 

registration number, inclusion of a drug 

in our database of drugs, or assignment 

of an NDC number does not denote 

approval of the establishment or the 


jlentini on PROD1PC65 with PROPOSAL2
51320 Federal Register / Vol. 71, No. 167 / Tuesday, August 29, 2006 / Proposed Rules 

drug or any other drugs of the 

establishment, nor does it mean that the 

drug may be legally marketed. Any 

representation that creates an 

impression that a drug is approved or is 

legally marketable because it appears in 

our database of drugs, has been assigned 

a NDC number, or the establishment has 

been assigned an establishment 

registration number, is misleading and 

constitutes misbranding. Failure to 

comply with proposed § 207.37 also 

constitutes misbranding. We are 

proposing to add this provision to 

clarify that a drug’s marketing approval 

status is determined, for example, under 

section 505 or 512 of the act, section 351 

of the PHS Act, and parts 314, 514 (21 

CFR part 514), and 601 of the 

regulations, and not under section 510 

of the act or part 207 of the regulations. 

Under proposed § 207.77(c), neither 

registration nor listing constitutes a 

determination by FDA that a product is 

a drug as defined by section 201(g)(1) of 

the act. This provision reflects a 

revision and relocation of current 

§ 207.20(e) to proposed § 207.77(c). 

Current § 207.20(e) states that 

registration and listing do not constitute 

an admission, agreement, or 

determination that a product is a drug 

as defined under section 201(g) of the 

act. Proposed § 207.77(c) also states that 

registration and listing may be evidence 

that a facility is manufacturing, 

repacking, relabeling, or salvaging drugs 

or that a product is a drug. Thus, the 

proposed rule revises current § 207.20(e) 

such that, while neither registration nor 

listing constitutes a determination by 

FDA that a product is a drug as defined 

by the act, registration and listing may 

be evidence that a facility is 

manufacturing, repacking, relabeling, or 

salvaging drugs or that a product is a 

drug. 

FDA is proposing to delete the 

statement in current § 207.35(c) that 

validation of registration and the 

assignment of a drug listing number do 

not, in themselves, establish that the 

holder of the registration is legally 

qualified to deal in such drugs. As 

explained in sections IV.B and IV.C of 

this document, FDA is proposing to 

discontinue the validation of 

registration. As explained previously in 

this document, the provision on the 

legal status of registration and listing is 

included in proposed § 207.77, and 

proposed § 207.37(c) sets forth 

restrictions pertaining to the use of the 

NDC number (e.g., the NDC number 

must not be used to denote FDA 

approval of the drug). 

3. What Registration and Listing 

Information Would Be Made Available 

for Public Disclosure? 

Current § 207.37 pertains to the public 

availability of registration and listing 

information. Proposed § 207.81 would 

revoke, in part, and revise current 

§ 207.37. The heading ‘‘Inspection of 

registrations and drug listings’’ in 

current § 207.37 would be changed to 

‘‘What registration and listing 

information will we make available for 

public disclosure?’’ This heading would 

more accurately describe the scope of 

the provision in that the provision 

relates to the type of registration and 

listing information that we intend to 

make available for public disclosure. 

The proposal would revoke the 

introductory text of current § 207.37(a), 

which includes a description of the 

types of forms available for inspection, 

the addresses at which such forms can 

be inspected, and the addresses that 

requests for verification of registration 

numbers and requests for locations of 

registered establishments can be 

directed. We are proposing to revoke 

this introductory text because these 

forms would no longer be used under 

the proposed scheme. Instead, we 

intend to make most information that is 

available for public disclosure 

accessible via the Internet. This 

initiative would be consistent with the 

GPEA and would also help to reduce the 

number of Freedom of Information Act 

(5 U.S.C. 552) requests we receive for 

registration and listing information. 

Accordingly, we are also proposing to 

revoke current § 207.37(b), which sets 

forth the address to which requests for 

information about drug registration and 

listing can be directed. We note that 

persons may still submit Freedom of 

Information Act requests to the agency 

for drug registration and listing 

information that is not available on the 

Internet. 

Current § 207.37(a)(1) sets forth 11 

categories of information that, when 

compiled, will be available for public 

disclosure. Proposed § 207.81(a) would 

simplify this section to reference the 

following information as generally 

available for public disclosure: All 

registration information and, after a 

drug is listed, all information obtained 

for that drug under proposed §§ 207.33, 

207.49, 207.53, and 207.54, except for 

that information obtained under 

proposed §§ 207.33(d)(1)(ii) and 

207.54(b)(1) or the information that 

would otherwise be exempt from 

disclosure under proposed § 207.81(b) 

or (c). 

Proposed § 207.81(a) would add 

registration information to the list of the 

types of information that would 

generally be considered to be publicly 

available. Registration information is 

currently available for public inspection 

as referenced in § 207.37(a). 

For various reasons, proposed 

§ 207.81(a) would not include certain 

specific categories of information that 

are listed in current § 207.37. The 

provision relating to a list of all drug 

products arranged by labeled 

indications or pharmacological category 

would not be included in the proposal 

because we currently do not compile or 

index drug registration and listing 

information by labeled indication. The 

provisions related to a list of drug 

products newly marketed or for which 

marketing is resumed, a list of drug 

products discontinued, and information 

that has become a matter of public 

knowledge would be deleted because 

these categories of information would 

also be disclosable under the general 

provision of proposed § 207.81(a). 

We are proposing to exempt proposed 

§§ 207.33(d)(1)(ii) and 207.54(b)(1) from 

proposed § 207.81(a) because this 

information may disclose a business 

relationship between the manufacturer, 

repacker, relabeler, or drug product 

salvager and the business from which 

they obtained the drug, and may 

constitute commercial or financial 

information that is exempt from public 

disclosure under § 20.61(c). We are 

proposing to exempt from public 

disclosure the information collected 

under proposed § 207.33(d)(1)(ii), which 

would require that repackers or 

relabelers, to obtain an NDC number, 

must provide, among other things, the 

NDC number assigned to the drug 

immediately before the drug is received 

by the repacker or relabeler. We also are 

proposing to exempt from public 

disclosure the information collected 

under proposed § 207.54(b)(1), which 

would require that drug product 

salvagers, to list a drug, must provide, 

among other things, the NDC number 

assigned to the drug immediately before 

the drug is received by the drug product 

salvager. 

In addition to these changes, the 

proposal would make some 

fundamental changes to the disclosure 

provision in current § 207.37. We are 

proposing to add one category of listing 

information to the list of information 

that would generally be regarded as 

publicly available information. 

Specifically, proposed § 207.81 

generally would make available for 

public disclosure a drug product’s 

inactive ingredients when provided 

under § 207.33(c)(2)(ii) and (c)(3). When 

the firm provides the approved 

application number, we can link to the 


jlentini on PROD1PC65 with PROPOSAL2
Federal Register / Vol. 71, No. 167 / Tuesday, August 29, 2006 / Proposed Rules 51321 

application and retrieve the names of 

the inactive ingredients included in the 

approved application. We will then 

make the names of the inactive 

ingredients available to consumers 

unless they are subject to trade secret 

protection, as discussed below. 

Proposed § 207.81 would change the 

current provision in § 207.37(a)(2). 

Current § 207.37(a)(2)(ii) and (a)(2)(iii) 

provide that information on inactive 

ingredients will not be available for 

public disclosure (except that any of the 

information will be available for public 

disclosure if it has become a matter of 

public knowledge or if we find that it 

would be inconsistent with the 

protection of the public health). 

We are proposing, under 

§ 207.33(c)(2)(ii), to give manufacturers 

the opportunity at the time of listing to 

identify inactive ingredients that they 

consider trade secret. Information 

identified by the applicant as trade 

secret would not be routinely posted on 

the Internet. Public disclosure of 

inactive ingredients not designated as 

trade secret at the time of listing would 

be authorized by the proposed 

regulations. We would evaluate claims 

of trade secret protection based on the 

definition of a trade secret in § 20.61(a) 

when making disclosure decisions in 

response to requests made under the 

Freedom of Information Act for this 

information and would withhold the 

information from public disclosure, 

when appropriate, under § 207.81(c). 

This evaluation is consistent with how 

FDA evaluates requests asking for 

inactive ingredient information that is 

included in approved U.S. applications. 

When manufacturers submit the 

approved application number instead of 

listing inactive ingredients under 

proposed § 207.33(c)(2)(ii), they 

similarly would need to identify any 

inactive ingredients they considered to 

be trade secret. Proposed 

§§ 207.33(c)(2)(ii), 207.81(a), and 

207.81(c) would strike a balance 

between manufacturers’ commercial 

interests and the fact that it would 

generally be inconsistent with 

protection of the public health to 

withhold inactive ingredient 

information. We expect that 

manufacturers would only avail 

themselves of the opportunity to claim 

trade secret protection in extremely 

limited circumstances. We note that 

information in a drug’s labeling, 

including the names of inactive 

ingredients, is not trade secret 

information. 

The proposal to add information 

about inactive ingredients to the list of 

categories considered to be public 

information is also consistent with 

section 510(f) of the act. Section 510(f) 

of the act generally provides that listing 

information shall be exempt from 

inspection unless the Secretary finds 

that such an exemption would be 

inconsistent with protection of the 

public health. We find that exempting, 

among other things, a list of inactive 

ingredients from public disclosure 

would be inconsistent with the 

protection of the public health. It is 

important for consumers to know the 

inactive ingredients of the drugs they 

might be taking because such 

information can be important in certain 

situations. For example, some inactive 

ingredients can trigger allergic reactions 

in patients. If a particular inactive 

ingredient appeared to trigger such 

reactions in an individual, and the name 

of the inactive ingredient was available 

to the public, individuals and their 

caregivers would be able to access such 

information to prevent potentially 

serious reactions. Additionally, some 

inactive ingredients may be particularly 

toxic to individuals with certain 

medical conditions and some may 

exacerbate a person’s medical condition. 

If inactive ingredient information is 

available for drugs, individuals and 

their caregivers could get this 

information and avoid adverse 

reactions. We could also use inactive 

ingredients information to help us 

investigate possible drug contamination, 

counterfeiting, or adulteration. For 

example, if a drug appeared to be linked 

to an unexpected number of adverse 

drug events or seemed less effective 

than expected, an analysis of the drug 

showing the presence of unidentified 

(i.e., not previously listed) inactive 

ingredients in that drug could suggest 

that the drug was adulterated or 

counterfeit, or that the unidentified 

inactive ingredient may interfere with 

the drug’s mode of action. Additionally, 

the presence of an unidentified inactive 

ingredient in a drug product may 

suggest contamination or that the drug 

was not manufactured by the legitimate 

manufacturer. Generally, we believe that 

knowing about a drug’s inactive 

ingredients and having such 

information readily available in an 

electronic database is consistent with 

protection of the public health. 

We recognize that because we may 

make a large amount of registration and 

listing information publicly available 

under proposed § 207.81, there may be 

instances where some of the information 

authorized by this proposed rule for 

public disclosure could identify 

business relationships. We believe that 

many of these business relationships 

could be identified currently, but that 

the electronic registration and listing 

system may make it somewhat easier to 

do so. For example, a contractual 

relationship that might not otherwise be 

publicly disclosed may be revealed 

when a manufacturer of a sole source 

material provides the drug’s established 

name under proposed § 207.33(c)(1)(ii) 

or when a manufacturer provides 

registration numbers of each 

establishment where manufacturing is 

performed under proposed § 207.49(d). 

Also, for example, business 

relationships between private label 

distributors and manufacturers, 

repackers, relabelers may be revealed 

when providing information under 

§ 207.33(c) or (d)(2). However, we 

believe this would be a rare event and 

that exemption of the information 

required by these regulatory provisions 

from public disclosure would be 

inconsistent with protection of the 

public health. For example, we believe 

that we should not exempt from public 

disclosure the names of inactive 

ingredients that would be submitted 

under proposed § 207.33(c)(2)(ii) 

because of the remote possibility that 

the names, along with other information 

that may be disclosed under this 

proposal, could reveal a business 

relationship. We believe that the 

potential public health benefits of 

releasing the names of the inactive 

ingredients justify our decision not to 

exempt them from public disclosure 

because they outweigh the remote 

possibility that a business relationship 

could be revealed. Therefore we have 

concluded that the public interest in 

disclosure of most registration and 

listing information supports the 

proposals in the rulemaking. 

We also note that, for foreign 

manufacturers, foreign repackers, 

foreign relabelers, and foreign drug 

product salvagers, the name of each 

importer and the names of persons who 

import a drug or offer a drug for import 

would be required for registration and 

we are proposing that this information 

would be available for public 

disclosure. Disclosure of this 

information would be consistent with 

section 510(f) of the act, which requires 

that any registration filed be made 

available for inspection. 

We invite comments on which 

specific registration and listing 

information should be available for 

public disclosure. We request that you 

identify the specific registration and 

listing information on which you are 

commenting and explain why you 

believe the information should or 

should not be publicly disclosed. 

Proposed § 207.81(b) would make one 

other conforming change to the current 


jlentini on PROD1PC65 with PROPOSAL2
51322 Federal Register / Vol. 71, No. 167 / Tuesday, August 29, 2006 / Proposed Rules 

disclosure provision. Current 

§ 207.37(a)(2) sets forth three categories 

of information that will not be available 

for public disclosure (except that any of 

the information will be available for 

public disclosure if it has become a 

matter of public knowledge or if we find 

that confidentiality would be 

inconsistent with protection of the 

public health). Proposed § 207.81(b) 

would retain the category treating as 

nondisclosable any information 

submitted as the basis upon which it 

has been determined that a particular 

drug product is not subject to section 

505 or 512 of the act. As explained 

previously in this document, we are 

moving two previously nondisclosable 

categories (now disclosable) regarding 

information on inactive ingredients to 

proposed § 207.81(a) that relate to 

information generally regarded as 

publicly available. Those categories, in 

current § 207.37(a)(2)(ii) and (a)(2)(iii), 

would be disclosable under proposed 

§ 207.81(a). Proposed § 207.81(c) would 

allow FDA to determine, in limited 

circumstances and on a case-by-case 

basis, that it would be consistent with 

protection of the public health and the 

Freedom of Information Act to exempt 

from public disclosure specific 

information in paragraph (a) of this 

section. As explained previously in this 

document, we are proposing, under 

§ 207.33(c)(2)(ii), to give manufacturers 

the opportunity at the time of listing to 

identify inactive ingredients that they 

consider trade secret and therefore, 

prohibited from disclosure under 

§ 20.61. There may be other appropriate 

reasons for exempting certain drug 

listing and registration information from 

public disclosure. For example, FDA 

may decide for security reasons, and 

consistent with the Freedom of 

Information Act, not to publicly disclose 

the manufacturing site location for 

certain drugs. 

G. Conforming Actions 

1. Withdrawal from Sale of Drugs with 

Approved Marketing Applications 

We are proposing to revise our human 

drug regulations on applications for 

approval to market a new drug to make 

them consistent with proposed part 207. 

Under current § 314.81(b)(3)(iii)(a), 

holders of new drug applications must 

report to us the withdrawal from sale of 

a drug product. Under this provision, 

the information must be submitted on 

Form FDA 2657 within 15 working days 

of the drug product’s withdrawal from 

sale. The following information must be 

submitted: The NDC number; the 

identity of the drug by established name 

and by proprietary name; the new drug 

application number or abbreviated 

application number; and the date of 

withdrawal from sale. The reason for 

withdrawal of the drug from sale is 

requested but not required to be 

submitted. Section 314.81(b)(3)(iii)(b) 

provides the address for submitting the 

completed form, and 

§ 314.81(b)(3)(iii)(c) states that reporting 

under § 314.81(b)(3)(iii) constitutes 

compliance with the requirements 

under current § 207.30(a) to report ‘‘at 

the discretion of the registrant when the 

change occurs.’’

We are proposing to revise this 

requirement to be consistent with the 

requirements in proposed §§ 207.57 and 

207.61. Proposed § 314.81(b)(3)(iii)(a) 

would provide that within 30 calendar 

days of the withdrawal of an approved 

drug from sale, applicants who are 

manufacturers, repackers, or relabelers 

subject to proposed part 207 would be 

required to submit certain information 

about the withdrawn drug in electronic 

format, in accordance with the 

applicable requirements described in 

§ 207.61(a). 

Under proposed § 314.81(b)(3)(iii)(b), 

applicants who are not subject to 

proposed part 207 would submit the 

information specified under proposed 

§ 314.81(b)(3)(iii)(a) on the appropriate 

form, which would be submitted to the 

Drug Listing Branch, Food and Drug 

Administration, CDER Central 

Document Room, 5901B Ammendale 

Rd., Beltsville, MD 20705–1266. We are 

proposing to require applicants who are 

subject to proposed part 207 to submit 

the information specified under 

proposed § 314.81(b)(3)(iii)(a) in 

electronic format, in accordance with 

the applicable requirements described 

in proposed § 207.61(a). Consistent with 

the proposed requirements in § 207.61, 

and discussed in section IV.E.3 of this 

document, these applicants would be 

required to obtain an account number, 

user name, and password to sign onto 

the electronic drug registration and 

listing system. We are considering this 

requirement because we believe the 

electronic submission of this 

information would be more efficient for 

applicants than the preparation and 

mailing of paper forms. Electronic 

submission would also make our review 

and processing of this information more 

efficient. We request comments on 

requiring applicants who are not subject 

to proposed part 207 to submit 

electronically the information specified 

in proposed § 314.81(b)(3)(iii)(a). 

Currently, we do not have a provision 

in our regulations for reporting 

withdrawals from sale of biological 

products. We are proposing to revise our 

regulations to include such a provision. 

Under proposed § 601.2(f), holders of 

BLAs must report to us, electronically in 

accordance with part 207, the 

withdrawal from sale of licensed 

biological products. The information 

must be submitted to us within 30 

working days of the biological product’s 

withdrawal from sale. The following 

information would be submitted: The 

holder’s name; product name; BLA 

number; the NDC number, if applicable; 

and the date of withdrawal from sale. 

The reason for the withdrawal of the 

biological product would be requested 

but not required. 

2. Proposed Revisions to Other 

Regulations 

In addition to the revisions of 

regulations discussed previously in this 

document, we are also proposing 

revisions to other FDA regulations as a 

result of this proposed rule. The 

proposed revisions are as follows: 

• Section 20.100(c)(9): The reference 

to § 207.37 would be changed to 

§ 207.81 to correspond to the proposed 

provision on disclosure of registration 

and listing information. 

• Section 20.116: The reference to 

§ 207.37 would be changed to § 207.81 

to correspond to the proposed provision 

on disclosure of registration and listing 

information. 

• Section 201.1(f): The reference to 

§ 207.3(b) would be changed to § 207.1 

to correspond to the proposed 

definitions section. 

• Section 330.1(b): As explained in 

section IV.C.5 of this document, the 

NDC number would be required to 

appear on OTC drug labels. 

• Section 514.111(a)(12): As 

explained in section IV.B.2 of this 

document, we would refuse to approve 

an NADA if the drug is manufactured in 

an establishment that is not registered. 

• Section 515.10(b)(8): The reference 

to ‘‘§§ 207.20 and 207.21’’ would be 

changed to ‘‘part 207’’ as a result of the 

proposed reorganization and revision of 

part 207. 

• Section 607.3(b): Current § 607.3(b) 

defines ‘‘blood and blood product’’ to 

mean a drug which consists of human 

whole blood, plasma, or serum or any 

product derived from human whole 

blood, plasma, or serum, hereinafter 

referred to as ‘‘blood product.’’ The 

current definition also states that ‘‘blood 

and blood product’’ also means those 

products that meet the definition of a 

device under the act and that are 

licensed under section 351 of the PHS 

Act. We are proposing to amend this 

definition to add the phrase ‘‘as well as 

licensed biologic components used in 

the manufacture of a licensed device.’’

This proposed revision is intended to 


jlentini on PROD1PC65 with PROPOSAL2
Federal Register / Vol. 71, No. 167 / Tuesday, August 29, 2006 / Proposed Rules 51323 

clarify that licensed biologic 

components used in the manufacture of 

a licensed device are covered under the 

definition of ‘‘blood and blood product’’

and that manufacturers of licensed 

biologic components used in the 

manufacture of a licensed device are 

required to register and list under part 

607. It is important that manufacturers 

of licensed biologic components used in 

the manufacture of a licensed device 

register and list because licensed 

devices are used to ensure the safety of 

blood and blood products. 

• Section 607.3(k): We are proposing 

to define ‘‘importer’’ as a company or 

individual in the United States that is 

the owner, consignee, or recipient of the 

foreign establishment’s blood product 

that is imported into the United States. 

• Section 607.7: Current § 607.7(a) 

states that all owners or operators of 

establishments that engage in the 

manufacturing of blood and blood 

products are required to register, and 

that registration and listing of blood and 

blood products must comply with part 

607. Current § 607.7(a) also states that 

registration does not permit blood banks 

or similar establishments to ship blood 

products in interstate commerce. 

Current § 607.7(b) and (c) explain how 

the registration form for these 

establishments may be obtained from 

CBER and where the completed form 

should be mailed to. 

We are proposing to delete current 

§ 607.7(b) and (c) and explain where to 

obtain establishment registration forms 

and where to send completed forms in 

proposed § 607.22(b) (discussed below 

in this document). We are deleting these 

provisions from current § 607.7 to 

eliminate redundancy in part 607. We 

are proposing to redesignate paragraph 

(a) in § 607.7 as the introductory 

paragraph. 

• Section 607.22: For clarity, we are 

proposing to revise the title of current 

§ 607.22—‘‘How and where to register 

establishments and list blood 

products’’—to read ‘‘How to register 

blood product establishments and list 

blood products.’’

Current § 607.22(a) requires the first 

registration of an establishment to be on 

Form FDA 2830 (Blood Establishment 

Registration and Product Listing), 

provides the mailing address where the 

Form FDA 2830 may be obtained and 

submitted, states that FDA will furnish 

a Form FDA 2830 before November 15 

of each year to establishments whose 

registration for that year was validated 

under § 607.35, and states that the 

completed form must be mailed to us 

before December 31 of that year. Current 

§ 607.22(b) states that the first and 

subsequent blood product listing 

updates shall be on Form FDA 2830. 

We are proposing to reorganize and 

update current § 607.22 as follows: 

Initial and subsequent registrations and 

product listings by a blood product 

establishment for blood products would 

be on Form FDA 2830 (Blood 

Establishment Registration and Product 

Listing). Manufacturers may obtain, 

complete, and submit the form in the 

following ways: 

• Complete the form online and 

submit electronically at http:// 

www.fda.gov/cber/blood/bldreg.htm; 

this information must be submitted in 

accordance with part 11 of this chapter, 

except for the requirements in 

§ 11.10(b), (c), and (e) and the 

corresponding requirements in § 11.30 

(as discussed in section IV.E.7 of this 

document); or 

• Download the form from the 

Internet at http://www.fda.gov/cber/ 

blood/bldreg.htm, and mail the 

completed form to the address in 

§ 607.22(e); or 

• Request the form by mail using the 

address in § 607.22(e), or by e-mail at 

bloodregis@cber.fda.gov, and mail the 

completed form to the address in 

§ 607.22(e). 

• For subsequent annual registration 

renewals, we will furnish the 

establishment’s most recent Form FDA 

2830 before November 15 of each year. 

The updated Form FDA 2830 would be 

submitted to us before December 31 of 

that year. 

• Forms may be requested from and 

mailed to: Center for Biologics 

Evaluation and Research (HFM–370), 

1401 Rockville Pike, suite 200N, 

Rockville, MD 20852–1448. 

We are proposing these revisions to 

current § 607.22 to make the registration 

and blood product listing process for 

blood product establishments more 

efficient by utilizing the latest 

technology for completing and 

submitting registration and listing 

forms. 

• Section 607.25(b)(1): Current 

§ 607.25(b) lists the information 

required for blood product listing. 

Currently, blood establishments that 

manufacture bulk product substances 

and finished dosage forms must list 

their products under part 607 and also 

under part 207 to receive a NDC 

number. We are proposing to revise 

current § 607.25(b)(1) to delete the 

phrase ‘‘including bulk product 

substances as well as finished dosage 

forms’’ because we are proposing to 

require these manufacturers to list only 

under part 207 to reduce their reporting 

burden. In addition, we are proposing to 

add the phrase ‘‘if any’’ after ‘‘by 

proprietary name’’ because not all of 

these products have a proprietary name. 

We are also proposing to delete the 

reference to Form FDA 2250 (National 

Drug Code Directory Input) because this 

form is no longer being used by CDER 

or CBER. 

• Section 607.35: For clarity, we are 

proposing to revise the title of current 

§ 607.35—‘‘Notification of registrant; 

blood product establishment registration 

number and NDC Labeler Code’’—to 

read ‘‘Blood product establishment 

registration number.’’

Current § 607.35(a) states that FDA 

will send a validated copy of Form FDA 

2830 as evidence of registration to the 

registering establishment, and that FDA 

will assign a permanent registration 

number to each establishment. We are 

proposing to revoke the provision that 

we will send a validated copy of Form 

FDA 2830 to blood establishments. All 

registration information will be 

available to registered blood 

establishments on the Internet; 

therefore, to increase efficiency we will 

discontinue sending the validated copy 

of Form FDA 2830. Proposed § 607.35 

would state only that we will assign a 

permanent registration number to each 

blood product establishment registered 

in accordance with part 607. 

Current § 607.35(b) states that if a 

registered blood product establishment 

has not previously participated in the 

NDC system or in the National Health 

Related Items Code system, the NDC 

numbering system must be used. We are 

proposing to revoke this section because 

blood product manufacturers that obtain 

a NDC number for their products will 

register under proposed part 207 and 

not under part 607. We are also 

proposing to delete reference to the 

National Health Related Items Code 

system because it is a voluntary system 

for medical device manufacturers that is 

managed by CDRH. 

Current § 607.35(c) states that 

although establishment registration and 

blood product listing are required, 

validation of registration and the 

assignment of a NDC Labeler Code do 

not, in themselves, establish that the 

holder of the registration is legally 

qualified to deal in such products. We 

are proposing to incorporate into 

proposed § 607.39 the provision that 

validation of registration does not 

establish that the holder of the 

registration is legally qualified to deal in 

such products. We are proposing to 

revoke the provision concerning the 

assignment of a Labeler Code because 

the NDC number requirements would be 

covered under proposed part 207 and 

not proposed part 607. 


jlentini on PROD1PC65 with PROPOSAL2
51324 Federal Register / Vol. 71, No. 167 / Tuesday, August 29, 2006 / Proposed Rules 

• Section 607.37(a): Current 

§ 607.37(a) states that a copy of Form 

FDA 2830 will be available for 

inspection under section 510(f) of the 

act at FDA headquarters and at each of 

the FDA district offices. In addition, 

current § 607.37(a) states that FDA will 

provide by mail verification of 

registration number and location of a 

registered establishment. Current 

§ 607.37(a) also gives examples of the 

blood product listing information that 

will be available for public disclosure. 

Under proposed § 607.37(a), 

information submitted on Form FDA 

2830 would be available for inspection 

at http://www.fda.gov/cber/blood/ 

bldregdata.htm and at the Department 

of Health and Human Services, Food 

and Drug Administration, Office of 

Communication, Training, and 

Manufacturers Assistance (HFM–40), 

Center for Biologics Evaluation and 

Research, 1401 Rockville Pike, suite 

200N, Rockville, MD 20852–1448. 

• Section 607.39: Current § 607.39 

states that registration of an 

establishment or assignment of a 

registration number or assignment of a 

NDC number does not in any way 

denote approval of the firm or its 

products, and that any representation 

that creates an impression of official 

approval because of registration is 

misleading and constitutes misbranding. 

We are proposing to revise current 

§ 607.39 to delete the reference to the 

NDC number, to incorporate the 

provision from current § 607.35(c) that 

validation of registration does not 

establish that the holder of registration 

is legally qualified to deal in blood 

products, and to revise the title 

accordingly. Manufacturers of blood 

products that obtain a NDC number 

would not register under proposed part 

607; therefore, it is not necessary to 

reference NDC numbers under this part. 

Proposed § 607.39 would state that 

registration of an establishment, 

validating registration, or obtaining a 

registration number does not in any way 

denote approval of the firm or its 

products nor does it establish legal 

authority for the holder of the 

registration number to market such 

products. 

• Section 607.40: As discussed in 

section IV.A.2 of this document, we are 

proposing to revoke current § 207.40, 

establishment registration and drug 

listing requirements for foreign 

establishments, and revise and move the 

requirements elsewhere in proposed 

part 207. Consistent with the revisions 

to proposed part 207, we are proposing 

to revoke certain provisions of current 

§ 607.40(a) and (b). We are proposing to 

revoke the exemption in current 

§ 607.40(a) relating to foreign 

establishments whose blood products 

enter a foreign trade zone and are 

reexported from that foreign trade zone 

without having entered United States 

commerce. We are also proposing to 

revoke, in part, current § 607.40(b), 

which allows for blood, blood 

components, Source Plasma, or Source 

Leukocytes, or a component or part, 

under section 801(d)(4) of the act, to be 

imported or offered for import into the 

United States even if the product is not 

listed and manufactured, prepared, 

propagated, compounded, or processed 

at a registered foreign establishment. We 

are proposing to eliminate these two 

exemptions because of certain statutory 

changes that have occurred since the 

publication of the final rule on foreign 

establishment registration and listing. 

Those changes include, as discussed in 

section IV.A.2 of this document, 

enactment of the Bioterrorism Act, 

which reflects Congress’ desire to 

increase the Nation’s ability to prepare 

for and respond effectively to 

bioterrorism and other public health 

emergencies. Consistent with the 

provisions of the Bioterrorism Act, we 

are proposing to amend § 607.40(c) to 

require each foreign establishment to 

submit the name of each importer of the 

foreign establishment’s blood products 

that is known to the establishment, and 

the name of each person who imports or 

offers for import such blood products to 

the United States. 

We are also proposing to amend 

§§ 607.40(d) and (d)(3) to require each 

foreign establishment to submit the 

telephone and fax numbers and e-mail 

address of its United States agent. The 

name, address, and phone number of 

the United States agent is required 

under current § 607.40(d). We are 

proposing to require the submission of 

the information on importers and 

persons who import because the 

Bioterrorism Act requires foreign 

establishments to submit, among other 

things, the name of each importer of 

such blood product that is known to the 

establishment, and the name of each 

person who imports or offers for import 

such blood product to the United States 

for purposes of importation. In addition 

to the name, the proposal would require 

that the address, telephone and fax 

numbers, and e-mail address of each 

importer and of each person who 

imports or offers for import be provided 

to enable us to contact these persons. 

Proposed § 607.40(d)(3) would also 

require the foreign establishment to 

report changes in the United States 

agent’s name, address, telephone and 

fax numbers, and e-mail address to FDA 

within 30 calendar days of the change. 

Currently, § 607.40(d)(3) requires 

notification to FDA within 10-business 

days. 

Proposed § 607.40(e) would make 

electronic registration and listing 

mandatory for foreign establishments, 

consistent with proposed § 607.22(a). 

For those foreign establishments that are 

unable to register and list blood 

products using the electronic 

registration and listing system, we are 

proposing waiver provisions in 

§ 607.40(f)(1). We may grant a request 

for a waiver from a foreign 

establishment if the foreign 

establishment does not have an e-mail 

address and access to a computer and an 

Internet service provider that can access 

the electronic registration and listing 

system. We are also proposing in 

§ 607.40(f)(2) to require that waiver 

requests include a telephone number 

and/or mailing address where the 

agency can contact the foreign 

establishment. In addition, we are 

proposing to add § 607.40(f)(3) which 

states that if the agency grants the 

waiver request, the foreign 

establishment must register and list 

blood products in accordance with 

§ 607.22(b) or (c). 

• Section 607.65: Proposed § 607.65 

would be amended by redesignating 

paragraph (f) as paragraph (g) and by 

adding new paragraph (f). Proposed 

§ 607.65(f) would exempt certain blood 

product manufacturers from registration 

and product listing under part 607 

because FDA is proposing that 

manufacturers of these products register 

and list only under part 207. Because 

these products routinely bear NDC 

numbers, FDA believes it is more 

efficient to have manufacturers of these 

products register and list under part 

207. The products that would be 

included under proposed § 607.65(f) are 

all plasma derivatives such as albumin, 

Immune Globulin, Factor VIII, and 

Factor IX, bulk product substances such 

as fractionation intermediates or pastes, 

recombinant versions of plasma 

derivatives or animal derived plasma 

derivatives. Under current § 607.20, 

manufacturers of plasma derivatives 

such as albumin, Immune Globulin, 

Factor VIII, and Factor IX are required 

to register and list under part 607 and 

under part 207 to obtain an NDC 

number. 

• Sections 1271.1(a), 1271.1(b)(2), 

and 1271.20: We are proposing to 

amend §§ 1271.1(a), 1271.1(b)(2), and 

1271.20 by removing ‘‘207.20(f)’’ and by 

adding in its place ‘‘207.9(c)(2)’’. 

• Section 1271.3: For consistency 

with parts 207 and 607, we are 

proposing to define ‘‘importer’’ at 


jlentini on PROD1PC65 with PROPOSAL2
Federal Register / Vol. 71, No. 167 / Tuesday, August 29, 2006 / Proposed Rules 51325 

proposed § 1271.3(mm) to mean a 

company or individual in the United 

States that is the owner or consignee or 

recipient of the foreign establishment’s 

HCT/P that is imported into the United 

States. For consistency with part 607, 

we are proposing to define ‘‘United 

States agent’’ at proposed § 1271.3(nn) 

to mean a person residing or 

maintaining a place of business in the 

United States whom a foreign 

establishment designates as its agent. 

The definition of ‘‘United States agent’’

would exclude mailboxes, answering 

machines or services, or other places 

where an individual acting as the 

foreign establishment’s agent is not 

physically present. The United States 

agent would be responsible for helping 

FDA communicate with you, 

responding to questions concerning 

your HCT/Ps that are imported or 

offered for import to the United States, 

and helping FDA schedule inspections. 

• Section 1271.22: We are proposing 

to make electronic registration and 

listing mandatory for HCT/P 

establishments. As a result, we are 

proposing to revise current § 1271.22 as 

follows: 

Replace ‘‘Form FDA 3356’’ in current 

§ 1271.22(a) with ‘‘the electronic 

registration and listing system at http:// 

www.fda.gov/cber/tissue/tisreg.htm’’; 

Revise current § 1271.22(b) and (c) to 

implement the electronic registration 

and listing system at http:// 

www.fda.gov/cber/tissue/tisreg.htm and 

remove references such as ‘‘Form FDA 

3356,’’ mailing addresses, and telephone 

numbers. 

In the Federal Register of January 19, 

2001 (‘‘Human Cells, Tissues, and 

Cellular and Tissue-Based Products; 

Establishment Registration and Listing,’’

(66 FR 5447)), FDA announced its 

intention to develop an electronic 

submission process for HCT/P 

registration and listing. The agency has 

developed such a system and it is 

currently in use on a voluntary basis. 

Consistent with proposed 

§ 207.61(a)(4), proposed § 1271.22(b) 

states that FDA will periodically issue 

guidance on how to provide registration 

and listing information in electronic 

format (for example, method of 

transmission, media, file formats, 

preparation, and organization of files) 

for HCT/Ps. 

Consistent with proposed 

§ 207.61(a)(1), proposed § 1271.22(c) 

states that HCT/P manufacturers must 

provide the information under 

§ 1271.22(a) in accordance with part 11, 

except for the requirements in 

§ 11.10(b), (c), and (e) and the 

corresponding requirements in § 11.30. 

• Section 1271.23: Proposed 

§ 1271.23 would permit HCT/P 

establishments that do not have an email address and access to a computer 

and an Internet service provider that can 

access the Web-based FDA registration 

and listing database to request a waiver 

from electronic registration and listing. 

This is consistent with proposed 

§ 207.65 and the Bioterrorism Act. 

• Section 1271.25: We are proposing 

to amend § 1271.25, ‘‘What information 

is required for establishment registration 

and HCT/P listing,’’ as follows: 

Delete the reference to ‘‘Form FDA 

3356’’ in current § 1271.25; 

Amend current § 1271.25(a)(2) and 

(a)(3) to require the submission of the 

telephone and fax numbers and an email address; 

Add § 1271.25(a)(5) to require each 

foreign establishment to also submit the 

name, the address, telephone and fax 

numbers, and e-mail address of each 

importer that is known to the 

establishment and the name of each 

person who imports or offers for import 

such HCT/P to the United States for 

purposes of importation; 

Add proposed § 1271.25(a)(6) to 

require each foreign establishment to 

also submit, the name, address, 

telephone and fax numbers, and e-mail 

address of its United States agent. Under 

proposed § 1271.25(a)(6), each foreign 

establishment would have only one 

United States agent, and that United 

States agent must reside or maintain a 

place of business in the United States. 

Upon request from FDA, the United 

States agent must assist us in 

communications with the foreign 

establishment, respond to questions 

concerning the foreign establishment’s 

products that are imported or offered for 

import into the United States, and assist 

us in scheduling inspections of the 

foreign establishment. If we are unable 

to contact the foreign establishment 

directly or expeditiously, we may 

provide information or documents to 

the United States agent. The foreign 

establishment would report to FDA 

changes in the United States agent’s 

name, address, telephone and fax 

numbers, and e-mail address within 30 

calendar days of the change. 

Add proposed § 1271.25(d) to clarify 

that if your HCT/P is regulated as a 

drug, device, and/or biological product 

under current § 1271.20, you must 

submit the information required under 

part 207 using the procedures under 

part 1271. 

• Section 1271.26: For consistency 

with proposed § 207.29(a), we are 

proposing to amend current § 1271.26 to 

include a change in the United States 

agent’s name, address, telephone and 

fax numbers, and e-mail address. All 

changes in proposed § 1271.26 would be 

reported within 30 calendar days 

instead of the current requirement to 

report the change within 5 days. 

• Section 1271.37 would be revised to 

delete the reference to ‘‘Form FDA 

3356’’. 

3. Compliance Verification Reports 

On November 26, 2004 (69 FR 68831), 

FDA withdrew its September 2, 1993, 

proposal (58 FR 46587; Docket Number 

92N–0291) to amend part 207 to require 

the completion of ‘‘compliance 

verification reports.’’ These reports are 

printouts of information as reported to 

FDA on Form FDA 2657 or Form FDA 

2658. FDA had periodically mailed to 

domestic establishments the compliance 

verification report for listed prescription 

drugs and requested that the 

establishments verify or correct the 

information and return it to the agency 

within 30 calendar days. The 

completion of the report served to 

satisfy, in most cases, the drug listing 

updates required under current 

§ 207.30(a). FDA provided this service 

to increase the accuracy of its 

computerized drug listing files. Because 

FDA is now proposing to require the 

electronic submission of all registration 

and most listing information, FDA in 

anticipation of this proposal has already 

withdrawn the September 2, 1993, 

proposal and has discontinued the use 

of the compliance verification reports. 

Electronic submission of registration 

and most listing information would 

make it easier for establishments to 

register and list. In addition, FDA’s 

electronic registration and listing 

database would save registration and 

listing information that was submitted, 

thereby making it easier for 

establishments to access, review, and 

update information. 

V. Legal Authority 

We have the legal authority to amend 

our regulations on foreign and domestic 

establishment registration and listing for 

human drugs, including drugs that are 

regulated under a BLA, and animal 

drugs. The statutory basis for our 

authority includes sections 201, 301, 

501, 502, 503, 505, 506, 506A, 506B, 

506C, 510, 512, 513–516, 518–520, 701, 

704, 721, 801, and 903 of the act (21 

U.S.C. 321, 331, 351, 352, 353, 355, 356, 

356a, 356b, 356c, 360, 360b, 360c–360f, 

360h–360j, 371, 374, 379e, 381, and 

393); 15 U.S.C. 1451–1561; the PHS Act; 

and section 122, Public Law 105–115, 

111 Stat. 2322 (21 U.S.C. 355 note). 

Section 510(c) of the act requires 

every person upon first engaging in the 

manufacture, preparation, propagation, 


jlentini on PROD1PC65 with PROPOSAL2
51326 Federal Register / Vol. 71, No. 167 / Tuesday, August 29, 2006 / Proposed Rules 

compounding, or processing of a drug to 

immediately register with the Secretary 

his name, place of business, and the 

establishment. The provisions in section 

510(b) and (d) of the act require annual 

registration and registration of 

additional establishments, respectively. 

Section 510(i) of the act requires any 

establishment within any foreign 

country engaged in the manufacture, 

preparation, propagation, compounding, 

or processing of a drug that is imported 

or offered for import into the United 

States to register with the Secretary by 

providing certain information. These 

provisions, together with section 701(a) 

of the act (among others), authorize us 

to require the submission of the 

registration information specified in the 

proposal. The information specified in 

this proposal would help us identify 

who is manufacturing, repacking, 

relabeling, or salvaging drugs and where 

those operations are being performed. In 

addition, some information (e.g., official 

contact information) would help us 

communicate with establishments more 

effectively and schedule inspections 

more efficiently. 

Section 510(j)(1) of the act requires 

every person who registers to file with 

the Secretary, at the time of registration, 

a list of all drugs that are being 

manufactured, prepared, propagated, 

compounded, or processed by the 

registrant for commercial distribution. 

That list must be prepared in the form 

and manner prescribed by the Secretary 

and must be accompanied by a copy of 

labeling (or the label and package insert) 

and, in some cases, advertising. Section 

510(j)(2) of the act requires listing 

information updates every June and 

December. This listing information gives 

us a current inventory of marketed 

drugs. These provisions of the act and 

others, together with section 701(a) of 

the act, provide authority for requiring 

the submission of listing information set 

forth in this proposal. The drug listing 

information specified in this proposal 

would help us: (1) Develop a more 

current, robust inventory of drugs as a 

counter-terrorism measure; (2) more 

effectively administer our postmarketing 

surveillance programs; (3) facilitate 

recalls of products; (4) identify drugs or 

ingredients in short supply in the event 

of a national emergency; and (5) identify 

drugs marketed in violation of the law. 

Sections 510(j)(1), (i), and (p), and 

701(a) of the act also give us the 

discretion to require that registration 

and listing information be submitted in 

electronic format. Electronic receipt of 

registration and listing information 

would enable us to shift resources from 

more ministerial tasks, such as data 

entry, to the important public health 

objectives described previously in this 

document. Additional authority for 

requiring that content of labeling be 

submitted in electronic form stems 

from, among others, sections 201(n) and 

(p), 501, 502, 503, 505, 510(j)(1)(A) and 

(j)(1)(B), and 512 of the act. The 

certification requirement would help us 

with the efficient enforcement of the act 

because we would be able to distinguish 

between situations where there has been 

noncompliance with registration and 

listing requirements from situations 

where there have been no changes in 

information. The failure to register or 

list is a prohibited act under section 

301(p) of the act and the failure to do 

either renders a drug misbranded under 

section 502(o) of the act. 

We also have the authority to require 

the appropriate NDC number (in 

human-readable form) on certain drug 

labels for the efficient enforcement of 

various sections of the act. The 

appropriate NDC number in human 

readable form would, among other 

things, serve as a backup for the 

appropriate NDC number encoded in 

the bar code. That is, the human 

readable form of the NDC number could 

be manually keyed into a computer 

system by a health care provider if the 

bar code is damaged, cannot be read, or 

is otherwise illegible. Our legal 

authority to impose the human readable 

NDC number requirement, at least in 

part, is similar to that for requiring bar 

codes on labels (69 FR 9120, 9147–

9149). These sections include sections 

201(n) and (p), 501, 502, 503, 505, and 

701(a) of the act, and sections 351 and 

361 of the PHS Act. 

Other sections of the act also provide 

authority for the human-readable NDC 

number requirement. The failure to 

register and list are prohibited acts and 

render drugs misbranded under sections 

301(p) and 502(o) of the act. It would be 

possible for FDA investigators to read 

the NDC number on the drug’s label and 

review information in our database to 

ascertain compliance with registration 

and listing requirements. Where a drug 

does not bear the appropriate NDC 

number, investigators can conduct 

further followup to discern, for 

example, whether there has been a 

failure to comply with registration and 

listing requirements (including those for 

NDC numbers). Accordingly, sections 

201, 301(p), 502(o), 510, and 701(a) of 

the act provide additional authority for 

requiring the appropriate NDC number 

in human readable form on certain drug 

labels. 

There is also additional legal 

authority for the rule’s requirements as 

to biological products regulated under 

the PHS Act. Section 351(a) of the PHS 

Act provides for the approval, as well as 

the suspension and revocation, of 

biologics license applications. The 

human-readable NDC requirement for 

biological drugs and blood and blood 

components is designed to ensure the 

continued safe and effective use of 

licensed biological products. 

Additionally, section 361 of the PHS 

Act authorizes regulations necessary to 

prevent the introduction, transmission, 

or spread of communicable diseases. 

With specific regard to blood and blood 

components, the human- readable NDC 

number requirement will aid in the 

control of units that are at risk of 

spreading communicable diseases. 

VI. Analysis of Economic Impacts 

A. Introduction 

We have examined the proposed rule 

under Executive Order 12866 and the 

Regulatory Flexibility Act (5 U.S.C. 

601–612), and the Unfunded Mandates 

Reform Act of 1995 (Public Law 104–4), 

and the Congressional Review Act. 

Executive Order 12866 directs 

regulatory agencies to assess all costs 

and benefits of available regulatory 

alternatives and, when regulation is 

necessary, to select regulatory 

approaches that maximize net benefits 

(including potential economic, 

environmental, public health and safety, 

and other advantages; distributive 

impacts; and equity). This proposed rule 

is not considered economically 

significant under Executive Order 

12866. 

Under the Regulatory Flexibility Act 

(as amended by the Small Business 

Regulatory Enforcement Fairness Act), if 

a regulation has a significant economic 

impact on a substantial number of small 

entities, we must analyze regulatory 

options that would minimize the impact 

on small entities. We have conducted a 

preliminary regulatory flexibility 

analysis for the proposed rule, and we 

believe it will not have a significant 

impact on a substantial number of small 

entities. 

Section 202(a) of the Unfunded 

Mandates Reform Act of 1995 (UMRA) 

requires that agencies prepare a written 

statement of anticipated costs and 

benefits before proposing any rule that 

may result in expenditures by State, 

local, and tribal governments, in the 

aggregate, or by the private sector of 

$100 million (adjusted annually for 

inflation) in any one year. Currently, 

such a statement is required if costs 

exceed about $115 million for any one 

year. UMRA does not require us to 

prepare a statement of costs and benefits 

for the proposed rule because the 

proposed rule is not expected to result 


jlentini on PROD1PC65 with PROPOSAL2
Federal Register / Vol. 71, No. 167 / Tuesday, August 29, 2006 / Proposed Rules 51327 

in any 1-year expenditure that would 

exceed $115 million. 

The Congressional Review Act 

requires that regulations determined to 

be major must be submitted to Congress 

before taking effect. 

We contracted with the Eastern 

Research Group, Inc. (ERG), to collect 

data, interview industry experts, and 

estimate the costs and benefits of the 

proposed rule. The analysis and 

references in support of the effects of 

the proposed rule are summarized in 

table 2 and are included in the docket 

as Reference 3. Although we were 

unable to quantify specific benefits 

attributable to the proposed rule, we 

believe the ultimate use of electronic 

registration and listing data justify 

taking this action. 

TABLE 2.—SUMMARY OF ANNUAL COSTS AND BENEFITS OF THE PROPOSED RULE1

Annual Discount Rate Average Annual 

Costs (in Millions) Average Annual Benefits Average Annual Net Benefits 

3% $5.6 Unquantified. Benefits accrue by having accurate and unique identification of drugs that would allow greater use of technology. N/A 

7% $5.8 Unquantified. Benefits accrue by having accurate and unique identification of drugs that would allow greater use of technology. N/A 

1Based on 10-year evaluation period. 

B. Objective 

The objective of the proposed 

regulation is to update our process for 

registering drug establishments and 

listing drugs. The current system does 

not allow for timely updates of 

important information and the current 

system for NDC numbers has introduced 

the potential for the misidentification 

and mistaken administration of drugs. 

We believe that electronic submission of 

registration and listing information, as 

well as our assignment of specific 

identifiers (i.e., the NDC number), 

would improve the quality and 

timeliness of information available to 

health care professionals and 

consumers. We further believe that 

these quality improvements would 

result in safer and more effective use of 

drugs by providing up-to-date and easily 

accessible relevant information. We also 

believe that we should develop and 

maintain a high quality database of 

drugs available on the market to 

enhance future uses of technology in the 

delivery of health care. 

C. Baseline Conditions and Scope 

As discussed elsewhere in this 

preamble, we currently maintain 

databases that contain establishment 

registration and drug listing 

information. However, these databases 

rely on paper forms that manufacturers, 

repackers, relabelers, drug product 

salvagers, and private label distributors 

of drugs (both human and animal) must 

submit to us. The completed forms are 

then entered into our databases. These 

databases are intended to include 

identification of establishments 

involved in the manufacturing, 

preparation, propagation, compounding 

or processing of drugs, including the 

repacking, relabeling, and salvaging of 

drugs (human and animal prescription 

and OTC drugs, as well as active 

pharmaceutical ingredients), the 

procedures that take place at each 

establishment (e.g., repacking, or 

relabeling), and a list of each drug being 

manufactured, prepared, propagated, 

compounded, or processed for 

commercial distribution at each site. We 

rely on these databases to identify 

manufacturers, repackers, relabelers, 

drug product salvagers, and private 

label distributors, of human and animal 

drugs, specific drugs or ingredients, to 

facilitate recalls or information alerts in 

the case of potential safety concerns, 

and to otherwise exercise competent 

oversight of this important industry. 

The quality and completeness of these 

databases depends on prompt 

submission of updated information from 

manufacturers, repackers, relabelers, 

drug product salvagers, and (currently) 

private label distributors, as well as our 

immediate inclusion of the data into our 

system. We are currently unable to 

verify the accuracy of the information 

submitted, and some manufacturers, 

repackers, relabelers, drug product 

salvagers, and private label distributors 

are not prompt in informing us of 

changes. For example, some changes in 

processing or packaging might be 

submitted periodically rather than when 

such changes actually occur. In 

addition, forms may be mishandled, or 

even lost, which further reduces 

confidence in the databases. 

Using a 5-digit labeler code, we 

estimate that we have the capacity for 

NDC numbers for up to 100,000 

registered establishments, each having a 

capacity for up to 100,000 product/ 

package size combinations (using the 5 

remaining digits). If a registered 

establishment requires more than 

100,000 product/package size codes, we 

could issue that establishment an 

additional labeler code. We currently 

have about 25,000 active establishments 

in our registration database, utilizing 

less than half of the 5-digit labeler code 

capacity. We currently issue about 1,000 

new labeler codes annually. If we reach 

NDC number capacity (possibly in 30 to 

50 years), we could propose to either 

add alphanumeric capability or expand 

the number of numeric digits to 11 or 

12 (current § 207.35(b)(2)(i) states that 

FDA will go from a 5- to 6-digit labeler 

code if needed). This change in NDC 

numbers will necessitate advances in 

current UPC technology (due to the 

need for bar code reading), which we 

anticipate will likely occur prior to our 

reaching the 10-digit NDC numeric 

capacity. 

TABLE 2A.—COUNT OF POTENTIALLY AFFECTED HEALTHCARE ENTITIES

Type of Entity Establishments Source Additional Comment 

Pharmaceutical manufacturers 

(human) 

666 Orange Book, 

2003 

Includes only those pharmaceutical firms that have at least one 

currently marketed product in the United States. Might be an 

overestimate due to the possibility of applicant name duplication 

in the database. Does not include firms that only manufacture 

unapproved drug products. 


jlentini on PROD1PC65 with PROPOSAL2
51328 Federal Register / Vol. 71, No. 167 / Tuesday, August 29, 2006 / Proposed Rules 

TABLE 2A.—COUNT OF POTENTIALLY AFFECTED HEALTHCARE ENTITIES—Continued 

Type of Entity Establishments Source Additional Comment 

Pharmaceutical manufacturers 

(animal) 

80 Census, 2004 Includes firms that own establishments that manufacture animal 

drugs. Includes some firms that manufacture both human and 

animal drugs, so overstates the number that manufacture animal 

drugs exclusively. Does not include firms that only manufacture 

unapproved drug products. 

Pharmacies 67,434 Listed below Sum of pharmacy categories (chain store headquarters offices are 

not counted in this total) 

Chain store (headquarters office) 25 NWDA, 2000 Covers headquarters for firms ranging from CVS (4,100 stores) to 

companies operating over approximately 35 stores. 

Chain 20,493 NACDS, 2001 National Association of Chain Drug Stores Web site (http:// 

www.nacds.org) 

Independent 24,500 NCPA, 2002 National Community Pharmacists Association Web site (http:// 

www.ncpanet.org) 

Mass merchant 5,910 NACDS, 2001 National Association of Chain Drug Stores Web site (http:// 

www.nacds.org) 

Supermarket 8,531 NACDS, 2001 National Association of Chain Drug Stores Web site (http:// 

www.nacds.org) 

Institutional 7,950 ERG, 2001 Profile of the Pharmaceutical Compounding Industry: Draft Final 

Report. Submitted to FDA, Office of Policy, Planning, and Legislation, Office of the Commissioner, August 27, 2001. 

Mail order 50 ERG, 2001 Based on discussions with Winkelman (2004) 

Pharmacy benefit management 

companies (PBMs) 

76 ERG, 2001 Profile of the Prescription Drug Wholesaling Industry: Final Report, 

February 12, 2001. Submitted to Office of Policy, Planning, and 

Legislation, Office of the Commissioner, FDA. The figure is reported by SMG Marketing Group, Inc. 

Hospitals 6,116 AHA, 2002 American Hospital Association Web site (http://www.ahadata.org) 

Compendium companies 5 ERG, 2004 Estimate based on discussions with Winkelman (2004) 

Wholesalers/distributors 6,500 ERG, 2001 Profile of the Prescription Drug Wholesaling Industry: Final Report, 

February 12, 2001. Submitted to Office of Policy, Planning, and 

Legislation, Office of the Commissioner, FDA. The report notes 

that this is probably an underestimate. 

Group purchasing organizations 701 ERG, 2001 See note in previous row. 

State Medicare agencies 50 ERG, 2003 Allocated one per State. 

Physician offices 195,655 Census, 2000 NAICS 62111 from County Business Patterns 2000, U.S. Census 

Bureau. 

Dentist offices 116,494 Census, 2000 NAICS 62121 from County Business Patterns 2000, U.S. Census 

Bureau. 

Note: ERG did not include various health care facilities, such as nursing homes and rehabilitative care facilities, that generally do not have onsite pharmacies. 

The pharmaceutical and biological 

products industries (as defined by the 

North American Industrial 

Classification System (NAICS)) consist 

of 1,218 establishments (NAICS 325412 

and NAICS 325414). ERG examined the 

2003 ‘‘Approved Drug Products With 

Therapeutic Equivalence Evaluations’’

(the ‘‘Orange Book’’) to estimate the 

number of companies currently 

operating establishments that are 

marketing drugs. While the Orange Book 

covers only products approved under 

section 505 of the act, there is sufficient 

overlap between manufacturers of 

products listed in the Orange Book and 

manufacturers of other types of products 

(e.g., manufacturers of OTC monograph 

products and animal drugs) to provide 

a basis for estimating the industry sector 

affected by the proposed rule. ERG 

estimates that a total of 666 companies 

own and operate manufacturing 

establishments. In addition, according 

to U.S. Census data, there are an 

estimated 80 companies that 

manufacture animal drugs in the United 

States. (There is likely overlap between 

human and animal drug companies.) 

Finally, the packaging and labeling 

services industry (NAICS 561910) 

consists of 229 companies. Each of these 

establishments would be affected by the 

proposed rule. 

Several provisions of the proposed 

rule affect establishments rather than 

companies. We used FDA’s drug 

registration system to estimate that there 

are approximately 9,700 domestic sites. 

There are approximately 200,000 

distinct packaged products of human 

and animal (both prescription and OTC) 

drugs. The information generated by the 

drug listing process is used by many 

organizations for many purposes. Each 

specific drug is entered into our listing 

database. If the drug is later withdrawn 

from the market, for example, this is 

also noted. The pharmaceutical industry 

is undergoing corporate changes 

through mergers, acquisitions, and 

closings. These activities result in 

additional reporting requirements (via 

the current paper system) to keep our 

databases up-to-date. However, the 

magnitude of information required to 


jlentini on PROD1PC65 with PROPOSAL2
Federal Register / Vol. 71, No. 167 / Tuesday, August 29, 2006 / Proposed Rules 51329 

keep the system current and the number 

of activities that would generate changes 

in the data have weakened our ability to 

rely on the current database. 

In addition, the current drug listing 

system includes the use of the NDC 

system. Using this system, 

manufacturers, repackers, and relabelers 

of drugs (including human prescription, 

human OTC, certain biologics, and 

animal drugs) assign unique NDC 

numbers to each drug. An NDC number 

consists of 10 characters, including a 4- 

or 5- character labeler code, a 4- or 3- 

character product code, and a 1- or 2- 

character package code, and is 

presented in one of three formats (4–4–

2, 5–3–2, or 5–4–1). Manufacturers, 

repackers, and relabelers notify us of the 

assigned NDC number at the time of 

drug listing, and the numbers may be 

printed on the label and labeling of each 

drug. 

As discussed earlier in this document, 

we currently assign the labeler code to 

registered manufacturers, repackers, and 

relabelers of drugs. The manufacturer, 

repacker, or relabeler assigns the 

product code and package code to its 

drugs and must report the NDC number 

to us. Currently, when a manufacturer, 

repacker, or relabeler withdraws a drug 

from the distribution chain, NDC 

numbers for the discontinued drugs may 

be reused after 5 years. 

This process and format for NDC 

numbers was introduced over 20 years 

ago as a means of identifying individual 

drugs by distinguishing, among other 

things, between specific strengths and 

package sizes for reimbursement 

purposes. Since the NDC system was 

created in 1969, a variety of uses for the 

NDC number have developed within the 

healthcare industry. 

We have used the NDC number to 

facilitate recalls of drugs for a number 

of years. The identification system 

allows for notification throughout the 

distribution chain in the event of a 

recall or other warning about specific 

drugs. 

The development of computerized 

systems and the ability to electronically 

transmit information have had a major 

effect on the ways NDC numbers are 

used. Because the NDC numbers are 

designed to be unique identifiers, many 

sectors of the industry have built 

systems to maximize the usefulness of 

this information. Compendium service 

companies assemble and distribute 

information to retail stores, hospitals, 

prescription benefit managers (PBMs), 

insurance companies, and electronic 

medical record companies among other 

users. These users rely on NDC numbers 

to identify drugs within their tracking or 

processing systems. The NDC numbers 

are incorporated into their internal 

software to facilitate scanning (such as 

by cashiers or hospital personnel) or for 

the operation of data processing systems 

for reimbursement (both private and 

public) or inventory management. In 

addition, these compendium databases 

often include drug price information 

directly associated with the NDC 

numbers. 

In some cases, the designers of the 

information systems that use NDC 

numbers convert the NDC number for 

use in industry databases. They add a 

zero to result in a consistent 11-digit 

format (5–4–2). Also, while visual use of 

NDC numbers uses hyphens to 

differentiate between the labelerproduct-package codes, these hyphens 

are not read when scanned (as a bar 

code, for example). Because three 

formats are used within the current NDC 

system, removing hyphens introduces 

potential duplicates. 

Other government entities, such as the 

Center for Medicare and Medicaid 

Services (CMS) and the Drug 

Enforcement Administration (DEA) use 

the NDC numbers to meet their mission 

requirements. The numbers are used to 

provide data for negotiated rebates or 

notification of distribution of controlled 

substances. 

Companies are continually updating 

their drug information and price data. 

Generic relabeling companies and OTC 

manufacturers often repackage or 

remarket their products. These fairly 

constant revisions present a challenge to 

both compendium companies and us 

because maintaining the accuracy of the 

NDC database relies on prompt 

notification of any changes, but 

notification is not always prompt or 

consistent. 

The NDC components (labeler, 

product, and package codes) have 

presented issues that may compromise 

the current database. For example, we 

assign only one labeler code to each 

manufacturer, repacker, or relabeler, but 

many companies have multiple labeler 

codes due to mergers and acquisitions 

and may use them to distinguish 

between different divisions within the 

new company. Pharmaceutical 

companies have taken different 

approaches to handling product codes. 

For example, some firms assign product 

codes sequentially while others use 

predefined blocks of numbers for each 

operating division. Similarly, the 

methods used to assign package codes 

are not uniform. 

Many repackers currently use the 

manufacturer’s NDC number instead of 

their own when repacking drugs into 

smaller packages for pharmacies. 

Among the reasons such repackers do 

this is because Medicaid and other 

third-party payers use the NDC number 

presented on the drug to file rebate 

claims with the manufacturers. Such 

repackers sometimes present the 

manufacturer’s NDC number in an effort 

to fall under the manufacturer’s 

agreement with payers. 

D. The Proposed Regulation 

This proposed regulation would 

require the electronic submission of 

registration and listing information. The 

proposed rule would require, for 

example, drug product salvagers to list 

drugs and would not permit private 

label distributors to register 

establishments or list drugs, and would 

specifically define the responsibilities 

associated with each type of 

establishment covered by the proposal. 

The proposed rule would not permit 

manufacturers, repackers, and relabelers 

to assign the product code and package 

code for newly listed drugs. We would 

assign the entire NDC number for drugs. 

Under the proposed rule, the 

electronic establishment registration 

and drug listing system must be used to 

enter and update all registration, listing, 

and NDC number information no later 

than 9 months after the effective date of 

a final rule. (We are proposing that any 

final rule based on the proposal become 

effective 90 days after publication in the 

Federal Register.) Manufacturers, 

repackers, and relabelers would have 

until 9 months after the effective date of 

a final rule to review and update the 

NDC number information in our 

databases for each of their drugs to 

ensure that it complies with the 

proposal. In addition, manufacturers, 

repackers, and relabelers would have, 

for prescription drugs, 3 years after the 

effective date of a final rule and, for 

OTC drugs, 7 years after the effective 

date of a final rule, to ensure that the 

appropriate NDC number correctly 

appears on the label of each of their 

listed drugs, in accordance with the 

proposal. These costs have been 

accounted elsewhere in this analysis. 

By requiring electronic drug 

registration and listing, this proposed 

rule would enhance the use of 

technology and provide the basis for 

efficiencies in the proper use of drugs. 

For example, the use of bar coded 

information to avoid adverse events 

associated with medication errors 

requires consistent information on the 

drug label. Other initiatives, such as 

electronic prescribing, may require the 

electronic accessibility of this 

information. This proposed rule would 

be an important step for the timely and 

useful availability of information that 

would benefit patients. 


jlentini on PROD1PC65 with PROPOSAL2
51330 Federal Register / Vol. 71, No. 167 / Tuesday, August 29, 2006 / Proposed Rules 

E. Costs 

The major potential cost of the 

proposed rule is the assignment of NDC 

numbers by FDA. Although the 

proposed rule includes a selected 

alternative to minimize this cost, the 

potential impact could be very large, 

and is discussed in the Alternatives 

section of this document. Other costs 

associated with electronically 

submitting registration and listing 

information are discussed later. Costs 

have been analyzed and discounted 

using the methodology suggested by 

OMB’s Circular A–4 (September 2003). 

1. Costs of a Single Method of Assigning 

NDC Numbers 

Currently, each manufacturer, 

repacker, and relabeler has its own 

method for assigning the product code 

and package code to its drugs. Under the 

proposed rule, we would assign the 

product code and package code. 

Existing NDC numbers would not be 

affected, as long as they meet the 

proposed requirement for NDC 

numbers. 

Because, the proposed changes to the 

NDC numbering system would affect 

product codes and package codes, and 

because NDC numbers are used by some 

sectors of the health care industry for 

reimbursement or inventory purposes, 

we expect that the proposed changes 

would have some effect on the data 

processing infrastructure. The primary 

area of impact would be in PBM tasks 

such as generation and maintenance of 

drug formularies for insurance coverage 

purposes. Other areas that would be 

affected include data analyses 

conducted by manufacturers, repackers, 

and relabelers, especially with respect 

to rebate predictions and market 

forecasts. 

a. Pharmaceutical manufacturers. 

Changes to the NDC number would 

likely affect rebate processing by 

manufacturers as well as the ability of 

pharmaceutical firms to conduct market 

research analyses. 

Common practice in the prescription 

pharmaceutical industry includes 

agreements that provide rebates from 

manufacturers to large insurance payers 

for use of a manufacturer’s drugs by the 

insurer’s enrollees. Medicaid and other 

large programs have negotiated these 

rebates with individual manufacturers. 

Each firm’s staff reviews invoices, 

makes corrections, resolves disputes, 

and remits rebate payments to insurers 

based on reported volumes of sales to 

patients enrolled in the insurance plans. 

Most manufacturers use the current 

NDC numbers to identify the dispensed 

products during this process. A 

common practice among manufacturers 

is to group reimbursement data by 

product code in order to analyze 

payment history and resolve disputes 

with insurance carriers. 

Because new product codes may be 

assigned without sequencing under the 

proposed rule, this may require 

manufacturers to devote more staff-time 

to manually group products for rebate 

processing. Additional data entry work 

would be required if, for example, an 

additional data field were added to 

reports in order to retain the ability to 

sort products on the basis of product 

codes. 

Market research departments within 

the pharmaceutical industry also use the 

current configuration of NDC numbers 

when conducting analyses that affect 

product pricing and packaging. The 

ability to sort by product code allows for 

efficient use of data records, and 

randomization of product codes would 

result in additional staff-time to conduct 

rebate processing. 

Initially, the loss of the ability to 

group products based on sequential 

product codes could require staff to 

either manually sort products or map 

the new randomized NDC number into 

another, internal sorting system. Over 

time, as new NDC numbers are assigned 

with new product codes and package 

codes, we expect that all manufacturers, 

repackers, and relabelers would 

eventually use automated mapping 

systems to track product codes. ERG has 

determined through interviews with 

industry information technology staff 

that it would take approximately 80 

hours of programming to devise, 

validate, and introduce an automated 

mapping system for each affected 

company. In addition, ERG interviews 

determined that approximately 100 new 

packaged products are marketed per 

year for each manufacturer, and it 

would take approximately 0.083 hours 

(5 minutes) per product to map and 

validate the assigned NDC number to a 

new internal number for each internal 

database. ERG further determined that 

an average manufacturer is likely to 

have three internal databases that would 

utilize the new NDC numbers. Each 

manufacturer would require about 25 

hours of programmer time per year in 

maintenance of these systems. The 2003 

Bureau of Labor Statistics (BLS) has 

published hourly pay and benefit rates 

of $64 for senior computer 

programmers. Thus, each manufacturer 

would incur first-year costs of about 

$5,100 (80 hours x $64 per hour) and 

annual costs of about $1,600 (100 

product packages x 0.083 hours x 3 

databases x $64 per hour). During 2003, 

according to estimates based on FDA’s 

Orange Book and the Census of 

Manufacturers, 746 manufacturing 

companies marketed at least one 

prescription, OTC, or animal drug 

product in the United States (666 

domestic human drug manufacturers 

and 80 domestic animal drug 

manufacturers). These manufacturers 

would incur first-year costs of $3.8 

million ($5,100 x 746 companies) and 

annual costs of $1.2 million ($1,600 x 

746 companies) because of newly 

assigned product codes and package 

codes. 

Although not included as a cost of the 

proposed regulation, we estimate that 

foreign manufacturers of drug and 

biological products would incur firstyear and annual costs due to the 

proposed rule. The magnitude of any 

costs would depend on the specific 

prevailing wage rate for computer 

programmers in the respective 

countries. We note that foreign 

establishments would also experience 

some increase in costs because of the 

proposed rule. OMB Circular A–4 

allows for the consideration of 

regulatory costs to foreign 

establishments, and requires such an 

analysis if the costs are significant. 

However, the relatively small marginal 

costs of the proposed rule and the 

undertainty of the effect, if any, on 

consumer prices convinced us to limit 

the analysis on the costs to domestic 

establishments and companies. 

b. Pharmacies. We believe that retail 

pharmacies (that would not be required 

to register or list) would generally be 

unaffected by the proposed rule because 

most pharmacy processing systems do 

not use the internal component of NDC 

codes. In those cases where pharmacies 

use the components, we believe 

software vendors will make any 

appropriate revisions. 

However, ERG found that large 

pharmacy chains were concerned about 

possible changes in NDC numbers. 

Some large chains use the current NDC 

numbers for the adjudication of claims. 

(‘‘Adjudication’’ refers to the process by 

which pharmacists submit 

reimbursement claims to customer 

health plans.) Most formularies are built 

and maintained by PBMs or individual 

State Medicaid plans, but the chains 

have noted an increase in smaller plans 

that are maintained by individual retail 

stores. In order to serve these small, 

local insurance plans, data entry staff at 

the participating stores enter NDC 

numbers of the requested drugs using 

‘‘wild card’’ symbols (such as asterisks) 

to indicate that any number in the wild 

card position is acceptable. For 

example, the package code of an NDC 

number may be entered as a wild card 


jlentini on PROD1PC65 with PROPOSAL2
Federal Register / Vol. 71, No. 167 / Tuesday, August 29, 2006 / Proposed Rules 51331 

symbol to indicate that any package or 

strength of the indicated product is 

acceptable for reimbursement under that 

specific insurance plan. This ability 

allows data entry clerks to add groups 

of products quickly. 

The proposed assignment by us of 

product codes and package codes could 

affect this practice. Several executives 

in the chain drug industry asserted to 

ERG that this change would result in 

possibly hiring as many as four 

additional data entry clerks. Although 

other respondents felt that this claim 

overstated the expected increased effort, 

they could not provide alternative 

estimates. According to the BLS, the 

annual salary for a data entry operator 

in 2003 was $33,240 plus about 38 

percent in benefits. We have used 

approximately $50,000 per year as 

typical annual compensation for this 

industry. Therefore, using this estimate 

of additional staff, each affected chain 

would experience an increased annual 

cost of $200,000 (4 additional clerks x 

$50,000). 

According to the National Wholesale 

Drug Association, there are 25 large 

chain headquarters offices of 

corporations that operate at least 35 

separate retail drug store outlets. ERG 

expects that only 10 percent of these 

corporations would potentially be 

affected by the proposed rule because 

relatively few chain stores use software 

that enables the use of ‘‘wild card’’ data 

entry for portions of the NDC numbers. 

This results in total industry annual 

operating costs of $500,000 (25 large 

chain operations x 0.10 x $200,000). 

c. Pharmaceutical benefit managers. 

PBMs are the entities that build 

formularies and adjudication services 

for insurance plans. The software used 

for these services usually makes use of 

the NDC number. For example, when a 

PBM builds a formulary for an 

insurance plan, the data entry staff may 

enter the NDC numbers of the selected 

drugs into processing software. As 

discussed previously in the section on 

the expected effect on retail pharmacy 

chains, wild card symbols may be used 

to indicate that any number in the 

position of the wild card symbol is 

acceptable to the formulary and, thus, 

reimbursable. This practice works in 

cases where the product code of the 

NDC number is in sequence. In some 

cases, only the labeler code may be 

entered and wild card symbols are used 

for the rest of the NDC number to signify 

that any product from that company 

(i.e., manufacturer, repacker, relabeler, 

or private label distributor) is 

acceptable. This use of wild card 

symbols allows data entry clerks to 

quickly add groups of products, and 

according to respondents of ERG 

interviews, saves substantial time. 

Several managers of PBMs suggested 

that manual entry of all NDC numbers 

would be similar to those of pharmacy 

chain operators and could result in 

hiring as many as four additional 

employees (FTEs) per year. Using the 

BLS data, the annual salary of $33,240 

and industry benefits of approximately 

38 percent of salary results in typical 

compensation of around $50,000 per 

FTE. If so, then increased costs to PBMs 

would be approximately $200,000 per 

year per affected PBM (4 additional 

clerks x $50,000). 

However, not all PBMs would be 

affected by this change in NDC 

numbers. In discussions with ERG, only 

one supplier of adjudication software 

was identified as providing the ‘‘wild 

card’’ feature. This provider estimated 

that his clients constituted about 10 

percent of the industry, so we have 

assumed that about 10 percent of the 

PBMs use this feature. Therefore, ERG 

has estimated that only 10 percent of 

PBMs would likely experience 

increased costs because of the proposed 

rule. ERG identified 76 PBMs for a 2001 

profile of the prescription drug 

wholesaling industry (Ref. 4). Using this 

estimate, annual costs of the proposed 

rule for this industry segment are 

estimated to be $1.5 million (76 PBMs 

x 0.10 affected by the proposed rule x 

$200,000). 

d. Other entities. ERG examined the 

potential effect of the proposed 

revisions to the NDC number on 

hospitals, compendium companies, 

wholesalers/distributors, group 

purchasers, State Medicaid agencies, 

physician offices, and dental offices. 

None of these sectors were identified as 

being significantly affected by the 

proposed rule. These sectors maintained 

that as long as the NDC number 

maintained its format, any adjustments 

would be minimal. In particular, 

respondents asserted that preservation 

of the labeler code in the NDC number 

would be sufficient for many of these 

users of NDC numbers. Other users of 

the NDC numbers (such as hospitals) are 

expected to be able to accommodate any 

changes without major modifications to 

their data systems. 

e. Total costs of NDC number revision. 

Overall, we expect that revising the 

process by which NDC numbers are 

assigned will have a one-time cost 

during the first year of $3.8 million and 

annual, recurring costs of $3.2 million. 

2. Other Costs of the Proposed Rule 

Potential costs of the proposed rule 

also include: (1) The costs and cost 

savings for obtaining NDC numbers and 

recurring electronic registration and 

listing submissions; (2) the costs of label 

revisions for some drugs to include NDC 

numbers; (3) the costs of setting up 

electronic submissions of registration 

information, listing information, and 

content of labeling; and (4) the costs of 

continuing the submission of content of 

labeling. In addition, discussions with 

industry revealed two areas of potential 

concern that are not specific costs of the 

proposed rule. The first area of concern 

is potential delay in the assignment of 

NDC numbers, and the second area of 

concern is the use of repacker or 

relabeler NDC numbers on drug labels 

(rather than the manufacturer’s NDC 

number) and the effect on negotiated 

reimbursements with third-party payers, 

including CMS. 

a. Costs and cost savings for obtaining 

NDC numbers and recurring electronic 

registration and listing submissions. 

This category consists of eight types of 

identified costs or cost savings: 

• Costs for prospectively obtaining 

NDC numbers for human prescription 

drug products, human OTC drug 

products, animal prescription drug 

products, animal OTC drug products, 

and active pharmaceutical ingredients. 

• Costs for electronic submission of 

new drug listings. 

• Costs for electronic submission of 

changes to drug listings. 

• Costs to certify no drug listing 

changes. 

• Costs for drug product salvagers to 

list. 

• Costs to register new establishments 

electronically. 

• Costs to review and update 

establishment registration 

electronically, including certifying no 

changes. 

• Costs to obtain user accounts from 

FDA. 

Currently, manufacturers, repackers, 

relabelers, and drug product salvagers 

register establishments and (except for 

salvagers) list their drugs. This can be a 

time-consuming procedure involving 

different forms that collect data for later 

computer entry. Forms must be 

completed by hand and changes to 

information to be submitted to us 

require that the entire form be redone. 

With electronic submission of this 

information under the proposed rule, 

information may be keyed in and any 

changes may be made to the information 

submitted. Information would not have 

to be resubmitted each time. We expect 

the proposed rule will result in 

substantial time and cost savings in the 

use of electronic submissions. 

New NDC numbers for drugs: ERG 

used FDA drug listing data to determine 

that over 11,000 new domestic drug 


jlentini on PROD1PC65 with PROPOSAL2
51332 Federal Register / Vol. 71, No. 167 / Tuesday, August 29, 2006 / Proposed Rules 

listings occur each year (foreign drug 

listings are not counted in this analysis). 

The time required to submit information 

and coordinate with FDA for an NDC 

number is estimated to be 0.5 hours per 

drug (incremental to the time required 

for a firm to assign NDC numbers to 

themselves.) The BLS reports that the 

compensation (including benefits) for a 

mid-level manager within this industry 

is $51.73. We expect the annual cost to 

obtain NDC numbers for new drugs to 

equal about $0.3 million (11,000 new 

drug listings x 0.5 hours x $51.73 per 

hour.) 

Electronic submission of new drug 

listings: Currently, it takes 

approximately 2.5 hours to compile, 

copy, and mail drug listings to FDA. 

The annual cost for this activity is 

currently $1.4 million (11,000 drug 

listings x 2.5 hours x $51.73 per hour.) 

We expect that this activity will only 

require approximately 1 hour per drug 

listing if submitted electronically under 

the proposed rule. The annual cost 

would then be $0.6 million (11,000 new 

drug listings x 1 hour x $51.73 per 

hour.) Electronic submission of drug 

listings would result in annual cost 

savings of $0.8 million. 

Electronic submission of changes to 

drug listings: Currently, any changes to 

drug listings entail that the entire form 

be redone by hand. Therefore, 

approximately 2.5 hours is currently 

required to compile, copy, and mail any 

change to FDA. FDA’s drug listing data 

estimate that there are approximately 

36,000 changes to domestic drug listings 

each year. The current cost of this 

activity is $4.7 million (36,000 annual 

changes x 2.5 hours x $51.73 per hour.) 

Electronic submission of changes is 

expected to require only 0.5 hours per 

submission. The expected annual cost of 

using electronic submissions would be 

$0.9 million (36,000 annual changes x 

0.5 hours x $51.73 per hour). Electronic 

submission of changes to drug listings 

would result in annual cost savings of 

$3.8 million. 

Electronic certification of no drug 

listing changes: As discussed earlier in 

this document, there are 83,600 

domestic drug listings that must be 

reviewed twice a year to certify that 

there are no changes to the listing. There 

are approximately 36,000 annual 

changes to domestic drug listings, so we 

expect 131,200 annual certifications 

((83,600 drug listings x 2 annual 

reviews)—36,000 changes). The time 

required to electronically certify that 

there have been no changes is not 

expected to be more than 0.25 hours (15 

minutes.) The total cost of certification 

of no drug listing changes is $1.7 

million (131,200 annual certifications x 

0.25 hours x $51.73.) 

Drug product salvagers: According to 

industry experts, only about 5 percent of 

all listed drugs may be salvaged during 

any year. According to our listing data, 

there are approximately 83,600 

domestic drug listings (foreign listings 

are not counted here), so approximately 

4,200 domestic drugs are estimated to be 

salvaged each year (83,600 x 0.05.) 

Since the original manufacturer usually 

acts as the salvager, under the proposed 

rule, the original drug listing would be 

available electronically and could be 

easily copied to produce the drug listing 

for the salvaged drug. We expect that 

copying and submitting that drug listing 

(or withdrawal) would take 0.167 hours 

(10 minutes) and result in total annual 

costs of only $36,000 (4,200 salvaged 

drugs x 0.167 hours x $51.73 per hour.) 

Electronic submission of new 

establishment registrations: According 

to our registration database, there are an 

average of approximately 1,100 new 

sites registered each year, of which 

about 900 are domestic. The current 

registration process for new 

establishments takes 2.5 hours. The 

annual cost to register new 

establishments is about $0.1 million 

(900 new domestic registrations x 2.5 

hours x $51.73 per hour). The proposed 

rule will require new registrations to be 

done electronically and we expect this 

will take approximately 1 hour per 

registration. The cost of registering new 

establishments with the proposed rule 

would equal about $47,000 (900 new 

domestic registrations x 1 hour x $51.73 

per hour.) The use of electronic 

submissions for new establishments 

would result in cost savings of about 

$0.1 million. 

Electronic review and update of 

establishment registration: There are 

currently 9,700 domestic registered sites 

that must reregister each year, including 

certification of no changes to their 

registration information, and there are 

about 1,500 annual updates to domestic 

registration forms. The current estimate 

for this activity is 2.5 hours per 

submission for a current cost of about 

$1.4 million ((9,700 registered sites + 

1,500 annual updates) x 2.5 hours x 

$51.73 per hour). We expect each 

annual registration will take 0.5 hours 

and each amendment will be expedited 

and take only 0.25 hours under the 

proposed rule. Annual registration 

would have a cost of about $0.3 million 

(9,700 registered sites x 0.5 hours x 

$51.73 per hour). FDA has estimated 

that expedited updates of changes to 

registration under the proposed rule 

would require only 0.25 hours (15 

minutes) per update. The cost of this 

activity under the proposed rule would 

be only $20,000 (1,500 annual updates 

x 0.25 hours x $51.73 per hour.) This 

includes the costs to review and certify 

that there are no changes to registration 

information. The proposed rule is 

expected to result in annual cost savings 

of $1.1 million from electronic review 

and update of establishment 

registration. 

FDA user accounts: Prior to 

submitting electronic registration and 

listing information, the proposed rule 

requires manufacturers, repackers, 

relabelers, and drug product salvagers to 

obtain a user account from FDA. The 

proposed rule has us contacting each 

manufacturer, repacker, relabeler, and 

drug product salvager to request 

information to establish an account. 

FDA data suggest that 8,300 such 

requests would be made, based on 

primary registrants, of which 6,700 

would be domestic firms. We expect 

each request to take about 0.25 hours 

(15 minutes.) The total one-time cost of 

this requirement is about $0.1 million 

(6,700 companies x 0.25 hours x $51.73 

per hour.) 

Total cost savings of electronic 

registration and listing: Overall, the 

proposed rule is expected to result in 

annual cost savings of approximately 

$3.8 million due to electronic 

submission of registration and listing 

information. There is a one-time cost of 

$0.1 million for obtaining FDA user 

accounts. 

Some manufacturers expressed 

concerns about potential time lags due 

to our assignment of product codes and 

package codes, but the electronic 

process should provide for prompt 

responses to requests for NDC numbers 

from FDA. Also, manufacturers 

commented that if labeler codes must be 

consolidated across subsidiaries or 

divisions, additional costs would occur. 

We do not anticipate that we will 

receive requests for waiver of the 

requirement to submit registration and 

listing information electronically. 

However, if we receive waiver requests, 

we do not expect the costs to exceed 

those that would be incurred by paper 

submission of the information. 

b. Costs of label revisions to include 

NDC numbers. The proposed rule would 

require that appropriate human-readable 

NDC numbers appear on the labels of all 

drugs that are required to be listed, 

including biological products and active 

pharmaceutical ingredients. 

Prescription human drugs: Many 

manufacturers, repackers, relabelers and 

private label distributors, particularly 

those subject to the regulation 

addressing bar code label requirements 

(‘‘Bar Code Label Requirements for 


jlentini on PROD1PC65 with PROPOSAL2
Federal Register / Vol. 71, No. 167 / Tuesday, August 29, 2006 / Proposed Rules 51333 

12The number of separately packaged drug 

products is the number of drugs times the number 

of dosage forms times the number of concentrations 

times the number of package sizes. There are 

currently about 78,000 separate domestic 

prescription separately packaged drug products 

based on NDC number listings. 

Human Drug Products and Human 

Biological Products’’; 69 FR 9120, 

February 26, 2004), already voluntarily 

include the NDC number in humanreadable form under the barcode 

representation, as space permits. This 

proposed rule would require the 

appropriate human-readable NDC 

number to appear on drug labels for 

drugs subject to the listing 

requirements. Some packaging lines for 

prescription drugs have already been 

retooled to accommodate the unit-of-use 

requirement as set forth in the bar code 

rule. The costs of retooling these 

package lines have been analyzed in the 

bar code rule. However, we still expect 

as many as 60 percent of all prescription 

separately packaged drug products12 to 

be revised because of the proposed rule. 

Currently, human-readable NDC 

numbers appear with an ‘‘N’’ or ‘‘NDC’’

prefix. The proposed rule would require 

use of only the ‘‘NDC’’ prefix. In 

addition, there are classes of 

prescription drugs that are exempt from 

the bar code rule that would be subject 

to the requirement in this proposed rule 

(i.e., that the drug labels for drugs 

subject to listing requirements bear the 

appropriate NDC number in humanreadable form). There are some products 

(e.g. allergenic extracts) that do not 

currently print NDC numbers on labels 

that would be obligated to do so under 

the proposed rule. 

We lack specific data on the 

proportion of affected labels, but believe 

that 50 percent would be revised to 

include the ‘‘NDC’’ prefix and an 

additional 10 percent may be accounted 

in one of the other categories. (Although 

the exact proportion of labels affected 

by this provision is unknown, we expect 

between 25 and 75 percent of all drug 

labels to require revisions. We have 

assumed that 50 percent of all labels 

will be affected for analytic purposes.) 

Therefore, ERG estimated that 46,800 

separately packaged drug products 

would need revised relabels under the 

proposed rule. 

Prescription drugs would be required 

to have revised labels that include 

appropriate human-readable NDC 

numbers within 3 years of the effective 

date of the final rule. Therefore, 

incremental regulatory costs would 

occur for any product label not revised 

during routine label changes that may 

occur during the 3-year period. (ERG 

has assumed that no incremental cost 

occurs if required label changes occur 

during other label revisions.) FDA has 

examined a number of prescription drug 

files and found that prescription 

products are sometimes revised as 

frequently as once a year. However, 

some prescription products rarely have 

label revisions in response to market 

conditions. We have assumed that 25 

percent of prescription drug labels 

would not be revised during the 3-year 

implementation period in the absence of 

the proposed rule, or 11,700 separately 

packaged drug products. 

ERG has estimated weighted label 

revisions as costing an average of about 

$1,600 per separately packaged product 

(Ref. 5.) The cost of revising 

prescription human drug labels to 

include NDC numbers is estimated to 

total $18.7 million (11,700 separately 

packaged drug products x $1,600 per 

label revision.) However, these costs are 

not expected until 3 years after the 

implementation of the final rule because 

companies would not know if there 

would be market driven label changes 

and therefore wait until the end of the 

implementation period. The present 

values of the cost of these label 

revisions are $17.1 million (using a 3- 

percent annual discount rate) and $15.3 

million (using a 7-percent annual 

discount rate.) 

OTC human drugs: FDA has estimated 

that only 30 percent of all human OTC 

separately packaged products currently 

have human-readable NDC numbers 

printed on labels. However, the 

proposed rule allows for a 7-year 

implementation period for OTC drugs to 

include NDC numbers on labels. Based 

on previous studies of the OTC drug 

industry (Ref. 5), ERG has estimated that 

virtually all OTC drugs have label 

revisions within 6-year periods. Label 

changes over this period are mostly 

motivated by marketing trends and 

because ample space is usually available 

on most OTC labels, the inclusion of 

NDC numbers could be accommodated 

during these revisions at minimal 

additional cost. 

However, ERG discussions with 

industry contacts raised concerns about 

the new label requirements as they 

apply at the OTC unit-of-use level (e.g., 

blister packs). Most drugs marketed as 

units-of-use, including those subject to 

the bar code rule, would require label 

changes, but not changes to packaging 

or printing equipment, and are of 

sufficient size to accommodate humanreadable NDC numbers. However, some 

packaging lines for unit-of-use OTC 

products not subject to the bar code rule 

might need to be retooled to 

accommodate human-readable NDC 

numbers. These modifications are 

expected to be fairly challenging and the 

costs of applying NDC numbers to 

blister packs would be in addition to 

normal label revisions. ERG discussed 

the costs of these changes and found 

that line retooling costs to be 

approximately 150 percent of a normal 

label revision, or $2,400 for each 

affected drug. Industry consultants 

estimated that as many as 5,000 unitsof-use packaged OTC human drugs 

could be affected. The cost to label 

units-of-use drugs is $12.0 million 

(5,000 drugs x $2,400 per drug). Unlike 

voluntary label revisions, manufacturers 

are not expected to routinely retool 

production lines during the 

implementation period. Therefore, 

affected companies are expected to 

upgrade lines during the 7-year 

implementation period with an industry 

cost of $1.7 million each year. The 

present values of this cost are equal to 

$10.6 million (using a 3-percent annual 

discount rate) and $9.2 million (using a 

7-percent discount rate). 

Prescription and OTC animal drugs: 

ERG estimated that each of the 2,100 

registered domestic animal drug sites 

produce 4 separately packaged drug 

products and that normal label revisions 

occur at the same rate as for human 

drugs. In addition, industry consultants 

have estimated that approximately 40 

percent of animal drugs currently have 

readable NDC numbers on labels and 

would not be affected by the proposed 

rule. Thus, ERG expects that of the 60 

percent of labels that would need 

revisions, 75 percent would be revised 

in the normal course of business during 

the 3 years after implementation of the 

final rule. Therefore, a total of 

approximately 1,300 animal drugs 

would require revised labels to include 

human readable NDC numbers (both 

prescription and OTC) (2,100 sites x 4 

separately packaged products x 0.6 

needing label revisions x 0.25). Using a 

weighted cost per labeling revision of 

$1,600, the cost during the third year to 

the industry of applying NDC numbers 

to labels due to the proposed rule would 

be $ 2.1 million (2,100 separately 

packaged products x $1,600 per label 

change). The present value of this cost 

is $1.9 million (using a 3-percent annual 

discount rate) and $1.7 million (using a 

7-percent discount rate). We do not 

believe there will be costs associated 

with retooling package lines for animal 

drugs. 

Active pharmaceutical ingredients. 

Active pharmaceutical ingredients 

would be required to bear appropriate 

human-readable NDC numbers on drug 

labels under the proposed rule. 

Currently, many active pharmaceutical 

ingredients are shipped with bills of 


jlentini on PROD1PC65 with PROPOSAL2
51334 Federal Register / Vol. 71, No. 167 / Tuesday, August 29, 2006 / Proposed Rules 

lading that are prepared for each 

shipment and an NDC number could be 

easily added for a negligible incremental 

cost. For the purposes of this analysis, 

we have assumed that 50 percent of all 

active pharmaceutical ingredients will 

be required to add human-readable NDC 

numbers as a result of this proposed 

rule. According to FDA’s current 

registration and listing data, there are 

about 4,300 domestic bulk drug 

substances so about 2,150 are expected 

to require label changes because of the 

proposed rule. The costs of providing 

label changes for active pharmaceutical 

ingredients are assumed to be equal to 

the cost of label revisions for 

prescription drug products, or $1,600 

per revised label. The total cost of 

revising active pharmaceutical 

ingredient labels is $3.4 million (2,150 

labels x $1,600 per label). We have no 

data on voluntary label revisions for 

active pharmaceutical ingredients and 

have assumed that the revisions will 

occur throughout the implementation 

period (approximately $1.1 million per 

year). The present values for this cost 

are $3.2 million (using a 3-percent 

annual discount rate) and $3.0 million 

(using a 7-percent annual discount rate). 

Total costs of label revisions. The 

overall incremental costs of label 

revisions under the proposed rule have 

present values of $34.0 million (using a 

3-percent annual discount rate) and 

$30.3 million (using a 7-percent 

discount rate). 

c. Costs of setting up electronic 

submission of registration, listing, and 

content of labels. The proposed rule 

would require manufacturers, repackers, 

relabelers, and drug product salvagers of 

drugs, including human and animal 

drug products, active pharmaceutical 

ingredients, and biological products to 

register establishments, list drugs, and, 

for manufacturers, to provide the 

content of labeling electronically using 

specific software. Most, but not all, 

manufacturers of human prescription 

drug and biological drug products are 

already subject to requirements to 

submit content of labeling in electronic 

format, but manufacturers of OTC 

monograph and animal drug products 

not currently subject to these labeling 

requirements would not necessarily 

have this software. The current 

requirement to submit content of 

labeling in electronic form does not 

extend to repackers and relabelers. In 

addition, active pharmaceutical 

manufacturers producing ingredients for 

OTC drug products may not have the 

correct software to submit registration 

and listing information electronically. 

According to discussions with 

industry consultants, approximately 75 

percent of drug product manufacturers 

market only OTC monograph products. 

Using U.S. Census estimates of the 

industry, we believe about 550 firms 

would need to purchase needed 

software for electronic submissions for 

content of labeling. We note that this 

estimate is based on the first level of 

ownership and does not account for 

multiple layers of corporate hierarchy. 

We surveyed a range of prices for 

software (such as Adobe Acrobat 

Standard, for example) that would be 

expected to be used in a professional 

environment. The estimated price of 

this software is approximately $250, 

with some variance for the specific 

desired features and sophistication. We 

note that this cost represents the 

marginal difference between any current 

software and new software with the 

capability to work with assigned NDC 

numbers, and is an incremental cost of 

the proposed rule. After discussing this 

estimate with industry IT personnel, we 

expect $250 to represent a reasonable 

cost of software acquisition. In addition, 

training for 2 employees is expected to 

cost $150 per employee. Training is 

expected to require 6 hours for each 

employee at a cost of $51.73 per hour 

(based on fully loaded BLS wage rates 

for mid-level management within this 

industry). The total cost per firm is 

about $1,000 ($250 + (2 employees x 

$150) + (2 employees x 6 hours x 

$51.73) for a total cost to the OTC 

monograph industry for software 

acquisition and training to be $0.6 

million to submit content of labeling 

electronically. 

We expect similar costs of $1,000 

would accrue for all 350 companies that 

are predominantly involved in 

medicinal and botanical manufacturing 

(Census, 2004), which includes active 

pharmaceutical ingredient 

manufacturers, in order for these 

companies to electronically submit 

registration and listing information. 

According to Small Business 

Administration data, as well as industry 

consultants, there are approximately 

250 repackers and relabelers that serve 

the pharmaceutical industry. Each of 

these entities would require software 

and training in order to register and list. 

Finally, there are 80 firms that, 

according to U.S. Census data, 

predominantly or secondarily 

manufacture animal drugs that would 

require software and training to 

electronically submit content of 

labeling. The total costs of software 

acquisition and training for these 

segments is an additional $0.7 million 

((350 active pharmaceutical ingredient 

manufacturers + 250 repackers and 

relabelers + 80 animal drug 

manufacturers) x $1,000). 

The overall cost of software 

acquisition and training under the 

proposed rule is $1.4 million. 

d. Costs of continuing submissions of 

content of labeling. Additional costs 

might be incurred to submit the 

incremental content of labeling for a 

small proportion of drugs for which 

there have been labeling changes. The 

content of labeling, as described 

elsewhere in this proposal, must be 

submitted electronically. Makers of 

active pharmaceutical ingredients are 

not affected by this provision because 

they would not be expected to submit 

content of labeling electronically. 

For affected OTC drugs, we have 

assumed that two content of labeling 

submissions per listed drug will occur 

twice a year to account for the 

possibility of multiple dosage forms and 

concentrations in a product line. 

Animal products are expected to have 

an average of 1.5 content of labeling 

submissions per product twice a year. 

According to our drug listing system, 

there are about 30,400 domestic OTC 

drugs and about 4,200 domestic animal 

drugs. Using the assumption that each 

submission would entail 0.25 hours (15 

minutes), and using the industry wage 

rate of $51.73 per hour, the annual cost 

of this provision is $1.7 million 

((((30,400 domestic OTC drugs x 2 

content of labeling submittals) + (4,200 

domestic animal drugs x 1.5 content of 

labeling submittals)) x 2 times per year) 

x 0.25 hours per submission x $51.73 

per hour). 

e. Delays in NDC Assignment. We 

understand from discussions with 

manufacturers that many manufacturing 

processes are dependent on timely 

assignment of NDC numbers. According 

to industry consultants, before drugs 

can be mass-produced, manufacturers of 

both prescription and OTC drug 

products need to know the NDC number 

for the production run. Currently, 

manufacturers control the assignment of 

NDC numbers once they have a labeler 

code, so this is not a problem that could 

affect the production process. There is 

concern about delays in production 

because new NDC numbers assigned by 

us might not be timely from a 

manufacturer’s viewpoint and could 

result in major costs. 

However, in discussions with several 

manufacturers, comments to ERG 

reflected that if the assignment of NDC 

numbers by FDA was done 

electronically and transmitted to the 

companies electronically, there would 

likely be a negligible impact on 

operations. Since FDA intends to assign 

and transmit NDC numbers 


jlentini on PROD1PC65 with PROPOSAL2
Federal Register / Vol. 71, No. 167 / Tuesday, August 29, 2006 / Proposed Rules 51335 

electronically, we do not believe this 

provision would result in additional 

costs to industry. 

f. Effect of the proposed rule on thirdparty reimbursement. Under the 

proposal, repackers and relabelers 

would not be allowed to use the 

manufacturer’s human-readable NDC 

numbers on their drug labels. Many 

companies noted that reimbursement 

arrangements are contracted between 

drug manufacturers and third-party 

payers (including Medicaid programs) 

that provide for rebates for sales of a 

manufacturer’s drug. Most 

reimbursement plans use NDC numbers 

as the appropriate billing code, and 

repackers and relabelers note that they 

are not part of the negotiated rebate 

plans between manufacturers and thirdparty payers. Repackers and relabelers 

further claim that profit margins for 

their firms will not allow for such 

reimbursements. Thus, the process of 

negotiating these payments would be 

affected by the proposed rule, but we 

did not estimate the outcome of future 

negotiations. 

g. Other potential costs. The proposed 

rule might have other impacts on 

various industry sectors. For example, 

the relationships between drug 

manufacturers and private label 

distributors may be altered because of 

the proposed registration, listing, and 

NDC requirements. Some industry 

sources have asserted that the proposed 

rule may make private label distributors 

unprofitable and that manufacturers 

would directly supply drugs to retailers. 

We are unable to assess this impact, and 

are unsure whether it would, in fact, 

result in market inefficiencies, but note 

that there would likely be changes in 

the current relationships between these 

sectors. We specifically request 

comment on any economic impact the 

proposal would have on this 

relationship between drug 

manufacturers and private label 

distributors. 

3. Costs to FDA for Implementing the 

Proposed Rule 

We do not expect a major increase in 

the need for internal resources 

associated with the proposed rule. 

Activities related to the assignment of 

NDC numbers are expected to be 

equivalent to our current activity of 

receiving notifications from industry 

and manually inputting the information 

into our databases. Similarly, we expect 

any increased workloads caused by 

increased submissions of registration or 

listing information or content of labeling 

to be approximately equivalent to the 

internal reduction in workload from 

electronically updating our databases. 

The database of NDC numbers for 

marketed drugs would require 

maintenance and updating to ensure the 

quality of the data, and we would make 

this database available for other users, 

but the costs associated with activity 

have been accounted for in previous 

rule-making (see Bar Code Label 

Requirements for Human Drug Products 

and Human Biological Products, 69 FR 

9120 at 9156). The registration and 

listing information will also be included 

in the database and we do not expect 

any additional costs to be associated 

with maintenance of this information. 

However, the requirement that 

manufacturers, repackers, relabelers, 

and drug product salvagers obtain a user 

account from us would require 

increased use of our resources. We have 

estimated that 6,700 entities would be 

contacted in order to provide them with 

their user accounts, and that each 

contact would require 0.25 hours (15 

minutes). This would require about 

1,600 hours of FDA resources, or about 

0.8 FTEs. The current weighted cost per 

FTE is approximately $120,000, so the 

one-time cost to FDA for providing 

access codes for the proposed rule 

would be approximately $0.1 million. 

4. Total Costs of the Proposed Rule 

Table 3 shows the initial investment 

costs and annual costs of the proposed 

rule over a 10-year period by cost 

category. 

TABLE 3.—UNDISCOUNTED COSTS OF PROPOSED RULE BY CATEGORY (IN MILLIONS OF DOLLARS) 

Cost Category Initial Investment/One 

Time Annual Costs/Recurring 

Single Method of Assigning NDC Numbers $3.8 $3.2 

Electronic Drug Registration and Listing $0.2 (-$3.8) 

Label Revisions $36.2 ———

Software Acquisition and Training $1.3 ———

Continued COL Submissions ———- $1.7 

Table 4 shows the expected 

expenditures per year for the evaluation 

period and includes total present values 

based on 7 percent and 3 percent 

discount rates. Recurring costs include 

the retooling of OTC packaging systems 

to provide NDC numbers for units-ofuse during the first 7 years of the 

proposed regulation. 

TABLE 4.—COSTS PER YEAR FOR THE

PROPOSED RULE (IN MILLIONS OF

DOLLARS) 

Year One-Time 

Costs 

Recurring 

Costs 

1 $8.1 $1.1 

2 $2.8 $1.1 

3 $23.7 $1.1 

4 $1.7 $1.1 

5 $1.7 $1.1 

6 $1.7 $1.1 

TABLE 4.—COSTS PER YEAR FOR THE

PROPOSED RULE (IN MILLIONS OF

DOLLARS)—Continued 

Year One-Time 

Costs 

Recurring 

Costs 

7 $1.8 $1.1 

8 - $1.1 

9 - $1.1 

10 - $1.1 

Present Value 3% - $38.1 3% - $9.4 

7% - $33.0 7% - $7.7 


jlentini on PROD1PC65 with PROPOSAL2
51336 Federal Register / Vol. 71, No. 167 / Tuesday, August 29, 2006 / Proposed Rules 

Average annualized costs of the 

proposed rule are estimated to be $5.6 

million using a 3 percent annual 

discount rate or $5.8 million using a 7 

percent annual discount rate. 

F. Benefits 

Benefits of the proposed rule will 

result because the improved processes 

in the proposed regulation would 

generate up-to-date, complete 

medication information, including NDC 

numbers, to support a growing number 

of medical and health information 

technology initiatives. The potential 

benefits of these initiatives are 

significant. For example, the final 

regulation that required bar coded NDC 

numbers on some human drugs and 

biological products (69 FR 9120) 

estimated benefits of approximately $5 

billion per year for the avoidance of 

over 500,000 adverse drug events 

associated with medication errors. 

These benefits are dependent on correct 

and unique NDC numbers being read by 

scanners at patient bedsides. The lack of 

accurate NDC numbers may delay the 

acceptance of this technology and 

decrease the potential patient benefits. 

We have estimated that if the lack of 

reliable NDC numbers would delay the 

rate of technological acceptance by 1 

year, the potential benefits of the bar 

code regulation would be reduced by 

about $600 million per year and an 

average of 25,000 additional adverse 

drug events would occur. 

We believe it is critical to other 

patient safety initiatives, such as 

DailyMed or electronic prescribing, that 

a reliable and consistent NDC 

numbering system be in place. The 

potential benefits of these initiatives 

could be similar to the benefits of the 

bar code rule, and any delay in 

implementing these programs because 

of the lack of electronic access to 

reliable identifying information could 

seriously limit their impacts. 

The proposed rule would allow 

increased access to information in our 

databases. Increased use of these 

databases to efficiently treat patients 

would rely on the availability of 

information electronically. A key 

element for encouraging the use of 

technology to ensure public health will 

be the assurance that NDC numbers are 

unique and accurately identify drugs. 

The proposed rule would accomplish 

this by making assignment of NDC 

numbers our responsibility, rather than 

a responsibility diffused throughout the 

industry. In addition, by ensuring that 

these NDC numbers are available in 

human-readable format, patients and 

others would be able to access 

important patient safety information 

from the DailyMed system, the NDC 

Directory, or other drug information 

electronic systems without the use of 

bar code scanners. Human-readable 

NDC numbers would allow patients to 

report any adverse events easily and 

ensure that our adverse event reporting 

system is as accessible as possible. Also, 

the human-readable NDC number would 

enable us to trace the origin of each 

product (a particularly important issue 

when dealing with recalls or drug 

quality issues) and more easily identify 

drug products and their sources (this is 

particularly important when dealing 

with import and counterfeiting issues). 

We specifically request comments on 

quantitative benefits resulting from the 

requirement that the NDC number be 

included on the drug label. 

The proposed rule would increase the 

efficiency of the registration and listing 

process by eliminating most paper 

submissions. We would be able to 

review the submitted information more 

quickly and contact submitting firms 

immediately if any additional 

information were needed. The resulting 

database of registered establishments 

and listed drugs would provide the 

basis for increased patient safety by 

being complete and up-to-date. For 

example, an electronic database of drugs 

would allow for timely notification of 

any recalls of unsafe drugs and 

identification of affected manufacturers, 

repackers, relabelers, or drug product 

salvagers. 

By changing the way that NDC 

numbers are assigned, we would 

increase the confidence that each drug 

being manufactured, repacked, or 

relabeled for commercial distribution 

has a unique identifier that we have 

assigned. After we have introduced 

increased oversight for new product 

codes and package codes, the likelihood 

of unsafe counterfeit drug products 

entering the supply chain would decline 

because would-be counterfeiters would 

be unsure of numerical sequences used 

for NDC numbers. Our assignment of 

NDC numbers would reduce the 

possibility of duplicate numbers 

appearing in various medical and 

reimbursement databases. Currently, 

firms have been reusing NDC numbers 

at times without informing us, and this 

practice has added uncertainty into 

these systems. There has been reported 

confusion about coverage of drugs for 

reimbursement and our control of the 

NDC system would ensure that only 

qualified drugs are subject to 

reimbursement. 

In addition, the current NDC number 

makeup (using dashes to distinguish 

between the components) allows for 

potential duplicate numbers when the 

dashes are not read by scanners reading 

NDC numbers encoded in bar codes. 

This happens because the components 

used to indicate labeler codes, product 

codes, and package codes are of 

differing lengths, and are currently 

separated by hyphens. If those NDC 

numbers are barcoded, the differing 

components may lead to duplicate 

numbers since bar code scanners don’t 

read hyphens. This would not happen 

under the proposed rule. 

Although we know that the proposed 

rule will result in significant benefits, 

we are not able to quantify these 

benefits. We are confident that moving 

to electronic registration and listing 

processes, as well as assignment of NDC 

numbers, would encourage 

development of technology in the 

delivery of health care. We know that 

the successful development of medical 

and health information technology 

initiatives (such as the DailyMed, bar 

code label, and the electronic 

prescription drug program described 

below) will depend in large part on an 

accurate, reliable NDC number and that 

this proposed rule would further that 

development. Therefore, there are real 

benefits associated with the proposed 

changes to the NDC number and the 

NDC number assignment process. 

However, we are not able to quantify 

those benefits because they rely in part 

on further development of technology 

initiatives. Similarly, there are 

significant benefits associated with the 

proposed changes to the collection of 

registration and listing information. For 

example, ready access to complete and 

accurate registration and listing 

information helps to ensure the success 

of many of our programs, such as 

postmarketing surveillance (including 

FDA inspections), bioterrorism 

initiatives, responses to drug shortages, 

and user fee assessments. We know 

there are benefits associated with the 

efficiencies achieved by improved 

access to more complete information, 

but we are not able to quantify those 

benefits. 

We also note that continuation of a 

paper registration and listing system is 

likely to act as a deterrent to investment 

in new initiatives. As discussed earlier 

in this document, the recently issued 

final regulation that requires NDC 

numbers to be encoded in bar codes on 

certain prescription drugs, certain OTC 

products, and human blood products 

helps to avoid adverse drug events due 

to medication errors. The benefits for 

that rule would be reduced by as much 

as $600 million per year if unique NDC 

numbers are not universally available 

and this results in delays in the use of 

this technology. Lack of universal 


jlentini on PROD1PC65 with PROPOSAL2
Federal Register / Vol. 71, No. 167 / Tuesday, August 29, 2006 / Proposed Rules 51337 

identifiers would likely discourage 

investment in machine-readable 

technology and make access to 

electronic information difficult. 

The proposed rule would provide 

necessary assurances to health 

professionals and patients that they 

have access to up-to-date labeling 

information and that the safety of the 

drug supply is assured. It would also 

encourage investment in installed 

scanners and readers at points of 

administration such as hospitals or 

physician clinics that rely on this 

information. The existence of this 

system may support the development of 

electronic prescribing or other 

efficiencies in health care that may save 

money and reduce medication errors 

that may cause adverse reactions in 

patients. The electronic prescription 

drug program (electronic prescribing) 

established by the Medicare 

Modernization Act promotes uniform 

standards that permit (among other 

things) electronic exchange of drug 

labeling and drug listing information 

maintained by us and by the National 

Library of Medicine. The goal behind 

the program is to reduce transcription 

and dispensing errors (which, in turn, 

lead to medication errors) and to 

prevent adverse drug interactions. The 

proposal to assign the NDC number, 

resulting in an accurate and reliable 

NDC number, would also facilitate 

development of the DailyMed). The 

DailyMed is an up-to-date, 

computerized repository of medication 

information, including drug product 

labeling. The DailyMed, maintained by 

the National Library of Medicine in 

cooperation with FDA, is a new way to 

distribute current and comprehensive 

medication information in a 

computerized format for use in health 

care information systems. Health care 

information suppliers will be able to use 

the information from the DailyMed in 

their computer systems, allowing 

providers, patients, and the public 

access to reliable, up-to-date 

information on the medications they 

use. The DailyMed would enable drug 

product users and health care providers 

to have electronic access to up-to-date 

information about a drug. 

Although the scope of the proposed 

rule does not extend beyond registration 

and listing, the high-quality, electronic 

database that would result from the 

proposed rule would enable future uses 

of technology for the public benefit. 

G. Small Business Analysis and 

Discussion of Alternatives 

We believe the proposed rule is 

unlikely to have a significant impact on 

a substantial number of small entities. 

Despite this, we have prepared an initial 

regulatory flexibility analysis and invite 

comment from affected entities. 

1. Affected Sectors and Nature of 

Impacts 

The proposed rule would directly 

affect manufacturers of pharmaceutical 

and biological products (NAICS 325412 

and NAICS 325414), packaging services 

(NAICS 561910), retail pharmacy chains 

(NAICS 446110; Pharmacies), and 

prescription benefit managers (NAICS 

524292; Insurance Plan Administrative 

Services, Third Party). We assessed data 

on these industries from the 2002 

Economic Censuses and estimated 

revenues per establishment. The 

affected establishments are shown in 

table 2a of this document. Although 

other economic measures, such as 

profitability, may provide preferable 

alternatives to revenues as a basis for 

estimating the significance of regulatory 

impacts in some cases, use of any 

reasonable estimate of profits would not 

change the results of this analysis. As 

discussed earlier in the Analysis of 

Economic Impacts (see section VI.B of 

this document), we are proposing this 

rule in order to improve the quality and 

timeliness of information available to 

patients and health care professionals. 

We believe this improvement would 

result in improved outcomes by 

providing better uses of medicines by 

patients. 

a. Pharmaceutical manufacturers 

(NAICS 325412). The Small Business 

Administration (SBA) has defined as 

small any entity in this industry with 

fewer than 750 employees. According to 

census data, 94 percent of the industry 

is considered small. The average annual 

revenue for these small entities is $54.7 

million per entity. Small entities would 

be affected by the proposed rule. We 

estimate the annualized compliance cost 

for small entities in this industry to 

average $30,200. This is about 0.1 

percent of their annual revenue. We 

believe this cost does not constitute a 

significant impact on a substantial 

number of small entities in this 

industry. 

b. Biological product manufacturers 

(NAICS 325414). The SBA has defined 

as small any entity in this industry with 

fewer than 750 employees. According to 

census data, 97 percent of the industry 

is considered small. The average annual 

revenue for these small entities is $15.5 

million per entity. Small manufacturers 

of biological products would be affected 

by the proposed rule. We estimate the 

annualized compliance cost for a small 

entity in this industry to be $30,200. 

This is about 0.2 percent of their annual 

revenues. We believe this does not 

constitute a significant impact on a 

substantial number of small entities in 

this industry. 

c. Packaging services (NAICS 561910). 

The SBA has defined as small any entity 

in this industry that has less than $6.5 

million in annual revenue. On this 

basis, almost 94 percent of the industry 

is considered small. The average annual 

revenue for small entities is $1.4 million 

per entity. We have not identified 

specific regulatory costs of compliance 

to this industry. We have no confident 

data that the extent of electronic 

registration and listing would increase 

or decrease costs to these entities. At 

this point, we tentatively believe the 

proposed rule would not constitute a 

significant impact on a substantial 

number of small entities in this industry 

and solicit comment in this area. 

d. Retail pharmacy chains (NAICS 

446110). The SBA has defined as small 

any entity in this industry that has less 

than $6.5 million in revenue. On this 

basis, almost 100 percent of the industry 

is considered small. The average annual 

revenue for small entities is $3.8 million 

per entity. We expect that some large 

pharmacy chains with 35 or more 

operations would experience increased 

operating cost of $200,000 due to the 

proposed rule. However, these large 

chains do not meet the criteria for small 

entities because their annual revenues 

are at least $133 million ($3.8 million 

times 35 outlets). We do not believe this 

impact constitutes a significant impact 

on a substantial number of small entities 

in this industry. 

We do not believe that independent 

retail pharmacies will be adversely 

affected by the proposed rule because 

most pharmacy systems do not use the 

internal component of NDC numbers. 

We found no evidence of any impacts, 

but specifically request comment on this 

issue. 

e. Prescription benefit managers 

(NAICS 524292). The SBA has defined 

as small any entity in this industry that 

has less than $6.5 million in annual 

revenues. On this basis, over 92 percent 

of the industry is considered small. The 

average annual revenue for small 

entities is $1.6 million per entity. We 

are unable to distinguish PBMs from 

other insurance administrative services, 

but have used aggregate industry data. 

Some PBMs would be expected to 

experience annual cost increases of 

$200,000 due to the proposed rule. This 

constitutes 12.5 percent of annual 

revenues for the affected entities. 

However, of the 11,584 small entities in 

this industry (there are only 76 PBMs of 

any size) we expect that between 7 and 

8 entities would be affected. We do not 

believe this constitutes a significant 


jlentini on PROD1PC65 with PROPOSAL2
51338 Federal Register / Vol. 71, No. 167 / Tuesday, August 29, 2006 / Proposed Rules 

impact on a substantial number of small 

entities in this industry. 

2. Alternatives 

We considered several alternatives to 

the proposed rule. Each is discussed 

below. 

a. Completely reassign NDC numbers, 

including existing numbers. We 

considered removing the existing format 

of the NDC number and reassigning 

randomized numbers for all products. 

We believe this would improve the 

robustness of the NDC and allow more 

numbers to be available for future drugs 

as well as improve our industry 

oversight responsibilities. However, 

discussions with industry 

representatives suggested that the firstyear cost of such an approach could 

reach more than $900 million. 

Pharmaceutical manufacturers would be 

required to completely remap the newly 

assigned NDC numbers so that existing 

data processing, rebate, and market 

analyses tasks could continue. While 

individual retail pharmacies would not 

likely be affected, chain stores and 

PBMs would require large internal 

reprogramming in order to manage 

repayment options. Additional quality 

control procedures would be required to 

ensure proper reimbursement. 

Wholesalers and distributors would also 

require major internal reprogramming to 

account for the loss of sequential NDC 

numbers. For this alternative, each State 

Medicaid program would require an 

estimated $3 million to reprogram 

reimbursement software so that each 

prescription could be tracked. This 

alternative is described in more detail in 

Reference 3. 

b. Implementation period. We 

considered (and are still considering) 

different implementation periods. 

Under the proposal, manufacturers, 

repackers, and relabelers of prescription 

drugs would have 3 years to provide 

NDC numbers on their labels, while 

manufacturers, repackers, and relabelers 

of OTC drugs would have 7 years. We 

examined a total of 25 different 

implementation plans. These plans 

include prescription products having 

between 1 year and 5 years to comply 

and OTC products having between 5 

years and 9 years to comply with the 

proposed rule. Table 5 shows the 

difference in average annualized costs 

between the current implementation 

plan and the other 24 combinations. 

TABLE 5.—DIFFERENCES IN ANNUALIZED COSTS OF DIFFERING IMPLEMENTATION PERIODS (IN MILLIONS OF DOLLARS; 7 

PERCENT DISCOUNT RATE) 

5 Year OTC 6 Year OTC 7 Year OTC 8 Year OTC 9 Year OTC 

1 Year Prescription +$2.1 +$2.0 +$1.9 +$1.9 +$1.9 

2 Year Prescription +$1.4 +$1.2 +$1.2 +$1.2 +$1.1 

3 Year Prescription +$0.2 0 —— -$0.1 -$0.1 

4 Year Prescription -$0.9 -$1.0 -$1.0 -$1.0 -$1.1 

5 Year Prescription -$1.4 -$1.5 -$1.5 -$1.6 -$1.6 

There was relatively little difference 

in changes to the OTC drug 

implementation period because of the 

ongoing normal revisions to labeling. 

Only if a 5-year implementation period 

is selected are there noticeable cost 

increases. However, shorter 

implementation periods for prescription 

products increase costs by about 20 

percent for a 2-year implementation 

period and about 33 percent for a 1-year 

period. Conversely, while longer 

implementation periods would reduce 

annualized costs by similar amounts, 

the delay in ensuring that medical 

information technologies would be able 

to use efficiencies expected from the 

proposed rule seemed high. Therefore, 

we selected the proposed 

implementation periods as a reasonable 

balance. We solicit public comment on 

the proposed implementation period 

and the effect on expected costs and 

benefits. 

c. Exemption for small entities. We 

considered exempting small entities, but 

rejected the alternative due to the 

relatively modest impact of this 

initiative on small businesses and the 

lack of label standardization that would 

result. Any potential exemptions to this 

proposed rule would be on a product 

basis, not an entity basis. In addition, 

benefits of having a standardized 

identification system would be reduced 

by such blanket exemptions. 

Outreach: We will specifically solicit 

comment from affected small entities on 

the proposed rule. 

d. Conclusion. We have analyzed the 

expected impacts of the proposed rule. 

This proposal is expected to have 

average annualized costs of $5.6 million 

(using a 3 percent annual discount rate) 

or $5.8 million (using a 7 percent 

annual discount rate). The benefits 

include assurance of correct NDC 

numbers, which would also mean 

correct bar-coded information, and 

electronic access to important product 

information for patients that will 

improve public health. Despite the fact 

that we are unable to specifically 

quantify patient benefits directly 

attributable to the proposed rule, we 

believe the benefits would be greater 

than the expected costs and the 

proposed rule should be implemented. 

VII. Paperwork Reduction Act of 1995 

This proposed rule contains 

collections of information that are 

subject to review by the Office of 

Management and Budget (OMB) under 

the Paperwork Reduction Act of 1995 

(the PRA) (44 U.S.C. 3501 3520). 

‘‘Collection of information’’ includes 

any request or requirement that persons 

obtain, maintain, retain, or report 

information to the agency, or disclose 

information to a third party or to the 

public (44 U.S.C. 3502(3) and 5 CFR 

1320.3(c)). The title, description, and 

respondent description of the 

information collection are shown under 

this section with an estimate of the 

annual reporting burden. Included in 

the estimate is the time for reviewing 

instructions, searching existing data 

sources, gathering and maintaining the 

data needed, and completing and 

reviewing the collection of information. 

We invite comments on these topics: 

(1) Whether the collection of 

information is necessary for proper 

performance of FDA’s functions, 

including whether the information will 

have practical utility; (2) the accuracy of 

FDA’s estimate of the burden of the 

proposed collection of information, 

including the validity of the 

methodology and assumptions used; (3) 

ways to enhance the quality, utility, and 

clarity of the information to be 


jlentini on PROD1PC65 with PROPOSAL2
Federal Register / Vol. 71, No. 167 / Tuesday, August 29, 2006 / Proposed Rules 51339 

13The electronic submission of registration and 

listing information would remain voluntary for 

blood products. 

collected; and (4) ways to minimize the 

burden of the collection of information 

on respondents, including through the 

use of automated collection techniques, 

when appropriate, and other forms of 

information technology. 

Title: Requirements for Foreign and 

Domestic Establishment Registration 

and Listing for Human Drugs, Including 

Drugs that are Regulated Under a 

Biologics License Application, and 

Animal Drugs 

Description: The proposed rule would 

reorganize, consolidate, clarify, and 

modify current regulations on 

registering establishments and listing 

human and animal drugs under part 

207, blood and blood products under 

part 607, and HCT/Ps under part 1271. 

The proposal describes when and how 

to register and list and what information 

must be submitted for registration and 

listing. The proposal makes certain 

changes to the NDC system for drugs 

and would require the appropriate NDC 

number to appear on drug labels (for 

drugs subject to the drug listing 

requirements). The proposed regulations 

would require the electronic submission 

of all registration and most listing 

information instead of the current use of 

paper forms.13

FDA currently reviews completed 

registration and listing forms and other 

submissions required under current 

parts 207, 607, and 1271. The 

information collection for current part 

207 is approved by OMB until 

December 31, 2007, under OMB Control 

Number 0910–0045. The information 

collection for current part 607 and Form 

FDA 2830 is approved by OMB until 

March 31, 2009, under OMB Control 

Number 0910–0052. The information 

collection for current part 1271 and 

Form FDA 3356 is approved by OMB 

until July 31, 2007, under OMB Control 

Number 0910–0469. 

FDA has estimated, in Tables 6, 7, and 

8 of this document, the burden to 

comply with all of the information 

collection requirements for proposed 

parts 207, 607, and 1271. These 

estimates are based on FDA’s experience 

in reviewing registration and listing 

submissions and on the number of 

submissions currently received, the 

number of respondents submitting this 

information, and the number of 

registered establishments and listed 

drugs, blood products, and HCT/Ps 

currently in FDA’s database. The 

estimates discussed below are for each 

section of proposed parts 207, 607, and 

1271 that contain a reporting burden 

under the PRA. 

A. Registration Information Under Part 

207 

1. Proposed Requirements 

Under proposed § 207.17, 

manufacturers, repackers, relabelers, 

and drug product salvagers must register 

establishments. This is consistent with 

current registration requirements, 

except that currently private label 

distributors may submit information 

(similar to registration information) to 

obtain a labeler code from FDA. In 

addition, the estimates include PET 

drug producers who would not be 

exempt from registration under the 

proposal. 

Under proposed § 207.21, domestic 

manufacturers, domestic repackers, 

domestic relabelers, and domestic drug 

product salvagers must complete initial 

registration of each establishment no 

later than 5 calendar days after 

beginning to manufacture, repack, 

relabel, or salvage a drug. In addition, 

foreign manufacturers, foreign 

repackers, foreign relabelers, and foreign 

drug product salvagers must register 

each establishment before the drug is 

imported or offered for import into the 

United States. This is consistent with 

current registration requirements, 

except that the proposal would include 

additional foreign establishments as a 

result of the revocation of the exemption 

for drugs that enter a foreign trade zone 

and are re-exported from that foreign 

trade zone without having entered U.S. 

commerce, and for drugs imported 

under section 801(d)(3) of the act. 

The information that must be 

provided to FDA for registration is 

described under proposed § 207.25. The 

information that would be required 

under proposed § 207.25 differs from 

the information currently required for 

registration. The following currently 

required information would not be 

required under the proposal: The kind 

of ownership or operation and the title 

of each corporate officer and director. 

New information required under the 

proposal would be the type of 

operations performed at each 

establishment and contact information 

about the official contact and the United 

States agent, each importer of the drug 

that is known to the establishment, and 

each person who imports or offers for 

import the drug to the United States. 

Under proposed § 207.29, 

manufacturers, repackers, relabelers, 

and drug product salvagers must review 

annually their registration information. 

During the review, manufacturers, 

repackers, relabelers, and drug product 

salvagers must report all changes to 

their registration information or certify 

that no changes have occurred. In 

addition to the annual review and 

update, manufacturers, repackers, 

relabelers, and drug product salvagers 

must submit expedited reports of certain 

changes within 30 calendar days of the 

change. Currently, manufacturers, 

repackers, relabelers, and drug product 

salvagers must renew their registration 

information annually and submit certain 

amendments to registration within 5 

days of a change. Proposed § 207.29 

differs from the current requirement to 

submit amendments to registration in 

the following ways: The proposal would 

lengthen the current time period for 

reporting changes to registration 

information from 5 days (10 business 

days for a change in United States agent 

information) to 30 calendar days. The 

proposal would revoke the current 

requirement to report a change in 

individual ownership and corporate or 

partnership structure, and the current 

requirement to submit a signed 

statement for a change in a registered 

establishment’s firm name. New 

requirements under the proposal would 

be to certify that no changes have 

occurred and to report as expedited 

updates certain changes within 30 

calendar days, such as the close or sale 

of an establishment. Modified 

requirements would be to submit within 

30 calendar days a change in the name 

or address of an establishment and a 

change in contact information for the 

official contact and United States agent. 

2. Burden Estimates 

Based on the number of new 

establishments that currently register 

each year by submitting Form FDA 

2656, we estimate that approximately 

987 manufacturers, repackers, 

relabelers, and drug product salvagers 

will provide electronically 

approximately 1,128 new establishment 

registrations annually. Based on the 

number of registered establishments in 

our database, we estimate that 

approximately 8,343 manufacturers, 

repackers, relabelers, and drug product 

salvagers will provide approximately 

12,137 annual reviews and updates of 

registration information or reviews and 

certifications that no changes have 

occurred. Based on the number of 

changes to registration information that 

have been submitted annually on Form 

FDA 2656e, we estimate that 

approximately 775 manufacturers, 

repackers, relabelers, and drug product 

salvagers will provide approximately 

1,921 expedited updates. 

The estimates include the registration 

of establishments for both domestic and 


jlentini on PROD1PC65 with PROPOSAL2
51340 Federal Register / Vol. 71, No. 167 / Tuesday, August 29, 2006 / Proposed Rules 

foreign manufacturers, repackers, 

relabelers, and drug product salvagers. 

The estimates for the number of 

manufacturers, repackers, relabelers, 

and drug product salvagers excludes the 

number of private label distributors 

currently in the database that submit 

information to receive a labeler code. 

The estimates include an additional 80 

PET drug producers who would not be 

exempt from registration under the 

proposal, and approximately 30 

manufacturers of plasma derivatives. In 

addition, the estimates include five 

additional foreign establishments that 

would be required to register as a result 

of the revocation of the exemption for 

drugs that enter a foreign trade zone and 

are reexported from that foreign trade 

zone without having entered U.S. 

commerce, and for drugs imported 

under section 801(d)(3) of the act. 

We estimate that it will take 

approximately 60 minutes to provide 

electronically the initial registration 

information for each new establishment. 

This estimate is only until 

manufacturers, repackers, relabelers, 

and drug product salvagers become 

familiar with using the electronic drug 

registration and listing system. We 

intend to lower this burden estimate to 

approximately 30 minutes when we 

submit to OMB the request to renew 

approval of this information collection. 

We also estimate that it will take 

approximately 30 minutes for each 

annual review and update of registration 

information or each review and 

certification that no changes have 

occurred. This estimate is only until 

manufacturers, repackers, relabelers, 

and drug product salvagers become 

familiar with using the electronic drug 

registration and listing system. We 

intend to lower this burden estimate to 

approximately 15 minutes when we 

submit to OMB the request to renew 

approval of this information collection. 

We also estimate that it will take 

approximately 15 minutes to provide 

each expedited update. This estimate is 

only until manufacturers, repackers, 

relabelers, and drug product salvagers 

become familiar with using the 

electronic drug registration and listing 

system. We intend to lower this burden 

estimate to approximately 5 minutes 

when we submit to OMB the request to 

renew approval of this information 

collection. 

The burden hour estimates above are 

based on our familiarity with the 

content of current registration forms and 

submissions and the times required by 

industry volunteers to input registration 

information during our electronic drug 

registration and listing system pilot 

project (discussed in section IV.E.3 of 

this document). The estimates are an 

average of the time it would take to 

register a domestic or foreign 

establishment and an average of the 

time it would take to review registration 

information and update several 

registration items in the database or 

review registration information and only 

certify that no changes have occurred. 

We note that these estimates for the 

electronic submission of this 

information would be a reduction in the 

currently approved estimate of 2.50 

hours (OMB Control Number 0910–

0045) for preparing and mailing to FDA 

Form FDA 2656. 

We intend to migrate into our new 

database current registration 

information that had been submitted 

using paper forms. As a result, current 

manufacturers, repackers, relabelers, 

and drug product salvagers would 

require additional time to review in the 

new database all current registration 

information and make any necessary 

revisions. We assume that this one-time 

initial review will be the first annual 

review and update using the electronic 

system, and we estimate it will take an 

average of 30 minutes for each review 

and update. 

B. Listing Information Under Part 207 

1. Proposed Requirements 

Under proposed § 207.41, 

manufacturers, repackers, relabelers, 

and drug product salvagers must list 

drugs they manufacture, repack, relabel, 

or salvage for commercial distribution 

(this includes drugs they manufacture, 

repack, relabel, or salvage for a private 

label distributor). This proposed 

requirement is consistent with the 

current listing requirements, except that 

drug product salvagers are not currently 

required to list under part 207 and 

private label distributors may submit 

listing information directly to FDA. 

Under proposed § 207.45, 

manufacturers, repackers, relabelers, 

and drug product salvagers must list, at 

the time of initial registration of an 

establishment, any drug being 

manufactured, repacked, relabeled, or 

salvaged for commercial distribution at 

that establishment. This is consistent 

with the current listing requirements, 

except that drug product salvagers are 

not currently required to list under part 

207. 

Under the proposal, the humanreadable NDC number must appear on 

the drug’s label (for drugs subject to the 

listing requirements). The information 

that must be provided electronically to 

us by manufacturers, repackers, and 

relabelers (including drug product 

salvagers who repack and relabel) to 

receive an NDC number is described 

under proposed § 207.33. Currently, the 

human-readable NDC number is not 

required to appear on the drug’s label, 

but most prescription drugs and about 

one-third of the OTC drug products 

have the NDC number on the label. We 

currently assign a labeler code to each 

manufacturer, repacker, relabeler, and 

private label distributor to be part of the 

NDC number, and the manufacturer, 

repacker, relabeler, and private label 

distributor assigns the remainder of the 

NDC number to each drug product. 

Under the proposal, for drugs listed 

after the effective date of the proposal, 

the NDC number for a drug must be 

obtained from us before (or at the time) 

that drug is listed. Some of the 

information currently required to list 

the drug would be submitted under the 

proposal to receive the NDC number. 

The assigned NDC number would be 

submitted as part of the listing 

information and would serve as a link 

to the information already submitted for 

the drug to obtain the NDC number. 

The information that must be 

provided electronically to us by 

manufacturers, repackers, and relabelers 

to list a drug is described under 

proposed §§ 207.49, 207.53, 207.54, 

207.55, and 207.61. As mentioned 

previously in this document, drug 

product salvagers are not currently 

required to list the drugs they salvage. 

The listing information and the NDC 

number information required under the 

proposal is consistent with the 

information currently submitted to FDA 

on Forms FDA 2657 or 2658, except for 

the following: (1) The proposal would 

require identification information about 

the name of each importer of the drug 

that is known to the establishment and 

each person who imports or offers for 

import a drug to the United States 

(importer information is currently 

required under the Bioterrorism Act); (2) 

the content of labeling would be 

submitted electronically (for approved 

human drugs, the information collection 

burden for this requirement is 

accounted for under current 

§ 314.50(l)(1)(i), approved under OMB 

Control Number 0910–0001); (3) the 

quantity of the active pharmaceutical 

ingredient would be required for all 

drugs subject to the listing requirements 

(unless the approved application 

number is provided) (this requirement is 

substantially the same as the current 

requirement); (4) the name of the 

inactive ingredients for certain drugs 

would be required under the proposal 

(unless the approved application 

number is provided); (5) repackers and 

relabelers would be required to submit 


jlentini on PROD1PC65 with PROPOSAL2
Federal Register / Vol. 71, No. 167 / Tuesday, August 29, 2006 / Proposed Rules 51341 

the NDC number assigned to the drug 

immediately before they received the 

drug; (6) additional information to 

identify the manufacturer, repacker, 

relabeler, and drug product salvager 

would be required (such as e-mail 

address, fax number, and labeler code); 

(7) the submission of a representative 

sampling of labeling would include 

advertisements under § 202.1(l)(1); (8) 

certain listing information would not 

have to be submitted if the approved 

U.S. application number for the drug is 

provided; (9) the DMF number would be 

submitted by the manufacturer to obtain 

an NDC number for an active 

pharmaceutical ingredient; and (10) 

drug product salvagers (who do not 

repack or relabel) would submit the lot 

number and expiration date and NDC 

number assigned to the drug 

immediately before the drug is received 

by the drug product salvager. 

Under proposed § 207.57, 

manufacturers, repackers, relabelers, 

and drug product salvagers must review 

each June and December all drug listing 

information that has been provided to 

us and must report all material changes 

or certify that no changes have occurred. 

Manufacturers, repackers, and relabelers 

must also notify us at this time if any 

listed drug has been discontinued from 

marketing or if any discontinued drug 

has resumed marketing and provide 

listing information for any drug not yet 

listed. Under the proposal, all 

manufacturers, repackers, relabelers, 

and drug product salvagers must review 

the listing information for each drug 

listed and report any material changes. 

Current regulations do not specify that 

the information for each listed drug 

needs to be reviewed, nor is a 

certification required if there are no 

changes. Only material changes to 

listing information must be reported. 

Under the proposal and consistent with 

section 510 of the act, manufacturers, 

repackers, relabelers, and drug product 

salvagers must also update their listing 

information for drug products that have 

not been previously listed at the time 

registration information for each 

establishment is updated. 

Under proposed § 207.33(f), 

manufacturers, repackers, and relabelers 

must notify us of a change in any of the 

drug characteristics (except certain 

identifying information) for an NDC 

number in § 207.33, and we would 

assign a new NDC number for that drug. 

Under proposed § 314.81(b)(3)(iii), 

applicants under part 314 must report 

electronically within 30 calendar days 

the withdrawal of an approved drug 

product from sale (the current 

requirement is to report within 15 days). 

2. Burden Estimates 

Based on the current receipts of 

Forms FDA 2657 and 2658 for new 

listings, we estimate that approximately 

1,812 manufacturers, repackers, 

relabelers, and drug product salvagers 

will provide electronically 

approximately 13,821 new listings 

annually. 

Based on the number of drugs in our 

listing database and the current receipts 

of Forms FDA 2657 and 2658 for 

changes to listing information (and, 

until recently, the number of receipts of 

compliance verification reports), we 

estimate that approximately 2,278 

manufacturers, repackers, relabelers, 

and drug product salvagers will provide 

approximately 22,568 June and 22,568 

December reviews and updates of listing 

information (a total of 45,136 

submissions annually), and that 

approximately 5,594 manufacturers, 

repackers, relabelers, and drug product 

salvagers will provide approximately 

81,980 June and 81,980 December 

reviews and certifications that no 

changes have occurred (a total of 

163,960 submissions annually). 

The estimates for the number of drug 

listings submitted by manufacturers, 

repackers, relabelers, and drug product 

salvagers include both domestic and 

foreign listings and the listings that 

would be submitted by manufacturers, 

repackers, relabelers, and drug product 

salvagers for private label distributors. 

The estimates also include the time for 

submitting information for an NDC 

number under proposed § 207.33. The 

drugs that would be listed include PET 

drugs, an additional 57 drugs listed by 

approximately 5 foreign establishments 

as a result of the revocation of the 

exemptions for foreign establishments, 

and approximately 30 plasma 

derivatives. The estimates for the 

number of June and December reviews 

and updates of listing information or 

reviews and certifications that no 

changes have occurred would include 

the number of changes to drug 

characteristics submitted to obtain a 

new NDC number under proposed 

§ 207.33(f) and the reports of the 

withdrawal of an approved drug from 

sale under § 314.81(b)(3)(iii) and, for 

biological products, under § 601.2(f). 

Based on our familiarity with the 

content of current listing forms and 

submissions and the time required to 

input listing information during our 

electronic drug registration and listing 

system pilot project, we estimate that it 

will take manufacturers, repackers, 

relabelers, and drug product salvagers 

approximately 1 hour and 30 minutes to 

provide electronically information for 

each drug they list for the first time (for 

both foreign and domestic listings). This 

estimate is an average of the time it will 

take manufacturers, repackers, 

relabelers, and drug product salvagers, 

with drug product salvagers taking 

considerably less time than 

manufacturers. This estimate includes 

the time for submitting the content of 

labeling in electronic format under 

proposed § 207.61(a)(2) and for 

submitting other labeling and 

advertisements in paper or electronic 

format under proposed §§ 207.49(g) and 

(h) and 207.53(d) and (e). This estimate 

is only until manufacturers, repackers, 

relabelers, and drug product salvagers 

become familiar with using the 

electronic drug registration and listing 

system. We intend to lower this burden 

estimate to approximately 45 minutes 

when we submit to OMB the request to 

renew approval of this information 

collection. 

We also estimate that it will take 

approximately 30 minutes for each June 

and December review and update of 

listing information, and approximately 

15 minutes for each review and 

certification that no changes have 

occurred. These estimates include the 

time for submitting any labeling and 

advertisements for each drug, changes to 

the drug’s characteristics submitted for 

a new NDC number under proposed 

§ 207.33(f), and reports of the 

withdrawal of an approved drug from 

sale under § 314.81(b)(3)(iii). This 

estimate is only until manufacturers, 

repackers, relabelers, and drug product 

salvagers become familiar with using 

the electronic drug registration and 

listing system. We intend to lower this 

burden estimate to approximately 15 

minutes for each review and update and 

approximately 5 minutes for each 

review and certification when we 

submit to OMB the request to renew 

approval of this information collection. 

We note that these estimates for the 

electronic submission of this 

information would be a reduction in the 

currently approved estimate of 2.50 

hours (OMB Control Number 0910–

0045) for preparing and mailing to FDA 

Form FDA 2657 and FDA Form FDA 

2658. 

We intend to migrate into our new 

electronic drug registration and listing 

system current listing information that 

had been submitted using paper forms. 

As a result, current manufacturers, 

repackers, relabelers, and drug product 

salvagers will need additional time to 

review all current listing information in 

the new database and make any 

necessary revisions. We estimate that it 

will take on average 45 minutes to 

review and update each drug’s listing 


jlentini on PROD1PC65 with PROPOSAL2
51342 Federal Register / Vol. 71, No. 167 / Tuesday, August 29, 2006 / Proposed Rules 

information (the listing information 

includes information submitted for an 

NDC number). 

C. Registration and Listing Information 

Under Part 607 

1. Proposed Requirements 

Under proposed § 607.22, 

manufacturers may electronically 

obtain, complete, and submit to FDA 

Form FDA 2830 (Blood Establishment 

Registration and Product Listing) or may 

request a copy of the form by e-mail. 

Currently, under § 607.22, 

manufacturers must register 

establishments and list blood products 

on Form FDA 2830. The proposal is 

consistent with the current requirement 

to register establishments and list 

products approved under OMB Control 

Number 0910–0052. 

Under proposed § 607.25(b)(1), blood 

establishments are required to list blood 

products by the established and 

proprietary name. This proposal is 

consistent with the current listing 

requirement approved under OMB 

Control Number 0910–0052. Currently, 

blood establishments list bulk product 

substances as well as finished dosage 

forms under both parts 607 and 207 to 

obtain an NDC number. The proposal 

would reduce reporting burden by 

requiring blood establishments to list 

only under part 607. To be consistent 

with part 207, we are also proposing to 

delete the reference in part 607 to Form 

FDA 2250 (National Drug Code 

Directory Input) because this form is no 

longer being used by CDER or CBER. 

Under proposed § 607.40, foreign 

establishments must register each 

establishment before their blood 

product enters a foreign trade zone and 

are reexported from that foreign trade 

zone without having entered U.S. 

commerce. This proposal is consistent 

with the current registration 

requirement in that establishments must 

register before their blood products are 

imported or offered for import into the 

United States. The proposal would also 

include additional foreign 

establishments as a result of the 

revocation of the exemption under 

section 801(d)(4) of the act for blood 

products that enter a foreign trade zone 

and are reexported from that foreign 

trade zone without having entered U.S. 

commerce. Under the proposal, we are 

requiring additional information for 

each foreign establishment. The 

proposal would also require the foreign 

establishment to report to FDA changes 

in the United States agent’s name, 

address, telephone and fax numbers, 

and e-mail address within 30 calendar 

days of the change. The proposal would 

lengthen the time period from 10 

business days to 30 calendar days for 

reporting changes in the United States 

agent to FDA. 

2. Burden Estimates 

Based on the number of new 

establishments that currently register 

with FDA each year, we estimate that 

approximately 15 foreign establishments 

would provide new establishment 

registrations annually. Based on the 

number of registered establishments in 

our database, we estimate that 

approximately 21 foreign establishments 

would provide approximately 105 

annual reviews and updates of 

registration information or reviews and 

certifications that no changes have 

occurred. Based on the number of 

changes to registration information that 

have been submitted annually on Form 

FDA 2830, we estimate that 

approximately 21 foreign establishments 

would provide approximately 80 

product listing updates. 

The estimates above include 10 

foreign establishments with blood 

products that enter a foreign trade zone 

and are reexported from that foreign 

trade zone without having entered U.S. 

commerce under section 801(d)(4) of the 

act. We estimate that it would take 

approximately 60 minutes to provide 

the initial registration and listing 

information for each new establishment. 

We estimate that it would take 

approximately 30 minutes for each 

annual review and update of registration 

and listing information, including each 

review and certification that no changes 

have occurred. 

We estimate that it would take 

approximately 15 minutes to provide 

the product listing update for each 

establishment. 

The burden hour estimates above are 

based on institutional experience with 

the current registration and listing 

requirements. The estimates are an 

average of the time it would take to 

register a foreign establishment and an 

average of the time it would take to 

review registration and listing 

information and update several 

registration and listing items in the 

database or review information and only 

certify that no changes have occurred. 

D. Registration and Listing Information 

Under Part 1271 

1. Proposed Requirements 

Under proposed § 1271.22, 

establishments must register, list 

products, and provide updates 

electronically. The current regulation 

requires registration, listing, and 

updates either electronically or in paper 

form using Form FDA 3356 and is 

approved under OMB Control Number 

0910–0469. 

Under proposed § 1271.25, 

establishments would submit the 

telephone and fax numbers, and e-mail 

address of the reporting official. Each 

foreign establishment would submit the 

name, the address, telephone and fax 

numbers, and e-mail address of each 

importer that is known to the 

establishment and the name of each 

person who imports or offers for import 

such HCT/P to the United States. 

Foreign establishments would also 

submit the name, the address, telephone 

and fax numbers, and e-mail address of 

their United States agent. 

Under proposed § 1271.26, 

establishments must report a change to 

the United States agent’s name, address, 

telephone and fax number, and e-mail 

address. The proposal would also 

lengthen to 30 calendar days the current 

requirement of reporting the changes 

within 5 days. 

2. Burden Estimates 

Based on the number of new 

establishments that currently register 

with FDA each year, we estimate that 

approximately 300 establishments 

would provide new establishment 

registration annually. Based on 

information from FDA’s database, we 

estimate that approximately 2,000 

establishments are registered and listed 

with FDA. The number of 

establishments that currently register 

and list with FDA include both foreign 

and domestic establishments. Based on 

information from FDA’s database, we 

estimate that approximately 1,400 

establishments would provide 

establishment and listing updates. If no 

change has occurred, an update is not 

required. Based on the number of 

establishments from FDA’s database, we 

estimate that approximately 1,800 

establishments would provide 

approximately 2,100 changes to 

establishment ownership or location, or 

changes to the United States agent’s 

information. 

We estimate that it would take 

approximately 45 minutes to provide 

the initial registration and listing 

information for each new establishment. 

We estimate that it would take 

approximately 30 minutes for each 

annual review and update of registration 

and listing information for each 

establishment. 

We estimate that it would take 

approximately 15 minutes for each 

establishment to provide a change in 

ownership and location, or a change to 

the United States agent’s information. 


jlentini on PROD1PC65 with PROPOSAL2
Federal Register / Vol. 71, No. 167 / Tuesday, August 29, 2006 / Proposed Rules 51343 

The burden hour estimates above are 

based on institutional experience with 

the current registration and listing 

requirements. The estimates are an 

average of the time it would take to 

register an establishment, and an 

average of the time it would take to 

review registration and listing 

information, and update several 

registration and listing items in the 

database. 

E. User Account Information for 

Electronic System 

Under proposed § 207.61, 

establishment registration and drug 

listing information must be submitted to 

us in electronic format. In addition, the 

content of labeling must be submitted in 

electronic format. Other labeling and 

advertisements may be provided in 

paper or electronic format. Electronic 

format submissions must be in a form 

that we can process, review, and 

archive. Prior to accepting registration 

and listing information from the online 

system, we may need to authenticate the 

source (that is, manufacturer, repacker, 

relabeler, or drug product salvager) 

providing the data. We are proposing to 

authenticate entry into the electronic 

drug registration and listing system by 

establishing user accounts based on the 

current registration information. We 

would contact currently registered 

manufacturers, repackers, relabelers, or 

drug product salvagers and request that 

they provide electronic contact 

information to establish an 

administration account. 

We estimate that approximately 8,343 

manufacturers, repackers, relabelers, 

and drug product salvagers will provide 

this information (approximately 8,343 

submissions) and that it will take 

approximately 15 minutes to provide 

the requested information. 

F. Waiver Request Information 

1. Part 207 

Under proposed § 207.65, 

manufacturers, repackers, relabelers, 

and drug product salvagers may request 

a waiver from the requirement in 

§ 207.61 that information must be 

provided to us in electronic format. We 

expect very few waiver requests because 

only a computer, Internet access, and an 

email address are needed to register and 

list. 

We estimate that approximately two 

manufacturers, repackers, relabelers, or 

drug product salvagers would request a 

waiver annually, and that each request 

would take approximately 1 hour to 

prepare and submit to us. 

In those instances when we grant a 

request for a waiver, we intend to make 

available to the manufacturer, repacker, 

relabeler, or drug product salvager paper 

forms—revised Form FDA 2656 for 

registration and revised Form FDA 2657 

for listing (the listing form would 

include a section for submitting the 

information required to obtain an NDC 

number). We intend to request public 

comment and OMB approval for the 

revised forms before the effective date of 

any final rule. The proposed form will 

be available from the Division of 

Compliance Risk Management and 

Surveillance, Office of Compliance, 

Center for Drug Evaluation and Research 

(HFD–330), Food and Drug 

Administration, 5600 Fishers Lane, 

Rockville, MD 20857, 301–827–8920, 

herbert.gerstenzang@fda.hhs.gov or 

john.gardner@fda.hhs.gov. 

2. Part 607 

Under proposed § 607.40(f)(1), foreign 

establishments may request a waiver 

from the requirement in § 607.40(e) that 

information must be provided to FDA in 

electronic format. We expect very few 

waiver requests because only a 

computer, Internet access, and an e-mail 

address are needed to register and list. 

We estimate that approximately two 

manufacturers would request a waiver 

annually, and that each request would 

take approximately 1 hour to prepare 

and submit to us. 

In those instances when we grant a 

request for a waiver, we intend to make 

available to the manufacturer the paper 

form—Form FDA 2830 for registration 

and listing. 

3. Part 1271 

Under proposed § 1271.23, 

manufacturers may request a waiver 

from the requirement in § 1271.22 that 

information must be provided to FDA in 

electronic format. We expect few waiver 

requests because only a computer, 

Internet access, and an e-mail address 

are needed to register and list. 

We estimate that approximately 100 

manufacturers would request a waiver 

annually, and that each request would 

take approximately 1 hour to prepare 

and submit to FDA. 

In those instances when we grant a 

request for a waiver, we intend to make 

available to the manufacturer the paper 

form—revised Form FDA 3356 for 

registration and listing. We intend to 

request public comment and OMB 

approval for the revised form before the 

effective date of any final rule. 

G. Public Disclosure Exemption 

Requests 

Under proposed § 207.81(c), 

manufacturers, repackers, relabelers, 

and drug product salvagers may request 

that certain information in proposed 

§ 207.81(a) not be made available from 

their registration and listing 

information. Based on our experience 

with registration and listing information 

inspection requests under current 

§ 207.37, we estimate that 

approximately 100 manufacturers, 

repackers, relabelers, or drug product 

salvagers would submit this request 

annually, and that each request would 

take approximately 1 hour to prepare 

and submit to us. 

H. Revised Labeling Submitted With 

Annual Report 

Under the proposal, the NDC number 

must appear on all drug labels for drugs 

subject to the listing requirements. 

Manufacturers, repackers, and relabelers 

for drug products that do not already 

have an NDC number on the label 

would be required to include the NDC 

number assigned by us. Manufacturers, 

repackers, and relabelers for drug 

products that have an NDC number on 

the label as it is currently required 

would be required to examine their 

current NDC number to ensure that it 

complies with the NDC number 

requirements in proposed §§ 201.2, 

207.33, and 207.37, and would have to 

obtain a new NDC number from us if 

necessary. 

When there is a change in the NDC 

number on a drug label, or when an 

NDC number is added to a label, 

application holders must submit revised 

labeling to us with their annual reports 

under § 314.81(b)(2) for human drugs, 

§ 514.80(b)(4) for animal drugs 

(‘‘periodic reports’’ are required instead 

of ‘‘annual reports’’), and § 601.12(f)(3) 

for biological drugs. The submission of 

annual reports (or periodic reports for 

animal drugs) under these regulations is 

already approved by OMB under 

Control Number 0910–0001 for human 

drugs (approval expires 5/31/08), 

Control Number 0910–0284 for animal 

drugs (approval expires 9/30/06), and 

Control Number 0910–0338 for 

biological products (approval expires 9/ 

30/08). There would be no additional 

information collection burden 

associated with any labeling revision 

because of a new NDC number assigned 

by us because it would be ‘‘public 

disclosure of information originally 

supplied by the Federal government to 

the recipient for the purpose of 

disclosure to the public’’ and exempt 

under the PRA (5 CFR 1320.3(c)(2)). 

However, we have estimated a burden of 

approximately 5 minutes per annual 

report as the time required to state in 

the annual report that the labeling has 

been revised to include a new NDC 

number and the additional time 


jlentini on PROD1PC65 with PROPOSAL2
51344 Federal Register / Vol. 71, No. 167 / Tuesday, August 29, 2006 / Proposed Rules 

required to submit to us the revised 

labeling with the annual report. For the 

number of submissions, we estimate 

that no more than approximately onehalf of all annual reports submitted for 

products already listed with FDA on the 

effective date of the final rule would 

include this information. 

I. Capital Costs 

There are one-time capital costs 

associated with this proposed 

rulemaking. These costs are discussed 

in section VI of this document, 

‘‘Analysis of Economic Impacts.’’

We specifically request comments on 

the burden hour estimates described 

previously in this document and in 

tables 6, 7, and 8 of this document. 

Description of Respondents: 

Manufacturers, repackers, relabelers, 

and drug product salvagers. 

Burden Estimate: Tables 6, 7, and 8 of 

this document provide an estimate of 

the annual reporting burden for the 

proposed registration and listing 

requirements. 

TABLE 6.—ESTIMATED ANNUAL REPORTING BURDEN UNDER PROPOSED PART 207 

21 CFR Sections and Reporting Requirements No. of 

Respondents 

No. of Responses 

Per Respondent 

Total Annual 

Responses 

Hours Per 

Registration 

and Listing 

Total Hours 

Initial Establishment Registration (207.25) 987 1.14 1,128 1 hour 1,128 

Annual Review and Update of Registration Information (207.29) 8,343 1.45 12,137 .50 hours 6,068 .5 

Expedited Updates (207.29) 775 2.46 1,921 .25 hours 480 .25 

Initial Listing and NDC Number Information (207.33, 

207.49, 207.53, 207.54, 207.55) 1,812 7.63 13,821 1.50 hrs. 20,731 .50 

Review and Update of Listing Information (June and 

December) (207.33, 207.37, 207.57, 

314.81(b)(3)(iii), 601.2(f)) 2,278 19.81 45,136 .50 hours 22,568 

Review and Certification of Listing Information (June 

and December) (207.57, 601.2(f)) 5,594 29.29 163,960 .25 hours 40,990 

Review of registration information already in FDA 

database on effective date of final rule 8,343 1.45 12,137 .50 hours 6,068 .5 

Review of listing information already in FDA database 

on effective date of final rule 7,962 13.13 104,548 .75 hours 78,411 

User accounts for electronic system 8,343 1 8,343 .25 hours 2,085 .75 

Waiver requests (207.65) Revised Forms FDA 2656 

and 2657 2 1 2 1 hour 2 

Public disclosure exemption requests (207.81(c)) 100 1 100 1 hour 100 

Annual report revision for new NDC number 

(314.81(b)(2), 514.80(b)(4), 601.12(f)(3)) 3,981 13.13 52,289 5 minutes 871 .5 

Total Reporting Burden 179,505 

TABLE 7.—ESTIMATED ANNUAL REPORTING BURDEN UNDER PROPOSED PART 607 

21 CFR Sections No. of 

Respondents 

No. of Responses 

Per Respondent 

Total Annual 

Responses 

Hours Per 

Registration 

and Listing 

Total Hours 

Initial Establishment Registration and Blood Product 

Listing (607.40) 15 1 15 1 15 

Annual Review and Update of Establishment Registration and Blood Product Listing (607.40) 21 5 105 0.5 52 .5 

Product Listing Update (607.40) 21 3.8 80 0.25 20 

Waiver requests (607.40(f)(1)) Revised Form FDA 

2830 2 1 2 1 2 

Total Reporting Burden 89 .5 


jlentini on PROD1PC65 with PROPOSAL2
Federal Register / Vol. 71, No. 167 / Tuesday, August 29, 2006 / Proposed Rules 51345 

TABLE 8.—ESTIMATED ANNUAL REPORTING BURDEN UNDER PROPOSED PART 1271 

21 CFR Sections No. of 

Respondents 

No. of Responses 

Per Respondent 

Total Annual 

Responses 

Hours Per 

Registration 

and Listing 

Total Hours 

Initial Establishment Registration and Listing 

(1271.25) 300 1 300 0.75 225 

Annual Review and Update of Establishment Registration and Listing (1271.25) 2,000 1.4 1,400 0.5 501 .5 

Waiver requests (1271.23) Revised Form FDA 3356 100 1 100 1 100 

Amend Establishment Registration (1271.26) 1800 1.16 2100 0.25 525 

Total Reporting Burden 1550 .5 

In compliance with section 3507(d) of 

the PRA, we have submitted the 

information collection provisions of this 

proposed rule to OMB for review. 

Interested persons are requested to fax 

comments regarding information 

collection to the Office of Information 

and Regulatory Affairs, OMB, New 

Executive Office Bldg., 725 17th St. 

NW., rm. 10235, Washington DC 20503, 

Attn: Desk Officer for FDA, FAX: (202) 

395–6974. 

VIII. Environmental Impact 

We have determined under 21 CFR 

25.30(h) and 25.30(k) that this action is 

of a type that does not individually or 

cumulatively have a significant effect on 

the human environment. Therefore, 

neither an environmental assessment 

nor an environmental impact statement 

is required. 

IX. Proposed Effective Date 

We propose that any final rule based 

on this proposal become effective 90 

days after publication in the Federal 

Register. 

X. Proposed Compliance Dates 

We are proposing that our electronic 

drug registration and listing system be 

used to enter and update all registration, 

listing, and NDC number information no 

later than 9 months after the effective 

date of a final rule. As discussed in 

section IV.C.4.a of this document, 

manufacturers, repackers, and relabelers 

would have until 9 months after the 

effective date of a final rule to review 

and update the NDC number 

information in our database for each of 

their drugs to ensure that it complies 

with proposed §§ 201.2, 207.33, 207.37, 

610.60, and 610.61. In addition, as 

discussed in section IV.C.4.b of this 

document, manufacturers, repackers, 

and relabelers would have, for 

prescription drugs, 3 years after the 

effective date of a final rule and, for 

OTC drugs, 7 years after the effective 

date of a final rule, to ensure that the 

appropriate NDC number correctly 

appears on the label of each of their 

listed drugs, in accordance with the 

requirements in proposed §§ 201.2, 

207.33, 207.37, 610.60, and 610.61. We 

are considering shortening the 

compliance dates by which the 

appropriate NDC number must appear 

on drug labels to 2 years after the 

effective date of a final rule for 

prescription drugs and 5 years after the 

effective date of a final rule for OTC 

drugs. We discuss this issue further in 

section VI of this document, ‘‘Analysis 

of Economic Impacts.’’

We specifically request comments on 

these proposed compliance dates. 

XI. Federalism 

We have analyzed this proposed rule 

in accordance with the principles set 

forth in Executive Order 13132. We 

have determined that the rule does not 

contain policies that have substantial 

direct effects on the States, on the 

relationship between the National 

Government and the States, or on the 

distribution of power and 

responsibilities among the various 

levels of government. Accordingly, we 

have concluded that the rule does not 

contain policies that have federalism 

implications as defined in the Executive 

order and, consequently, a federalism 

summary impact statement is not 

required. 

XII. Request for Comments 

Interested persons may submit to the 

Division of Dockets Management (see 

ADDRESSES) written or electronic 

comments regarding this proposal. 

Submit a single copy of electronic 

comments or two paper copies of any 

mailed comments, except that 

individuals may submit one paper copy. 

Comments are to be identified with the 

docket number found in brackets in the 

heading of this document. Received 

comments may be seen in the Division 

of Dockets Management between 9 a.m. 

and 4 p.m., Monday through Friday. 

XIII. References 

The following references have been 

placed on display at the Division of 

Dockets Management (see ADDRESSES) 

and may be seen by interested persons 

between 9 a.m. and 4 p.m., Monday 

through Friday. 

1. Letter from John M. Coster, Vice 

President, Policy and Programs, NACDS, and 

Lisa Clowers, Senior Vice President, Industry 

Relations, HDMA, to Michael D. Jones, FDA, 

dated September 27, 2004. 

2. Letter from the Deputy Director, Division 

of Prescription Drug Compliance and 

Surveillance, CDER, FDA to John M. Coster, 

National Association of Chain Drug Stores, 

August 24, 1997. 

3. Eastern Research Group, Inc., Foreign 

and Domestic Establishment Registration and 

Listing Requirements for Human Drugs, 

Certain Biological Drugs, and Animal Drugs, 

August 2005. 

4. Eastern Research Group, Inc., Profile of 

the Prescription Drug Wholesale Industry, 

February 2001. 

5. Eastern Research Group, Inc., Cost 

Impacts of the Over-the-Counter 

Pharmaceutical Labeling Regulation, March 

1999. 

List of Subjects 

21 CFR Part 20 

Confidential business information, 

Courts, Freedom of information, 

Government employees. 

21 CFR Part 201 

Drugs, Labeling, Reporting and 

recordkeeping requirements. 

21 CFR Part 207 

Drugs, Reporting and recordkeeping 

requirements. 

21 CFR Part 314 

Administrative practice and 

procedure, Confidential business 

information, Drugs, Reporting and 

recordkeeping requirements. 


jlentini on PROD1PC65 with PROPOSAL2
51346 Federal Register / Vol. 71, No. 167 / Tuesday, August 29, 2006 / Proposed Rules 

21 CFR Part 330 

Over-the-counter drugs. 

21 CFR Parts 514 and 515 

Administrative practice and 

procedure, Animal drugs, Confidential 

business information, Reporting and 

recordkeeping requirements. 

21 CFR Part 601 

Administrative practice and 

procedure, Biologics, Confidential 

business information. 

21 CFR Part 607 

Blood. 

21 CFR Part 610 

Biologics, Labeling, Reporting and 

recordkeeping requirements. 

21 CFR Part 1271 

Biologics, Drugs, Human cells and 

tissue-based products, Medical devices, 

Reporting and recordkeeping 

requirements. 

Therefore, under the Federal Food, 

Drug, and Cosmetic Act, the Public 

Health Service Act, and under authority 

delegated to the Commissioner of Food 

and Drugs, it is proposed that 21 CFR 

parts 20, 201, 207, 314, 330, 514, 515, 

601, 607, 610, and 1271 be amended as 

follows: 

PART 20—PUBLIC INFORMATION 

1. The authority citation for 21 CFR 

part 20 continues to read as follows: 

Authority: 5 U.S.C. 552; 18 U.S.C. 1905; 

19 U.S.C. 2531–2582; 21 U.S.C. 321–393, 

1401–1403; 42 U.S.C. 241, 242, 242a, 242l, 

242n, 243, 262, 263, 263b–263n, 264, 265, 

300u–300u–5, 300aa-l. 

§ 20.100 [Amended] 

2. Section 20.100 is amended in 

paragraph (c)(9) by removing ‘‘§ 207.37’’

and by adding in its place ‘‘§ 207.81’’. 

3. Section 20.116 is revised to read as 

follows: 

§ 20.116 Drug and device registration and 

listing information. 

Information submitted to the Food 

and Drug Administration pursuant to 

section 510(a) through (j) of the act shall 

be subject only to the special disclosure 

provisions established in §§ 207.81 and 

807.37 of this chapter. 

PART 201—LABELING 

4. The authority citation for 21 CFR 

part 201 continues to read as follows: 

Authority: 21 U.S.C. 321, 331, 351, 352, 

353, 355, 358, 360, 360b, 360gg–360ss, 371, 

374, 379e; 42 U.S.C. 216, 241, 262, 264. 

§ 201.1 [Amended] 

5. Section 201.1 is amended in 

paragraph (f) by removing ‘‘§ 207.3(b)’’

and by adding in its place ‘‘§ 207.1’’. 

6. Section 201.2 is revised to read as 

follows: 

§ 201.2 Drugs; National Drug Code (NDC) 

number. 

(a) What drugs must have an NDC 

number in human-readable form on the 

label? Drugs subject to the drug listing 

requirements of part 207 of this chapter 

must have labels that bear the 

appropriate NDC number in humanreadable form, in accordance with the 

provisions of this section. 

(b) What is the appropriate NDC 

number? The appropriate NDC number 

is the NDC number of the manufacturer, 

repacker or relabeler (including a drug 

product salvager who repacks or 

relabels the drug), or private label 

distributor, as defined in § 207.1 of this 

chapter, that is the last manufacturer, 

repacker, relabeler, or private label 

distributor responsible for the drug 

immediately before it is received by the 

wholesaler or retailer. The appropriate 

NDC number is assigned to the drug as 

described in §§ 207.33 and 207.37 of 

this chapter. The unique NDC number 

assigned to each package size and type 

of a drug must appear on the 

corresponding label for the particular 

package size and type of the drug. 

(c) May any other NDC number 

appear on the label? No. Only the 

appropriate NDC number required by 

paragraph (b) of this section to appear 

on the label may appear on the label. 

(d) What prefix must be used to 

identify the NDC number on the label? 

The NDC number in human-readable 

form must be immediately preceded by 

the letters NDC. 

(e) Must the NDC number appear at a 

specific location on the label? No. 

However, the appropriate NDC number 

must appear clearly on the drug’s label 

as defined by section 201(k) of the 

Federal Food, Drug, and Cosmetic Act. 

7. Section 201.25 is amended in 

paragraph (c)(1) introductory text by 

adding a sentence after the first sentence 

and by adding paragraph (e) to read as 

follows: 

§ 201.25 Bar code label requirements. 

* * * * * 

(c) * * * 

(1) * * * For purposes of this section 

‘‘appropriate NDC number’’ is described 

in § 201.2(b). * * * 

* * * * * 

(e) Can a drug that is not subject to the 

bar code requirement display a bar 

code? A drug product that is subject to 

the drug listing requirements of part 207 

of this chapter but is not subject to this 

section may display a bar code on the 

label only if the bar code meets the 

requirements of paragraph (c) of this 

section. 

8. Part 207 is revised to read as 

follows: 

PART 207—REQUIREMENTS FOR 

FOREIGN AND DOMESTIC 

ESTABLISHMENT REGISTRATION 

AND LISTING FOR HUMAN DRUGS, 

INCLUDING DRUGS THAT ARE 

REGULATED UNDER A BIOLOGICS 

LICENSE APPLICATION, AND ANIMAL 

DRUGS 

Subpart A—General 

Sec. 

207.1 What definitions and interpretations 

of terms apply to this part? 

207.5 What is the purpose of this part? 

207.9 Who does this part cover? 

207.13 Who is exempt from the registration 

and listing requirements? 

Subpart B—Registration 

207.17 Who must register? 

207.21 When must initial registration 

information be provided? 

207.25 What information is required for 

registration? 

207.29 What are the requirements for 

reviewing and updating registration 

information? 

Subpart C—National Drug Code Number 

207.33 What is the National Drug Code 

(NDC) number, who must obtain it, and 

what information must be submitted? 

207.37 What restrictions pertain to the use 

of NDC numbers? 

Subpart D—Listing 

207.41 Who must list drugs? 

207.45 When must initial listing 

information be provided? 

207.49 What listing information is required 

for manufacturers? 

207.53 What listing information is required 

for repackers and relabelers? 

207.54 What listing information is required 

for drug product salvagers who are not 

repackers or relabelers? 

207.55 What additional drug listing 

information may be required? 

207.57 What are the requirements for 

reviewing and updating listing 

information? 

Subpart E—Electronic Format for 

Registration and Listing 

207.61 How is registration and listing 

information provided to FDA? 

207.65 How is a waiver from the electronic 

format requirement requested? 

Subpart F—Miscellaneous 

207.69 What are the requirements for an 

official contact and a United States 

agent? 

207.77 What legal status is conferred by 

registration and listing? 

207.81 What registration and listing 

information will we make available for 

public disclosure? 


jlentini on PROD1PC65 with PROPOSAL2
Federal Register / Vol. 71, No. 167 / Tuesday, August 29, 2006 / Proposed Rules 51347 

Authority: 21 U.S.C. 321, 331, 351, 352, 

355, 360, 360b, 371, 374, 381, 393; 42 U.S.C. 

262, 264, 271. 

Subpart A—General 

§ 207.1 What definitions and 

interpretations of terms apply to this part? 

The definitions and interpretations of 

terms in section 510 of the act apply to 

the terms used in this part. The 

following definitions also apply to this 

part: 

Act means the Federal Food, Drug, 

and Cosmetic Act (52 Stat. 1040, et seq., 

as amended (21 U.S.C. 301, et seq.)), 

except as otherwise provided. 

Active pharmaceutical ingredient 

means any substance that is intended to 

furnish pharmacological activity or 

other direct effect in the diagnosis, cure, 

mitigation, treatment, or prevention of 

disease, or to affect the structure or any 

function of the body. Active 

pharmaceutical ingredient does not 

include intermediates used in the 

synthesis of the substance. 

Commercial distribution means any 

distribution of a human drug except for 

investigational use under part 312 of 

this chapter, and any distribution of an 

animal drug or an animal feed bearing 

or containing an animal drug for 

noninvestigational uses, but the term 

does not include internal or interplant 

transfer of an active pharmaceutical 

ingredient between registered 

establishments within the same parent, 

subsidiary, and/or affiliate company. 

For foreign manufacturers, foreign 

repackers, foreign relabelers, foreign 

drug product salvagers, foreign private 

label distributors, and foreign 

establishments, the term ‘‘commercial 

distribution’’ has the same meaning 

except the term does not include 

distribution of any drug that is neither 

imported nor offered for import into the 

United States. 

Content of labeling means: (1) For 

human prescription drugs that the 

manufacturer regards as subject to 

section 505 of the act or section 351 of 

the Public Health Service Act: The 

content of the prescription drug labeling 

(as specified in §§ 201.56, 201.57, and 

201.80 of this chapter), including all 

text, tables, and figures. 

(2) For human prescription drugs that 

the manufacturer regards as not subject 

to section 505 of the act or section 351 

of the Public Health Service Act: The 

labeling equivalent to the content of the 

prescription drug labeling (as specified 

in §§ 201.56, 201.57, and 201.80 of this 

chapter), including all text, tables, and 

figures. 

(3) For human over-the-counter (OTC) 

drugs: The content of the drug facts 

labeling required by § 201.66 of this 

chapter, including all text, tables, and 

figures. 

(4) For animal drugs (including, but 

not limited to, drugs that the 

manufacturer regards as subject to 

section 512 of the act): The content of 

the labeling that accompanies the drug 

that is necessary to enable safe and 

proper administration of the drug (e.g., 

the labeling specified in §§ 201.1 and 

201.5 of this chapter), including all text, 

tables, and figures. 

Domestic for the purposes of 

registration and listing under this part, 

when used to modify the term 

‘‘manufacturer,’’ ‘‘repacker,’’

‘‘relabeler,’’ ‘‘drug product salvager,’’

‘‘private label distributor,’’ or 

‘‘establishment,’’ refers to a 

manufacturer, repacker, relabeler, drug 

product salvager, private label 

distributor, or establishment within any 

State or Territory of the United States, 

the District of Columbia, or the 

Commonwealth of Puerto Rico. 

Drug(s) for the purposes of 

registration and listing under this part, 

has the meaning given in section 

201(g)(1) of the act. 

Drug product salvager means a person 

who owns or operates an establishment 

that engages in drug product salvaging. 

When not modified by ‘‘domestic’’ or 

‘‘foreign,’’ the term includes both 

domestic drug product salvagers and 

foreign drug product salvagers. 

Drug product salvaging means 

applying manufacturing controls such 

as those required by current good 

manufacturing practice in parts 210 and 

211 of this chapter to drug products and 

segregating out those drug products that 

may have been subjected to improper 

storage conditions (such as extremes in 

temperature, humidity, smoke, fumes, 

pressure, age, or radiation) for the 

purpose of returning the products to the 

marketplace. 

Establishment for purposes of 

registration and drug listing means a 

place of business under one 

management at one geographic location. 

One geographic location may include 

separate buildings within the same city 

if their activities are closely related to 

the same business enterprise and are 

under the supervision of the same local 

management. When not modified by 

‘‘domestic’’ or ‘‘foreign,’’ the term 

includes both domestic and foreign 

establishments. 

Establishment registration number 

means the number assigned by FDA to 

the establishment during the 

establishment registration process 

required in this part. 

Foreign for the purposes of 

registration and listing under this part: 

(1) When used to modify the term 

‘‘manufacturer,’’ ‘‘repacker,’’

‘‘relabeler,’’ ‘‘drug product salvager,’’ or 

‘‘private label distributor’’ refers to a 

manufacturer, repacker, relabeler, drug 

product salvager, or private label 

distributor who is located in a foreign 

country and who manufactures, repacks, 

relabels, salvages, or distributes a drug 

that is imported or offered for import 

into the United States. 

(2) When used to modify the term 

‘‘establishment’’ refers to an 

establishment that is located in a foreign 

country and is the site where a drug that 

is imported or offered for import into 

the United States was manufactured, 

repacked, relabeled, salvaged, or 

distributed. 

Importer means, for purposes of this 

part, a company or individual in the 

United States that is an owner, 

consignee, or recipient, even if not the 

initial owner, consignee, or recipient, of 

the foreign establishment’s drug that is 

imported into the United States. An 

importer does not include the consumer 

or patient who ultimately purchases, 

receives, or is administered the drug, 

unless the foreign establishment ships 

the drug directly to the consumer or 

patient. 

Manufacture means each step in the 

manufacture, preparation, propagation, 

compounding, or processing of a drug. 

Manufacture includes the making by 

chemical, physical, biological, or other 

procedures or manipulations of a drug, 

including control procedures applied to 

the final product or to any part of the 

process. Manufacture includes 

manipulation, sampling, testing, or 

control procedures applied to the final 

product or to any part of the process, 

including, for example, analytical 

testing of drugs, for another registered 

establishment’s drug. For purposes of 

this part, and in order to clarify the 

responsibilities of the different parties, 

the term manufacture is defined and 

used separately from the terms relabel, 

repackage, and salvage, although the 

term ‘‘manufacture, preparation, 

propagation, compounding, or 

processing,’’ as used in section 510 of 

the act, includes relabeling, 

repackaging, and drug product salvaging 

activities. 

Manufacturer means a person who 

owns or operates an establishment that 

manufactures a drug. This term 

includes, but is not limited to, control 

laboratories, contract laboratories, 

contract manufacturers, contract 

packers, contract labelers, and other 

entities that manufacture a drug as 

defined in this paragraph. For purposes 

of this part, and in order to clarify the 

responsibilities of the different parties, 


jlentini on PROD1PC65 with PROPOSAL2
51348 Federal Register / Vol. 71, No. 167 / Tuesday, August 29, 2006 / Proposed Rules 

the term manufacturer is defined and 

used separately from the terms relabeler, 

repacker, and drug product salvager, 

although the term ‘‘manufacture, 

preparation, propagation, compounding, 

or processing,’’ as used in section 510 of 

the act, includes the activities of 

relabelers, repackers, and drug product 

salvagers. Repackers, relabelers, and 

drug product salvagers are subject to the 

provisions of this part that are 

applicable to repackers, relabelers, and 

drug product salvagers, but are not 

subject to the provisions of this part that 

are applicable to manufacturers. When 

not modified by ‘‘domestic’’ or 

‘‘foreign,’’ the term includes both 

domestic manufacturers and foreign 

manufacturers. 

Material change means any change in 

any drug listing information, as required 

under §§ 207.49, 207.53, 207.54, 207.55, 

or 207.57 except changes in 

arrangement or printing of labeling, 

labeling changes of an editorial nature, 

or inclusion of a bar code or NDC 

number on the label. 

Person who imports or offers for 

import means, for purposes of this part, 

an agent, broker, or other entity, other 

than a carrier, that the foreign 

establishment uses to facilitate the 

import of its drug into the United States. 

Private label distributor means a 

person who owns or operates an 

establishment that commercially 

distributes, under its own label or trade 

name, any drug manufactured, 

repacked, relabeled, or salvaged by a 

registered establishment. When not 

modified by ‘‘domestic’’ or ‘‘foreign,’’

the term includes both domestic private 

label distributors and foreign private 

label distributors. 

Relabel means to change the label or 

labels on a drug or drug package, or add 

to the labeling for a drug or drug 

package, without repacking the drug or 

drug package. 

Relabeler means a person who owns 

or operates an establishment that 

relabels a drug. When not modified by 

‘‘domestic’’ or ‘‘foreign,’’ the term 

includes both domestic relabelers and 

foreign relabelers. 

Repack means to repack or repackage 

or otherwise change the container or 

wrapper of a drug or drug package. 

Repacker means a person who owns 

or operates an establishment that 

repacks a drug or drug package. When 

not modified by ‘‘domestic’’ or 

‘‘foreign,’’ the term includes both 

domestic repackers and foreign 

repackers. 

Representative sampling of 

advertisements means typical 

advertising material (including the 

promotional material described in 

§ 202.1(l)(1) of this chapter, but 

excluding labeling as determined in 

§ 202.1(l)(2) of this chapter), that gives 

a balanced picture of the promotional 

claims used for the drug. 

Representative sampling of any other 

labeling means typical labeling material 

(including the promotional material 

described in § 202.1(l)(2) of this chapter, 

but excluding labels and package 

inserts) that gives a balanced picture of 

the promotional claims used for the 

drug. 

§ 207.5 What is the purpose of this part? 

Establishment registration 

information helps us to identify who is 

manufacturing, repacking, relabeling, or 

salvaging drugs and where those 

operations are being performed. Drug 

listing information gives us a current 

inventory of marketed drugs. Both types 

of information facilitate our 

implementation and enforcement of the 

act and are used for many important 

public health purposes. 

§ 207.9 Who does this part cover? 

(a) This part applies to domestic 

manufacturers, domestic repackers, 

domestic relabelers, and domestic drug 

product salvagers, not exempt under 

section 510(g) of the act or § 207.13, 

regardless of whether their drugs enter 

interstate commerce. 

(b) This part applies to foreign 

manufacturers, foreign repackers, 

foreign relabelers, and foreign drug 

product salvagers, not exempt under 

§§ 207.13(c) through (h). 

(c) This part applies to certain 

manufacturers of drugs regulated under 

a biologics license application (BLA): 

(1) Except as provided in paragraphs 

(c)(2) and (c)(3) of this section, this part 

applies to manufacturers of drugs 

regulated under a BLA, including but 

not limited to the following: 

(i) Plasma derivatives such as 

albumin, Immune Globulin, Factor VIII 

and Factor IX, and recombinant versions 

of plasma derivatives or animal derived 

plasma derivatives; 

(ii) Vaccines; 

(iii) Allergenic products; 

(iv) Bulk product substances such as 

fractionation intermediates or pastes; 

and 

(v) Therapeutic biological products. 

(2) This part, as well as part 1271 of 

this chapter, applies to establishments 

solely engaged in the manufacture (as 

defined in § 1271.3(e) of this chapter) of 

human cells, tissues, and cellular and 

tissue-based products (HCT/Ps) (as 

defined in § 1271.3(d) of this chapter) 

that, under § 1271.20 of this chapter, are 

also drugs regulated under section 351 

of the Public Health Service Act or 

section 505 of the act. These 

establishments must: 

(i) Register and list those HCT/Ps with 

the Center for Biologics Evaluation and 

Research by following the procedures 

described in subpart B of part 1271 of 

this chapter, instead of the procedures 

for registration and listing described in 

this part, and 

(ii) Submit to the Center for Biologics 

Evaluation and Research the 

information specified in 

§§ 207.33(c)(2)(i) and (c)(2)(ii), 

207.49(a), (b), (g), and (h)(2), 207.53(a), 

(c), (d), and (e)(2), 207.54(b)(1), and 

207.55. 

(3) This part does not apply to owners 

and operators of human blood and 

blood product establishments, except as 

provided in paragraphs (c)(1)(i) and 

(c)(1)(iv) of this section. Establishments 

that collect or process whole blood and 

blood products as well as 

establishments involved in testing of 

whole blood and blood products must 

register and list under part 607 of this 

chapter. Manufacturers of licensed 

devices and manufacturers of licensed 

biologic components used in a licensed 

device must register and list under part 

607 of this chapter. 

(d) This part does not apply to 

establishments that solely manufacture, 

prepare, propagate, compound, 

assemble, or process medical devices. 

Registration and listing regulations for 

such establishments are codified in part 

807 of this chapter. 

§ 207.13 Who is exempt from the 

registration and listing requirements? 

Except as provided in § 207.13(i), the 

following classes of persons are exempt 

from registration and drug listing in 

accordance with this part under section 

510(g) of the act or because we have 

found, under section 510(g)(5) of the act, 

that their registration is not necessary 

for the protection of the public health. 

This exemption is limited to 

establishment registration and drug 

listing requirements and does not 

relieve a person from other statutory or 

regulatory obligations. 

(a) Pharmacies. (1) Pharmacies that: 

(i) Operate in conformance with all 

applicable local laws regulating the 

practice of pharmacy, including all 

applicable local laws regulating the 

dispensing of prescription drugs; 

(ii) Regularly engage in dispensing 

prescription drugs upon prescription of 

practitioners licensed by law to 

administer these drugs to patients under 

their professional care; and 

(iii) Do not manufacture (as defined in 

§ 207.1), repack, or relabel drugs for sale 

other than in the regular course of the 


jlentini on PROD1PC65 with PROPOSAL2
Federal Register / Vol. 71, No. 167 / Tuesday, August 29, 2006 / Proposed Rules 51349 

practice of pharmacy, including 

dispensing and selling drugs at retail. 

(2) The exemption in paragraph (a) of 

this section is limited to pharmacies 

located in any State as defined in 

section 201(a)(1) of the act. 

(b) Hospitals, clinics, other health 

care entities, and public health 

agencies. (1) Hospitals, clinics, other 

health care entities, and public health 

agencies that: 

(i) Operate establishments in 

conformance with all applicable local 

laws regulating the practice of pharmacy 

and medicine, including all applicable 

local laws regulating the dispensing of 

prescription drugs; 

(ii) Regularly engage in dispensing 

prescription drugs, other than human 

blood or blood products, upon 

prescription of practitioners licensed by 

law to administer these drugs to patients 

under their professional care; and 

(iii) Do not manufacture (as defined in 

§ 207.1), repack, or relabel drugs other 

than in the regular course of the practice 

of pharmacy, including dispensing. 

(2) The exemption in paragraph (b) of 

this section is limited to hospitals, 

clinics, other health care entities, and 

public health agencies located in any 

State as defined in section 201(a)(1) of 

the act. 

(c) Practitioners who are licensed by 

law to prescribe or administer drugs and 

who manufacture, repack, or relabel 

drugs solely for use in their professional 

practice. 

(d) Manufacturers, repackers, 

relabelers, or drug product salvagers 

who manufacture, repack, relabel, or 

salvage drugs solely for use in research, 

teaching, or chemical analysis and not 

for sale. 

(e) Manufacturers, repackers, 

relabelers, and drug product salvagers of 

harmless inactive ingredients that are 

excipients, colorings, flavorings, 

emulsifiers, lubricants, preservatives, or 

solvents that become components of 

drugs. 

(f) Manufacturers, repackers, 

relabelers, or drug product salvagers of 

Type B or Type C medicated feeds, 

except for manufacturers, repackers, 

relabelers, or drug product salvagers of 

Type B or Type C medicated feeds made 

from Category II, Type A medicated 

articles. This exemption does not apply 

to persons that would otherwise be 

required to register (such as 

manufacturers, repackers, relabelers, or 

drug product salvagers of certain freechoice feeds, as defined in § 510.455 of 

this chapter, or certain liquid feeds, as 

defined in § 558.5 of this chapter, where 

the specifications and/or formulas are 

not published and a feed mill license is 

required). All manufacturers, repackers, 

relabelers, or drug product salvagers of 

Type B or Type C medicated feeds are 

exempt from listing. 

(g) Any manufacturer, repacker, 

relabeler, or drug product salvager of a 

virus, serum, toxin, or analogous 

product intended for the treatment of 

domestic animals who holds an 

unsuspended and unrevoked license 

issued by the Secretary of Agriculture 

under the animal virus-serum-toxin law 

of March 4, 1913 (37 Stat. 832 (21 U.S.C. 

151 et seq.)), provided that this 

exemption from registration applies 

only to the manufacturer, repacker, 

relabeler, or drug product salvager of 

that animal virus, serum, toxin, or 

analogous product. 

(h) Carriers, in their receipt, carriage, 

holding, or delivery of drugs in the 

usual course of business as carriers. 

(i) The exemptions provided in 

paragraphs (a) through (h) of this section 

do not apply to such persons if they: 

(1) Manufacture (as defined in 

§ 207.1), repack, relabel, or salvage 

compounded positron emission 

tomography drugs as defined in section 

201(ii) of the act. 

(2) Manufacture (as defined in 

§ 600.3(u) of this chapter) a biological 

product subject to licensing under 

section 351 of the Public Health Service 

Act; 

(3) Manufacture (as defined in 

§ 1271.3(e) of this chapter) an HCT/P 

that, under § 1271.20 of this chapter, are 

also drugs regulated under section 351 

of the Public Health Service Act or 

section 505 of the act; or 

(4) Engage in activities that would 

otherwise require them to register under 

this part. 

Subpart B—Registration 

§ 207.17 Who must register? 

(a) All manufacturers, repackers, 

relabelers, and drug product salvagers 

must register establishments in 

accordance with this part. When 

operations are conducted at more than 

one establishment and joint ownership 

and control among all the 

establishments exists, the parent, 

subsidiary, and/or affiliate company 

may submit registration information for 

all establishments. 

(b) Private label distributors must not 

register with us unless they also 

manufacture, repack, relabel, or salvage 

drugs and are required to register under 

paragraph (a) of this section. 

§ 207.21 When must initial registration 

information be provided? 

Domestic manufacturers, domestic 

repackers, domestic relabelers, and 

domestic drug product salvagers must 

register each establishment no later than 

5 calendar days after beginning to 

manufacture, repack, relabel, or salvage 

a drug. Foreign manufacturers, foreign 

repackers, foreign relabelers, and foreign 

drug product salvagers must register 

each establishment before a drug 

manufactured, repacked, relabeled, or 

salvaged at the establishment is 

imported or offered for import into the 

United States. 

§ 207.25 What information is required for 

registration? 

Manufacturers, repackers, relabelers, 

and drug product salvagers must 

provide the following information to us: 

(a) Name of the owner or operator of 

each establishment; if a partnership, the 

name of each partner; if a corporation, 

the name of each corporate officer and 

director, and the place of incorporation; 

(b) Name of each establishment; 

(c) Any trade name(s) of the 

establishment, names under which the 

establishment conducts business, and 

additional names by which the 

establishment is known; 

(d) Address of each establishment; 

(e) Registration number of each 

establishment, if previously assigned by 

us; if not previously assigned by us, we 

will assign a registration number after 

we receive the registration information; 

(f) Type of operations performed at 

each establishment (for example, 

manufacturing, repacking, relabeling, or 

salvaging); 

(g) Name, address, telephone and fax 

numbers, and e-mail address of the 

official contact, as provided in 

§ 207.69(a), for each establishment; and 

(h) With respect to foreign 

establishments only, for drugs 

manufactured, repacked, relabeled, or 

salvaged at the establishment, the name, 

address, telephone and fax numbers, 

and e-mail address must also be 

provided for: 

(1) The United States agent, as 

provided in § 207.69(b); 

(2) Each importer of such drug in the 

United States that is known to the 

establishment; and 

(3) Each person who imports or offers 

for import such drug to the United 

States. 

§ 207.29 What are the requirements for 

reviewing and updating registration 

information? 

(a) Expedited updates. Manufacturers, 

repackers, relabelers, and drug product 

salvagers must update their registration 

information no later than 30 calendar 

days after: 

(1) Closing or selling an 

establishment; 

(2) Changing an establishment’s name 

or address; or 


jlentini on PROD1PC65 with PROPOSAL2
51350 Federal Register / Vol. 71, No. 167 / Tuesday, August 29, 2006 / Proposed Rules 

(3) Changing the name, address, 

telephone and fax numbers, or e-mail 

address of the official contact or the 

United States agent. A manufacturer, 

repacker, relabeler, and drug product 

salvager, official contact, or United 

States agent may notify us about a 

change of information for the designated 

official contact or United States agent, 

but only a manufacturer, repacker, 

relabeler, or drug product salvager may 

designate a new official contact or 

United States agent. 

(b) Annual review and update of 

registration information. Manufacturers, 

repackers, relabelers, and drug product 

salvagers must review and update all 

registration information required under 

§ 207.25 for each establishment. 

(1) The first review and update must 

occur no later than 1 year after the date 

of initial registration, and subsequent 

reviews and updates must occur no later 

than annually thereafter from the date of 

initial registration. 

(2) The updates must reflect all 

changes that have occurred since the 

last annual review and update. 

(3) If no changes have occurred since 

the last annual registration 

(accomplished through the review and 

update of registration information), 

manufacturers, repackers, relabelers, 

and drug product salvagers must certify 

that no changes have occurred. 

Subpart C—National Drug Code 

Number 

§ 207.33 What is the National Drug Code 

(NDC) number, who must obtain it, and 

what information must be submitted? 

(a) What is the NDC number? The 

NDC number is a unique 10 digit 

number with 3 segments. The three 

segments are the labeler code, the 

product code, and the package code. We 

will assign the complete NDC number 

(that will include the existing labeler 

code, if any) to each drug that is subject 

to the listing requirements in this part. 

(b) Who must obtain an NDC number? 

(1) Manufacturers, repackers, or 

relabelers, must obtain an NDC number 

from us for each drug that is subject to 

the drug listing requirements in this 

part. 

(2) Drug product salvagers must 

obtain an NDC number from us for each 

drug that is subject to the drug listing 

requirements in this part only if they 

repack or relabel the salvaged drug. 

Drug product salvagers must follow the 

requirements for repackers and 

relabelers in paragraphs (d), (e), (f), and 

(g) of this section. 

(3) If you are a private label 

distributor, the manufacturer, repacker, 

relabeler or drug product salvager 

(described in paragraph (b)(2) of this 

section) who manufactures, repacks, or 

relabels a drug for you is responsible for 

obtaining an NDC number from us for 

each drug that is subject to the drug 

listing requirements in this part. 

(c) What information must a 

manufacturer submit before we will 

assign an NDC number to a drug? Before 

we assign an NDC number to a drug, the 

manufacturer must submit the 

information required under paragraphs 

(c)(1), (c)(2), or (c)(3) of this section. If 

that information changes (or as 

otherwise specified in paragraph (f) of 

this section), we will assign a new NDC 

number as described in paragraph (f) of 

this section. 

(1) Assigning an NDC number to an 

active pharmaceutical ingredient. We 

will assign a unique NDC number to a 

drug that is an active pharmaceutical 

ingredient when the manufacturer 

provides the following information for 

the drug: 

(i) The manufacturer’s name, address, 

telephone and fax numbers, e-mail 

address, and labeler code; 

(ii) The drug’s established name and 

proprietary name, if any; 

(iii) The package size and type; and 

(iv) The Drug Master File number or 

Veterinary Master File number, if any, 

assigned to the active pharmaceutical 

ingredient. 

(2) Assigning an NDC number to a 

manufacturer’s drug other than an 

active pharmaceutical ingredient. We 

will assign a unique NDC number to a 

drug when the manufacturer provides, 

in addition to the information described 

in paragraphs (c)(1)(i) and (c)(1)(ii) of 

this section, the following information 

for the drug: 

(i) The name and quantity of each 

active pharmaceutical ingredient unless 

the approved U.S. application number is 

provided; 

(ii) Unless the approved U.S. 

application number is provided, the 

name of each inactive ingredient for 

each human and animal drug that the 

manufacturer regards as subject to 

section 505 or section 512 of the act or 

section 351 of the Public Health Service 

Act, and for each human over-thecounter drug that the manufacturer 

regards as not subject to section 505 of 

the act, and whether the name of the 

inactive ingredient falls under § 20.61 of 

this chapter or is otherwise prohibited 

from disclosure and, if so, why; 

(iii) The dosage form; 

(iv) The package size and type, 

including immediate unit-of-use 

container; 

(v) The drug’s marketing status (e.g., 

prescription or OTC); 

(vi) The drug or drug product type 

(e.g., human drug or animal drug); and 

(vii) For each drug product subject to 

the listing requirements and covered 

under § 206.1, including products that 

are exempted under § 206.7(b), 

manufacturers must provide the size, 

shape, color, and code imprint (if any). 

(3) Assigning an NDC number to a 

drug manufactured for a private label 

distributor. We will assign a unique 

NDC number to a drug manufactured for 

a private label distributor when the 

manufacturer provides, in addition to 

the information described in paragraph 

(c)(1) of this section (for active 

pharmaceutical ingredients 

manufactured for a private label 

distributor) or paragraph (c)(2) of this 

section (for all other drugs 

manufactured for a private label 

distributor), the following information 

for the drug: 

(i) The private label distributor’s 

name, address, telephone and fax 

numbers, e-mail address, and labeler 

code; and 

(ii) The drug’s proprietary name, if 

any, assigned by the private label 

distributor. 

(d) What information must the 

repacker or relabeler submit before we 

will assign an NDC number to a drug? 

Before we assign an NDC number to a 

drug, the repacker or relabeler must 

submit the information required under 

paragraphs (d)(1) or (d)(2) of this 

section. If that information changes, we 

will assign a new NDC number as 

described in paragraph (f) of this 

section. 

(1) Assigning an NDC number to a 

repacker’s or relabeler’s drug. We will 

assign a unique NDC number to a drug, 

including an active pharmaceutical 

ingredient, when the repacker or 

relabeler of the drug provides the 

following information for the drug: 

(i) The repacker or relabeler’s name, 

address, telephone and fax numbers, email address, and labeler code; 

(ii) The NDC number assigned to the 

drug immediately before the drug is 

received by the repacker or relabeler; 

(iii) The type of operation performed 

for the drug (that is, whether repacking 

or relabeling); 

(iv) The drug’s established name and 

proprietary name, if any; and 

(v) For the repacker only, the package 

size and type, including immediate 

unit-of-use container, if any. 

(2) Assigning an NDC number to the 

drug repacked or relabeled for a private 

label distributor. We will assign a 

unique NDC number to a drug repacked 

or relabeled for a private label 

distributor when the repacker or 

relabeler provides, in addition to the 


jlentini on PROD1PC65 with PROPOSAL2
Federal Register / Vol. 71, No. 167 / Tuesday, August 29, 2006 / Proposed Rules 51351 

information described in paragraph 

(d)(1) of this section, the following 

information for the drug: 

(i) The private label distributor’s 

name, address, telephone and fax 

numbers, e-mail address, and labeler 

code; and 

(ii) The drug’s proprietary name, if 

any, assigned by the private label 

distributor. 

(e) How must the information be 

submitted to us? The information 

required in paragraphs (c), (d), and (f) of 

this section must be provided to us in 

accordance with § 207.61(a)(1)(ii) and 

(b), unless we grant a waiver under 

§ 207.65. 

(f) What changes in the information 

will require a new NDC number? (1) 

Manufacturers, repackers, and relabelers 

must obtain a new NDC number for a 

drug when there is a change in any of 

the information for the drug required 

under paragraphs (c) and (d) of this 

section. Changes must be submitted to 

us in accordance with paragraphs (e) 

and (g) of this section. However, we will 

not assign a new NDC number when the 

change involves only the following 

contact information for the 

manufacturer, repacker, relabeler, or 

private label distributor: Name, address, 

telephone and fax numbers, and e-mail 

address. 

(2) In addition to the requirements in 

paragraph (f)(1) of this section, 

manufacturers must obtain a new NDC 

number when there is a change in an 

inactive ingredient for each human 

prescription drug that the manufacturer 

regards as not subject to section 505 of 

the act and for each animal drug that the 

manufacturer regards as not subject to 

section 512 of the act. 

(g) When must a manufacturer, 

repacker, or relabeler provide the 

information for an NDC number? A 

manufacturer, repacker, or relabeler 

must provide the information in 

paragraphs (c), (d), and (f) of this section 

to us either before or at the time drug 

listing information is required under 

§ 207.45 or § 207.57. 

§ 207.37 What restrictions pertain to the 

use of NDC numbers? 

Manufacturers, repackers, and 

relabelers must not: 

(a) Use an NDC number to represent 

a different drug than the drug to which 

the NDC number has been assigned 

under § 207.33. 

(b) Use a different NDC number if 

marketing is resumed for a drug that 

was discontinued earlier. If marketing is 

resumed for a drug, and no changes 

have been made to the drug that would 

require a new NDC number under 

§ 207.33(f), the drug must have the same 

NDC number that was assigned to it 

under § 207.33 before marketing was 

discontinued. 

(c) Use the NDC number to denote 

FDA approval of that drug. 

(d) Use the NDC number on products 

that are not subject to this part, such as 

dietary supplements and medical 

devices. 

Subpart D—Listing 

§ 207.41 Who must list drugs? 

(a) Manufacturers, repackers, 

relabelers, and drug product salvagers 

who are subject to the registration 

requirements under § 207.17 must list 

their drugs being manufactured, 

repacked, relabeled, or salvaged for 

commercial distribution. Domestic 

manufacturers, domestic repackers, 

domestic relabelers, and domestic drug 

product salvagers who are subject to the 

registration requirements under § 207.17 

must list such drugs regardless of 

whether the drugs enter interstate 

commerce. When operations are 

conducted at more than one 

establishment and there exists joint 

ownership and control among all the 

establishments, listing information may 

be submitted by the parent, subsidiary, 

and/or affiliate company for drugs at all 

establishments. 

(b) Manufacturers, repackers, 

relabelers, and drug product salvagers 

who engage in more than one activity 

for drugs must list each drug in 

accordance with the requirements for 

the activity engaged in for that drug. For 

example, a company may manufacture 

Drug X and relabel Drug Y. The 

company must provide the information 

described in § 207.49 for Drug X and the 

information described in § 207.53 for 

Drug Y. 

(c) Manufacturers, repackers, 

relabelers, and drug product salvagers 

must provide all listing information to 

us for drugs that they manufacture, 

repack, relabel, or salvage for private 

label distributors. Private label 

distributors must not list drugs that they 

do not manufacture, repack, relabel, or 

salvage for commercial distribution. 

§ 207.45 When must initial listing 

information be provided? 

At the time of initial registration of an 

establishment, manufacturers, 

repackers, relabelers, and drug product 

salvagers must list any drug being 

manufactured, repacked, relabeled, and 

salvaged for commercial distribution at 

that establishment. 

§ 207.49 What listing information is 

required for manufacturers? 

Manufacturers must provide all of the 

following listing information to us for 

each drug they list, including a drug 

manufactured for a private label 

distributor: 

(a) The NDC number, assigned by us 

under § 207.33, for each drug; the NDC 

number must be provided for the drug 

to be considered listed; 

(b) The route of administration of the 

drug; 

(c) The approved U.S. application 

number or approved U.S. BLA number, 

if any; 

(d) The registration number of each 

establishment where the manufacturing 

is performed for the drug; 

(e) The schedule of the drug under 

section 202 of the Controlled Substances 

Act, if applicable; 

(f) With respect to foreign 

establishments only, unless previously 

provided under § 207.25(h), the name, 

address, telephone and fax numbers, 

and e-mail address of each importer of 

such drug in the United States that is 

known to the establishment, and of each 

person who imports or offers for import 

such drug to the United States; 

(g) Labeling—(1) Human prescription 

drugs. Unless the approved U.S. 

application number is provided under 

paragraph (c) of this section, a copy of 

all current labeling (except that only one 

representative container or carton label 

need be submitted where differences 

exist only in the quantity of contents 

statement or the bar code), including the 

content of labeling for each human 

prescription drug; 

(2) Human OTC drugs—(i) 

Manufacturer regards as subject to 

section 505 of the act or section 351 of 

the Public Health Service Act. A copy of 

all current labeling (except that only one 

representative container or carton label 

need be submitted where differences 

exist only in the quantity of contents 

statement or the bar code), including the 

content of labeling for each human OTC 

drug that the manufacturer regards as 

subject to section 505 of the act or 

section 351 of the Public Health Service 

Act, unless the approved U.S. 

application number is provided under 

paragraph (c) of this section; 

(ii) Manufacturer regards as not 

subject to section 505 of the act or 

section 351 of the Public Health Service 

Act. A copy of the current label (except 

that only one representative container or 

carton label need be submitted where 

differences exist only in the quantity of 

contents statement or the bar code), the 

content of labeling, the package insert (if 

any), and a representative sampling of 

any other labeling for each human OTC 

drug that the manufacturer regards as 

not subject to section 505 of the act or 

section 351 of the Public Health Service 

Act; 


jlentini on PROD1PC65 with PROPOSAL2
51352 Federal Register / Vol. 71, No. 167 / Tuesday, August 29, 2006 / Proposed Rules 

(3) Animal drugs—(i) Manufacturer 

regards as subject to section 512 of the 

act. A copy of all current labeling 

(except that only one representative 

container or carton label need be 

submitted where differences exist only 

in the quantity of contents statement), 

including the content of labeling, for 

each animal drug that the manufacturer 

regards as subject to section 512 of the 

act; 

(ii) Manufacturer regards as not 

subject to section 512 of the act. For all 

other animal drugs, a copy of the 

current label (except that only one 

representative container or carton label 

need be submitted where differences 

exist only in the quantity of contents 

statement), the package insert, the 

content of labeling, and a representative 

sampling of any other labeling, for each 

drug that the manufacturer regards as 

not subject to section 512 of the act; 

(h) Advertisements. (1) A 

representative sampling of 

advertisements for human prescription 

drugs that the manufacturer regards as 

not subject to section 505 of the act or 

section 351 of the Public Health Service 

Act; 

(2) If we request it, for good cause, a 

copy of all advertisements for a 

particular drug described in paragraph 

(h)(1) of this section, including those 

described in § 202.1(l)(1) of this chapter. 

Such advertisements must be submitted 

within 30 calendar days after our 

request; and 

(i) If the drug is manufactured for a 

private label distributor, the name, 

address, labeler code, telephone and fax 

numbers, and e-mail address of the 

private label distributor. 

§ 207.53 What listing information is 

required for repackers and relabelers? 

Repackers and relabelers must 

provide all of the following listing 

information to us for each drug they list, 

including a drug repacked or relabeled 

for a private label distributor: 

(a) The NDC number, assigned by us 

under § 207.33, for each drug; the NDC 

number must be provided for the drug 

to be considered listed; 

(b) The registration number of each 

establishment where the repacking or 

relabeling is performed for the drug; 

(c) With respect to foreign 

establishments only, unless previously 

provided under § 207.25(h), the name 

address, telephone and fax numbers, 

and e-mail address of each importer of 

such drug in the United States that is 

known to the establishments, and of 

each person who imports or offers for 

import such drug to the United States; 

(d) Labeling—(1) Human prescription 

drugs. If any change in labeling is made 

to the drug repacked or relabeled, a 

copy of all changed labeling for each 

human prescription drug that is 

repacked or relabeled; 

(2) Human OTC drugs—(i) 

Manufacturer regards as subject to 

section 505 of the act or section 351 of 

the Public Health Service Act. If any 

change in labeling is made to the drug 

repacked or relabeled, a copy of all 

changed labeling for each human OTC 

drug that is repacked or relabeled; 

(ii) Manufacturer regards as not 

subject to section 505 of the act or 

section 351 of the Public Health Service 

Act. A copy of the current label, a copy 

of any changes made to the package 

insert, if there is one, and a 

representative sampling of any other 

labeling for each human OTC drug that 

the manufacturer of the drug regards as 

not subject to section 505 of the act or 

section 351 of the Public Health Service 

Act; 

(3) Animal drugs. A copy of the 

current label, a copy of changes made to 

each animal drug labeling, and a 

representative sampling of any other 

labeling for each animal drug; 

(e) Advertisements. (1) A 

representative sampling of 

advertisements for human prescription 

drugs that the repacker or relabeler 

regards as not subject to section 505 of 

the act or section 351 of the Public 

Health Service Act; 

(2) If we request it for good cause, a 

copy of all advertisements for a 

particular drug described in paragraph 

(e)(1) of this section, including those 

described in § 202.1(l)(1) of this chapter. 

Such advertisements must be submitted 

within 30 calendar days after our 

request; and 

(f) If the drug is repacked or relabeled 

for a private label distributor, the name, 

address, labeler code, telephone and fax 

numbers, and e-mail address of the 

private label distributor. 

§ 207.54 What listing information is 

required for drug product salvagers who 

are not repackers or relabelers? 

(a) Drug product salvagers who also 

repack and relabel the drugs they 

salvage must list those drugs as a 

repacker or relabeler in accordance with 

§ 207.53. 

(b) Drug product salvagers who do not 

otherwise repack or relabel drugs they 

salvage must provide all of the 

following listing information to us for 

each drug they list, including a drug 

salvaged for a private label distributor: 

(1) The NDC number assigned to the 

drug immediately before the drug is 

received by the drug product salvager; 

the NDC number must be provided for 

the drug to be considered listed; 

(2) The lot number and expiration 

date of the salvaged drug product; 

(3) The registration number of each 

establishment where the drug product 

salvager salvages the drug; 

(4) With respect to foreign 

establishments only, unless previously 

provided under § 207.25(h), the name 

address, telephone and fax numbers, 

and e-mail address of each importer of 

such drug in the United States that is 

known to the establishment, and of each 

person who imports or offers for import 

such drug to the United States; and 

(5) If the drug is salvaged for a private 

label distributor, the name, address, 

labeler code, telephone and fax 

numbers, and e-mail address of the 

private label distributor. 

§ 207.55 What additional drug listing 

information may be required? 

For a particular drug product, upon 

our request, the manufacturer, repacker, 

relabeler, or drug product salvager must 

briefly state the basis for its belief that 

the drug product is not subject to 

section 505 or 512 of the act or section 

351 of the Public Health Service Act. 

§ 207.57 What are the requirements for 

reviewing and updating listing information? 

Manufacturers, repackers, relabelers, 

and drug product salvagers must review 

and update their drug listing 

information required under §§ 207.49, 

207.53, 207.54, and 207.55. 

(a) Manufacturers, repackers, 

relabelers, and drug product salvagers 

must provide listing information, during 

the annual review and update of 

registration information, for any drug 

that has not been previously listed. 

(b) Manufacturers, repackers, 

relabelers, and drug product salvagers 

must review and update their listing 

information each June and December of 

every year. They must: 

(1) Provide listing information, in 

accordance with §§ 207.49, 207.53, 

207.54, and 207.55, for any drug 

manufactured, repacked, relabeled, or 

salvaged for commercial distribution 

that has not been previously listed; 

(2) Submit the date that they 

discontinued the manufacture, 

repacking, relabeling, or salvaging for 

commercial distribution of a listed drug 

and provide the expiration date of the 

last lot manufactured, repacked, 

relabeled, or salvaged; 

(3) Submit the date that they resumed 

the manufacture, repacking, or 

relabeling for commercial distribution of 

a drug previously discontinued and 

provide any other listing information 

not previously required or submitted; 

(4) Submit any material changes in 

any information previously submitted 


jlentini on PROD1PC65 with PROPOSAL2
Federal Register / Vol. 71, No. 167 / Tuesday, August 29, 2006 / Proposed Rules 51353 

pursuant to §§ 207.49, 207.53, 207.54, 

207.55, or this section; or 

(5) Certify that no changes have 

occurred if no changes have occurred 

since the last review and update. If a 

drug is discontinued and we have 

received the information required under 

paragraph (b)(2) of this section, no 

further certifications are necessary for 

the discontinued drug. 

Subpart E—Electronic Format for 

Registration and Listing 

§ 207.61 How is registration and listing 

information provided to FDA? 

(a) Electronic format. (1) 

Manufacturers, repackers, relabelers, 

and drug product salvagers that are 

subject to the registration and listing 

requirements of this part must provide 

the following information to us by using 

our electronic drug registration and 

listing system, in accordance with part 

11 of this chapter, except for the 

requirements in § 11.10(b), (c), and (e) 

and the corresponding requirements in 

§ 11.30: 

(i) Establishment registration 

information in §§ 207.25 and 207.29; 

(ii) Information required for an NDC 

number in § 207.33; and 

(iii) Drug listing information in 

§§ 207.49 (except paragraphs (g) and 

(h)), 207.53 (except paragraphs (d) and 

(e)), 207.54, 207.55, and 207.57. 

(2) The content of labeling required 

under § 207.49(g)(1) through (g)(3) must 

be provided to us in an electronic 

format, in accordance with part 11 of 

this chapter, except for the requirements 

in § 11.10(a), (c) through (h), and (k) and 

the corresponding requirements in 

§ 11.30. The NDC number must also be 

provided with the content of labeling for 

each drug. 

(3) Advertisements and labeling (other 

than the content of labeling) required 

under §§ 207.49(g) and (h) and 207.53(d) 

and (e) may be provided to us in paper 

or electronic format in accordance with 

part 11 of this chapter, except for the 

requirements in § 11.10(a), (c) through 

(h), and (k) and the corresponding 

requirements in § 11.30. The NDC 

number must also be provided with 

such advertisements and labeling for 

each drug. 

(4) The information provided in 

electronic format must be in a form that 

we can process, review, and archive. We 

may periodically issue guidance on how 

to provide registration and listing 

information in electronic format (for 

example, method of transmission, 

media, file formats, preparation and 

organization of files). 

(b) English language. Registration and 

listing information must be provided in 

the English language. Labeling must also 

be provided in the English language, 

except as provided in § 201.15(c) of this 

chapter. 

§ 207.65 How is a waiver from the 

electronic format requirement requested? 

(a) If the information under 

§ 207.61(a) cannot be submitted 

electronically, a waiver may be 

requested. We may grant a waiver 

request if the manufacturer, repacker, 

relabeler, or drug product salvager does 

not have an e-mail address and access 

to a computer and an Internet service 

provider that can access our electronic 

drug registration and listing system. 

(b) Waiver requests must include a 

telephone number and/or mailing 

address where we can contact the 

manufacturer, repacker, relabeler, or 

drug product salvager. 

(c) If we grant the waiver request, we 

will provide information on how to 

submit registration and/or listing 

information. 

Subpart F—Miscellaneous 

§ 207.69 What are the requirements for an 

official contact and a United States agent? 

(a) Official contact. Manufacturers, 

repackers, relabelers, and drug product 

salvagers that are subject to the 

registration requirements of this part 

must designate an official contact for 

each establishment. The official contact 

is responsible for: 

(1) Ensuring the accuracy of 

registration and listing information; and 

(2) Reviewing, disseminating, routing, 

and responding to communications 

from us. 

(b) United States agent. (1) Each 

foreign manufacturer, foreign repacker, 

foreign relabeler, or foreign drug 

product salvager must designate a single 

United States agent. The United States 

agent is responsible for: 

(i) Helping us communicate with the 

foreign manufacturer, foreign repacker, 

foreign relabeler, or foreign drug 

product salvager; 

(ii) Responding to questions 

concerning those drugs that are 

imported or offered for import to the 

United States; and 

(iii) Helping us schedule inspections. 

(2) The United States agent must 

reside or maintain a place of business in 

the United States. 

(3) A United States agent may not be 

a mailbox, answering machine or 

service, or other place where a person 

acting as the United States agent is not 

physically present. 

(4) If we are unable to contact a 

foreign manufacturer, foreign repacker, 

foreign relabeler, or foreign drug 

product salvager directly or 

expeditiously, we may provide 

information or documents to the United 

States agent. We will consider such an 

action to be equivalent to providing the 

same information or documents to the 

foreign manufacturer, foreign repacker, 

foreign relabeler, or foreign drug 

product salvager. 

§ 207.77 What legal status is conferred by 

registration and listing? 

(a) Registration of an establishment or 

listing of a drug does not denote 

approval of the establishment, the drug, 

or other drugs of the establishment, nor 

does it mean that a product may be 

legally marketed. Any representation 

that creates an impression of official 

approval or that a drug is approved or 

is legally marketable because of 

registration or listing is misleading and 

constitutes misbranding. 

(b) Assignment of an establishment 

registration number, inclusion of a drug 

in our database of drugs, or assignment 

of an NDC number does not denote 

approval of the establishment or the 

drug or any other drugs of the 

establishment, nor does it mean that the 

drug may be legally marketed. Any 

representation that creates an 

impression that a drug is approved or is 

legally marketable because it appears in 

our database of drugs, has been assigned 

a NDC number, or the establishment has 

been assigned an establishment 

registration number, is misleading and 

constitutes misbranding. Failure to 

comply with § 207.37 also constitutes 

misbranding. 

(c) Neither registration nor listing 

constitutes a determination by FDA that 

a product is a drug as defined by section 

201(g)(1) of the act. Registration and 

listing may, however, be evidence that 

a facility is manufacturing, repacking, 

relabeling, or salvaging drugs or that a 

product is a drug. 

§ 207.81 What registration and listing 

information will we make available for 

public disclosure? 

(a) Except as provided in paragraphs 

(b) and (c) of this section, the following 

information will be made available for 

public disclosure upon request or at our 

own discretion: 

(1) All registration information; and 

(2) After a drug is listed, all 

information obtained for that drug 

under §§ 207.33, 207.49, 207.53, and 

207.54, except for that information 

obtained under 207.33(d)(1)(ii) and 

207.54(b)(1). 

(b) Unless information is publicly 

available or we find that confidentiality 

would be inconsistent with the 

protection of the public health, we will 


jlentini on PROD1PC65 with PROPOSAL2
51354 Federal Register / Vol. 71, No. 167 / Tuesday, August 29, 2006 / Proposed Rules 

not make publicly available any 

information submitted as the basis upon 

which it has been determined that a 

particular drug product is not subject to 

section 505 or 512 of the act. 

(c) We may determine, in limited 

circumstances and on a case-by-case 

basis, that it would be consistent with 

the protection of the public health and 

the Freedom of Information Act to 

exempt from public disclosure specific 

information in paragraph (a) of this 

section. In such instances, a 

manufacturer, repacker, relabeler, or 

drug product salvager must demonstrate 

that specific information is exempt or is 

otherwise prohibited by law from public 

disclosure. If we agree, we will not 

make such information publicly 

available. 

PART 314—APPLICATIONS FOR FDA 

APPROVAL TO MARKET A NEW DRUG 

8. The authority citation for 21 CFR 

part 314 continues to read as follows: 

Authority: 21 U.S.C. 321, 331, 351, 352, 

353, 355, 355a, 356, 356a, 356b, 356c, 371, 

374, 379e. 

9. Section 314.81 is amended by 

revising paragraph (b)(3)(iii) to read as 

follows: 

§ 314.81 Other postmarketing reports. 

* * * * * 

(b) * * * 

(3) * * * 

(iii) Withdrawal of approved drug 

product from sale. (a) Within 30 

calendar days of the withdrawal of an 

approved drug from sale, applicants 

who are manufacturers, repackers, or 

relabelers subject to part 207 of this 

chapter must submit the following 

information about the drug in electronic 

format, in accordance with the 

applicable requirements described in 

§ 207.61(a): 

(1) The National Drug Code (NDC) 

number; 

(2) The identity of the drug by 

established name and by proprietary 

name, if any; 

(3) The new drug application number 

or abbreviated application number; 

(4) The date of withdrawal from sale. 

We request that the reason for 

withdrawal of the drug from sale be 

included with the information. 

(b) Within 30 calendar days of the 

withdrawal of an approved drug from 

sale, applicants who are not subject to 

part 207 of this chapter must submit the 

information listed in paragraphs (a)(1) 

through (a)(4) of this section. The 

information must be submitted on the 

appropriate form, which must be 

submitted to the Drug Listing Branch, 

Food and Drug Administration, CDER 

Central Document Room, 5901B 

Ammendale Rd., Beltsville, MD 20705–

1266. 

* * * * * 

§ 314.125 [Amended] 

10. Section 314.125 is amended in 

paragraph (b)(11) by removing the 

words ‘‘or processed’’. 

PART 330—OVER-THE-COUNTER 

(OTC) HUMAN DRUGS WHICH ARE 

GENERALLY RECOGNIZED AS SAFE 

AND EFFECTIVE AND NOT 

MISBRANDED 

11. The authority citation for 21 CFR 

part 330 continues to read as follows: 

Authority: 21 U.S.C. 321, 351, 352, 353, 

355, 360, 371. 

12. Section 330.1 is amended by 

revising paragraph (b) to read as follows: 

§ 330.1 General conditions for general 

recognition as safe, effective, and not 

misbranded. 

* * * * * 

(b) The establishment(s) in which the 

drug is manufactured is registered, and 

the drug is listed, in compliance with 

part 207 of this chapter. The appropriate 

National Drug Code (NDC) number must 

appear on the drug’s label in accordance 

with §§ 201.2, 207.33, and 207.37 of this 

chapter. 

* * * * * 

PART 514—NEW ANIMAL DRUG 

APPLICATIONS 

13. The authority citation for 21 CFR 

part 514 continues to read as follows: 

Authority: 21 U.S.C. 321, 331, 351, 352, 

353, 360b, 371, 379e, 381. 

14. Section 514.111 is amended by 

adding paragraph (a)(12) to read as 

follows: 

§ 514.111 Refusal to approve an 

application. 

(a) * * * 

(12) The drug will be produced in 

whole or in part in an establishment 

that is not registered and not exempt 

from registration under section 510 of 

the act and part 207 of this chapter. 

* * * * * 

PART 515—MEDICATED FEED MILL 

LICENSE 

15. The authority citation for 21 CFR 

part 515 continues to read as follows: 

Authority: 21 U.S.C. 360b, 371. 

§ 515.10 [Amended] 

16. Section 515.10 is amended in 

paragraph (b)(8) by removing the phrase 

‘‘§§ 207.20 and 207.21’’ and by adding 

in its place the phrase ‘‘part 207’’. 

PART 601—LICENSING 

17. The authority citation for 21 CFR 

part 601 continues to read as follows: 

Authority: 15 U.S.C. 1451–1561; 21 U.S.C. 

321, 351, 352, 353, 355, 356b, 360, 360c–

360f, 360h–360j, 371, 374, 379e, 381; 42 

U.S.C. 216, 241, 262, 263, 264; sec. 122, Pub. 

L. 105–115, 111 Stat. 2322 (21 U.S.C. 355 

note). 

18. Section 601.2 is amended by 

adding paragraph (f) to read as follows: 

§ 601.2 Applications for biologics 

licenses; procedures for filing. 

* * * * * 

(f) Withdrawal from sale of approved 

biological products. A holder of a 

biologics license application (BLA) must 

report to FDA, electronically in 

accordance with part 207 of this 

chapter, the withdrawal from sale of an 

approved biological product. The 

information must be submitted to FDA 

within 30 working days of the biological 

product’s withdrawal from sale. The 

following information must be 

submitted: The holder’s name; product 

name; BLA number; the National Drug 

Code number, if applicable; and the date 

of withdrawal from sale. The reason for 

the withdrawal of the biological product 

is requested but not required to be 

submitted. 

PART 607—ESTABLISHMENT 

REGISTRATION AND PRODUCT 

LISTING FOR MANUFACTURERS OF 

HUMAN BLOOD AND BLOOD 

PRODUCTS 

19. The authority citation for 21 CFR 

part 607 continues to read as follows: 

Authority: 21 U.S.C. 321, 331, 351, 352, 

355, 360, 371, 374, 381, 393; 42 U.S.C. 262, 

264, 271. 

20. Section 607.3 is amended by 

revising the second sentence in 

paragraph (b), and by adding new 

paragraph (k) to read as follows: 

§ 607.3 Definitions. 

* * * * * 

(b) * * * For the purposes of this part 

only, blood and blood product also 

means those products that meet the 

definition of a device under the Federal 

Food, Drug, and Cosmetic Act and that 

are licensed under section 351 of the 

Public Health Service Act, as well as 

licensed biologic components used in 

the manufacture of a licensed device. 

* * * * * 

(k) Importer means a company or 

individual in the United States that is 

the owner, consignee, or recipient of the 

foreign establishment’s blood product 

that is imported into the United States. 

21. Section 607.7 is revised to read as 

follows: 


jlentini on PROD1PC65 with PROPOSAL2
Federal Register / Vol. 71, No. 167 / Tuesday, August 29, 2006 / Proposed Rules 51355 

§ 607.7 Establishment registration and 

product listing of blood banks and other 

firms manufacturing human blood and 

blood products. 

All owners or operators of 

establishments that engage in the 

manufacturing of blood products are 

required to register, pursuant to section 

510 of the Federal Food, Drug, and 

Cosmetic Act. Registration and listing of 

blood products shall comply with this 

part. Registration does not permit any 

blood bank or similar establishment to 

ship blood products in interstate 

commerce. 

22. Section 607.22 is revised to read 

as follows: 

§ 607.22 How to register blood product 

establishments and list blood products. 

Initial and subsequent registrations 

and product listings by a blood product 

establishment for blood products must 

be on Form FDA 2830 (Blood 

Establishment Registration and Product 

Listing). Manufacturers may obtain, 

complete, and submit the form in the 

following ways: 

(a) Complete the form online and 

submit electronically at http:// 

www.fda.gov/cber/blood/bldreg.htm; 

this information must be submitted in 

accordance with part 11 of this chapter, 

except for the requirements in 

§ 11.10(b), (c), and (e), and the 

corresponding requirements in § 11.30; 

or 

(b) Download the form from the 

Internet at http://www.fda.gov/cber/ 

blood/bldreg.htm, and mail the 

completed form to the address in 

§ 607.22(e); or 

(c) Request the form by mail using the 

address in § 607.22(e), or by e-mail at 

bloodregis@cber.fda.gov, and mail the 

completed form to the address in 

§ 607.22(e). 

(d) For subsequent annual registration 

renewals, FDA will furnish the 

establishment’s most recent Form FDA 

2830 before November 15 of each year. 

The updated Form FDA 2830 must be 

submitted to FDA before December 31 of 

that year. 

(e) Forms may be requested from and 

mailed to: Center for Biologics 

Evaluation and Research (HFM–370), 

1401 Rockville Pike, suite 200N, 

Rockville, MD 20852–1448. 

23. Section 607.25 is amended by 

revising paragraph (b)(1) to read as 

follows: 

§ 607.25 Information required for 

establishment registration and blood 

product listing. 

* * * * * 

(b) * * * 

(1) A list of blood products by 

established name as defined in section 

502(e) of the act and by proprietary 

name, if any, which are being 

manufactured for commercial 

distribution and which have not been 

included in any list previously 

submitted on Form FDA 2830 (Blood 

Establishment Registration and Product 

Listing). 

* * * * * 

24. Section 607.35 is revised to read 

as follows: 

§ 607.35 Blood product establishment 

registration number. 

A permanent registration number will 

be assigned to each blood product 

establishment registered in accordance 

with this part. 

25. Section 607.37 is amended by 

revising the introductory text of 

paragraph (a) to read as follows: 

§ 607.37 Inspection of establishment 

registrations and blood product listings. 

(a) Information submitted on the Form 

FDA 2830 (Blood Establishment 

Registration and Product Listing) will be 

available for inspection under section 

510(f) of the act, on the Internet at 

http://www.fda.gov/cber/blood/ 

bldregdata.htm, and at the Department 

of Health and Human Services, Food 

and Drug Administration, Office of 

Communication, Training and 

Manufacturers Assistance (HFM–40), 

Center for Biologics Evaluation and 

Research, 1401 Rockville Pike, suite 

200N, Rockville, MD 20852–1448. The 

following information submitted under 

the blood product listing requirements 

is illustrative of the type of information 

that will be available for public 

disclosure when it is compiled: 

* * * * * 

26. Section 607.39 is revised to read 

as follows: 

§ 607.39 Misbranding by reference to 

establishment registration, validation of 

registration, or to registration number. 

Registration of an establishment, 

validation of registration, or assignment 

of a registration number does not in any 

way denote approval of the firm or its 

products nor does it mean that the 

products may be legally marketed. Any 

representation that creates an 

impression of official approval because 

of establishment registration, validation 

of registration, or possession of a 

registration number is misleading and 

constitutes misbranding. 

27. Section 607.40 is amended by 

revising paragraphs (a), (b), (c), the 

introductory text of (d), and (d)(3), and 

by adding new paragraphs (e) and (f) to 

read as follows: 

§ 607.40 Establishment registration and 

blood product listing requirements for 

foreign blood product establishments. 

(a) Every foreign blood product 

establishment must comply with the 

requirements for domestic blood 

product establishments in subpart B of 

this part, unless exempt under subpart 

D of this part. 

(b) No blood product may be imported 

or offered for import into the United 

States unless it complies with the blood 

product listing requirements in subpart 

B of this part and is manufactured, 

prepared, propagated, compounded, or 

processed at a registered foreign 

establishment. Blood products imported 

or offered for import under the 

investigational use provisions of part 

312 of this chapter are not subject to the 

requirements in subpart B of this part. 

All establishment registration and blood 

product listing information must be in 

the English language. 

(c) Each foreign establishment 

required to register under paragraph (a) 

of this section must, as part of the 

establishment registration and blood 

product listing, submit the name and 

address of the establishment, the name 

of each importer of the foreign 

establishment’s blood products that is 

known to the establishment, the name of 

each person who imports or offers for 

import such blood products to the 

United States, and the name of the 

individual responsible for submitting 

establishment registration and blood 

product listing information. Any 

changes in this information must be 

reported to FDA at the intervals 

specified for updating establishment 

registration information in § 607.26. 

(d) Each foreign establishment 

required to register under paragraph (a) 

of this section must submit the name, 

address, telephone and fax numbers, 

and e-mail address of its United States 

agent as part of its initial and updated 

registration information in accordance 

with subpart B of this part. Each foreign 

establishment must designate only one 

United States agent. 

* * * * * 

(3) The foreign establishment or the 

United States agent must report changes 

in the United States agent’s name, 

address, telephone and fax numbers, 

and e-mail address to FDA within 30 

calendar days of the change. 

(e) Each foreign establishment 

required to register under paragraph (a) 

of this section must register and list 

blood products using the electronic 

registration and listing system, in 

accordance with § 607.22(a). 

(f)(1) If the foreign establishment 

cannot submit the information 

electronically under § 607.40(e), the 


jlentini on PROD1PC65 with PROPOSAL2
51356 Federal Register / Vol. 71, No. 167 / Tuesday, August 29, 2006 / Proposed Rules 

establishment may request a waiver. 

FDA may grant a waiver request if the 

foreign establishment does not have an 

e-mail address and access to a computer 

and an Internet service provider that can 

access the electronic registration and 

listing system. 

(2) Waiver requests must include a 

telephone number and/or mailing 

address where the agency can contact 

the foreign establishment. 

(3) If the agency grants the waiver 

request, the foreign establishment must 

register and list blood products in 

accordance with § 607.22(b) or (c). 

28. Section 607.65 is amended by 

redesignating paragraph (f) as paragraph 

(g) and by adding new paragraph (f) to 

read as follows: 

§ 607.65 Exemptions for blood product 

establishments. 

* * * * * 

(f) Persons who engage solely in the 

production of any plasma derivative, 

such as albumin, Immune Globulin, 

Factor VIII and Factor IX, bulk product 

substances such as fractionation 

intermediates or pastes, or recombinant 

versions of plasma derivatives or animal 

derived plasma derivatives. This 

paragraph does not exempt such 

persons from registration and listing 

under part 207 of this chapter. 

* * * * * 

PART 610—GENERAL BIOLOGICAL 

PRODUCTS STANDARDS 

29. The authority citation for 21 CFR 

part 610 continues to read as follows: 

Authority: 21 U.S.C. 321, 331, 351, 352, 

353, 355, 360, 360c, 360d, 360h, 360i, 371, 

372, 374, 381; 42 U.S.C. 216, 262, 263, 263a, 

264. 

30. Section 610.60 is amended by 

revising paragraph (a)(2) to read as 

follows: 

§ 610.60 Container label. 

(a) * * * 

(2) The name, address, license 

number of the manufacturer, and the 

NDC number in accordance with part 

207 of this chapter. 

* * * * * 

31. Section 610.61 is amended by 

revising paragraph (b) to read as follows: 

§ 610.61 Package label. 

* * * * * 

(b) The name, address, license 

number of the manufacturer, and the 

NDC number in accordance with part 

207 of this chapter. 

* * * * * 

PART 1271—HUMAN CELLS, TISSUES, 

AND CELLULAR AND TISSUE-BASED 

PRODUCTS 

32. The authority citation for 21 CFR 

part 1271 continues to read as follows: 

Authority: 42 U.S.C. 216, 243, 263a, 264, 

271. 

§ 1271.1 [Amended] 

33. Section 1271.1 is amended in 

paragraphs (a) and (b)(2) by removing 

‘‘207.20(f)’’ and by adding in its place 

‘‘207.9(c)(2)’’. 

34. Section 1271.3 is amended by 

adding paragraphs (mm) and (nn) to 

read as follows: 

§ 1271.3 How does FDA define important 

terms in this part? 

* * * * * 

(mm) Importer means a company or 

individual in the United States that is 

the owner, consignee, or recipient of the 

foreign establishment’s HCT/P that is 

imported into the United States. 

(nn) United States agent means a 

person residing or maintaining a place 

of business in the United States whom 

a foreign establishment designates as its 

agent. This definition excludes 

mailboxes, answering machines or 

services, or other places where an 

individual acting as the foreign 

establishment’s agent is not physically 

present. 

§ 1271.20 [Amended] 

35. Section 1271.20 is amended by 

removing ‘‘207.20(f)’’ and by adding in 

its place ‘‘207.9(c)(2)’’. 

36. Section 1271.22 is added to read 

as follows: 

§ 1271.22 How do I register and submit an 

HCT/P list? 

(a) You must use the electronic 

registration and listing system at http:// 

www.fda.gov/cber/tissue/tisreg.htm in 

accordance with § 1271.25 for: 

(1) Establishment registration, 

(2) HCT/P listings, and 

(3) Updates of registration and HCT/ 

P listing. 

(b) FDA will periodically issue 

guidance on how to provide registration 

and listing information in electronic 

format (for example, method of 

transmission, media, file formats, 

preparation, and organization of files). 

(c) You must provide the information 

under paragraph (a) of this section in 

accordance with part 11 of this chapter, 

except for the requirements in 

§ 11.10(b), (c), and (e) and the 

corresponding requirements in § 11.30. 

37. Section 1271.23 is added to part 

1271 to read as follows: 

§ 1271.23 How is a waiver from the 

electronic format requirements requested? 

(a) You may request a waiver from the 

requirement in § 1271.22 that 

information must be provided to FDA in 

electronic format if you do not have an 

e-mail address and access to a computer 

and an Internet service provider that can 

access the Web-based FDA registration 

and listing database. 

(b) Requests for a waiver must include 

a telephone number and/or mailing 

address where FDA can contact the 

person making the request. 

(c) If FDA grants the request for a 

waiver, FDA will inform you how to 

submit your registration and/or listing 

information. 

38. Section 1271.25 is amended by 

revising introductory paragraph (a), 

paragraphs (a)(2) and (a)(3), and by 

adding new paragraphs (a)(5), (a)(6), and 

(d) to read as follows: 

§ 1271.25 What information is required for 

establishment registration and HCT/P 

listing? 

(a) Your establishment registration 

must include: 

* * * * * 

(2) Each location, including the street 

address, telephone and fax numbers, 

email address, and the postal service zip 

code of the establishment; 

(3) The name, address, telephone and 

fax numbers, e-mail address, and title of 

the reporting official; 

* * * * * 

(5) Each foreign establishment must 

also submit the name, address, 

telephone and fax numbers, and e-mail 

address of each importer that is known 

to the establishment, and the name of 

each person who imports or offers for 

import such HCT/P to the United States 

for purposes of importation; and 

(6) Each foreign establishment must 

also submit the name, address, 

telephone and fax numbers, and e-mail 

address of its United States agent. Each 

foreign establishment must designate 

only one United States agent. 

(i) The United States agent must 

reside or maintain a place of business in 

the United States. 

(ii) Upon request from FDA, the 

United States agent must assist FDA in 

communications with the foreign 

establishment, respond to questions 

concerning the foreign establishment’s 

products that are imported or offered for 

import into the United States, and assist 

FDA in scheduling inspections of the 

foreign establishment. If the agency is 

unable to contact the foreign 

establishment directly or expeditiously, 

FDA may provide information or 

documents to the United States agent, 

and such an action must be considered 


jlentini on PROD1PC65 with PROPOSAL2
Federal Register / Vol. 71, No. 167 / Tuesday, August 29, 2006 / Proposed Rules 51357 

to be equivalent to providing the same 

information or documents to the foreign 

establishment. 

(iii) The foreign establishment or the 

United States agent must report changes 

in the United States agent’s name, 

address, telephone and fax numbers, 

and e-mail address to FDA within 30 

calendar days of the change. 

* * * * * 

(d) In addition, if your HCT/P is 

described under § 1271.20, you must 

submit the information required under 

part 207 of this chapter using the 

procedures under this subpart. 

39. Section 1271.26 is revised to read 

as follows: 

§ 1271.26 When must I amend my 

establishment registration? 

If the ownership or location of your 

establishment changes, or if there is a 

change in the United States agent’s 

name, address, telephone and fax 

numbers, and e-mail address, you must 

submit an amendment to registration 

within 30 calendar days of the change. 

§ 1271.37 [Amended] 

40. Section 1271.37 is amended in the 

introductory text of paragraph (a) by 

removing the phrase ‘‘Form FDA 3356’’

and adding in its place the phrase 

‘‘registration and listing information’’. 

Dated: August 22, 2006. 

Jeffrey Shuren, 

Assistant Commissioner for Policy. 

[FR Doc. 06–7172 Filed 8–23–06; 3:48 pm] 

BILLING CODE 4160–01–S 


jlentini on PROD1PC65 with PROPOSAL2