57942 Federal Register / Vol. 69, No. 187 / Tuesday, September 28, 2004 / Notices 

‘‘Guidance for Industry: Animal Drug 

Sponsor Fees Under the Animal Drug 

User Fee Act’’ and follow the directions. 

Copies of this guidance may be obtained 

on the Internet from the CVM home 

page at http://www.fda.gov/cvm.

Dated: September 21, 2004.

Jeffrey Shuren,

Assistant Commissioner for Policy.

[FR Doc. 04–21677 Filed 9–27–04; 8:45 am]

BILLING CODE 4160–01–S

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES

Food and Drug Administration

[Docket No. 2004D–0410]

Draft Guidance for Industry and Food 

and Drug Administration Staff: 

Application User Fees for Combination 

Products; Availability

AGENCY: Food and Drug Administration, 

HHS.

ACTION: Notice.

SUMMARY: The Food and Drug 

Administration (FDA) is announcing the 

availability of a draft document entitled 

‘‘Guidance for Industry and FDA Staff: 

Application User Fees for Combination 

Products.’’ This draft guidance provides 

guidance to industry and FDA staff on 

marketing application user fees for 

combination products. The guidance 

also describes how the ‘‘barrier to 

innovation’’ waiver provision under the 

prescription drug user fee provisions of 

the Federal Food, Drug, and Cosmetic 

Act (act) may be applied to innovative 

combination products in the infrequent 

situation where FDA requires the 

submission of two marketing 

applications.

DATES: Submit written or electronic 

comments on this draft guidance by 

November 29, 2004 to ensure their 

adequate consideration in preparation of 

the final guidance. General comments 

on agency guidance documents are 

welcome at any time.

ADDRESSES: Submit written requests for 

single copies of the draft guidance to the 

Office of Combination Products, 15800 

Crabbs Branch Way, suite 200, 

Rockville, MD 20855. Send one selfaddressed adhesive label to assist that 

office in processing your requests. See 

the SUPPLEMENTARY INFORMATION section 

for information on electronic access to 

the guidance.

Submit written comments on the draft 

guidance to the Division of Dockets 

Management (HFA–305), Food and Drug 

Administration, 5630 Fishers Lane, rm. 

1061, Rockville, MD 20852. Submit 

electronic comments to http://

www.fda.gov/dockets/ecomments.

FOR FURTHER INFORMATION CONTACT:

Mark D. Kramer, Office of Combination 

Products (HFG–3), Food and Drug 

Administration, 15800 Crabbs Branch 

Way, suite 200, Rockville, MD 20855, 

301–427–1934.

SUPPLEMENTARY INFORMATION:

I. Background

A combination product is a product 

comprised of any combination of a drug 

and a device; a biological product and 

a device; a drug and a biological 

product; or a drug, device and a 

biological product. Depending upon the 

type of combination product, approval, 

clearance or licensure may be obtained 

through submission of a single 

marketing application, or through 

separate marketing applications for the 

individual constituent parts of the 

combination product. For most 

combination products, a single 

marketing application is sufficient for 

the product’s approval, clearance, or 

licensure. In some cases, two marketing 

applications may be submitted for a 

combination product when one 

application would suffice. For example, 

a sponsor may choose to submit two 

applications when one would suffice in 

order to receive some benefit from 

having two applications. In other cases, 

FDA may determine that two marketing 

applications are necessary.

In 1992, Congress passed the 

Prescription Drug User Fee Act 

(PDUFA). PDUFA authorized FDA to 

collect fees from companies that 

produce certain human drug and 

biological products. The Medical Device 

User Fee and Modernization Act of 2002 

amended the act to provide for user fees 

for the review of device applications. 

When a company requests approval of a 

new drug, device or biological product 

prior to marketing, it must submit an 

application along with a fee to support 

the review process.

This document provides guidance to 

industry and FDA staff on marketing 

application user fees for combination 

products as defined under 21 CFR 

3.2(e). The guidance document explains 

that combination products for which a 

single marketing application is 

submitted will be assessed the user fee 

associated with that particular type of 

marketing application. The document 

explains that, if a sponsor chooses to 

submit two marketing applications 

when one would suffice, a user fee for 

each application would ordinarily be 

assessed. The document also explains 

that, in the infrequent situation where 

FDA requires two marketing 

applications for a combination product, 

two application fees would ordinarily 

be assessed. However, the guidance also 

describes how the PDUFA ‘‘barrier to 

innovation’’ waiver provision may be 

applied to innovative combination 

products for which FDA requires the 

submission of two marketing 

applications. Such a waiver would 

provide a reduction in application user 

fees equivalent to the additional fee 

burden associated with the submission 

of two marketing applications. This 

guidance does not address how FDA 

will determine whether a single 

marketing application or multiple 

marketing applications should be 

submitted for a combination product. 

Such guidance is in development and 

will be provided separately for public 

review and comment.

II. Significance of Guidance

This draft guidance document is being 

issued consistent with FDA’s good 

guidance practices regulation (21 CFR 

10.115). The draft guidance, when 

finalized will represent the agency’s 

current thinking on application user 

fees for combination products. It does 

not create or confer any rights for or on 

any person and does not operate to bind 

FDA or the public. An alternative 

approach may be used if such approach 

satisfies the requirements of the 

applicable statute and regulations.

III. Electronic Access

To receive ‘‘Guidance for Industry 

and FDA Staff: Application User Fees 

for Combination Products,’’ you may 

either send a fax request to 301–427–

1935, or an e-mail request to 

combination@fda.gov to receive a hard 

copy or electronic copy of the 

document.

Persons with access to the Internet 

may obtain the draft guidance at either 

http://www.fda.gov/oc.combination/

default.htm or http://www.fda.gov/

ohrms/dockets/default.htm.

IV. Comments

The draft guidance is being 

distributed for comment purposes only 

and is not intended for implementation 

at this time. Interested persons may 

submit to the Division of Dockets 

Management (see ADDRESSES) written or 

electronic comments regarding the draft 

guidance. Submit written or electronic 

comments to ensure adequate 

consideration in preparation of the final 

guidance. 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 the

Federal Register / Vol. 69, No. 187 / Tuesday, September 28, 2004 / Notices 57943

brackets in the heading of this 

document. A copy of the draft guidance 

and received comments are available for 

public examination in the Division of 

Dockets Management between 9 a.m. 

and 4 p.m., Monday through Friday.

Dated: September 22, 2004.

Jeffrey Shuren,

Assistant Commissioner for Policy.

[FR Doc. 04–21673 Filed 9–23–04; 3:08 pm]

BILLING CODE 4160–01–S

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES

Food and Drug Administration

[Docket No. 2004N–0367]

Cumulative List of Exceptions and 

Alternative Procedures Approved by 

the Director of the Center for Biologics 

Evaluation and Research

AGENCY: Food and Drug Administration, 

HHS.

ACTION: Notice.

SUMMARY: The Food and Drug 

Administration (FDA) is announcing the 

availability a cumulative list of 

exceptions and alternative procedures to 

requirements regarding blood, blood 

components, and blood products that 

have been approved by the Director of 

the Center for Biologics Evaluation and 

Research (CBER). Also, FDA is 

announcing that this list is posted on 

the Internet and it will be periodically 

updated.

ADDRESSES: Copies of the cumulative 

list of exceptions and alternative 

procedures are available from the 

Division of Dockets Management (HFA–

305), Food and Drug Administration, 

5630 Fishers Lane, rm. 1061, Rockville, 

MD 20852, and the Office of 

Communication, Training and 

Manufacturers Assistance (HFM–40), 

Food and Drug Administration, suite 

200 N, 1401 Rockville Pike, Rockville, 

MD 20852–1448, 1–800–835–4709 or 

301–827–1800. See the SUPPLEMENTARY

INFORMATION section for electronic 

access to the cumulative list of 

exceptions and alternative procedures.

FOR FURTHER INFORMATION CONTACT:

Nathaniel L. Geary, Center for Biologics 

Evaluation and Research (HFM–17), 

Food and Drug Administration, suite 

200N, 1401 Rockville Pike, Rockville, 

MD 20852–1448, 301–827–6210.

SUPPLEMENTARY INFORMATION:

I. Background

The Director of CBER has approved 

exceptions or alternative procedures 

that have been requested by blood 

establishments under § 640.120 (21 CFR 

640.120). Section 640.120 grants the 

Director authority to approve exceptions 

or alternatives to any requirement in 

subchapter F (Biologics) of chapter I, 

parts 600 through 680 (21 CFR parts 600 

through 680) regarding blood, blood 

components, or blood products.

FDA is announcing publication of a 

cumulative list of exceptions and 

alternative procedures to requirements 

regarding blood, blood components, and 

blood products that have been approved 

by the Director of CBER. Also, FDA is 

announcing that this list is posted on 

the Internet and it will be periodically 

updated.

II. List of Approved Exceptions and 

Alternative Procedures (§ 640.120(b))

§ 600.15(a)

• Allow use of autologous units that 

were transported in a shipping 

container without ice and exposed to 

temperatures of 10.0 °C to 10.5 °C for 10 

minutes.

§ 606.60(b)

• Calibrate digital thermometer 

according to the schedule recommended 

by manufacturer, instead of monthly as 

required by regulation.

§ 606.65(e)

• Deviate from manufacturer’s 

instructions to use the Gen-Probe 

Procleix HIV–1/HCV Assay and Roche 

COBAS Ampliscreen HIV–1 and HCV 

nucleic acid tests on whole blood, red 

blood cells (RBC), platelets, source 

leukocytes, therapeutic exchange 

plasma, and recovered plasma intended 

for further manufacturing.

• Deviate from manufacturer’s 

instruction to use samples containing 

up to 200 milligrams (mg)/deciliters 

(dL) hemoglobin or 800 mg/dL 

triglycerides in the following assays: 

Abbott HIV AB HIV–1/HIV–2, (rDNA) 

EIA (LN3A77), Ortho Hepatitis B Core 

Antibody, Ortho Hepatitis B Surface 

Antigen ELISA System 2, and Roche 

Alanine Aminotransferase.

• Deviate from manufacturer’s 

instruction to use an alternate testing 

algorithm for confirming repeatedly 

reactive HIV–1 p24 antigen test results. 

Specifically, a licensed HIV–1 single 

unit Nucleic Acid Test will be 

performed in place of the HIV–1 p24 

antigen neutralization test and the 

results used for donor notification and 

counseling and recipient tracing.

• Deviate from manufacturer’s 

instructions to test donor specimens 

that were initially reactive using Ortho 

HbsAg System 3, in duplicate using 

Genetic Systems HbsAg EIA 3.0 (shaker 

method). If either or both of the donor 

samples test reactive using Genetic 

Systems HbsAg EIA 3.0 (shaker 

method), the donor specimen will be 

tested using Genetic Systems HbsAg 

Confirmatory 3.0 (shaker method).

§ 606.121

• Use of full face green labels for 

autologous use only units.

• Use of black print for all statements 

on container labels (omit use of 

statements in red print.) (Regulation 

revised—variance request no longer 

needed.)

• Use of ‘‘Autologous’’ on label in 

lieu of ‘‘Paid’’ or ‘‘Volunteer’’

• Omit special labeling from RBC 

with positive antibody screens that are 

suspended in additive solution, if the 

supernatant of the additive solution was 

tested using approved methods and 

found to be negative for unexpected 

antibodies.

• Place ABO/Rh label and ‘‘Donor 

Untested’’ on group and type label 

position.

• Print the anticoagulant name after 

the proper product name instead of 

preceding it. (Done for ISBT 128 labels.)

§ 606.122(m)

• Extend the storage time of thawed 

Fresh Frozen Plasma (FFP) at 1 to 6 °C 

to 24 hours, instead of 6 hours.

§ 606.151

• Omit performing a minor side 

crossmatch on RBC prepared in additive 

solutions that have not been screened 

for unexpected antibodies.

• Use of a computer (electronic) 

crossmatch instead of a major side 

crossmatch. (Regulation revised—

variance request no longer needed.)

• Use of a type and screen procedure 

as an alternative method for the 

antiglobulin crossmatch. (Regulation 

revised—variance request no longer 

needed.)

• Allow use of a recipient sample up 

to 72 hours old for pre-transfusion 

testing. (Regulation revised—variance 

request no longer needed.)

§ 610.40

• Ship source leukocytes to the 

manufacturer before infectious disease 

testing has been completed, provided 

the product is labeled that testing is not 

complete and stored in quarantine until 

the manufacturer has received the test 

results. (Regulation revised—variance 

request no longer needed.)

• Ship autologous blood unit to 

another establishment without testing 

unit for communicable disease agents. 

Testing performed on sample drawn on 

subsequent donation.

• Ship autologous blood unit to 

another establishment for processing 

and labeling and return to collecting 

facility without testing unit for 

communicable disease agents, provided 

neither facility has a crossover policy.

• Allow shipment under quarantine 

of untested source plasma labeled as