75682 Federal Register / Vol. 75, No. 233 / Monday, December 6, 2010 / Notices 

Oral presentations from the public will 

be scheduled between approximately 

1:30 p.m. and 2:30 p.m. on January 20, 

2011, and between approximately 10 

a.m. and 11 a.m. on January 21, 2011. 

Those individuals interested in making 

formal oral presentations should notify 

the contact person and submit a brief 

statement of the general nature of the 

evidence or arguments they wish to 

present, the names and addresses of 

proposed participants, and an 

indication of the approximate time 

requested to make their presentation on 

or before December 27, 2010. Time 

allotted for each presentation may be 

limited. If the number of registrants 

requesting to speak is greater than can 

be reasonably accommodated during the 

scheduled open public hearing session, 

FDA may conduct a lottery to determine 

the speakers for the scheduled open 

public hearing session. The contact 

person will notify interested persons 

regarding their request to speak by 

December 28, 2010. 

Persons attending FDA’s advisory 

committee meetings are advised that the 

agency is not responsible for providing 

access to electrical outlets. 

FDA welcomes the attendance of the 

public at its advisory committee 

meetings and will make every effort to 

accommodate persons with physical 

disabilities or special needs. If you 

require special accommodations due to 

a disability, please contact Diem-Kieu 

Ngo at least 7 days in advance of the 

meeting. 

FDA is committed to the orderly 

conduct of its advisory committee 

meetings. Please visit our Web site at 

http://www.fda.gov/ 

AdvisoryCommittees/ 

AboutAdvisoryCommittees/ 

ucm111462.htm for procedures on 

public conduct during advisory 

committee meetings. 

Notice of this meeting is given under 

the Federal Advisory Committee Act (5 

U.S.C. app. 2). 

Dated: December 1, 2010. 

Jill Hartzler Warner, 

Acting Associate Commissioner for Special 

Medical Programs. 

[FR Doc. 2010–30501 Filed 12–3–10; 8:45 am] 

BILLING CODE 4160–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. FDA–2000–N–0163; Formerly 

Docket No. 2000N–1219] 

Reclassification of Category IIIA 

Biological Products, Bacterial 

Vaccines and Related Biological 

Products; Implementation of Efficacy 

Review; Final Order; and Delmont 

Laboratories, Inc.: Denial of Request 

for a Hearing, and Revocation of 

License 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Notice; final order. 

SUMMARY: The Food and Drug 

Administration (FDA) is issuing a final 

order pursuant to the reclassification 

procedures under the biologics 

regulations; denying the request by 

Delmont Laboratories, Inc. (Delmont), 

for a hearing on FDA’s proposal to 

revoke Delmont’s license based on the 

proposed reclassification of its product, 

Polyvalent Bacterial Antigens with ‘‘No 

U.S. Standard of Potency,’’ Staphage 

Lysate® (SPL) (hereinafter referred to as 

SPL) into Category II (unsafe, 

ineffective, or misbranded); and 

revoking Delmont’s U.S. License No. 

299. The final order finalizes the 

proposed order published in the Federal 

Register of May 15, 2000 (65 FR 31003) 

(May 2000 proposal), to reclassify 

Category IIIA bacterial vaccines and 

bacterial antigens into Category I or 

Category II. 

DATES: The final order reclassifying 

Delmont’s SPL into Category II, and 

Sanofi Pasteur Inc.’s (Sanofi’s) Tetanus 

Toxoid Adsorbed and Tetanus and 

Diphtheria Toxoids Adsorbed For Adult 

Use (DECAVACTM) into Category I for 

both primary immunization and booster 

use is effective December 6, 2010. The 

revocation of Delmont’s license (U.S. 

License No. 299) is effective December 

6, 2010. 

FOR FURTHER INFORMATION CONTACT: 

Stephen Ripley, Center for Biologics 

Evaluation and Research (HFM–17), 

Food and Drug Administration, 1401 

Rockville Pike, Suite 200N, Rockville, 

MD 20852–1448, 301–827–6210. 

SUPPLEMENTARY INFORMATION: 

I. Background on the Efficacy Review 

Process 

In the Federal Register of February 

13, 1973 (38 FR 4319), FDA issued 

procedures for the review by 

independent advisory panels of the 

safety, effectiveness, and labeling of 

biological products licensed before July 

1, 1972. These procedures were later 

codified in § 601.25 (21 CFR 601.25) (38 

FR 32048 at 32052, November 20, 1973). 

Under § 601.25, FDA assigned 

responsibility for the initial review of 

each of the biological product categories 

to a separate independent advisory 

panel consisting of qualified experts. 

Each panel was charged with preparing 

for the Commissioner of Food and Drugs 

an advisory report which was to: (1) 

Evaluate the safety and effectiveness of 

the biological products for which a 

license had been issued; (2) review their 

labeling; and (3) identify the biological 

products that are safe, effective, and not 

misbranded. Each advisory panel report 

was also to include recommendations 

classifying the products reviewed into 

one of three categories. 

• Category I, designating those 

biological products determined by the 

panel to be safe, effective, and not 

misbranded. 

• Category II, designating those 

biological products determined by the 

panel to be unsafe, ineffective, or 

misbranded. 

• Category III, designating those 

biological products determined by the 

panel not to fall within either Category 

I or Category II on the basis of the 

panel’s conclusion that the available 

data were insufficient to classify such 

biological products, and for which 

further testing was therefore required. 

Category III products were assigned to 

one of two subcategories. Category IIIA 

products were those that would be 

permitted to remain on the market 

pending the completion of further 

studies. Category IIIB products were 

those for which the panel recommended 

license revocation on the basis of the 

panel’s assessment of potential risks and 

benefits. 

In accordance with § 601.25, after 

reviewing the conclusions and 

recommendations of the review panels, 

FDA would publish in the Federal 

Register a proposed order containing: 

(1) A statement designating the 

biological products reviewed into 

Categories I, II, IIIA or IIIB; (2) a 

description of the testing necessary for 

Category IIIA biological products; and 

(3) the complete panel report. Under the 

proposed order, FDA would propose to 

revoke the licenses of those products 

designated into Category II and Category 

IIIB. After reviewing public comments, 

FDA would publish a final order on the 

matters covered in the proposed order. 

Two original advisory panels 

reviewed the four Category IIIA 

products that are the subject of this final 

order. The advisory panel for Bacterial 

Vaccines and Bacterial Antigens with 


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Federal Register / Vol. 75, No. 233 / Monday, December 6, 2010 / Notices 75683 

‘‘no U.S. Standard of Potency’’ (the 

Original Antigen Panel) reviewed 

Delmont’s SPL product. The advisory 

panel for Bacterial Vaccines and 

Toxoids with Standards of Potency (the 

Original Toxoid Panel) reviewed 

Sanofi’s Tetanus Toxoid Adsorbed and 

Tetanus and Diphtheria Toxoids 

Adsorbed For Adult Use products. The 

above definition of Category IIIA was 

applied at the time of each advisory 

panel’s review and served as the basis 

for their recommendations. 

In the Federal Register of October 5, 

1982 (47 FR 44062), FDA revised 

§ 601.25 and codified § 601.26 (21 CFR 

601.26) to establish procedures to 

reclassify those products in Category 

IIIA into either Category I or Category II 

based on available evidence of safety 

and effectiveness. Under § 601.26, 

Category IIIA products that would be 

reclassified included products that an 

advisory panel had recommended be 

assigned to Category IIIA, that FDA had 

proposed to place into Category IIIA, or 

for which FDA had issued a final order 

reclassifying the products into Category 

IIIA. 

Under the procedures specified in 

§ 601.26, FDA appointed an advisory 

panel and used existing advisory panels 

to review Category IIIA products and to 

make recommendations to reclassify 

each Category IIIA product into 

Category I or Category II. FDA assigned 

the reclassification review of bacterial 

vaccines and bacterial antigens with ‘‘no 

U.S. standard of potency’’ to the 

Vaccines and Related Biological 

Products Advisory Committee 

(VRBPAC). FDA also assigned the 

reclassification review of bacterial 

vaccines and toxoids with standards of 

potency to the VRBPAC. 

During the reclassification review 

process, interested persons were 

permitted to attend meetings, appear 

before the advisory panels, and submit 

data to the panels for review. The 

advisory panels then submitted reports 

to FDA that recommended the 

reclassification of each Category IIIA 

product into either Category I or II. 

According to § 601.26, after reviewing 

the conclusions and recommendations 

of the advisory panels, FDA must 

publish in the Federal Register a 

proposed order containing: (1) A 

statement designating the products as 

Category I or Category II, (2) a notice of 

availability of the full panel report, (3) 

a proposal to accept or reject the 

findings of the advisory panels, and (4) 

a statement identifying those products 

that FDA proposes to permit to remain 

on the market because of a compelling 

medical need and because no suitable 

alternative exists as described in 

§ 601.26(d)(4). 

II. Category IIIA Products Subject to 

This Final Reclassification Order 

FDA published the May 2000 

proposal to reclassify Category IIIA 

bacterial vaccines and bacterial antigens 

into Category I or Category II. FDA 

based the proposed order on its review 

of all the evidence, and considered the 

findings and recommendations of the 

VRBPAC. The proposed order also 

announced FDA’s intent to revoke the 

biologics licenses for those bacterial 

vaccines and bacterial antigens that 

FDA proposed reclassifying into 

Category II. 

FDA agreed with VRBPAC’s 

recommendations and proposed that 

bacterial vaccines and toxoids with 

standards of potency be classified into 

two separate categories based upon their 

use as either a primary immunogen or 

as a booster immunogen. FDA proposed 

that some bacterial vaccines with 

standards of potency be classified into 

Category II for use as a primary 

immunogen, but into Category I for use 

as a booster immunogen. 

FDA further proposed that bacterial 

vaccines and bacterial antigens with ‘‘no 

U.S. standard of potency’’ be classified 

into Category II for all labeled 

indications, agreeing with the 

VRBPAC’s recommendations. 

A. Category IIIA Products That FDA 

Had Proposed To Reclassify Into 

Category II 

Five manufacturers of Category IIIA 

products that VRBPAC recommended 

for reclassification into Category II were 

subject to the May 2000 proposal (Table 

1 of this document). After publication of 

the May 2000 proposal, four of the five 

manufacturers voluntarily submitted to 

FDA requests for revocation of their 

licenses for the applicable products. 

Subsequently, FDA revoked these 

licenses. Therefore, no further action is 

required on these manufacturers’ 

products. The reclassification of the 

Category IIIA product of the remaining 

manufacturer, Delmont, is discussed in 

a later section of this document. 

TABLE 1—CATEGORY IIIA PRODUCTS THAT FDA HAD PROPOSED TO RECLASSIFY INTO CATEGORY II1 

Manufacturer/License No. Product(s) Proposed Category II 

indication 

Bioport Corporation, No. 1260 ............... Diphtheria and Tetanus Toxoids Adsorbed 2 ........................................................

Tetanus Toxoid Adsorbed 2 ..................................................................................

Primary immunogen. 

Delmont Laboratories, Inc., No. 299 ...... Polyvalent Bacterial Antigens with ‘‘No U.S. Standard of Potency’’ Staphage 

Lysate® (SPL).

All labeled indications. 

Hollister-Stier Laboratories LLC, No. 

1272.

Polyvalent Bacterial Vaccines with ‘‘No U.S. Standard of Potency’’ (Bacterial 

Vaccines Mixed Respiratory (MRV or MRVI), Bacterial Vaccines for Treatment, Special Mixtures) 3.

All labeled indications. 

Sanofi Pasteur Inc., No. 1725 ............... Tetanus Toxoid 4 ................................................................................................... Primary immunogen. 

Wyeth Laboratories, Inc., No. 3 ............. Tetanus and Diphtheria Toxoids Adsorbed (Adult Use) 5 .................................... Primary immunogen. 

1FDA is not relisting in this document the licenses FDA listed in and revoked before the May 2000 proposal. 

2The licenses for these products were transferred from Michigan Department of Public Health, No. 99, to BioPort Corporation, License No. 

1260 on November 12, 1998. The licenses were subsequently revoked by FDA on November 20, 2000, at the request of the manufacturer (66 

FR 29148 at 29149, May 29, 2001). 3The licenses for these products were transferred from Bayer, Inc., No. 8 to Hollister-Stier, LLC, No. 1272 on June 2, 1999. The licenses were 

subsequently revoked by FDA on August 3, 2000, at the request of the manufacturer (66 FR 29148 at 29149, May 29, 2001). 4The license for this product was transferred from Merrell-National Laboratories Division of Richardson-Merrell, Inc. (License No. 101) to 

Connaught Laboratories, Inc. (License No. 711) on January 3, 1978; from Connaught Laboratories, Inc. (License No. 711) to Aventis Pasteur, 

Inc. (License No. 1277) on December 9, 1999; and from Aventis Pasteur, Inc. (License No. 1277) to Sanofi Pasteur Inc. (License No. 1725) on 

December 19, 2005. The license for this product was subsequently revoked by FDA on July 16, 2009, at the request of the manufacturer. 5The license for this product was revoked by FDA on May 30, 2002, at the request of the manufacturer. 


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Delmont Laboratories, Inc., SPL 

On August 9, 2000, Delmont 

submitted to FDA a response to FDA’s 

May 2000 proposal to reclassify SPL 

into Category II. Information regarding 

Delmont’s response and FDA’s actions 

are discussed in section III of this 

document. 

B. Category IIIA Products That FDA Had 

Proposed To Reclassify Into Category I 

Four manufacturers of Category IIIA 

products, recommended by VRBPAC for 

reclassification into Category I for both 

primary and booster immunization, 

were subject to the May 2000 proposal 

(Table 2 of this document). After 

publication of the May 2000 proposal, 

three of the four manufacturers 

voluntarily submitted to FDA requests 

for revocation of their licenses. FDA 

subsequently revoked these licenses. 

Therefore, no further action is required 

on these manufacturers’ products. The 

reclassification of the Category IIIA 

products of the remaining manufacturer, 

Sanofi, is discussed in this section of 

this document. 

TABLE 2—CATEGORY IIIA PRODUCTS THAT FDA HAD PROPOSED TO RECLASSIFY INTO CATEGORY I FOR BOTH PRIMARY

AND BOOSTER IMMUNIZATION 1

Manufacturer/License No. Product(s) 

Lederle Laboratories, Division, American Cyanamid Company, No. 17 Tetanus Toxoid.2

Diphtheria and Tetanus Toxoids and Pertussis Vaccine Adsorbed.2

Diphtheria and Tetanus Toxoids Adsorbed.2

Tetanus and Diphtheria Toxoids Adsorbed (Adult Use).2

Tetanus Toxoid Adsorbed.2

Sanofi Pasteur Inc., License No. 1725 .................................................... Tetanus Toxoid Adsorbed.3

Tetanus and Diphtheria Toxoids Adsorbed (Adult Use).3

Swiss Serum and Vaccine Institute Berne, No. 21 .................................. Tetanus Toxoid Adsorbed.4

Wyeth Laboratories, Inc., No. 3 ............................................................... Diphtheria and Tetanus Toxoids Adsorbed.5

Tetanus Toxoid.5

Tetanus Toxoid Adsorbed.5

Diphtheria and Tetanus Toxoids and Pertussis Vaccine Adsorbed.5

1FDA is not relisting in this document the licenses FDA listed in and revoked before the May 2000 proposal. 

2The licenses for these products were revoked by FDA on March 4, 1994, July 24, 2002, May 10, 2002, May 10, 2002, and May 22, 2002, respectively, at the request of the manufacturer. 3The licenses for these products were transferred from Merrell-National Laboratories Division of Richardson-Merrell, Inc. (License No. 101) to 

Connaught Laboratories, Inc. (License No. 711) on January 3, 1978; from Connaught Laboratories, Inc. (License No. 711) to Aventis Pasteur, 

Inc. (License No. 1277) on December 9, 1999; and from Aventis Pasteur, Inc. (License No. 1277) to Sanofi Pasteur Inc. (License No. 1725) on 

December 19, 2005. 4The license for this product was revoked by FDA on August 29, 2000, at the request of the manufacturer. 

5The licenses for these products were revoked by FDA on May 30, 2002, May 30, 2002, May 30, 2002, and October 15, 2002, respectively, at 

the request of the manufacturer. 

1. Sanofi Pasteur Inc., Tetanus Toxoid 

Adsorbed 

The Original Toxoid Panel 

recommended that all licensed and 

marketed tetanus toxoid products be 

classified into Category I for booster 

immunization (50 FR 51002, December 

13, 1985). The Original Toxoid Panel 

reviewed Sanofi’s Tetanus Toxoid 

Adsorbed product and recommended 

that the product be placed into Category 

I for booster use and Category IIIA for 

primary immunization (50 FR 51002 at 

51029). FDA agreed with the Original 

Toxoid Panel’s recommendations to 

classify this product into Category I for 

booster use and Category IIIA for 

primary immunization (50 FR 51002 at 

51105 and 51106). The VRBPAC 

reviewed the Category IIIA primary 

immunization indication for Sanofi’s 

Tetanus Toxoid Adsorbed. Based on 

additional data from a clinical study 

performed by the firm, the VRBPAC 

recommended that the product be 

placed into Category I for primary 

immunization. (See Ref. 1, at pages 19 

and 20). FDA agrees with the Original 

Toxoid Panel’s and VRBPAC’s 

recommendations and is reclassifying 

Sanofi’s Tetanus Toxoid Adsorbed 

product into Category I for both primary 

immunization and booster use. 

2. Sanofi Pasteur Inc., Tetanus and 

Diphtheria Toxoids Adsorbed (Adult 

Use) 

The Original Toxoid Panel reviewed 

Sanofi’s Tetanus and Diphtheria 

Toxoids Adsorbed (Adult Use) and 

recommended that the product be 

placed into Category I for booster 

immunization and Category IIIA for 

primary immunization (50 FR 51002 at 

51040). FDA agreed with the Original 

Toxoid Panel’s recommendations to 

classify this product into Category I for 

booster use and Category IIIA for 

primary immunization (50 FR 51002 at 

51105 and 51106). The VRBPAC 

reviewed the Category IIIA primary 

immunization indication for Sanofi’s 

Tetanus and Diphtheria Toxoids 

Adsorbed (Adult Use). Based on 

additional data from a human clinical 

study performed by the firm, the 

VRBPAC recommended that the product 

be placed into Category I for primary 

immunization. (See Ref. 1, at pages 21 

and 22). FDA agrees with the Original 

Toxoid Panel’s and VRBPAC’s 

recommendations and is therefore 

reclassifying Sanofi’s Tetanus and 

Diphtheria Toxoids Adsorbed For Adult 

Use product into Category I for both 

primary immunization and booster use. 

III. Denial of a Hearing on Proposed 

License Revocation—Delmont 

Laboratories, Inc. 

A. Notice of Opportunity for a Hearing 

On August 9, 2000, Delmont 

submitted to FDA a written comment 

opposing FDA’s May 2000 proposal to 

reclassify its product, SPL, into Category 

II. Delmont proposed, instead, 

reclassifying SPL into Category I and 

submitted information supporting its 

proposal. FDA carefully considered the 

information that Delmont provided and 

found that the information did not 

support a reclassification of SPL into 

Category I. 

Accordingly, a Notice of Opportunity 

for Hearing (NOOH) on a proposal to 

revoke the license for Delmont’s SPL 

was published in the Federal Register of 

February 26, 2003 (68 FR 8908). In the 

NOOH, FDA provided a detailed 

analysis and discussion of the 

information that Delmont submitted in 

its response to FDA’s May 2000 

proposal. Further, in the NOOH, FDA 


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advised Delmont that a request for a 

hearing should identify the specific fact 

or facts that are genuine, substantial, 

and in dispute (§ 12.24(b)(1) (21 CFR 

12.24(b)(1)). FDA put Delmont on notice 

that mere allegations or denials are not 

enough to obtain a hearing 

(§ 12.24(b)(2)). FDA also put Delmont on 

notice that the Commissioner would 

deny a hearing request if the 

Commissioner concluded that the data 

and information submitted are 

insufficient to justify the factual 

determination urged, even if accurate 

(§ 12.24(b)(3)). 

B. Delmont’s Hearing Request 

On April 28, 2003, Delmont submitted 

to FDA a letter objecting to FDA’s 

proposal to revoke its license and 

requested a hearing. In the letter, 

Delmont did not submit any evidence 

that raised a genuine and substantial 

issue of fact justifying a hearing. 

Instead, Delmont resubmitted data on 

SPL that it previously submitted to FDA 

and made procedural arguments for why 

it is entitled to a hearing. Specifically, 

Delmont argued that FDA applied the 

wrong effectiveness standard when 

evaluating the studies that Delmont 

previously submitted, and that FDA 

used incorrect procedures when 

proposing to reclassify SPL and to 

revoke Delmont’s license. 

C. Commissioner’s Determination That 

Delmont Has Not Justified a Hearing 

As explained in subsection 1 in this 

section of this document, FDA applied 

the correct effectiveness standard to 

SPL. In subsection 2 in this section of 

this document, we explain that SPL 

does not satisfy that standard. 

Specifically, this document explains 

why most of the data on which Delmont 

relies came from studies that do not 

meet that standard either because they 

were not human studies or were not 

adequately controlled studies. For the 

few studies that were controlled or even 

partially controlled, this document 

explains why they did not show that 

SPL is effective. Therefore, Delmont 

fails to raise a genuine and substantial 

issue of fact regarding the effectiveness 

of SPL for resolution at a hearing. 

Moreover, the procedural objections that 

Delmont raises do not create a basis for 

a hearing (§ 12.24(b)(1)). These 

arguments are discussed in subsection 3 

of this section of this document. 

1. Biologics Effectiveness Standard 

Under FDA regulations, codified from 

the final rule published on February 13, 

1973 (38 FR 4319 at 4322), biologics 

manufacturers, like Delmont, whose 

products were licensed before 1972, 

must prove that their products are 

effective by submitting data from 

‘‘controlled clinical investigations’’ as 

defined in § 314.126 (21 CFR 314.126) 

(‘‘Adequate and well-controlled 

studies’’), unless FDA waives that 

requirement (§ 601.25(d)(2)). To obtain a 

waiver, the sponsor must show that 

controlled clinical investigations are 

‘‘not reasonably applicable to the 

biological product or essential to the 

validity of the investigation, and that an 

alternative method of investigation is 

adequate to substantiate effectiveness’’ 

(§ 601.25(d)(2)) (emphasis added). 

Delmont attempted to argue that FDA 

should not have applied that standard to 

SPL. Instead of arguing that controlled 

clinical investigations are not 

reasonably applicable to SPL or 

essential to the validity of SPL 

investigations, and instead of advancing 

an alternative method of investigation 

and explaining why it would be 

adequate to substantiate SPL’s 

effectiveness, Delmont simply argued 

that FDA should never require data from 

controlled clinical investigations for 

biologics. The basis for its argument is 

the following statement in the preamble 

to FDA’s proposed reclassification rule 

for Category IIIA products (46 FR 4634 

at 4635, January 16, 1981): ‘‘While it is 

clear * * * that the applicable statutory 

requirement for potency in the Public 

Health Service Act has been interpreted 

as requiring that a product be effective, 

the specific statutory criteria governing 

new drugs, ‘adequate and wellcontrolled clinical studies,’ have not 

been applied to biological drugs.’’ 

FDA’s final reclassification rule for 

Category IIIA products (47 FR 44062 at 

44067, October 5, 1982), however, 

confirmed that FDA ‘‘does indeed 

consider controlled clinical studies to 

be the preferred form of evidence for 

documenting a product’s effectiveness.’’ 

Furthermore, FDA clarified that ‘‘unless 

unusual circumstances justify a special 

exemption for a particular product,’’ 

controlled clinical investigations are 

required to establish effectiveness (47 

FR 44062 at 44067). 

In this case, Delmont did not attempt 

to show that SPL meets the criteria for 

a special exemption, namely, that an 

alternative method of investigation is 

adequate to substantiate SPL’s 

effectiveness, and that controlled 

clinical investigations are either 

inapplicable to SPL or not essential to 

the validity of the investigation. In fact, 

Delmont sponsored a controlled clinical 

trial of SPL (in patients suffering from 

the disease hidradenitis suppurativa), 

but as FDA explained at length in the 

February 26, 2003, NOOH, the data 

showed no statistically significant 

difference between SPL and a placebo. 

Therefore, the data were inadequate to 

demonstrate that the product was 

effective. See 68 FR 8908 at 8909. 

Clearly, FDA applied the correct 

standard when evaluating SPL. 

2. Application of the Standard to SPL 

Since FDA’s biologics review began, 

Delmont has submitted to FDA data on 

SPL at four different times: (a) Before 

1978, as part of FDA’s initial biologics 

review process; (b) between January and 

May 1978, to convince FDA to classify 

SPL into Category IIIA rather than IIIB 

so that Delmont could continue 

marketing SPL while obtaining data 

from effectiveness studies; (c) in 1983, 

as part of FDA’s reclassification 

procedures; and (d) in 1994, to 

supplement its reclassification data with 

the results of studies that were 

incomplete in 1983. As discussed in 

turn below, none of the data are 

sufficient to demonstrate that SPL is 

effective. 

a. Pre-1978 Data 

As part of FDA’s initial biologics 

review process, Delmont submitted data 

to the Original Antigen Panel. The 

Original Antigen Panel issued a report, 

which is published in the Federal 

Register of November 8, 1977 (42 FR 

58266 at 58270), that analyzed in detail 

all the studies that Delmont had 

submitted, and described deficiencies in 

each one. Based on that analysis, the 

Original Antigen Panel concluded that 

Delmont had provided ‘‘no substantial 

evidence of safety or effectiveness,’’ and 

‘‘no evidence presumptive of safety’’ (42 

FR 58266 at 58285). Consequently, the 

Original Antigen Panel recommended 

that FDA classify SPL into Category IIIB 

and revoke Delmont’s license (42 FR 

58266 at 58285). In the Federal Register 

of November 8, 1977, FDA issued a 

proposed order notifying Delmont that it 

agreed with the Original Antigen Panel’s 

findings and that it intended to revoke 

Delmont’s license (42 FR 58266 at 

58318). As discussed in subsection b.iii 

of this section of this document, FDA 

ultimately classified SPL into category 

IIIA based on additional safety data that 

Delmont submitted (44 FR 1544 at 1548, 

January 5, 1979), but FDA agreed with 

the Original Antigen Panel’s criticisms 

of SPL’s effectiveness data (44 FR 1544 

at 1546, comment 5) and ordered 

Delmont to complete and submit the 

effectiveness testing that the Original 

Antigen Panel had recommended (44 FR 

1544 at 1548). 


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b. January to May 1978 Data 

i. Delmont’s Hearing Request 

In response to FDA’s revocation 

proposal (42 FR 58266), Delmont 

requested a hearing on whether FDA 

should classify SPL into Category IIIA or 

IIIB, and submitted to FDA additional 

data on January 8, 1978, February 7, 

1978, March 31, 1978, and May 26, 

1978. Those submissions are all 

currently in the public docket relating to 

this matter, Docket No. 2000N–1219, as 

attachments to Delmont’s April 28, 

2003, hearing request. None of the data 

satisfied the controlled clinical 

investigations standard for proving 

effectiveness, as discussed in subsection 

b.iii of this section of this document, 

even though FDA eventually 

determined that the safety data were 

sufficient to classify SPL into Category 

IIIA to allow Delmont to continue 

marketing SPL while obtaining 

effectiveness data. 

ii. Deficiencies in Delmont’s Data 

(1). January 8, 1978, Submission 

In a letter dated January 8, 1978 

(Docket No. 2000N–1219, Item SUP1, 

Tab C to Delmont’s April 28, 2003, 

hearing request), Delmont submitted to 

FDA additional study reports. Delmont 

stated that the reports ‘‘show that no risk 

to human safety can result from 

continued marketing of SPL for a 

limited period while further studies are 

conducted.’’ As to effectiveness, 

however, Delmont said only that the 

study reports ‘‘demonstrate that further 

studies of SPL in accordance with FDA 

requirements for clinical investigations 

will very likely provide substantial 

evidence that the product is effective for 

its labeled indications * * *.’’ 

Therefore, Delmont admitted that the 

data it was submitting were collected 

from studies that were not conducted in 

accordance with FDA requirements for 

clinical investigations. 

Most of those studies failed to satisfy 

FDA’s controlled clinical investigations 

standard because they were preclinical 

studies not performed on humans, and 

therefore, were not clinical 

investigations. Specifically, those 

reports were as follows: ‘‘Chronic 

Toxicity Test of SPL in Rats’’ (Fujino, et 

al.) (Ref. 2); ‘‘Acute and Subacute 

Toxicity Tests of SPL’’ (Fujino, et al.) 

(mice and rats) (Ref. 3); 

‘‘Teratologenicity Study of SPL in Rats 

and Rabbits’’ (Hachihiko Hirayama) (Ref. 

4); ‘‘Effect of SPL on the Development of 

Skin Lesion in Mice after Inoculation 

with Herpes Simplex Virus’’ 

(Department of Microbiology, School of 

Medicine, Kyushu University) (Ref. 5); 

‘‘Chemotactic Accumulation of 

Macrophages in the Peritoneal Cavity 

after Inoculation of SPL and their 

Antitumor Activity’’ (Department of 

Microbiology, School of Medicine, 

Kyushu University) (mice) (Ref. 6); and 

‘‘S–27: Summary of Results of Tests 

Conducted at Fuji-Zoki Pharmaceutical 

Research Division’’ (safety tests in mice 

and guinea pigs) (Ref. 7). 

Two other studies that Delmont 

included in its January 8, 1978, 

submission, ‘‘Susceptibility of 

Staphylococcus aureus Clinical Isolates 

to Gratia Bacteriophage’’ (Shigeno, et al.) 

(Ref. 8) and ‘‘Influence of Staphage 

Lysates (SPL) on Immune Responses In 

Vitro’’ (Mitsuma, et al.) (Ref. 9), do not 

qualify as controlled clinical 

investigations because they were in 

vitro studies. Moreover, the limited data 

contained in the abstracts that Delmont 

submitted to FDA on these two studies 

limit their usefulness for any purpose. 

Therefore, they are not adequate to 

support reclassifying SPL into Category 

I. 

Delmont also submitted two reports 

on studies of SPL in humans, 

‘‘Immunopotiator Activity of Staphage 

Lysate (Mudd)’’ (Azuma, et al.) (Ref. 10) 

and ‘‘Immunochemotherapy for 

Infections—With Particular Reference to 

Staphage Lysate’’ (Tsuda, et al.) (Ref. 

11). Neither of those qualifies as a 

controlled clinical investigation, for a 

number of reasons. First, neither study 

was controlled as required in FDA’s 

1979 final order, which included 

Delmont’s product in Category IIIA (44 

FR 1544 at 1548). A fundamental 

characteristic of controlled clinical 

investigations is that they ‘‘use a design 

that permits a valid comparison with a 

control to provide a quantitative 

assessment of drug effect’’ 

(§ 314.126(b)(2)). A control is necessary 

to ‘‘distinguish the effect of a drug from 

other influences, such as spontaneous 

change in the course of the disease, 

placebo effect, or biased observation’’ 

(§ 314.126(a)). While different types of 

controls are permitted under different 

conditions, neither study reports that 

the investigators used controls. 

Second, both a protocol and a study 

result report should contain a clear 

statement of the objectives of the 

investigation and a summary of the 

methods of analysis (§ 314.126(b)(1)). 

Delmont did not submit the protocol for 

either study, and the resulting reports 

for the two studies did not explain how 

the investigators measured or analyzed 

the results of treating their study 

subjects with SPL. Although the Tsuda 

study report (see Ref. 11) contains a 

summary of clinical results in Table 8, 

which lists the investigators’ 

assessments of subjects’ responses to 

SPL—either ‘‘Excellent,’’ ‘‘Greatly 

improved,’’ or ‘‘Unimproved’’—the study 

does not state what criteria were used to 

reach those assessments. Moreover, as 

the report itself admits, ‘‘no conclusive 

statement can be made here because of 

the relatively small series studied.’’ 

Clearly, the reports do not provide 

‘‘sufficient details of the study design, 

conduct, and analysis to allow critical 

evaluation and a determination of 

whether the characteristics of an 

adequate and well-controlled study are 

present’’ (§ 314.126(a)). 

The studies also failed to meet other 

characteristics of a controlled 

investigation. The study reports fail to 

show that the ‘‘method of selection of 

subjects provides adequate assurance 

that they have the disease or condition 

being studied or evidence of 

susceptibility and exposure to the 

condition against which prophylaxis is 

directed’’ (§ 314.126(b)(3)). In the Tsuda 

study (see Ref. 11) the diseases being 

studied were chronic intractable 

staphylococcal infections or other viral 

infections. In the Azuma study (see Ref. 

10), the condition being studied was 

defensive capacity against infection 

generally. However, neither study report 

showed how the subjects were selected 

to meet these criteria. Similarly, the 

studies fail to show that the ‘‘method of 

assigning patients to treatment and 

control groups minimizes bias and is 

intended to assure comparability of the 

groups with respect to pertinent 

variables’’ (§ 314.126(b)(4)); fail to show 

that ‘‘[a]dequate measures [were] taken 

to minimize bias on the part of the 

subjects, observers, and analysts of the 

data’’ (§ 314.126(b)(5)); fail to 

demonstrate that the ‘‘methods of 

assessment of subjects’ response [were] 

well-defined and reliable’’ 

(§ 314.126(b)(6)); and fail to provide ‘‘an 

analysis of the results of the study 

adequate to assess the effects of the 

drug’’ (§ 314.126(b)(7)). Clearly, then, 

these two studies do not meet the 

criteria for controlled clinical 

investigations. 

Finally, Delmont submitted what it 

described as a protocol for ‘‘a study 

based on short- and long-term 

surveillance of patients receiving SPL 

therapy under the care of Arthur G. 

Baker, M.D.’’ The study had not begun, 

and Delmont had no results to report at 

that time. Therefore, it did not 

contribute to the effectiveness 

assessment. 

In summary, none of the submissions 

that Delmont included with its January 

8, 1978, letter constituted controlled 

clinical investigations. Thus, they were 

insufficient to establish SPL’s 

effectiveness at that time. 


jdjones on DSK8KYBLC1PROD with NOTICES
Federal Register / Vol. 75, No. 233 / Monday, December 6, 2010 / Notices 75687 

(2). February 7, 1978, Letter 

On February 7, 1978, Delmont sent to 

FDA additional data to support its 

request for a hearing on whether to 

classify SPL into Category IIIA or IIIB 

(Docket No. 2000N–1219, Item SUP1, 

Tab D to Delmont’s April 28, 2003, 

hearing request). Delmont categorized 

much of the data and reports as safety 

data, but did include a set of 

attachments that it labeled 

‘‘Effectiveness Data.’’ Delmont divided 

those attachments into ‘‘Controlled 

Studies,’’ and ‘‘Other Efficacy Data.’’ The 

Controlled Studies section contains only 

a protocol for a study that was then in 

early stages, and does not contain a 

report on the results of that study. Thus, 

Delmont admitted that its February 7, 

1978, submission did not contain 

effectiveness data that met the 

controlled clinical investigations 

standard. 

The ‘‘Other Efficacy Data’’ section was 

divided into two subsections: ‘‘Studies 

in Humans’’ and ‘‘Studies in Animals.’’ 

The first paper in the human studies 

subsection, Salmon G.G. and M. 

Symonds, ‘‘Staphage Lysate Therapy in 

Chronic Staphylococcal Infections,’’ 

(Ref. 12), is a duplicate of a published 

article that Delmont had submitted to 

the Original Antigen Panel in 1977. The 

Original Antigen Panel rejected that 

article, stating that in the article 

‘‘patients are said to have recovered 

because of antibody induction but no 

data demonstrating such responses are 

provided’’ (42 FR 58283). The next three 

reports were duplicates of reports that 

Delmont had submitted with its January 

8, 1978, letter, which are deficient for 

the reasons discussed previously in this 

section of this document. Finally, 

Delmont submitted two summaries of 

case studies, ‘‘Immune Stimulation 

Therapy for Inflammatory Disease of the 

Gut,’’ (Ref. 13) and ‘‘Immune 

Stimulation for Aphthous (Herpetic) 

Stomatitis & Rhinitis,’’ (Ref. 14) that Dr. 

Dale Rank had sent to Delmont. These 

reports contain little information, and 

therefore do not ‘‘provide sufficient 

details of study design, conduct, and 

analysis to allow critical evaluation and 

a determination of whether the 

characteristics of an adequate and wellcontrolled study are present’’ 

(§ 314.126(a)). Moreover, the terse case 

reports of Dr. Rank’s patients contain no 

indication that any type of control was 

used. 

Therefore, none of Delmont’s 

February 7, 1978, submissions satisfied 

the controlled clinical investigations 

standard. 

(3). March 31, 1978, Letter 

On March 31, 1978, Delmont sent to 

FDA another letter (Docket No. 2000N– 

1219, Item SUP1, Tab E to Delmont’s 

April 28, 2003, hearing request). That 

letter served primarily to answer 

questions that FDA had raised about the 

animal studies in Delmont’s January 8, 

1978, submission. The letter also 

included three new reports. One 

reported on tests in rabbits and another 

reported the results of in vitro assays, 

neither of which constituted controlled 

clinical investigations in humans. The 

letter also included a one-page ‘‘report of 

a double blind, placebo controlled trial 

for evaluation of SPL as a treatment for 

warts, dated March 7, 1978.’’ The onepage summary clearly did not ‘‘provide 

sufficient details of study design, 

conduct, and analysis to allow critical 

evaluation and a determination of 

whether the characteristics of an 

adequate and well-controlled study are 

present,’’ as § 314.126(a) requires, for 

many reasons. Among them are that it 

provided: No patient recruitment details 

on their diagnoses, as § 314.126(b)(3) 

requires; no explanation of patient 

inclusion and exclusion criteria 

(§ 314.126(b)(3)); no description of 

patient randomization procedures (if 

performed), as § 314.126(b)(4) requires; 

and no clinical descriptions or 

associated clinical measurements for the 

endpoints of ‘‘Excellent,’’ ‘‘Good,’’ and 

‘‘No change,’’ as § 314.126(b)(6) and 

(b)(7) require. Thus, Delmont’s March 

31, 1978, submissions did not satisfy the 

controlled clinical investigations 

standard. 

(4). May 26, 1978, Letter 

In a letter dated May 26, 1978 (Docket 

No. 2000N–1219, Item SUP1, Tab F to 

Delmont’s April 28, 2003, hearing 

request), Delmont submitted one last 

supplement to its comments on FDA’s 

proposal to classify SPL into Category 

IIIB. The letter stated that ‘‘[t]his 

information further supports Delmont’s 

position, set out in its January 8, 1978, 

comments, that SPL is safe and that an 

opportunity should be provided for the 

completion of clinical studies to provide 

additional information demonstrating 

the product’s effectiveness.’’ Thus, 

Delmont acknowledged that its May 

submissions did not demonstrate SPL’s 

effectiveness. 

The first set of documents contains 

case reports on 50 patients that Dr. 

Arthur Baker had treated with SPL. 

Delmont submitted those individual 

case reports to ‘‘show that no allergic 

reactions or adverse effects were 

observed in any of the patients who 

received SPL over extended periods of 

time.’’ Delmont did not include a study 

result report analyzing the data for 

effectiveness. 

The second set of documents consists 

of protocols for two clinical studies of 

SPL that Dr. John Silva was conducting. 

One was then underway at the 

Department of Veterans Affairs hospital 

in Biloxi, MS and the second had not 

begun. Delmont did not submit any 

effectiveness data from the ongoing 

study. Instead, it submitted a letter from 

Dr. Silva stating that no allergic 

reactions or other adverse effects had 

been observed. Therefore, the 

information related to safety rather than 

efficacy. 

iii. FDA’s 1979 Final Order on SPL 

On January 5, 1979 (44 FR 1544), FDA 

published a final order formally 

classifying into Category IIIA those 

products, including Delmont’s SPL, for 

which the data were insufficient to 

determine their safety and effectiveness, 

but which FDA would allow to remain 

on the market pending completion of 

testing. That final order confirmed that 

the Commissioner agreed with the 

Original Antigen Panel’s conclusions 

and recommendations about all the 

deficiencies in the Category IIIA data 

(44 FR 1544 at 1546, comment 5). It 

further confirmed that the 

manufacturers of those products had to 

submit data from controlled clinical 

investigations, and that their products 

could not remain in category IIIA 

indefinitely (44 FR 1544 at 1545 to 

1548). 

That final order also expressly 

confirmed that SPL was subject to the 

same requirement. The order stated as 

follows: ‘‘Because data submitted by 

Delmont Laboratories, Inc., have been 

found to be adequate to reclassify its 

staphage lysate types I and [III] 

combined, License No. 299, from 

Category IIIB to IIIA, the requirements 

concerning completion of testing and 

labeling apply to these products’’ (44 FR 

1544 at 1548) (emphasis added). The 

order also made clear that those testing 

requirements were the ones that the 

Original Antigen Panel had 

recommended; after listing all of the 

Category IIIA products, including SPL, 

the order stated that ‘‘[l]icenses remain 

in effect for these products pending 

conformance with the Panel’s 

recommendations and completion of 

testing’’ (44 FR 1544 at 1548) (emphasis 

added). As discussed above, the 

Original Antigen Panel was clear that all 

Category IIIA products reviewed by that 

Panel needed further clinical 

investigations to establish their 

effectiveness. 


jdjones on DSK8KYBLC1PROD with NOTICES
75688 Federal Register / Vol. 75, No. 233 / Monday, December 6, 2010 / Notices 

c. 1983 Data 

In December 1982, FDA assigned the 

VRBPAC to follow the reclassification 

procedures in § 601.26 (65 FR 31003 at 

31004) to reclassify the bacterial 

vaccines and antigens with ‘‘no U.S. 

standards of potency’’ that had been 

previously classified into Category IIIA, 

including SPL into either Category I or 

Category II. Under these procedures, 

Delmont submitted to the VRBPAC 

additional data on SPL. The VRBPAC 

held reclassification meetings in 

January, June, and September 1983 (65 

FR 31003 at 31006). 

After reviewing all of the data, 

VRBPAC voted to recommend placing 

SPL into Category II and to revoke 

Delmont’s license. VRBPAC’s Final 

Report provides VRBPAC’s detailed 

critique of all the data that Delmont 

submitted (see Ref. 1, at pages 47 to 54). 

The Final Report confirmed that the 

VRBPAC members voted unanimously 

to recommend placing SPL into 

Category II because the evidence was 

insufficient to prove effectiveness. (See 

Ref. 1, at page 55). We continue to agree 

with the VRBPAC’s analysis as 

described in that portion of the Final 

Report at page 55. 

d. 1994 Data 

On February 28, 1994, Delmont 

submitted to FDA results from a study 

on hidradenitis suppurativa (HS) that 

had just begun in 1983, along with the 

results from some other studies. (A copy 

of Delmont’s February 28, 1994, 

submission is attached as Tab C to 

comments that Delmont submitted to 

the Docket No. 2000N–1219, Item C1 on 

August 9, 2000). In FDA’s February 26, 

2003, NOOH, FDA published a detailed 

critique of Delmont’s 1994 data (68 FR 

8908 at 8909). Of all the study results 

that Delmont submitted, only the HS 

study, a prospective, double-blind, 

placebo controlled trial, constituted a 

controlled clinical investigation (68 FR 

8908 at 8909). The investigators in that 

study, however, found ‘‘[n]o significant 

differences between treatment groups or 

between the two centers’’ after 

performing efficacy analyses, and 

concluded that ‘‘[u]nder the conditions 

of the study, SPL was not demonstrated 

to be effective in the treatment of HS’’ 

(Delmont’s February 28, 1994, 

submission, at page 9). A third party 

that Delmont contracted with to perform 

a reanalysis of the data reached a more 

optimistic conclusion (Delmont’s 

February 28, 1994, submission, pages 9 

to 11, and 68 FR 8908 at 8909). But it 

reached that conclusion only after first 

unblinding the patient data and 

performing a subset analysis on a 

selected subgroup of patients based on 

a different method of assessing 

effectiveness (68 FR 8908 at 8909). Even 

then, the third party found no 

statistically significant difference 

between the patients treated with 

placebo and with SPL (68 FR 8908 at 

8909). 

The rest of Delmont’s 1994 data fails 

to satisfy the controlled clinical 

investigations standard, as FDA 

explained in its February 26, 2003, 

NOOH (68 FR 8908 at 8909). We 

continue to support the analysis 

described in the Federal Register 

document of February 26, 2003 (68 FR 

8908). 

Significantly, Delmont’s April 28, 

2003, hearing request does not attempt 

to argue that any of the data it submitted 

to FDA during the reclassification 

process in 1983 and 1994 satisfies the 

controlled clinical investigations 

standard or otherwise is adequate to 

demonstrate effectiveness. Instead, 

Delmont’s hearing request argues that 

the data that it submitted to FDA in 

1978 sufficiently demonstrates that SPL 

is effective. Delmont does not, however, 

discuss the specific data that it 

submitted in 1978 or explain why it is 

sufficient to prove that SPL is effective. 

Rather, Delmont argues that in 1978, 

FDA stated that Delmont’s data were 

sufficient to justify a hearing. What FDA 

actually stated, however, is that the data 

justified a hearing only on whether FDA 

should classify SPL into Category IIIA or 

IIIB—not Category I. In other words, 

FDA did not find that the data justified 

a hearing on whether SPL was 

effective—only on whether SPL was safe 

enough to allow Delmont to keep 

marketing it while Delmont conducted 

further effectiveness studies. Indeed, 

even Delmont admitted that further 

effectiveness studies were necessary. 

Therefore, Delmont has not raised a 

genuine and substantial issue of fact 

justifying a hearing as to whether SPL 

is effective. 

3. Delmont’s Procedural Objection 

Delmont also argues that FDA did not 

follow correct procedures during the 

effectiveness reclassification process 

and that, therefore, Delmont deserves a 

hearing on SPL’s effectiveness. 

Delmont’s specific objection is that 

because FDA issued a NOOH before 

finally reclassifying SPL into Category 

II, FDA has violated its own procedures 

and has deprived Delmont of fair notice 

and opportunity for judicial review. 

Delmont is incorrect that FDA 

violated its own procedures. The 

reclassification procedures, set forth in 

§ 601.26, are silent as to when FDA 

should issue an NOOH. However, the 

preamble to § 601.26 provides that the 

procedures for review and 

reclassification of the Category IIIA 

products were designed to be 

‘‘analogous to the procedures in § 601.25 

for the 1972 biologics review,’’ as 

Delmont itself admits (Delmont’s April 

28, 2003, hearing request, at page 4) (46 

FR 4634, January 16, 1981). Section 

601.25 required FDA to issue an NOOH 

before issuing its final classification 

order. Specifically, § 601.25(g) required 

FDA’s final classification order to 

address all matters in the proposed 

order, and § 601.25(f)(2) required that 

for products that FDA proposed to 

classify into Category II, FDA also 

include a license revocation proposal in 

the proposed order. However, before 

revoking a license, FDA first had to 

issue an NOOH (§ 601.5(b(1) (21 CFR 

601.5(b)(1)). Therefore, under § 601.25, 

FDA had to issue an NOOH before 

issuing a final classification order 

because that final classification order 

had to include the license revocation. 

Although § 601.26 is silent on this 

issue, as stated in the preamble, the 

agency did follow the process analogous 

to § 601.25 for this license revocation. In 

the proposed order issued at 65 FR 

31003, May 15, 2000, FDA stated that 

the proposed order contained the 

agency’s intent to revoke the licenses of 

certain products that the agency 

proposed to reclassify into Category II. 

The agency further stated that, after the 

end of the comment period on the 

proposed order, if it decided to proceed 

with the license revocation proceeding, 

it would publish a NOOH on the 

revocation of the license of each 

Category II product. The agency also 

stated it would issue a final order on all 

matters covered by the proposed order 

(65 FR at 31005). In fact, § 601.26(e) 

provides for the final order to cover all 

matters in the proposed order. As with 

the procedures under § 601.25, FDA 

included notice of its intent to revoke 

certain licenses in the proposed order. 

In order to finalize all matters in the 

proposed order in the final order, it was 

necessary for FDA to issue the NOOH 

prior to the final order. Therefore, 

contrary to Delmont’s arguments, FDA 

has not violated its procedures. 

In addition, Delmont is mistaken that 

FDA has deprived Delmont of fair notice 

and an opportunity for judicial review. 

This final order, which contains all of 

FDA’s reasons for denying Delmont a 

hearing and for revoking Delmont’s 

license, is final agency action that is 

reviewable in the courts (§ 12.28(d) (21 

CFR 12.28(d))). Moreover, Delmont has 

had years of notice that FDA intends to 

reclassify SPL into Category II and to 

revoke its license based on that 


jdjones on DSK8KYBLC1PROD with NOTICES
Federal Register / Vol. 75, No. 233 / Monday, December 6, 2010 / Notices 75689 

reclassification, and has availed itself of 

two opportunities to comment on and 

object to FDA’s proposal: (1) On August 

9, 2000, in response to FDA’s May 2000 

proposal, and (2) on April 28, 2003, in 

response to FDA’s NOOH (68 FR 8908). 

FDA has not deprived Delmont of fair 

notice, nor has FDA precluded Delmont 

from seeking judicial review. 

D. Denial of Hearing Request 

For the reasons stated previously in 

this document, the Commissioner of 

Food and Drugs (Commissioner) 

determines that Delmont has failed to 

raise a genuine and substantial issue of 

fact to justify a hearing on the proposed 

revocation of U.S. License No. 299 

issued to Delmont Laboratories, Inc. for 

Polyvalent Bacterial Antigens with ‘‘no 

U.S. Standard of Potency’’ (Staphage 

Lysate), and, therefore, denies 

Delmont’s request for a hearing. The 

Commissioner also determines that 

Delmont’s procedural arguments do not 

provide a basis for a hearing. 

IV. Categorization of Products—Final 

Order 

The Commissioner has considered all 

relevant information regarding the four 

Category IIIA bacterial vaccines and 

bacterial antigens subject to 

reclassification and concludes that 

FDA’s proposal for the reclassification 

of Category IIIA products into Category 

I or Category II is adopted as set forth 

in this section of this document and 

hereby formally classifies: 

Category I—Biological products 

determined to be safe, effective, and not 

misbranded, and which may continue to 

be introduced into interstate commerce. 

Sanofi Pasteur Inc., U.S. License No. 

1725: 

Tetanus Toxoid Adsorbed (primary 

and booster use), and 

Tetanus and Diphtheria Toxoids 

Adsorbed For Adult Use 

(DECAVACTM) (primary and 

booster use). 

Category II—Biological products 

determined to be unsafe, ineffective, or 

misbranded, and which may not 

continue to be introduced into interstate 

commerce. 

Delmont Laboratories Inc., U.S. License 

No. 299: 

Polyvalent Bacterial Antigens with 

‘‘No U.S. Standard of Potency’’ 

Staphage Lysate® (SPL) 

V. License Revocation—Final Order 

For the reasons set forth in this 

document, under section 351 of the 

Public Health Service Act (42 U.S.C. 

262) and 21 CFR 601.5(b)(1)(vi), the 

Commissioner revokes the license (U.S. 

License No. 299) issued to Delmont 

Laboratories, Inc., for Polyvalent 

Bacterial Antigens with ‘‘No U.S. 

Standard of Potency’’ Staphage Lysate®

(SPL). 

VI. References 

The following references have been 

placed on display in the Division of 

Dockets Management (HFA–305), Food 

and Drug Administration, 5630 Fishers 

Lane, rm. 1061, Rockville, MD 20852, 

and may be seen by interested persons 

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

through Friday. 

1. Final Report: Addendum to Previous 

Panel Reports for the Reclassification of 

Category IIIA Biologics, VRBPAC, 1984. 

2. Fujino, Ryuichi; Yuji Sugisaki; Junko 

Nakagawa; Masana Komatsu; and 

Hachihiko Hirayama, ‘‘Chronic Toxicity 

Test of SPL in Rats,’’ Fujizoki 

Pharmaceutical Co., Ltd., Shinjuku-ku, 

Tokyo. 

3. Fujino, Ryuichi; Yuji Sugisaki; Junko 

Nakagawa; Masana Komatsu; ‘‘Acute and 

Subacute Toxicity Tests of SPL,’’ Fujizoki 

Pharmaceutical Co., Ltd., Shinjuku-ku, 

Tokyo. 

4. Hirayama, Hachihiko, ‘‘Teratologenicity 

Study of SPL in Rats and Rabbits,’’ 

Fujizoki Pharmaceutical Co., Ltd., 

Nerima-ku, Tokyo. 

5. ‘‘Effect of SPL on the Development of 

Skin Lesion in Mice after Inoculation 

with Herpes Simplex Virus,’’ Department 

of Microbiology, School of Medicine, 

Kyushu University, Fukuoka, Japan. 

6. ‘‘Chemotactic Accumulation of 

Macrophages in the Peritoneal Cavity 

after Inoculation of SPL and their 

Antitumor Activity,’’ Department of 

Microbiology, School of Medicine, 

Kyushu University, Fukuoka, Japan. 

7. ‘‘S–27: Summary of Results of Tests 

Conducted at Fuji-Zoki Pharmaceutical 

Research Division,’’ Fujizoki 

Pharmaceutical Co., Ltd., Tokyo. 

8. Shigeno, N.; T. Mitsuma; and K. Kojima, 

‘‘Susceptibility of Staphylococcus aureus 

Clinical Isolates to Gratia Bacteriophage,’’ 

Junior College of Medical Technology 

and Nursing affiliated with Niigata 

University. 

9. Mitsuma, T.; N. Shigeno; K. Kojima; and 

M. Tanaka, ‘‘Influence of Staphage 

Lysates (SPL) on Immune Responses In 

Vitro,’’ Junior College of Medical 

Technology and Nursing affiliated with 

Niigata University and Santo Hospital. 

10. Azuma, C.; Y. Tokuda; and T. Shibata, 

‘‘Immunopotiator Activity of Staphage 

Lysate (Mudd),’’ Department of 

Dermatology, Tokyo College of Medicine, 

Tokyo. 

11. Tsuda, Shingo and Kikuo Minami, 

‘‘Immunochemotherapy for Infections— 

With Particular Reference to Staphage 

Lysate,’’ Department of Dermatology, 

Kurume University, School of Medicine, 

Kurume, Fukuoka Prefecture. 

12. Salmon, G.G. and M. Symonds, 

‘‘Staphage Lysate Therapy in Chronic 

Staphylococcal Infections,’’ Journal of 

the Medical Society of New Jersey, 

60:180–193 (1963). 

13. Rank, Dale, ‘‘Immune Stimulation 

Therapy for Inflammatory Disease of the 

Gut,’’ and ‘‘Immune Stimulation for 

Aphthous (Herpetic) Stomatitis & 

Rhinitis,’’ (Study Nov. 1975 to Dec. 

1977). 

14. Rank, Dale, ‘‘Immune Stimulation for 

Aphthous (Herpetic) Stomatitis & 

Rhinitis,’’ (Jan. 1976 to Jan. 1978). 

Dated: November 24, 2010. 

Leslie Kux, 

Acting Assistant Commissioner for Policy. 

[FR Doc. 2010–30441 Filed 12–3–10; 8:45 am] 

BILLING CODE 4160–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Health Resources and Services 

Administration 

National Advisory Council on Nurse 

Education and Practice; Notice for 

Request for Nominations 

SUMMARY: The Health Resources and 

Services Administration (HRSA) is 

requesting nominations to fill eight 

vacancies on the National Advisory 

Council on Nurse Education and 

Practice (NACNEP). 

Authority: 42 U.S.C. 297t, section 851 of 

the Public Health Service (PHS) Act, as 

amended by the Affordable Care Act. The 

NACNEP is governed by the Federal 

Advisory Committee Act, Public Law (Pub. 

L.) 92–463, as amended (5 U.S.C. Appendix 

2), which sets forth standards for the 

formation and use of advisory committees. 

DATES: The Agency must receive 

nominations on or before December 22, 

2010. Addresses: All nominations are to 

be submitted either by mail to Lakisha 

Smith, MPH, Designated Federal 

Official, NACNEP, Division of Nursing, 

Bureau of Health Professions (BHPr), 

Health Resources and Services 

Administration (HRSA), Parklawn 

Building, Room 9B–45, 5600 Fishers 

Lane, Rockville, MD 20857 or e-mail at 

Lsmith2@hrsa.gov. 

FOR FURTHER INFORMATION CONTACT: For 

additional information contact, Lakisha 

Smith, Executive Secretary, National 

Advisory Council on Nurse Education 

and Practice, by e-mail at 

Lsmith2@hrsa.gov or telephone at (301) 

443–5688. A copy of the current 

committee membership, charter and 

reports can be obtained by accessing the 

NACNEP Web site at http:// 

bhpr.hrsa.gov/nursing/nacnep.htm. 

SUPPLEMENTARY INFORMATION: Under the 

authorities that established the NACNEP 

and the Federal Advisory Committee 

Act, HRSA is requesting nominations 


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