Viruses, Serums, Toxins, and Analogous Products; Licenses, Inspections, Records, and Reports

SUMMARY: We are amending the regulations under the Virus-Serum-Toxin

Act to clarify certain provisions concerning licenses, inspections,

records, and reports. The effect of the rule is to ensure that

licensees are aware of the fact that licenses are issued on the

condition that the licensee permit inspection of establishments,

products, and records, and that a licensee must have at least one

product license in order to maintain a valid establishment license.

Failure to permit inspection will make the license subject to

suspension or revocation. We are also amending the regulations to

specify the types of records and reports that must be available for

inspection including records describing product development and

preparation and market suspensions and recalls. Finally, we are

amending the regulations to require that APHIS receive notification

immediately if there are indications which raise questions regarding

purity, safety, potency, or efficacy of a product, or if it appears

there may be a problem regarding the preparation, testing, or

distribution of a product. The rule is necessary to clarify and

simplify certain provisions of the regulations and to describe required

records with greater specificity.

EFFECTIVE DATE: November 8, 1996.

FOR FURTHER INFORMATION CONTACT: Dr. David A. Espeseth, Deputy

Director, Veterinary Biologics, APHIS, 4700 River Road Unit 148,

Riverdale, MD 20737 1237; 301-734-8245.

SUPPLEMENTARY INFORMATION:

Background

The Virus-Serum-Toxin Act of 1913 (21 U.S.C. 151-159, hereinafter

the Act), as amended, is intended to ensure that veterinary biological

products shipped in or from the United States are not worthless,

contaminated, dangerous, or harmful. To achieve that purpose, the Act

requires that such products be prepared in compliance with USDA

regulations at an establishment holding an unsuspended and unrevoked

USDA establishment license. No products may be imported into the United

States without a permit issued by the Administrator. Provisions

regarding veterinary biological product licenses, license suspensions,

and inspections appear in the regulations at 9 CFR parts 102, 105, and

116.

On March 6, 1995, we published in the Federal Register (60 FR

12159-12162, Docket No. 93-072-1) a proposal to amend parts 102, 104,

105, and 116. We proposed to amend the regulations to clarify that

licenses are issued on the condition that the licensee permit

inspection of establishments, products, and records, and that a

licensee must have at least one product license in order to maintain a

valid establishment license. Failure to permit inspection will make the

license subject to suspension or revocation. We also proposed to amend

the regulations to broaden the scope of records and reports to include

records describing product development and preparation, market

suspensions, and recalls, which must be available for inspection.

Finally, we proposed to amend the regulations to require that APHIS be

notified immediately if there are indications which raise questions

regarding purity, safety, potency, or efficacy of products, or if a

biological product appears to be unsatisfactory or is found to have

been prepared, tested, or distributed in violation of the Act and

regulations. The rule is necessary to clarify and simplify certain

provisions of the regulations.

We solicited comments concerning our proposal for 60 days ending

May 5, 1995. We received nine comments by that date. They were from

biologics producers, a biologics consultant, and a national trade

association. We carefully considered all of the comments we received.

They are discussed below.

One commenter expressed general approval of the rule as proposed.

The commenter, however, requested definitions of ``raw data,'' ``data

collection,'' ``method for changing raw data,'' and ``manufacturing

records'' under proposed Sec. 105.1 and ``unsatisfactory'' and

``immediately'' under proposed Sec. 116.5(b).

In response to this comment, APHIS notes that the terms ``raw

data,'' ``data collection,'' ``methods for changing raw data,'' and

``manufacturing records'' were not included in the proposed rule.

Therefore, APHIS believes that it would be inappropriate for the agency

to define these terms. APHIS believes that the use of the phrase ``to

be unsatisfactory'' is redundant with the phrase ``to have been

prepared, tested, or distributed in violation of the VSTA and

regulations'' which appears in the same sentence and has therefore

deleted it from the regulations to improve clarity and avoid confusion

as to its meaning when used in this context. Similarly, APHIS is

removing the reference to violation of the Act or regulations and

changing the language regarding preparation, testing, and distribution

to more accurately reflect the intent of paragraph (b) of Sec. 116.5.

The term ``immediately'' is self-explanatory in that notification

should occur without delay at the time a question regarding product

purity, safety, potency, or efficacy is raised. Therefore, APHIS is not

adding definitions of these terms in response to this comment.

One commenter requested that the rule for license termination after

5 years of inactivity be withdrawn and replaced with a provision for

recertification of the master seed to save the expense of relicensure.

The commenter explained that there are situations in which a vaccine

for which there has been no need suddenly comes into demand because of

a disease condition. The example presented was an erysipelothrix

vaccine in turkeys, the need for which is apparently resurfacing after

a lapse of 10 years. Other examples of resurfacing vaccines were given,

including variant chicken pox in the midwest and California, and

Newcastle Disease Bronchitis Vaccine B1 Type B1 Strain. The

commenter indicated that the latter vaccine has not been made for

[[Page 52872]]

17 years, but now has a significant international market.

In response to this commenter, the current regulation provides for

the producer to show intent to resume production within 6 months of

notification or have the product license or permit terminated. APHIS

proposed to amend the regulation to provide the opportunity for the

producer to resume production within 6 months of notification or

``within a mutually agreeable period'' should the producer have

evidence that the vaccine might be needed in the near future. The

proposed amendment allows the licensee to present a case to support a

mutually agreeable period of longer than 6 months before production is

resumed, if desired. If production is not resumed, the product license

would be terminated without prejudice and could be reissued at a later

date if master seed and master stocks are maintained and a market

develops for the product. The original Outline of Production and

licensing data could be resubmitted to support such applications and

should only require updating to meet new licensing requirements not

addressed when the product was originally licensed. The license

applicant should consult with APHIS for guidance prior to applying for

reissuance of such licenses. APHIS does not believe that a product

license should be maintained when no product is produced or no

establishment is maintained to support continuation of licensure. No

change to the regulations is made in response to this comment.

One commenter felt that the language in Sec. 116.1 lacked

specificity. Another commenter stated that the types of records

required for product development and manufacture should be specified.

In response to these commenters, APHIS notes that the proposed

amendment to Sec. 116.1 adds permittees under the regulations and

specifies the types of records that are to be maintained at the

permittees place of business. No change to the regulations is made in

response to these commenters.

Eight commenters raised concerns about the lack of clear criteria

in the proposal for the reporting of production data and consumer

complaints. One of the commenters raised the issue of how the firms'

submissions of consumer reports will be handled under the Freedom of

Information Act (FOIA). Another commenter indicated that many consumer

reports may deal with problems related to consumer misuse that is

beyond the control of the manufacturer. Consumer reports relevant to

this regulation would only be those where there is a valid product-

related complaint. The commenter also inquired into how complaints will

be resolved by the agency and what the relationship was between

consumer reports and the agency's proposed post-licensing monitoring

program. One commenter stated that records related to consumer reports

are already available for inspection at licensed establishments and

questioned whether the submission of additional reports was necessary.

Finally, several commenters suggested that the additional reporting

requirements would increase the level of paperwork required of both

APHIS and the manufacturer. These commenters expressed general concerns

about the need to reduce paperwork submissions in order to reduce

agency burden and to facilitate agency review of and response to

license applications.

In response to these comments, APHIS believes that its intent with

regard to reporting of certain consumer complaint reports was

misunderstood. The proposed rule was not intended to require the

implementation of a comprehensive postlicensing monitoring program but

was only intended to ensure that licensees inform APHIS when it appears

that a licensed product that has been released for marketing is

involved in an unusually high number of consumer complaints or appears

or has been found to be in violation of the Act or regulations.

Informing APHIS under such situations provides an early warning of

possible emerging product-related problems and ensures prompt action if

there is a problem. Open communication between licensees and APHIS is

essential for accurate responses to consumer inquiries and a rapid

resolution of such situations. In response to the comment regarding

access to consumer complaints under FOIA, all confidential business

information would be protected. APHIS is currently working on

regulations regarding FOIA requests related to the monitoring of

products.

Based on the comments, APHIS is revising proposed Sec. 116.5

concerning the submission of consumer reports with a more general

statement to clarify our intent that APHIS be notified when there are

indications which raise questions regarding the purity, safety,

potency, or efficacy of a product, or if it appears that there may be a

problem regarding the preparation, testing, or distribution of a

product.

Some examples of when APHIS should be informed include when there

are product-related data, information, or reports to show that a serial

is contaminated, that use of a product is associated with a high

incidence of adverse reactions, or that a product is associated with

the failure to protect against disease. It would be necessary to

provide available information describing circumstances surrounding

these situations such as contributory factors and plausible options to

help resolve the problem. Other examples of such circumstances when

notification would be warranted are when consumer reports suggest that

the use of a product may pose a risk to the public health, interest, or

safety.

APHIS is removing the reference to consumer reports from paragraph

(b) of Sec. 116.5 of the proposed rule by removing the phrase

``consumer reports concerning the use of products'' and substituting

the phrase ``there are indications which.'' This revision is intended

to remove concerns about the reporting of all claims, including those

which might be considered frivolous or invalid. The reference to

``immediately report'' has also been revised to read ``immediately

notify APHIS concerning'' to provide greater flexibility in the manner

in which information is provided to APHIS including telephone, E-mail,

facsimile, or letter rather than by ``report'' which suggests a more

formal communication. We have included in the regulations for

convenience purposes the addresses and phone numbers for these

alternative methods of notification. These changes should make it clear

that this rule codifies current program practice and does not result in

a net increase of the paperwork burden imposed on the manufacturer and

the agency.

One commenter objected to use of the term, ``When requested by the

Administrator,'' in Sec. 116.5, paragraph (a). The same commenter

believed that APHIS should define the rationale for submission more

specifically. Another commenter objected to the use of terms,

``complete information'' and ``including but not limited to'' for being

ambiguous.

In response to these comments, APHIS notes that these terms are

currently used in the regulations in part 116 without further

definition. In addition, APHIS believes that the rationale of proposed

Sec. 116.5, paragraph (a), is not intended to be significantly

different from that of current Secs. 116.1 and 116.5. These regulations

were last amended in 1974 (39 FR 16853-16873, Docket No. 74-10880, May

10, 1974). Current Sec. 116.1 reads in relevant part as follows:

Each licensee * * * shall maintain detailed records of

information necessary to give a complete accounting of the

activities within each establishment. Such activities shall include,

but shall not be limited to the items enumerated in this part.

[[Page 52873]]

(a) Records shall be made concurrently with the performance of

successive steps in the preparation of a biological product. Such

records shall include the date and where critical, the time that

each essential step was taken, the identity and quantity of

ingredients added or removed at each step, and any loss or gain from

start to finish in such preparation.

Current Sec. 116.5 reads in relevant part as follows:

When required by the Administrator, reports containing accurate

information of production activities in each establishment * * *

shall be prepared and forwarded to APHIS. Records necessary to make

such reports shall be maintained in each establishment.

The proposed amendment to Sec. 116.5, paragraph (a), merely

specifies in greater detail the type of information that should be

maintained or submitted to APHIS. As a commenter stated previously,

licensed establishments already make available records of consumer

reports for inspection. Therefore, much, if not all, of this

information should already be available or should already have been

made available to APHIS. No change to the regulations is made in

response to these comments.

Based on the rationale set forth in the proposed rule and in this

document, we are adopting the provisions of the proposal as a final

rule, with the changes discussed in this document.

Executive Order 12866 and Regulatory Flexibility Act

This rule has been reviewed under Executive Order 12866. The rule

has been determined to be not significant for purposes of Executive

Order 12866 and, therefore, has not been reviewed by the Office of

Management and Budget.

The rule amends the regulations in 9 CFR parts 102, 104, 105, and

116 to clarify existing provisions concerning licenses, inspections,

records, and reports. Licenses are issued on condition that the

licensee permit inspection of establishments, products, and records.

The rule provides that the failure to permit such inspection will make

the license subject to suspension or revocation. In order to hold a

valid establishment license, licensees are required to have at least

one unexpired, unsuspended, and unrevoked product license. Otherwise,

the establishment license will be invalid. We are also making

amendments concerning the content of records and reports and the

availability of their inspection.

The rule will make clear and unambiguous certain regulatory

provisions. No new requirements are added in the rule. Therefore, no

adverse economic impact is anticipated to result from the rule.

Under these circumstances, the Administrator of the Animal and

Plant Health Inspection Service has determined that this action will

not have a significant economic impact on a substantial number of small

entities.

Executive Order 12372

This program/activity is listed in the Catalog of Federal Domestic

Assistance under No. 10.025 and is subject to Executive Order 12372,

which requires intergovernmental consultation with State and local

officials. (See 7 CFR part 3015, subpart V.)

Executive Order 12988

This final rule has been reviewed under Executive Order 12988,

Civil Justice Reform. It is not intended to have retroactive effect.

This rule would not preempt any State or local laws, regulations, or

policies, unless they present an irreconcilable conflict with this

rule. There are no administrative procedures which must be exhausted

prior to a judicial challenge to the provisions of this rule.

Paperwork Reduction Act

In accordance with the Paperwork Reduction Act of 1995 (44 U.S.C.

3501 et seq.), the information collection or recordkeeping requirements

included in this rule have been approved by the Office of Management

and Budget (OMB), and there are no new requirements. The assigned OMB

control number is 0579-0013.

Regulatory Reform

This action is part of the President's Regulatory Reform

Initiative, which, among other things, directs agencies to remove

obsolete and unnecessary regulations and to find less burdensome ways

to achieve regulatory goals.

List of Subjects

9 CFR Part 102

Animal biologics, Reporting and recordkeeping requirements.

9 CFR Part 104

Animal biologics, Imports, Reporting and recordkeeping

requirements, Transportation.

9 CFR Part 105

Animal biologics.

9 CFR Part 116

Animal biologics, Reporting and recordkeeping requirements.

Accordingly, 9 CFR parts 102, 104, 105, and 116 are amended as

follows:

PART 102--LICENSES FOR BIOLOGICAL PRODUCTS

1. The authority citation for part 102 continues to read as

follows:

Authority: 21 U.S.C. 151-159; 7 CFR 2.22, 2.80, and 371.2(d).

2. In Sec. 102.2, the text is designated as paragraph (a) and a new

paragraph (b) is added to read as follows:

Sec. 102.2 Licenses required.

* * * * *

(b) An applicant who applies for an establishment license must also

apply for at least one product license. An establishment license will

not be issued without a license authorizing the production of a

biological product in the establishment.

3. In Sec. 102.4, paragraph (f) is revised, paragraph (g) is

redesignated as paragraph (h), and new paragraph (g) is added to read

as follows:

Sec. 102.4 U.S. Veterinary Biologics Establishment License.

* * * * *

(f) When a licensee no longer holds at least one unexpired,

unsuspended, or unrevoked product license authorizing the preparation

of a biological product, or is in the process of obtaining a product

license, the establishment license shall no longer be valid and shall

be returned to the Administrator. In the case where an establishment

license expires or is suspended or revoked, any product license

authorizing preparation of a product at such establishment shall be

invalid indefinitely or for as long as the suspension is in effect.

(g) Any license issued under this part to establishments in which

biological products are prepared shall be issued on condition that the

licensee permit the inspection of such establishments, products,

product preparation, and all relevant records as provided in part 115

of this subchapter. Failure to permit inspection may result in the

license being suspended or revoked.

* * * * *

PART 104--PERMITS FOR BIOLOGICAL PRODUCTS

4. The authority citation for part 104 continues to read as

follows:

Authority: 21 U.S.C. 151-159; 7 CFR 2.22, 2.80, and 371.2(d).

5. In Sec. 104.6, paragraph (b), the words ``Veterinary Services''

are removed and the words ``Animal and Plant Health Inspection

Service'' are added in their place.

6. In part 105, the heading for the part is revised to read as

follows:

[[Page 52874]]

PART 105--SUSPENSION, REVOCATION, OR TERMINATION OF BIOLOGICAL

LICENSES OR PERMITS

7. The authority citation for part 105 continues to read as

follows:

Authority: 21 U.S.C. 151-159; 7 CFR 2.22, 2.80, and 371.2(d).

8. In Sec. 105.1, paragraphs (a)(4) and (a)(5) are redesignated

paragraphs (a)(5) and (a)(6), new paragraph (a)(4) is added, and

redesignated paragraph (a)(5) is revised to read as follows:

Sec. 105.1 Suspension or revocation.

* * * * *

(a) * * *

(4) The licensee, permittee, or the foreign manufacturer has failed

to maintain and make available for inspection records in connection

with the development and preparation of product, has failed to provide

complete and accurate information when requested, or has failed to

provide complete and accurate information in the Outline of Production

or in reports and records;

(5) The licensee or permittee has violated or failed to comply with

any provision of the Virus-Serum-Toxin Act or the regulations in this

subchapter;

* * * * *

9. Section 105.4 is revised to read as follows:

Sec. 105.4 Termination of licenses and permits for inactivity.

(a) If a biological product has not been prepared by a licensee, or

imported by a permittee for a period of 5 years or more, the

Administrator may require the licensee to show intent to resume

production, or the permittee to show intent to resume importation,

within 6 months of notification. If the licensee does not resume

preparation, or the permittee does not resume importation, within 6

months of notification, or within a mutually agreeable period, the

product license, or permit, may be terminated by the Administrator.

(b) When a license or permit is terminated, the licensee or

permittee shall continue to be subject to the applicable records

provisions of Sec. 116.8.

10. In part 116, the heading for the part is revised to read as

follows:

PART 116--RECORDS AND REPORTS

11. The authority citation for part 116 continues to read as

follows:

Authority: 21 U.S.C. 151-159; 7 CFR 2.22, 2.80, and 371.2(d).

12. In Sec. 116.1, paragraphs (a), (b), and (c) are redesignated as

paragraphs (a)(1), (a)(2), and (a)(3), respectively; redesignated

paragraph (a)(1) is revised; the introductory paragraph is designated

as paragraph (a) and is revised; and new paragraphs (b) and (c) are

added to read as follows:

Sec. 116.1 Applicability and general considerations.

(a) Each licensee, permittee, and foreign manufacturer of

biological products imported into the United States shall maintain, at

the licensed or foreign establishment in which the products are

prepared, detailed records of information necessary to give a complete

accounting of all the activities within each establishment. Such

records shall include, but shall not be limited to, the items

enumerated in this part.

(1) Records shall be made concurrently with the performance of

successive steps in the development and preparation of biological

products, including new products under development. Such records shall

include the date and where critical, the time that each essential step

was taken, the identity and quantity of ingredients added or removed at

each step, and any gain or loss of product from the beginning to the

end of product preparation.

* * * * *

(b) In the case of imported products, each permittee shall maintain

at the permittee's place of business detailed and accurate records that

are relevant to each imported product and that include, but are not

limited to, importation documents, sampling records, test summaries,

shipping records, and inventory and disposition records as required in

Sec. 116.2.

(c) When authorized by the Administrator, the licensee, permittee,

or foreign manufacturer may maintain and retain records required under

this part at an alternative location. Such authorization shall be

confirmed by the filing of an addendum to the plot plan legend. The

addendum shall list the location of the records and the condition of

their storage and shall permit the inspection of the records by APHIS

inspectors, or foreign inspectors acting on behalf of APHIS.

(Approved by the Office of Management and Budget under control

number 0579-0013)

Secs. 116.2, 116.3, 116.4, and 116.6 [Amended]

13. At the end of Secs. 116.2, 116.3, 116.4, and 116.6, the

reference to OMB control number ``0579-0059'' is removed and the number

``0579-0013'' is added in its place.

14. Section 116.5 is revised to read as follows:

Sec. 116.5 Reports.

(a) When required by the Administrator, reports containing accurate

and complete information concerning biological products, including but

not limited to, product development and preparation, and market

suspensions and recalls, shall be prepared and submitted to the Animal

and Plant Health Inspection Service by the licensee, permittee, or

foreign manufacturer (whose products are being imported or offered for

importation). Unless otherwise authorized by the Administrator, records

necessary to make such reports shall be maintained in each

establishment.

(b) If, at any time, there are indications which raise questions

regarding purity, safety, potency, or efficacy of a product, or if it

appears that there may be a problem regarding preparation, testing, or

distribution of a product, the licensee, permittee, or foreign

manufacturer shall immediately notify Veterinary Biologics Field

Operations, APHIS, 223 South Walnut Avenue, Ames, Iowa 50010,

concerning the circumstances and the action taken, if any. Notification

may be either by mail, electronic mail, facsimile, or telephone. If by

electronic mail, [email protected]. If by facsimile, Area Code (515)

232-7120. If by telephone, Area Code (515) 232-5785.

(Approved by the Office of Management and Budget under control

number 0579-0013)

15. In Sec. 116.7, the second sentence is revised to read as

follows:

Sec. 116.7 Test records.

* * * Summaries of such tests shall be prepared from such records

and submitted to the Animal and Plant Health Inspection Service using

APHIS Form 2008 or an acceptable equivalent form prior to release of

the serial or subserial. * * *

* * * * *

16. Section 116.8 is revised to read as follows:

Sec. 116.8 Completion and retention of records.

All records (other than disposition records) required by this part

shall be completed by the licensee, permittee, or foreign manufacturer

before any portion of a serial of any product may be marketed in the

United States or exported. All records shall be retained at the

licensed or foreign establishment or permittee's place of business for

a period of two years after the expiration date of a product, or for

such longer period as may be required by the Administrator.

[[Page 52875]]

(Approved by the Office of Management and Budget under control

number 0579-0013)

Done in Washington, DC, this 4th day of October 1996.

A. Strating,

Acting Administrator, Animal and Plant Health Inspection Service.

[FR Doc. 96-25931 Filed 10-8-96; 8:45 am]

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