Guidance on Applications for Products Comprised of Living Autologous Cells Manipulated Ex Vivo and Intended for Structural Repair or Reconstruction; Availability

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. 95N-0200]

Guidance on Applications for Products Comprised of Living

Autologous Cells Manipulated Ex Vivo and Intended for Structural Repair

or Reconstruction; Availability

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA) is announcing the

availability of a guidance entitled ``Guidance on Applications for

Products Comprised of Living Autologous Cells Manipulated Ex Vivo and

Intended for Structural Repair or Reconstruction.'' The guidance was

prepared by the Center for Biologics Evaluation and Research (CBER) in

consultation with the Center for Devices and Radiological Health. The

document is intended to provide guidance on FDA's approach to the

regulation of living autologous cells manipulated ex vivo and intended

for structural repair or reconstruction (Manipulated Autologous cells

or MAS cells). The agency is also inviting comments on the guidance.

DATES: Written comments by August 26, 1996.

ADDRESSES: Submit written requests for single copies of the guidance

entitled ``Guidance on Applications for Products Comprised of Living

Autologous Cells Manipulated Ex Vivo and Intended for Structural Repair

or Reconstruction'' to the Division of Congressional and Public Affairs

(HFM-44), Center for Biologics Evaluation and Research, Food and Drug

Administration, 1401 Rockville Pike, Rockville, MD 20852-1448. Send one

self-addressed adhesive label to assist that office in processing your

requests. The guidance may also be obtained by mail or FAX by calling

the CBER Voice Information System at 1-800-835-4709.

Persons with access to the INTERNET may obtain the document in

several ways. Users of ``Web Browser'' software, such as Mosaic,

Netscape, or Microsoft Internet Explorer may obtain this document via

the World Wide Web by using the following Uniform Resource Locators:

http://www.fda.gov/cber/cberftp.html

ftp://ftp.fda.gov/CBER/

The document may also be obtained via File Transfer Protocol (FTP).

Requestors should connect to FDA's FTP Server,

FTP.FDA.GOV(192.73.61.21). CBER documents are maintained in a

subdirectory called ``CBER'' on the server. Logins with the user name

of anonymous are permitted, and the user's e-mail address should be

sent as the password. The ``READ.ME'' file in that subdirectory

describes the available documents that may be available as an ASCII

text file (*.TXT), or a WordPerfect 5.1 or 6.x document (*.w51,wp6), or

both. Finally, the guidance can be obtained by ``bounce-back e-mail''.

A message should be sent to: [email protected]''.

Submit written comments on the guidance to the Dockets Managements

Branch (HFA-305), Food and Drug Administration, 12420 Parklawn Dr., rm.

1-23, Rockville, MD 20857. Two copies of any comments are to be

submitted, except that individuals may submit one copy. Requests and

comments should be identified with the docket number found in brackets

in the heading of this document. A copy of the guidance and received

comments are available for public examination in the Dockets Management

Branch between 9 a.m. and 4 p.m., Monday through Friday.

FOR FURTHER INFORMATION CONTACT: Sharon A. Carayiannis, Center for

Biologics Evaluation and Research (HFM-630), Food and Drug

Administration, 1401 Rockville Pike, Rockville, MD 20852-1448, 301-594-

3074.

SUPPLEMENTARY INFORMATION:

FDA had recently become aware of the clinical use of MAS cell

products. MAS cells are defined as cells derived from a patient's

tissues, which are manipulated ex vivo, and then implanted locally into

the same patient with the intent of providing repair or reconstruction

of a structure. The repair and reconstruction does not involve systemic

action by the MAS cell product. Examples of MAS cells include

chondrocytes expanded ex vivo and implanted in focal cartilage defects

(see 60 FR 36808 at 36809 for additional information and references).

The commercialization and distribution of expanded cartilage cells to

provide a potential solution to a relatively common medical injury

suggested that numerous patients could be receiving these cells within

a short period of time.

In light of the potential public health significance of the MAS

cell products, the growth of a commercial industry potentially

affecting a large number of patients, and the need to decide which

existing regulatory authorities (e.g., device versus biologics) would

be appropriate to apply or whether a new regulatory framework was

required, the agency held a public hearing on November 16 and 17, 1995

(60 FR 36808). The intent of the meeting was to solicit information on

the nature and diversity of these products, and to receive comments on

the formulation and implementation of any new regulatory requirements.

The public hearing had 8 panels with 24 speakers, and there was general

consensus that the establishment, the production process, and the MAS

cell products should be of the highest quality. The speakers and

attendees also agreed that MAS cell products should benefit the

patient, but there was little consensus on the appropriate mechanism

that should be used to show this benefit.

In the Federal Register of March 7, 1996 (61 FR 9185), after

reviewing the comments and further internal discussions, the agency

published a notice announcing a Commissioner's roundtable to be held on

March 15, 1996. The roundtable was held to present the elements of a

planned regulatory framework intended to ensure patient safety and to

demonstrate patient benefit, while accommodating the development of

these therapies and the need for a flexible regulatory approach. Many

of the concepts presented at the roundtable were derived from ongoing

FDA Reinventing Government (REGO) initiatives. In the same Federal

Register notice, FDA also invited the submission of written comments

concerning FDA's draft plan for the regulation of MAS cells. Based on

the discussions at the March 15, 1996, roundtable and on a review of

all comments received, FDA has decided that, in light of the existing

and increased flexibility provided by REGO initiatives, FDA will apply

the regulatory framework as detailed and explained in the guidance.

CBER is

[[Page 26524]]

designated as the agency component with primary jurisdiction for the

premarket review and regulation of MAS cell products. The products are

subject to licensure as biological products under section 351 of the

Public Health Service Act (42 U.S.C. 262).

The guidance document includes discussions on the following: (1)

Background and recent events; (2) regulatory plan, including: A summary

and discussions of products to be regulated, registration and

inspection of establishments, clinical studies, investigational phase

and requirements for premarket approval, cost recovery, marketing

application, chemistry, manufacturing and controls section of a

biologics license application, formulation of an intercenter working

group, contracting of manufacture, lot release, and current good

manufacturing practice requirements; (3) registration and application

submission; and (4) submission of comments.

As with other procedural guidance documents, FDA does not intend

this guidance to be all-inclusive. Alternative approaches could be

warranted in specific situations, and certain aspects might not be

applicable in all situations. If an applicant believed a procedure

described in this guidance was inapplicable to a specific situation for

a particular product, the applicant could provide, for CBER's

consideration, information supporting an alternative process. If an

applicant chooses to use an alternative process, the applicant may wish

to discuss the matter further with the agency to prevent expenditure of

money and resources on activities that later might be determined to be

inappropriate to FDA. Although this guidance does not create or confer

any rights for or on any person, and does not operate to bind FDA or

the public, it does represent the agency's current thinking on the

regulation of MAS cell products.

Interested persons may, on or before (insert date 90 days after

date of publication in the Federal Register), submit written comments

on the guidance to the Dockets Management Branch (address above). Two

copies of any comments are to be submitted, except that individuals may

submit one copy. Comments and information are to be identified with the

docket number found in brackets in the heading of this document. The

guidance and received comments may be seen in the office above between

9 a.m. and 4 p.m., Monday through Friday.

Received comments on this document will be considered in

determining whether revisions to the guidance are warranted.

Dated: May 22, 1996.

William K. Hubbard,

Associate Commissioner for Policy Coordination.

[FR Doc. 96-13386 Filed 5-23-96; 11:13 am]

BILLING CODE 4160-01-F