Regulation of Biologics
and Biotechnology Products in the United States and Europe
University of Rhode Island
College of Pharmacy
Jurisdictional Issues within FDA:
Who Decides?
Suzanne O'Shea, Esq.
Product Classification Officer
Office of Combination Products
Food and Drug Administration
May 9, 2006
Jurisdictional Issues
Q: Which FDA Center
will regulate your product?
Q: And how do I find out?
A: It depends…
Who does what?
CBER oversees preparation of human cells, tissues, and cellular and tissue products (HCT/P's) that are regulated solely under section 361 of the PHS Act. For example, donor screening and good tissue practices.
CBER regulates HCT/P's regulated under section 351 of the PHS Act.
CDRH regulates HCT/P's that are classified as devices and regulated under the device provisions of the FD&C Act.
Many therapeutic biological products now regulated by CDER.
Combination products (biologic – device; drug – device, biologic - drug) are regulated based on their primary mode of action.
If the question is…
Am I eligible for regulation solely under
section 361 of the PHS Act?
Two options
1. Tissue Reference Group
2. Office of Combination Products
Option 1: Tissue Reference Group
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Created in 1998
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Comprised of
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3 representatives from CBER
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3 representatives from CDRH
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1 liaison from Office of Chief Counsel, and
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1 liaison from Office of Combination Products
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Meets every two weeks;
tries to respond to inquiries within 60 days
TRG makes product-specific recommendations as to
when a product meets the criteria for regulation solely under section 361 of the PHS Act.
Tissue Reference Group
If a product meets all criteria for regulation solely under section 361 of PHS Act, then CBER would regulate the product.
If a product DOES NOT meet all the criteria for regulation solely under section 361 of the PHS Act, then TRG will also make a recommendation whether product meets the definition of a biologic or a device, and which FDA Center will regulate the product.
Tissue Reference Group
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TRG website:
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TRG Annual report:
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To contact TRG:
Martha Wells
TRG Executive Secretary
Office of Cellular, Tissue and Gene Therapies
CBER
301-827-6106
Martha.wells@fda.hhs.gov
What happens if I disagree with TRG?
Option 2: Office of Combination Products
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OCP serves as appeal for TRG recommendations
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Does product meet criteria for regulation solely under section 361 of PHS Act?
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If no, is product a biologic or a device?
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Which Center will regulate the product?
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OCP may also make these determinations in absence of TRG recommendation. This is sponsor's option.
Office of Combination Products
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Created in December 2002
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Currently a staff of eight
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Created to address concerns about consistency, predictability, and transparency of the assignment, regulation, and review process
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Primary review responsibilities for specific products remains with CBER, CDER, or CDRH.
OCP's Missions
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As stated in MDUFMA, OCP is to ensure:
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prompt assignment of combination products to agency center
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Timely and effective premarket review of such products, and
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Consistent and appropriate postmarket regulation
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OCP is also required to
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Resolve disputes regarding timeliness of premarket review, and
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Prepare an annual report to Congress
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OCP serves as a resource to sponsors and FDA review staff.
Where is OCP?
Commissioners Office
Office of Combination Products
Center for Biologics Evaluation and Research
Center for Devices and Radiological Health
Center for Drug Evaluation and Research
What process does OCP use?
Request for Designation
21 CFR Part 3
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Voluntary
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15 page limitation
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60 day clock
or sponsor's recommendation takes effect -
RFD decision is binding unless a change is necessary to protect the public health or some other compelling reason
RFD Guidance Document
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Provides recommendations for information needed for each required section of an RFD
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Incorporates concepts of Primary Mode of Action Final Rule
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Goal: to ensure sponsors provide FDA the information needed to make an appropriate jurisdictional determination
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Available at www.fda.gov/oc/combination
RFD Guidance Document
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When the issue is whether your product is eligible for regulation solely under section 361 of the PHS Act, focus on:
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What is your product?
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Why would your product be used?
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How does your product work?
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How does your product meet all the criteria for regulation solely under section 361 of the PHS Act?
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How do you think your product should be assigned? Why?
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How does OCP decide?
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Consults closely with Center jurisdictional liaisons
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Consults with Office of Chief Counsel as necessary
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Considers law and precedent
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May request additional information from sponsor
What if I disagree with OCP's conclusion in an RFD?
Request for Reconsideration
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Submit within 15 days
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Less than 5 page submission, no new information
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FDA response within 15 days
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FDA has been known to change a decision upon reconsideration
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21 CFR 3.8(c)
If the question is…
I am a therapeutic biological product.
Am I regulated by CBER or CDER?
In June 2003, many therapeutic biological products transferred from CBER to CDER; some therapeutic biological products remain in CBER.
Transfer of Therapeutic Biological Products to the
Center for Drug Evaluation and Research
http://www.fda.gov/oc/combination/transfer.html
In general, CBER kept
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Cellular products
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Gene therapy
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Vaccines
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Allergenic extracts
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Antitoxins, antivenins, and venoms
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Blood, blood components, plasma derived products
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HCT/P's containing cells that have been harvested following in vivo administration of a CDER-regulated growth factor, cytokine, or monoclonal antibody, as well as HCT/P's requiring ex vivo manipulation.
Biological Products Transferred
to CDER
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Monoclonal antibodies
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Proteins for therapeutic use, including cytokines, enzymes, and other novel proteins. Includes therapeutic proteins derived from plants, animals, or microorganisms, and recombinant versions of these products.
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Immunomodulators: proteins or peptides that are not antigen specific and intended to treat disease by inhibiting or modifying a pre-exisiting immune response.
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Growth factors, cytokines, and monoclonal antibodies intended to mobilize, stimulate, decrease or otherwise alter the production of cells in vivo.
For a more detailed description of products transferred to CDER, see:
Transfer of Therapeutic Biological Products to the
Center for Drug Evaluation and Research at www.fda.gov/oc/combination/transfer.html
If there's still a question
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Call OCP
301-427-1934
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Call Center Jurisdictional Liaisons
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CDER: Warren Rumble 301-443-5581
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CBER: Sherry Lard 301-827-0379
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Submit an RFD to OCP
What about Combination Products?
Products comprised of an HCT/P and a drug, device or biologic. Which Center will regulate, and how will the decision be made?
Contact OCP!
Primary Mode of Action
Combination products are assigned
to an agency center based on the product's
primary mode of action.
21 U.S.C. § 503(g).
Final Rule defining PMOA issued on
August 25, 2005 and can be accessed at:
PMOA
Primary mode of action is the single mode of action of a combination product that provides the most important therapeutic action of the combination product. The most important therapeutic action is the mode of action expected to make the greatest contribution to the overall intended therapeutic effects of the combination product.
21 CFR 3.2(m)
PMOA Algorithm
If unable to determine most important therapeutic action with reasonable certainty, consider:
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Consistency: is there an agency component that regulates other combination products presenting similar questions of S & E with regard to combination product as a whole?
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Safety and Effectiveness: which agency component has the most expertise related to most significant S&E questions presented by combination product?
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PMOA
RFD Guidance Document
When the product is a combination product, and the issue is which Center will have primary jurisdiction, focus on these sections in the RFD:
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What is your product?
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Why would your product be used?
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How does your product work?
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What is your product's most important therapeutic action?
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What is the basis for your PMOA determination?
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How do you think your product should be assigned? Why? (use assignment algorithm if appropriate.)
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The Bottom Line
Call us!
Office of Combination Products
301-427-1934
combination@fda.hhs.gov