[Federal Register Volume 85, Number 44 (Thursday, March 5, 2020)]
[Notices]
[Pages 12932-12933]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2020-04531]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2003-D-0370]


Guidance for Industry: Exocrine Pancreatic Insufficiency Drug 
Products--Submitting New Drug Applications; Withdrawal of Guidance

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice; withdrawal.

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SUMMARY: The Food and Drug Administration (FDA or Agency) is announcing 
the withdrawal of a guidance for industry entitled ``Exocrine 
Pancreatic Insufficiency Drug Products--Submitting NDAs,'' which was 
issued in 2006. The guidance set forth the Agency's thinking on data 
and information that may support a new drug application (NDA) for a 
proposed pancreatic enzyme product (PEP) that contains pancreatin or 
pancrelipase and is intended for the treatment of exocrine pancreatic 
insufficiency (EPI). FDA is withdrawing the guidance because an NDA for 
such a product may not be submitted after March 23, 2020. Sponsors 
interested in submitting a biologics license application (BLA) for a 
proposed PEP should contact the Agency with any questions.

DATES: The withdrawal is effective March 23, 2020.

FOR FURTHER INFORMATION CONTACT: Kristiana Brugger, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 51, Rm. 6262, Silver Spring, MD 20993, 301-796-
3600.

SUPPLEMENTARY INFORMATION: FDA is withdrawing the guidance for industry 
entitled ``Exocrine Pancreatic Insufficiency Drug Products--Submitting 
NDAs,'' which was issued in 2006 (see 71 FR 19524 (April 14, 2006)). 
The guidance described FDA's thinking regarding the data and 
information that may support submission of NDAs, including submission 
of NDAs pursuant to section 505(b)(2) of the Federal Food, Drug and 
Cosmetic Act (FD&C Act) (21 U.S.C. 355(b)(2)), for products that 
contain the ingredients pancreatin or pancrelipase and are used to 
treat EPI.
    Pancreatic enzyme preparations of porcine or bovine origin that 
contain the ingredients pancreatin or pancrelipase have a long history 
of use for the treatment of EPI in children and adults with cystic 
fibrosis and chronic pancreatitis. These products have been available 
in the United States for decades, largely marketed as unapproved drugs. 
On April 28, 2004 (69 FR 23410), however, FDA announced that all orally 
administered PEPs are new drugs that must be approved via a marketing 
application for prescription use only, and explained the conditions for 
continued marketing of these drug products. The guidance explained 
FDA's thinking regarding ways in which sponsors of products containing 
pancreatin and pancrelipase could design drug development programs to 
demonstrate the safety and effectiveness of their products and satisfy 
the requirements for approval of an NDA, including an NDA submitted 
pursuant to section 505(b)(2) of the FD&C Act.
    Although most therapeutic biological products have been licensed 
under section 351 of the Public Health Service Act (PHS) (42 U.S.C. 
262), some protein products historically have been

[[Page 12933]]

approved under section 505 of the FD&C Act (21 U.S.C. 355). On March 
23, 2010, the Biologics Price Competition and Innovation Act of 2009 
(BPCI Act) was enacted as part of the Patient Protection and Affordable 
Care Act (Pub. L. 111-148). The BPCI Act clarified the statutory 
authority under which certain protein products will be regulated by 
amending the definition of a ``biological product'' in section 351(i) 
of the PHS Act to include a ``protein (except any chemically 
synthesized polypeptide),'' and describing procedures for submission of 
a marketing application for certain biological products. The Further 
Consolidated Appropriations Act, 2020 (Pub. L. 116-94) further amended 
the definition of a ``biological product'' in section 351(i) of the PHS 
Act to remove the parenthetical exception for ``any chemically 
synthesized polypeptide'' from the statutory category of ``protein'' 
(see Division N, section 605, of the Further Consolidated 
Appropriations Act, 2020). Products containing pancreatin or 
pancrelipase fall within FDA's interpretation of the term ``protein'' 
in the statutory definition of a biological product (for additional 
information, see the final rule entitled ``Definition of the Term 
`Biological Product' (85 FR 10057, February 21, 2020)
    The BPCI Act requires that a marketing application for a 
``biological product'' (that previously could have been submitted under 
section 505 of the FD&C Act) must be submitted under section 351 of the 
PHS Act; this requirement is subject to certain exceptions during a 10-
year transition period ending on March 23, 2020 (see section 7002(e)(1) 
to (3) and (e)(5) of the BPCI Act). On March 23, 2020 (i.e., the 
transition date), an approved application for a biological product 
under section 505 of the FD&C Act shall be deemed to be a license for 
the biological product under section 351 of the PHS Act (see section 
7002(e)(4)(A) of the BPCI Act; see also section 7002(e)(4)(B) of the 
BPCI Act). After March 23, 2020, all sponsors seeking approval of a 
biological product (that previously could have been submitted under 
section 505 of the FD&C Act) will need to submit a BLA under the PHS 
Act (see section 7002(e) of the BPCI Act). (For additional information, 
see FDA's guidance for industry entitled ``Interpretation of the 
`Deemed to be a License' Provision of the Biologics Price Competition 
and Innovation Act of 2009'' (December 2018), available at https://www.fda.gov/media/119272/download.)
    FDA is withdrawing the guidance because a marketing application for 
a proposed PEP that contains the ingredients pancreatin or pancrelipase 
may not be submitted under section 505 of the FD&C Act after March 23, 
2020. The guidance included a description of data and information that 
may support submission of NDAs, including 505(b)(2) applications, for 
these products. FDA anticipates that there will be different 
considerations that may inform development of proposed PEPs intended 
for submission in BLAs under section 351 of the PHS Act. FDA intends to 
issue guidance regarding how the concepts described in the withdrawn 
guidance would apply to proposed pancreatic enzyme products submitted 
under the PHS Act, including the extent of integration of various types 
of data and information about the use of PEPs into BLAs. In the 
interim, the Agency encourages sponsors interested in submitting a BLA 
for a PEP to contact the relevant review division in the Office of New 
Drugs in FDA's Center for Drug Evaluation and Research with any 
questions.

    Dated: March 2, 2020.
Lowell J. Schiller,
Principal Associate Commissioner for Policy.
[FR Doc. 2020-04531 Filed 3-4-20; 8:45 am]
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