[Federal Register: July 14, 2005 (Volume 70, Number 134)]
[Page 40719-40720]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]



Food and Drug Administration

[Docket No. 2005N-0262]

Submission of Chemistry, Manufacturing, and Controls Information 
in a New Drug Application Under the New Pharmaceutical Quality 
Assessment System; Notice of Pilot Program

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.


SUMMARY: The Food and Drug Administration (FDA) is seeking 
pharmaceutical companies to volunteer to participate in a pilot program 
involving the submission of chemistry, manufacturing, and controls 
(CMC) information consistent with the new pharmaceutical quality 
assessment system. The purpose of the pilot program is twofold. First, 
the pilot program will provide participating pharmaceutical companies 
with an opportunity to submit critical CMC information that 
demonstrates their understanding of quality by design, product 
knowledge, and process understanding of the drug substance and drug 
product in a new drug application (NDA). Second, the pilot program will 
enable the public and regulated industry to provide feedback that will 
assist FDA in developing a guidance for industry on the new quality 
assessment system.

DATES: Submit written and electronic requests to participate in the 
pilot program by October 31, 2005. Submit written and electronic 
comments on this pilot program by December 31, 2006.

ADDRESSES: Submit written requests to participate in the pilot program 
and written comments on the program to the Division of Dockets 
Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, 
rm. 1061, Rockville, MD 20852. Submit electronic requests to 
participate and electronic comments to http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.fda.gov/dockets/ecomments

FOR FURTHER INFORMATION CONTACT: Michael Folkendt, Center for Drug 
Evaluation and Research (HFD-800), Food and Drug Administration, 5600 
Fishers Lane, Rockville, MD 20857, e-mail: folkendtm@cder.fda.gov.


I. Background

    The Office of New Drug Chemistry (ONDC) in the Office of 
Pharmaceutical Science, Center for Drug Evaluation and Research, is 
establishing a modern, risk-based pharmaceutical quality assessment 
system, as described in a September 2004 White Paper entitled ``ONDC's 
New Risk-Based Pharmaceutical Quality Assessment System'' (http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.fda.gov/cder/gmp/gmp2004/ondc_reorg.htm
). This White Paper was 

published as part of the FDA final report on ``Pharmaceutical cGMPs for 
the 21st Century--A Risk-Based Approach'' (http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.fda.gov/cder/gmp/gmp2004/GMP_finalreport2004.htm

    The new quality assessment system will focus on critical 
pharmaceutical quality attributes (related to chemistry, formulation, 
manufacturing process design, and product performance) and their 
relevance to safety and effectiveness. The principles underlying this 
new quality assessment system can be found in the February 2005 
International Conference on Harmonization (ICH) draft guidance entitled 
``Q8 Pharmaceutical Development'' (http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.fda.gov/cder/guidance/6672dft.pdf
) and the September 2004 FDA guidance for industry entitled 

``PAT--A Framework for Innovative Pharmaceutical Development, 
Manufacturing, and Quality Assurance'' (http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.fda.gov/cder/guidance/6419fnl.htm
). These principles include the following: (1) 

Ensuring product quality and performance through the design of 
effective and efficient manufacturing processes; (2) establishing 
product and process specifications based on a mechanistic understanding 
of how formulation and process factors affect product performance; and 
(3) where applicable, continuous ``real time'' quality assurance.
    The new quality assessment system is intended to facilitate 
innovation and improvement throughout the product lifecycle and to 
provide regulatory flexibility for specification setting and 
postapproval changes based on scientific knowledge and understanding of 
product and process by applying quality-by-design principles. To take 
full advantage of the new quality assessment system, including 
appropriate regulatory flexibility, applicants should provide 
information in the CMC section of an NDA that demonstrates their 
product knowledge and process understanding at the time of submission. 
A CMC submission under the new system should contain a more 
comprehensive Quality Overall Summary (Module 2.3 of the ICH Common 
Technical Document (CTD) ``M4Q: The CTD--Quality'') and a more 
expansive Pharmaceutical Development section (Module 3.2.P.2, of the 
CTD). It should also include more relevant information on critical 
quality attributes and how they relate to clinical safety and 
effectiveness. The information provided should do the following: (1) 
Provide an appropriate level of confidence that quality has been built 
into the product by demonstrating the extent of product knowledge and 
process understanding at the time of submission, including information 
explaining critical steps and in-process controls to facilitate setting 
scientifically sound specifications and acceptance criteria, and (2) 
identify possible sources of variability in manufacturing by explaining 
how associated risks can be mitigated. At the same time, there would be 
less need for information that could be handled through inspectional 
oversight of current good manufacturing practices (cGMP) requirements 
(e.g., executed batch record, redundant chromatographic data, standard 
operating procedures). The pilot is also intended to provide enhanced 
clarity by distinguishing between information submitted and used in the 
pharmaceutical assessment process and information that is a condition 
of approval (e.g., that cannot be modified without further application/
supplement review).

II. Description of Pilot Program

    The pilot program will provide additional information for ONDC to 
use in implementing the new quality assessment system. FDA will work 
with each participant on an individual basis,

[[Page 40720]]

with review of the application being the primary goal. The process will 
include appropriate coordination between agency review and inspection 
staff. Based on experience gained during the pilot program and internal 
knowledge of manufacturing science, FDA will develop procedures and 
guidance for implementing the new quality assessment system.

A. Scope

    This program will be limited to 12 original NDAs to be submitted by 
December 31, 2006, in the CTD format, paper or electronic. If an 
applicant believes that a particular CMC supplement would be a good 
candidate for this pilot program, the applicant is encouraged to first 
contact ONDC to discuss its acceptability. Acceptance into this program 
will depend on the soundness of the drug development plan and the 
potential of the proposed application to affect the development of the 
new quality assessment system. Every effort will be made to ensure that 
all pharmaceutical companies have the opportunity to participate and 
that many different drug product types are included in this pilot 
    This pilot program only affects the CMC section of the NDA. 
Existing regulations and requirements for the submission of an NDA will 
not be waived, suspended, or modified for purposes of this pilot 
program. Participants must submit the NDA, paper or electronic, in 
accordance with 21 CFR part 314 and other relevant regulations.

B. Process

    Interested parties should submit to the Division of Dockets 
Management (see ADDRESSES) a written request to participate in the 
pilot program (identified with the docket number found in brackets in 
the heading of this document). The request should include the following 
items: (1) The contact person's name, company name, company address, 
and telephone number; (2) the name of the drug product and a brief 
description (e.g., dosage form, indication); (3) a summary of the drug 
development plan; (4) a statement of the potential of the proposed 
application to affect the development of the new quality assessment 
system; and (5) a timeline for end-of-phase-2 and pre-NDA meetings and 
NDA submission. All pharmaceutical companies requesting participation 
in the pilot program will be notified of their acceptance in writing by 
ONDC within 60 days of receipt of the request.
    Potential participants are encouraged to discuss their plans to 
participate in this pilot program with ONDC (e.g., as part of an end-
of-phase-2 or pre-NDA meeting). Meeting requests for participating 
applicants should be submitted in accordance with the CDER guidance for 
industry on ``Formal Meetings With Sponsors and Applicants for PDUFA 
Products'' (http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.fda.gov/cder/guidance/2125fnl.htm). Once 

agreement is reached on participation in this program, the applicant 
can meet with ONDC as frequently as needed before the submission and 
during the review process by submitting requests directly to ONDC.
    The quality assessment under this pilot program will be conducted 
under the direct oversight of the ONDC Office Director by a team of 
experienced scientists who have a good understanding of the new quality 
assessment system and a strong scientific background in pharmaceutical 
development and manufacturing.
    A pharmaceutical company may withdraw from participation in the 
pilot program at any time before the NDA is submitted by notifying ONDC 
in writing that it wishes to withdraw from the program.

III. Comments

    Interested persons may submit written comments on this pilot 
program to the Division of Dockets Management (see ADDRESSES). Two 
copies of any comments are to be submitted, except that individuals may 
submit one copy. Comments are to be identified with the docket number 
found in brackets in the heading of this document. FDA will consider 
these comments when developing a guidance on the new pharmaceutical 
quality assessment system. Received comments may be seen in the 
Division of Dockets Management between 9 a.m. and 4 p.m., Monday 
through Friday. While detailed information on participating NDAs will 
not be publicly available, names of participating applicants will be 
made public.

    Dated: July 7, 2005.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. 05-13829 Filed 7-13-05; 8:45 am]