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###### Department of Health and Human Services

###### Food and Drug Administration

          - [Docket No. FDA-2008-N-0355]

# AGENCY:

Food and Drug Administration, HHS.

# ACTION:

Notice.

# SUMMARY:

The Food and Drug Administration (FDA) is announcing an extension of the deadline for submitting requests to participate in a pilot program involving the submission of quality (chemistry, manufacturing, and controls (CMC)) information for biotechnology products in an Expanded Change Protocol consistent with the principles of quality-by-design and risk management in pharmaceutical manufacturing. Because the deadline for requests to participate in the pilot is being extended, FDA is also extending the application submission deadlines. FDA is also announcing an increase in the number of original applications being accepted into the pilot program.

# DATES:

Submit written and electronic requests to participate in the pilot program by September 30, 2010. Submit investigational new drug (IND) applications and postapproval supplements by March 31, 2011.

# ADDRESSES:

                        Submit written requests to participate in the pilot 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 in the pilot to                         *http://www.regulations.gov*.                    

# FOR FURTHER INFORMATION CONTACT:

                        Marilyn Welschenbach, Center for Drug Evaluation and Research, Food and Drug Administration, Bldg. 21, rm. 1514, 10903 New Hampshire Ave., Silver Spring, MD 20993-0002, e-mail:                         *Marilyn.Welschenbach@fda.hhs.gov*.                    

# SUPPLEMENTARY INFORMATION:

## I. Background

                    In the                     **Federal Register**                     of July 2, 2008 (73 FR 37972) (the July 2, 2008, notice), FDA announced that it is seeking volunteers from pharmaceutical companies to participate in a pilot program involving the submission of quality (CMC) information for biotechnology products in an Expanded Change Protocol, consistent with the principles of quality-by-design and risk management in pharmaceutical manufacturing. As explained in the July 2, 2008, notice, the Office of Pharmaceutical Science (OPS), in FDA's Center for Drug Evaluation and Research (CDER), is establishing a quality-by-design, risk-based approach to pharmaceutical quality, which is based on the FDA final report on “Pharmaceutical cGMPs for the 21st Century—A Risk-Based Approach” (                    *http://www.fda.gov/​cder/​gmp/​gmp2004/​GMP_​finalreport2004.htm*). The new quality-by-design approach will focus on critical quality attributes related to chemistry, formulation, and process design. Under quality-by-design, manufacturing will depend on a risk-based approach linking attributes and processes to product performance, safety, and efficacy.                

                    The principles underlying this new approach to a quality-by-design, risk-based assessment can be found in the International Conference on Harmonisation guidances, “Q8(R1) Pharmaceutical Development,” June 2009 (                    *http://www.fda.gov/​downloads/​Drugs/​GuidanceComplianceRegulatoryInformation/​Guidances/​ucm073507.pdf*), and “Q9 Quality Risk                           ( print page 47807)                        Management (ICH),” June 2006 (                    *http://www.fda.gov/​downloads/​Drugs/​GuidanceComplianceRegulatoryInformation/​Guidances/​ucm073511.pdf*), and FDA's guidances for industry entitled “PAT—A Framework for Innovative Pharmaceutical Development, Manufacturing, and Quality Assurance,” September 2004 (                    *http://www.fda.gov/​downloads/​Drugs/​GuidanceComplianceRegulatoryInformation/​Guidances/​ucm070305.pdf*), and “Quality Systems Approach to Pharmaceutical CGMP Regulations,” September 2006 (                    *http://www.fda.gov/​downloads/​Drugs/​GuidanceComplianceRegulatoryInformation/​Guidances/​ucm070337.pdf*). Quality-by-design and risk-based approaches are also described in “Q10 Pharmaceutical Quality Systems,” April 2009 (                    *http://www.fda.gov/​downloads/​Drugs/​GuidanceComplianceRegulatoryInformation/​Guidances/​ucm073517.pdf*).                

The agency's Office of New Drug Quality Assessment in OPS, CDER, initiated a pilot program (70 FR 40719, July 14, 2005) to gain experience in assessing CMC sections of new drug applications (NDAs) that demonstrate an applicant's product knowledge and process understanding at the time of submission. This pilot was extremely useful in helping identify appropriate information to be shared regarding quality-by-design for small molecules. Although many of the principles of quality-by-design apply equally to small molecules and more complex pharmaceuticals, the ability to assess relevant attributes is a much greater challenge for complex pharmaceuticals.

Because the pilot program initiated in 2005 proved constructive, on July 2, 2008, FDA announced this pilot program to provide additional information to FDA for use in facilitating quality-by-design, risk-based approaches for complex molecules. Based on experience gained during the pilot program and prior knowledge, FDA will develop procedures to facilitate implementing a quality-by-design, risk-based approach for complex products. In addition, the experience gained by FDA under this pilot is expected to facilitate the development of guidance for industry. The pilot is open to original submissions and postapproval supplements to biologics license applications (BLAs) and NDAs reviewed by the Office of Biotechnology Products (OBP).

The July 2, 2008, notice provided deadlines related to the submission of certain information related to the pilot program. To ensure inclusive and relevant results from the pilot program, this document extends the deadline for requests to participate in this pilot program for products regulated by OBP from September 30, 2009, to September 30, 2010. Because the deadline for requests to participate in the pilot is being extended, FDA is also extending the application submission deadlines. As explained in the July 2, 2008, notice, it is preferable for original applications to enter the pilot as INDs. FDA is extending the deadline for submission of INDs from March 31, 2010, to March 31, 2011. FDA is also extending the deadline for submission of postapproval supplements from March 31, 2010, to March 31, 2011. In addition, the pilot is being expanded from five to eight original applications for products reviewed by OBP (BLA or NDA) in Common Technical Document format, paper or electronic. See the July 2, 2008, notice for instructions on submitting requests to participate in the pilot program and additional information regarding the pilot program.

Dated: September 11, 2009.

David Horowitz,

Assistant Commissioner for Policy.

[FR Doc. E9-22378 Filed 9-16-09; 8:45 am]

BILLING CODE 4160-01-S