Guidance for Industry

Considerations for Plasmid DNA Vaccines for Infectious Disease
Indications

DRAFT GUIDANCE

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***Contains Nonbinding Recommendations***

*Draft -- Not for Implementation*

VI. **REFERENCES: REGULATIONS AND APPLICABLE GUIDANCE**

> **DOCUMENTS, AND RELEVANT PUBLICATIONS**

-   **U.S. CODE OF FEDERAL REGULATIONS**

    -   21 CFR PART 50 -- Protection of Human Subjects

    -   21 CFR PART 56 -- Institutional Review Boards

    -   21 CFR PART 58 - Good Laboratory Practice for Nonclinical
        Laboratory Studies

    -   21 CFR PART 210 -- Current Good Manufacturing Practice in
        Manufacturing, Processing, Packing, or Holding of Drugs; General

    -   21 CFR PART 211 -- Current Good Manufacturing Practice for
        Finished Pharmaceuticals

    -   21 CFR PART 312 -- Investigational New Drug Application

    -   21 CFR PART 600 -- Biological Products: General

    -   21 CFR PART 601 -- Licensing

    -   21 CFR PART 610 -- General Biological Products Standards

-   **POINTS TO CONSIDER DOCUMENTS**

1.  [Points to Consider in the Production and Testing of New Drugs and
    Biologicals Produced by Recombinant DNA Technology
    (4/85)](http://www.fda.gov/cber/gdlns/ptcdna.htm)

2.  [Supplement to the Points to Consider in the Production and Testing
    of New Drugs and Biologicals Produced by Recombinant DNA Technology:
    Nucleic Acid Characterization and Genetic Stability
    (4/92)](../05d-0047-bkg0001-Tab-02.pdf)

3.  [Points to Consider in the Characterization of Cell Lines Used to
    Produce Biologicals (7/93)](../05d-0047-bkg0001-Tab-03.pdf)

4.  [Points to Consider in the Manufacture and Testing of Monoclonal
    Antibody Products for Human Use
    (2/97)](../05d-0047-bkg0001-Tab-04.pdf)

-   **INTERNATIONAL CONFERENCE ON HARMONIZATION OF TECHNICAL
    REQUIREMENTS FOR REGISTRATION OF PHARMACEUTICALS FOR HUMAN USE (ICH)
    DOCUMENTS**

5.  [ICH; Guideline for Industry: Detection of Toxicity to Reproduction
    for Medicinal Products (9/94)](../05d-0047-bkg0001-Tab-05.pdf)

6.  [ICH; Guideline for Industry: Detection of Toxicity to Reproduction
    for Medicinal Products: Addendum on Toxicity to Male Fertility
    (4/96)](../05d-0047-bkg0001-Tab-06.pdf)

7.  [ICH; Quality of Biotechnological Products: Stability Testing of
    Biotechnological/Biological Products
    (2/04)](../05d-0047-bkg0001-Tab-07.txt)

***Contains Nonbinding Recommendations***

*Draft -- Not for Implementation*

-   **FDA GUIDELINES**

8.  [Guideline for Submitting Documentation for the Stability of Human
    Drugs and Biologics (2/87)](../05d-0047-bkg0001-Tab-08.pdf)

9.  [Guideline on Sterile Drug Products Produced by Aseptic Processing
    (6/87)](../05d-0047-bkg0001-Tab-09a.pdf); [Draft Guidance for
    Industry: Sterile Drug Products Produced by Aseptic
    Processing-Current Good Manufacturing Practice
    (8/03)](../05d-0047-bkg0001-Tab-09-GDL-vol2.pdf) (This draft
    guidance when finalized, will replace the 1987 Industry Guideline on
    Sterile Drug Products Produced by Aseptic Processing.)

10. [Guideline on Validation of the Limulus Amebocyte Lysate Test As An
    End-Product Endotoxin Test for Human and Animal Parenteral Drugs,
    Biological Products and Medical Devices
    (12/87)](../05d-0047-bkg0001-Tab-10.pdf)

11. [Guideline for the Determination of Test Residual Moisture in Dried
    Biological Products (1/90)](../05d-0047-bkg0001-Tab-11.pdf)

12. [Guideline on the Preparation of Investigational New Drug Products
    (3/91)](../05d-0047-bkg0001-Tab-12.pdf)

13. [FDA Guidance Concerning Demonstration of Comparability of Human
    Biological Products, Including Therapeutic Biotechnology-Derived
    Products (4/96)](../05d-0047-bkg0001-Tab-13.htm)

14. [Guidance for Industry: Guidance for Human Somatic Cell Therapy and
    Gene Therapy](../05d-0047-bkg0001-Tab-14.pdf)

-   **PUBLICATIONS RELEVANT TO THE ISSUE OF DNA VACCINE INDUCED NEONATAL
    TOLERANCE:**

15. [Bona C, Radu D, Kodera T. Molecular studies on the iversification
    of hemagglutinin-specific human neonatal repertoire subsequent to
    immunization with naked NDA. Vaccine. 2004 Apr 16; 22(13-14):
    1624-30.](http://www.fda.gov/ohrms/dockets/dailys/copyrighted.pdf)

16. [Bot A, Bona C. Genetic immunization of neonates. Microbes Infect.
    2002 Apr; 4(4):
    511-20.](http://www.fda.gov/ohrms/dockets/dailys/copyrighted.pdf)

17. [Ichino M, Mor G, Conover J, Weiss WR, Takeno M, Ishii KJ, Klinman
    DM. Factors associated with the development of neonatal tolerance
    after the administration of a plasmid DNA vaccine. J Immunol. 1999
    Apr 1; 162(7):
    3814-8.](http://www.fda.gov/ohrms/dockets/dailys/copyrighted.pdf)

18. [Wang Y, Xiang Z, Pasquini S, Ertl HC. Immune response to neonatal
    genetic immunization. Virology. 1997 Feb 17; 228(2):
    278-84.](http://www.fda.gov/ohrms/dockets/dailys/copyrighted.pdf)

19. [Mor G, Yamshchikov G, Sedegah M, Takeno M, Wang R, Houghten RA,
    Hoffman S, Klinman DM. Induction of neonatal tolerance by plasmid
    DNA vaccination of mice. J Clin Invest. 1996 Dec 15; 98(12):
    2700-5.](http://www.fda.gov/ohrms/dockets/dailys/copyrighted.pdf)

***Contains Nonbinding Recommendations***

*Draft -- Not for Implementation*

-   **PUBLICATIONS RELEVANT TO THE ISSUE OF PLASMID DNA BIODISTRIBUTION
    AND PERSISTENCE:**

20. [Kim BM, Lee DS, Choi JH, Kim CY, Son M, Suh YS, Baek KH, Park KS,
    Sung YC, Kim WB. In vivo kinetics and biodistribution of a HIV-1 DNA
    vaccine after administration in mice. Arch Pharm Res. 2003 Jun;
    26(6):493-8.](http://www.fda.gov/ohrms/dockets/dailys/copyrighted.pdf)

21. [Pilling AM, Harman RM, Jones SA, McCormack NA, Lavender D,
    Haworth R. The assessment of local tolerance, acute toxicity and DNA
    biodistribution following particle-mediated delivery of a DNA
    vaccine to minipigs. Toxicol Pathol. 2002 May-Jun; 30(3):
    298-305.](http://www.fda.gov/ohrms/dockets/dailys/copyrighted.pdf)

22. [Bureau MF, Naimi S, Torero Ibad R, Seguin J, Georger C, Arnould E,
    Maton L, Blanche F, Delaere P, Scherman D. Intramuscular plasmid DNA
    electrotransfer: biodistribution and degration. Biochim Biophys
    Acta. 2004 Jan 20; 1676(2):
    138-48.](http://www.fda.gov/ohrms/dockets/dailys/copyrighted.pdf)

23. [Wan Z, Troilo PJ, Wang X, Griffiths TG, Pacchione SJ, Barnum AB,
    Harper LB, Pauley CJ, Niu Z, Denisova L, Follmer TT, Rizzuto G,
    Ciliberto G, Fattori E, Monica NL, Manam S, Ledwith BJ. Detection of
    integration of plasmid DNA into host genomic DNA following
    intramuscular injection and electroporation. Gene Ther. 2004 Apr;
    11(8):
    711-21.](http://www.fda.gov/ohrms/dockets/dailys/copyrighted.pdf)

24. [Ledwith BJ, Manam S, Troilo PJ, Barnum AB, Pauley CJ, Griffiths TG
    2^nd^, Harper LB, Schock HB, Zhang H, Faris JE, Way PA, Beare CM,
    Bagdon WJ, Nichols WW. Plassmid DNA vaccines: assay for integration
    into host gnomic DNA. Dev Biol (Basel). 200; 104:
    33-43.](http://www.fda.gov/ohrms/dockets/dailys/copyrighted.pdf)

25. [Ledwith BJ, Manam S, Troilo PJ, Barnum AB, Pauley CJ, Griffiths TG
    2^nd^, Harper BL, Beare CM, Bagdon WJ, Nichols WW. Plasmid DNA
    vaccines: investigation of integration into host cellular DNA
    following intramuscular injection in mice. Intervirology. 200;
    43(4-6):
    258-72.](http://www.fda.gov/ohrms/dockets/dailys/copyrighted.pdf)