Skip to main content
SpringerLink
Log in

Quality Control and Regulatory Issues for Biotherapeutic Agents

  • Chapter
Biotherapeutic Agents and Infectious Diseases

  • 68 Accesses

Abstract

Biologic organisms that show promise as therapeutics have several routes for development, which begin in the microbiology laboratory and end in the medical marketplace. This chapter describes the regulations regarding biotherapeutics, and presents the differences between biotherapeutic agents and the other designations for biologics (dietary supplements, medical foods, and functional foods). In addition, the developmental pathway for a biotherapeutic agent and requirements for drug approval in the United States will be described. Finally, quality control and manufacturing concerns will be addressed. In this chapter, the goal is to describe how a microorganism goes from being just “an interesting bug on a Petri plate” to joining the arsenal of approved drugs and biologics for the treatment and prevention of disease.

On a long journey, the true reward comes not at the end, but is gathered piece by piece during the trek itself.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Code of Federal Regulations. (April 1, 1996 ) Title 21. Sections 610, 200–210, 312.

    Google Scholar 

  2. Federal Register. September 23, 1997. 61(184) 49,825–49,881.

    Google Scholar 

  3. Federal Register. February 6, 1997. 62, 5707–5708.

    Google Scholar 

  4. Federal Register. November 29, 1996. 61 60,661–60,671.

    Google Scholar 

  5. Code of Federal Regulations. (April 1, 1996 ) Title 21. Chapter I, Subchapter F—Biologics, Part 601—Licensing.

    Google Scholar 

  6. Silva, M., Jacobus, N. V., Deneke, C., and Gorbach, S. L. (1987) Antimicrobial substance from a human Lactobacillus strain. Antimicrob. Agents Chemother. 31, 1231–1233.

    Article  PubMed  CAS  Google Scholar 

  7. Meghrous, J., Eulige, P., Junelles, A. M., Ballongue, J., and Petitdemange, H. (1990) Screening of Bifidobacterium strains from bacteriocin production. Biotechnol. Lett. 12, 575–580.

    Article  CAS  Google Scholar 

  8. Brugier, S. and Patte, F. (1975) Antagonismes in vitro entre l’ultralevure et différents germes bactériens. Med. Paris 45, 3–8.

    Google Scholar 

  9. Meurman, J. H., Antila, H., Korhonen, A., and Salminen, S. (1995) Effect of Lactobacillus rhamnosus strain GG (ATCC 53103) on the growth of Streptococcus sobrinus in vitro. Eur. J. Oral Sci. 103, 253–258.

    Article  CAS  Google Scholar 

  10. Rolfe, R., Helebia, S., and Finegold, S. (1981) Bacterial interference between Clostridium difficile and normal fecal flora. J. Infect. Dis. 143, 470–475.

    Article  PubMed  CAS  Google Scholar 

  11. Coconnier, M.-H., Bernet, M.-E., Kerneis, S., Chauvière, G., Fourniat, J., and Servin, A. L. (1993) Inhibition of adhesion of enteroinvasive pathogens to human intestinal Caco-2 cells by Lactobacillus acidophilus strain LB decreases bacterial invasion. FEMS Microbiol. Lett. 110, 299–306.

    Article  PubMed  CAS  Google Scholar 

  12. Chauvière, G., Coconnier, M.-H., Kerneis, S., Darfeuille-Michaud, A., Joly, B., and Servin, A. L. (1992) Competitive exclusion of diarrheagenic Escherichia coli (ETEC) from human enterocyte-like Caco-2 cells by heat-killed Lactobacillus. FEMS Microbial. Lett. 91, 213–218.

    Article  Google Scholar 

  13. Reid, G., Chan, R. C., Bruce, A. W., and Costerton, J. W. (1985) Prevention of urinary tract infection in rats with an indigenous Lactobacillus casei strain. Infect. Immun. 49, 320–324.

    PubMed  CAS  Google Scholar 

  14. McGroarty, J. A. (1993) Probiotic use of lactobacilli in the human female urogenital tract. FEMS Immunol. Med. Microbiol. 6, 251–264.

    Article  PubMed  CAS  Google Scholar 

  15. De Cupere, E, Deprez, P., Demeulenaere, D., and Muylle, E. (1992) Evaluation of the effect of 3 probiotics on experimental Escherichia coli enterotoxaemia in weaned piglets. Zentralbi. Veterinarmed. B. 39, 277–284.

    Google Scholar 

  16. Duffy, L. C., Zielezny, M. A., Riepenhoff-Talty, M., Dryja, D., Sayahtaheri-Altaie, S., Griffiths, E., et al. (1993) Effectiveness of Bifidobacterium bifidum in experimentally induced MRV infection: dietary implications in formulas for newborns. Endocr. Regul. 27, 223–229.

    PubMed  CAS  Google Scholar 

  17. Elmer, G. W. and McFarland, L. V. (1987) Suppression by Saccharomyces boulardii of toxigenic Clostridium difficile overgrowth after vancomycin treatment in hamsters. Antimicrob. Agents Chemother. 31, 129–131.

    Article  PubMed  CAS  Google Scholar 

  18. Blehaut, H., Massot, J., Elmer, G. W., and Levy, R. H. (1989) Disposition kinetics of Saccharomyces boulardii in man and rat. Biopharm. Drug Dispos. 10, 353–364.

    Article  PubMed  CAS  Google Scholar 

  19. Berg, R. D. (1992) Translocation of enteric bacteria in health and disease, in Gut-Derived Infectious-Toxic Shock (GITS) (Cottier, H. and Kraft, R., Eds.), S. Karger AG, Basel, Switzerland, Curr. Studies Hematol. Blood Transfusion 59, 44–65.

    Google Scholar 

  20. Berg, R., Bernasconi, P., Fowler, D., and Gautreaux, M. (1993) Inhibition of Candida albicans translocation from the gastrointestinal tract of mice by oral administration of Saccharomyces boulardii. J. Infect. Dis. 168, 1314–1318.

    Article  CAS  Google Scholar 

  21. Pecquet, S., Guillaumin, D., Tancrede, C., and Andremont, A. (1991) Kinetics of Saccharomyces cerevisiae elimination from the intestines of human volunteers and effect of this yeast on resistance to microbial colonization in gnotobiotic mice. Appl. Environ. Microbial. 57, 3049–3051.

    CAS  Google Scholar 

  22. Food and Drug Administration. (1997) Guidance for Industry. Drug Metabolism! Drug Interaction Studies in the Drug Development Process: Studies In Vitro. US Department of Health and Human Services, Rockville, MD.

    Google Scholar 

  23. Orrhage, K., Lidbeck, A., and Nord, C. E. (1991) Effect of Bifidobacterium longum supplements on the human faecal microflora. Microbial. Ecology Health Dis. 4, 265–270.

    Article  Google Scholar 

  24. Lidbeck, A., Gustafsson, J.-A., and Nord, C. E. (1987) Impact of Lactobacillus acidophilus supplements on the human oropharyngeal and intestinal microflora. Scand. J. Infect. Dis. 19, 531–537.

    Article  PubMed  CAS  Google Scholar 

  25. Klein, S. M., Elmer, G. W., McFarland, L. V., Surawicz, C. M., and Levy, R. H. Recovery and elimination of the biotherapeutic agent, Saccharomyces boulardii, in healthy human volunteers. Pharm. Res. 10, 1615–1619.

    Google Scholar 

  26. Elmer, G. W., Moyer, K. A., Vega, R., Surawicz, C. M., Collier, A. C., Hooton, T. M., et al. (1995) Evaluation of Saccharomyces boulardii for patients with HIV-related chronic diarrhoea and in healthy volunteers receiving antifungals. Micro-ecology Ther. 25, 23–31.

    Google Scholar 

  27. Marteau, P., Pochart, P., Bouhnik, Y., Zidi, S., Goderel, I., and Rambaud, J.-C. (1992) Survie, dans l’intestin grêle, de Lactobacillus acidophilus et Bifidobacterium sp, ingérés dans un lait fermenté. Gastroenterol. Clin. Biol. 16, 25–28.

    PubMed  CAS  Google Scholar 

  28. Sheen, P., Oberhelman, R. A., Gilman, R. H., Cabrera, L., Verastegui, M., and Madico, G. (1995) Short report: a placebo-controlled study of Lactobacillus GG colonization in one-to three-year-old Peruvian children. Am. J. Trop. Med. Hyg. 52, 389–392.

    PubMed  CAS  Google Scholar 

  29. Bouhnik, Y., Pochart, P., Marteau, P., Arlet, G., Goderel, I., and Rambaud, J. C. (1992) Fecal recovery in humans of viable Bifidobacterium sp ingested in fermented milk. Gastroenterology 102, 875–878.

    PubMed  CAS  Google Scholar 

  30. Biller, J. A., Katz, A. J., Flores, A. F., Buie, T. M., and Gorbach, S. L. (1995) Treatment of recurrent Clostridium difficile colitis with Lactobacillus GG. J. Pediatr. Gastroenterol. Nutr. 21, 224–226.

    Article  PubMed  CAS  Google Scholar 

  31. Surawicz, C. M., McFarland, L. V., Elmer, G., and Chinn, J. (1989) Treatment of recurrent Clostridium difficile colitis with vancomycin and Saccharomyces boulardii. Am J. Gastroenterol. 84, 1285–1287.

    CAS  Google Scholar 

  32. McFarland, L. V., Surawicz, C. M., Greenberg, R. N., Fekety, R., Elmer, G. W., Moyer, K. A., et al. (1994) A randomized placebo-controlled trial of Saccharomyces boulardii in combination with standard antibiotics for Clostridium difficile disease. JAMA 271, 1913–1918.

    CAS  Google Scholar 

  33. Oksanen, R. J., Salminen, S., Saxelin, M., Hämäläinen, P., Ihantola-Vormisto, A., Muurasniemi-Isoviita, L., et al. (1990) Prevention of traveller’s diarrhoea by Lactobacillus GG. Ann. Med. 22, 53–56.

    Article  PubMed  CAS  Google Scholar 

  34. Gotz, V., Romankiewicz, J. A., Moss, J., and Murray, H. W. (1979) Prophylaxis against ampicillin-associated diarrhea with a lactobacillus preparation. Am. J. Hosp. Pharm. 36, 754–757.

    PubMed  CAS  Google Scholar 

  35. Saavedra, J. M., Bauman, N. A., Oung, I., Perman, J. A., and Yolken, R. H. (1994) Feeding of Bifidobacterium bi f id um and Streptococcus thermophilus to infants in hospital for prevention of diarrhoea and shedding of rotavirus. Lancet 344, 1046–1049.

    Article  PubMed  CAS  Google Scholar 

  36. Surawicz, C. M., Elmer, G. W., Speelman, P., McFarland, L. V., Chinn, J., and Van Belle, G. (1989) Prevention of antibiotic-associated diarrhea by Saccharomyces boulardii: a prospective study. Gastroenterology 96, 981–988.

    PubMed  CAS  Google Scholar 

  37. Mitra, A. K. and Rabbani, G. H. (1990) A double-blind, controlled trial of Bioflorin (Streptococcus faecium SF68) in adults with acute diarrhea due to Vibrio cholerae and enterotoxigenic Escherichia coli. Gastroenterology 99, 1149–1152.

    CAS  Google Scholar 

  38. Raza, S., Graham, S. M., Allen, S. J., Sultana, S., Cuevas, L., and Hart, C. A. (1995) Lactobacillus GG promotes recovery from acute nonbloody diarrhea in Pakistan. Pediatr. Infect. Dis. J. 14, 107–111.

    Article  CAS  Google Scholar 

  39. Tankanow, R. M., Ross, M. B., Ertel, I. J., Dickinson, D. G., McCormick, L. S., and Garfinkel, J. F. (1990) A double-blind, placebo-controlled study of the efficacy of Lactinex in the prophylaxis of amoxicillin-induced diarrhea. DICP Ann. Pharmacother. 24, 382–384.

    CAS  Google Scholar 

  40. Food and Drug Administration. (1987) Guideline for Submitting Documentation for the Stability of Human Drugs and Biologics. US Department of Health and Human Services, Rockville, MD.

    Google Scholar 

  41. Federal Register (1994) International Conference on Harmonization: Stability Testing of New Drugs Substances and Products; Guideline; Availability; Notice. 48, 754–48, 759.

    Google Scholar 

  42. Hughes, V. L. and Hillier, S. L. (1990) Microbiologic characteristics of Lactobacillus products used for colonization of the vagina. Obstet. Gynecol. 75, 244–248.

    PubMed  CAS  Google Scholar 

  43. Clements, M. L., Levine, M. M., Ristaino, P. A., Daya, V. E., and Hughes, T. P. (1983) Exogenous lactobacilli fed to man—their fate and ability to prevent diarrheal disease. Prog. Food Nutr. Sci. 7, 29–37.

    PubMed  CAS  Google Scholar 

  44. Center for Disease Control. (1995) CDC issues recommendations for preventing spread of vancomycin resistance [news]. Am. J. Health Syst. Pharm. 15, 1272–1274.

    Google Scholar 

  45. Lam, S., Singer, C., Tucci, V., Morthland, V. H., Pfaller, M. A., and Isenberg, H. D. (1995) The challenge of vancomycin-resistant enterococci: a clinical and epidemiologic study. Am. J. Infect. Control 23, 170–180.

    Article  PubMed  CAS  Google Scholar 

  46. McCracken, G. H., Jr. (1995) Emergence of resistant Streptococcus pneumoniae: a problem in pediatrics. Pediatr. Infect. Dis. J. 14, 424–428.

    Article  PubMed  Google Scholar 

  47. Neu, H. C. (1992) The crisis in antibiotic resistance. Science 257, 1064–1073.

    Article  PubMed  CAS  Google Scholar 

  48. Salyers, A. A. and Shoemaker, N. B. (1995) Conjugative transposons: the force behind the spread of antibiotic resistance genes among Bacteroides clinical isolates. Anaerobe 1, 143–150.

    Article  PubMed  CAS  Google Scholar 

  49. Habig, W. H. (1993) Potency testing of bacterial vaccines for human use. Vet. Microbiol. 37, 343–351.

    Article  PubMed  CAS  Google Scholar 

  50. Saxelin, M., Pessi, T., and Salminen, S. (1995) Fecal recovery following oral administration of Lactobacillus strain GG (ATCC 53103) in gelatine capsules to healthy volunteers. Int. J. Food Microbiol. 25, 199–203.

    Article  PubMed  CAS  Google Scholar 

  51. Millar, M. R., Bacon, C., Smith, S. L., Walker, V., and Hall, M. A. (1993) Enteral feeding of premature infants with Lactobacillus GG. Arch. Dis. Child. 69, 483–487.

    Article  PubMed  CAS  Google Scholar 

  52. Goldin, B. R., Gorbach, S. L., Saxelin, M., Barakat, S., Gualtieri, L., and Salminen, S. (1992) Survival of Lactobacillus species (strain GG) in human gastrointestinal tract. Dig. Dis. Sci. 37, 121–128.

    Article  PubMed  CAS  Google Scholar 

Download references

Authors
  1. Lynne V. McFarland
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Medicinal Chemistry, School of Pharmacy, University of Washington, Seattle, WA, USA

    Gary W. Elmer  & Lynne V. McFarland  & 

  2. Biocodex Inc., Seattle, WA, USA

    Lynne V. McFarland

  3. Department of Medicine, Harborview Medical Center, University of Washington, Seattle, WA, USA

    Christina M. Surawicz

Rights and permissions

Reprints and permissions

Copyright information

© 1999 Springer Science+Business Media New York

About this chapter

Cite this chapter

McFarland, L.V. (1999). Quality Control and Regulatory Issues for Biotherapeutic Agents. In: Elmer, G.W., McFarland, L.V., Surawicz, C.M. (eds) Biotherapeutic Agents and Infectious Diseases. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-711-6_1

Download citation

  • DOI: https://doi.org/10.1007/978-1-59259-711-6_1

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-4757-4652-5

  • Online ISBN: 978-1-59259-711-6

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation