Skip to main content
SpringerLink
Log in

Basic Principles of Sterile Product Formulation Development

  • Chapter
  • First Online:
Sterile Product Development

Part of the book series: AAPS Advances in the Pharmaceutical Sciences Series ((AAPS,volume 6))

Abstract

Sterile product formulation development is more than just deciding which excipients to use with the given drug substance. The development of a sterile product requires that specific critical quality attributes be considered and evaluated, regardless of the route of delivery or the type of registration application. The chapter begins with an overview of ICH Q8 Pharmaceutical Development requirements and Health Authority Quality by Design expectations with regard to raw materials, packaging, and manufacturing process. Each of the various stages of formulation and product development is then explored, from API characterization, formulation identification and development, stability and compatibility, process requirements, to patient in-use studies and other human factor considerations. Thus, the chapter offers the formulator an overview of the foundational principles associated with formulation development of sterile products, from preformulation to commercialization.

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 229.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 299.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 299.99
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

References

  • Agarwal S et al (2002) Textbook of ophthalmology, vol 1. Jaypee Brothers, New Delhi

    Google Scholar 

  • Allen TM, Cullis PR (2013) Liposomal drug delivery systems: from concept to clinical applications. Adv Drug Deliv Rev 65:36–48. doi:10.1016/j.addr.2012.09.037

    Article  PubMed  CAS  Google Scholar 

  • Carpenter JF, Manning MC (2002) Rational design of stable protein formulations: theory and practice. Kluwer Academic/Plenum, New York

    Book  Google Scholar 

  • Chaudhari P et al (2007) Solubility enhancement of hydrophobic drugs using synergistically interacting cyclodextrins and cosolvent. Curr Sci 92:1586–1591

    CAS  Google Scholar 

  • Code of Federal Regulations. 21CFR 211.65(a)

    Google Scholar 

  • Diebold Y, Calonge M (2010) Applications of nanoparticles in ophthalmology. Prog Retin Eye Res 29:596–609. doi:10.1016/j.preteyeres.2010.08.002

    Article  PubMed  CAS  Google Scholar 

  • Ellison G, Staumfhord JV Jr, Hummel JP (1958) Buffer capacities of human blood and plasma. Clin Chem 4:452–461

    PubMed  CAS  Google Scholar 

  • FDA Guidance for Industry (1998) ICH Q1B. Photostability of new active substances and medicinal products

    Google Scholar 

  • FDA Guidance for Industry (1999) Container closure systems for packaging human drugs and biologics

    Google Scholar 

  • FDA Guidance for Industry (2000) ICH Q6A guidance. Specifications: test procedures and acceptance criteria for new drug substances and new drug products—chemical substances

    Google Scholar 

  • FDA Guidance for Industry (2002) Liposome drug products chemistry, manufacturing and controls; human pharmacokinetics and bioavailability, and labeling documentation. Draft guidance

    Google Scholar 

  • FDA Guidance for Industry (2003) ICH Q1A(R2). Stability testing for new drug substances and medicinal products

    Google Scholar 

  • FDA Guidance for Industry (2006) ICH Q3B(R2). Impurities in new drug products

    Google Scholar 

  • FDA Guidance for Industry (2006) ICH Q9. Quality risk management

    Google Scholar 

  • FDA Guidance for Industry (2008) Container and closure system integrity testing in lieu of sterility testing as a component of the stability protocol for sterile products

    Google Scholar 

  • FDA Guidance for Industry (2008) ICH Q3A(R2) Impurities in new drug substances

    Google Scholar 

  • FDA Guidance for Industry (2009) ICH Q3D. Guideline for metal impurities. Concept paper

    Google Scholar 

  • FDA Guidance for Industry (2009) ICH Q8(R2). Pharmaceutical Development

    Google Scholar 

  • FDA Guidance for Industry (2011) Applying human factors and usability engineering to optimize medical device design. Draft guidance

    Google Scholar 

  • FDA Guidance for Industry (2012) ICH Q3C(R2): Residual solvents, tables and lists

    Google Scholar 

  • Gerbino P (2005) Remington: the science and practice of pharmacy, 21st edn. Lippincott Williams & Wilkins, Philadelphia

    Google Scholar 

  • Hofmann KL (1986) Sterile powder filling the learning curve. PDA J Pharm Sci Technol 40:198–206

    CAS  Google Scholar 

  • Inactive Ingredient Database. http://www.accessdata.fda.gov/scripts/cder/iig/index.cfm

  • Irani D (2008) Properties and composition of normal CSF. In: Irani D (ed) Cerebrospinal fluid in clinical practice. Elsevier, Philadelphia

    Google Scholar 

  • Jouyban A, Soltanpour S, Soltani S, Chan HK, Acree WE Jr (2007) Solubility prediction of drugs in water-cosolvent mixtures using Abraham solvation parameters. J Pharm Pharm Sci 10:263–277

    PubMed  CAS  Google Scholar 

  • Kasper JC, Friess W (2011) The freezing step in lyophilization: physico-chemical fundamentals, freezing methods and consequences on process performance and quality attributes of biopharmaceuticals. Eur J Pharm Biopharm 78:248–263. doi:10.1016/j.ejpb.2011.03.010

    Article  PubMed  CAS  Google Scholar 

  • Kasraian K, Kuzniar AA, Wilson GG, Wood JA (1999) Developing an injectable formula containing an oxygen-sensitive drug: a case study of danofloxacin injectable. Pharm Dev Technol 4:475–480

    Article  PubMed  CAS  Google Scholar 

  • Liu R (2008) Water insoluble drug formulation, 2nd edn. CRC, Boca Raton

    Book  Google Scholar 

  • Maheswaran R (2012) FDA perspectives: scientific considerations of forced degradation studies in ANDA submissions. Pharm Technol 36:73–80

    Google Scholar 

  • Meyer BK, Ni A, Hu B, Shi L (2007) Antimicrobial preservative use in parenteral products: past and present. J Pharm Sci 96:3155–3167

    Article  PubMed  CAS  Google Scholar 

  • Mishra M et al (2009) Basics and potential applications of surfactants—a review. Int J PharmTech Res 1:1354–1365, CODEN (USA). IJPRIF ISSN: 0974–4304

    CAS  Google Scholar 

  • Moser CL, Meyer BK (2011) Comparison of compendial antimicrobial effectiveness tests: a review. Pharm Sci Technol 12:222–226. doi:10.1208/s12249-010-9575-9

    Article  Google Scholar 

  • Moskowitz RW et al (2007) Osteoarthritis: diagnosis and medical/surgical management. Wolters Kluwer, Philadelphia

    Google Scholar 

  • Müller RH, Shegokar R, Keck CM (2011) 20 Years of lipid nanoparticles (SLN and NLC): present state of development and industrial applications. Curr Drug Discov Technol 8:207–227

    Article  PubMed  Google Scholar 

  • Nail SL, Jiang S, Chongprasert S, Knopp SA (2002) Fundamentals of freeze-drying. Pharm Biotechnol 14:281–360

    Article  PubMed  CAS  Google Scholar 

  • PDA Technical Report No 26 (2008) Sterilizing filtration of liquids

    Google Scholar 

  • Premixed Medications Frozen. Baxter catalog. Retrieved from http://www.ecomm.baxter.com/ecatalog/browseCatalog.do?lid=10001&hid=10001&cid=10016&key=3480b31688beaeb98335eb9d7c46aa6

  • Rowe R (2012) Handbook of pharmaceutical excipients, 7th edn. Pharmaceutics, London

    Google Scholar 

  • Rubino JT (2006) Cosolvents and cosolvency. In: Swarbrick J (ed) Encyclopedia of pharmaceutical technology, 3rd edn. CRC, Boca Raton

    Google Scholar 

  • Shi Y, Porter W, Merdan T, Li LC (2009) Recent advances in intravenous delivery of poorly water-soluble compounds. Expert Opin Drug Deliv 6:1261–1282. doi:10.1517/17425240903307423

    Article  PubMed  CAS  Google Scholar 

  • Sreevallia S, Egan TD, Kern SE (2005) Cyclodextrins as new formulation entities and therapeutic agents. Curr Opin Anaesthesiol 18:392–395

    Article  Google Scholar 

  • Stella V, He Q (2008) Cyclodextrins. Toxicol Pathol 36:30–42

    Article  PubMed  CAS  Google Scholar 

  • Stephens D, Li LC, Pec E, Robinson D (1999) A statistical experimental approach to cosolvent formulation of a water-insoluble drug. Drug Dev Ind Pharm 25:961–965

    Article  PubMed  CAS  Google Scholar 

  • Strickley R (2004) Solubilizing excipients in oral and injectable formulations. Pharm Res 21:201–230. doi:10.1023/B:PHAM.0000016235.32639.23

    Article  PubMed  CAS  Google Scholar 

  • Swaminathan J, Ehrhardt C (2012) Liposomal delivery of proteins and peptides. Expert Opin Drug Deliv 9:1489–1503. doi:10.1517/17425247.2012.735658

    Article  PubMed  CAS  Google Scholar 

  • Tonnesen HH (2004) Photostability of drugs and drug formulations, 2nd edn. CRC, Boca Raton, p 316

    Book  Google Scholar 

  • Uekama K, Hirayama F, Irie T (1998) Cyclodextrin drug carrier systems. Chem Rev 98:2045–2076. doi:10.1021/cr970025p

    Article  PubMed  CAS  Google Scholar 

  • Wong J et al (2008) Suspensions for intravenous (IV) injection: a review of development, preclinical and clinical aspects. Adv Drug Deliv Rev 60:939–954. doi:10.1016/j.addr.2007.11.008

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgment

The authors would like to acknowledge and thank Eric M. Witchey of CyberScribe, Inc. for assistance in the preparation of this manuscript.

Author information

Authors and Affiliations

  1. Product Development, JHP Pharmaceuticals, LLC, Parsippany, NJ, USA

    Martin A. Joyce Ph.D.

  2. Pharma CMC/IP, 21 Boxwood Road, Piscataway, NJ, 08854, USA

    Leonore C. Witchey-Lakshmanan Ph.D.

Authors
  1. Martin A. Joyce Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Leonore C. Witchey-Lakshmanan Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Pharmaceutical R&D-BioTx Pharmaceutical, Chesterfield, Missouri, USA

    Parag Kolhe

  2. LifeCell Corporation, Bridgewater, New Jersey, USA

    Mrinal Shah

  3. Drug Product Engineering, Amgen, Thousand Oaks, California, USA

    Nitin Rathore

Rights and permissions

Reprints and permissions

Copyright information

© 2013 American Association of Pharmaceutical Scientists

About this chapter

Cite this chapter

Joyce, M.A., Witchey-Lakshmanan, L.C. (2013). Basic Principles of Sterile Product Formulation Development. In: Kolhe, P., Shah, M., Rathore, N. (eds) Sterile Product Development. AAPS Advances in the Pharmaceutical Sciences Series, vol 6. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-7978-9_1

Download citation

Publish with us

Policies and ethics

Search

Navigation