How a Biologic Is Made

Manufacturing biologics is a complex process.1

Biologic medicines are manufactured using living cells that have been engineered to produce therapeutic proteins in large quantities. These proteins are very sensitive to their conditions of synthesis and handling, and a series of culturing and purification steps is required to produce a consistent, high-quality, active ingredient.2,3



CELL CULTURE4 RECOVERY & PURIFICATION5 FORMULATION TO DISTRIBUTION6
1. Process line development
2. Cell expansion
3. Cell culture
4.  Harvest
5.  Purification (multiple steps)
6.  Virus inactivation/removal
7.  Filling 
8.  Finishing
9.  Packaging & storage
10.  Quality assurance & characterization
11.  Stability testing

Complexities in Manufacturing Biosimilars3

The complexities of manufacturing biologic medicines also apply to biosimilars, which are approved on the basis of demonstrating similar quality, safety, and efficacy to originator biologic medicines.

In attempting to copy the originator product, biosimilar manufacturers must independently design their own cell cultures and production steps, which are considered proprietary knowledge. It is therefore impossible for biosimilar manufacturers to precisely replicate the manufacturing process of the original biologic of the active ingredient of the protein product. This creates a unique relationship between a biologic’s manufacturing process and the final product approved by regulators. 

 

Good Manufacturing Practice for Large Molecules

Good Manufacturing Practice for Large Molecules

References:

  1. Niederwieser D, Schmitz S. Biosimilar agents in oncology/haematology: from approval to practice. Eur J Haematol. 2011;86:277-288.
  2. Lybecker KM. The biologics revolution in the production of drugs. https://www.fraserinstitute.org/studies/biologics-revolution-in-the-production-of-drugs. Fraser Institute. Accessed November 23, 2016.
  3. US Department of Health and Human Services. Scientific considerations in demonstrating biosimilarity to a reference product. Guidance for industry. http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm291128.pdf. Accessed November 23, 2016.
  4. Desanvicente-Celis Z, Gomez-Lopez A, Anaya J-M. Similar biotherapeutic products: overview and reflections. Immunother. 2012;4:1841-1857.
  5. Bee JS, Randolph TW, Carpenter JF, Bishop SM, Dimitrova MN. Effects of surfaces and leachables on the stability of biopharmaceuticals. J Pharma Sci. 2011;100:4158-4170.
  6. Conner J, Wuchterl D, Lopez M, et al. The biomanufacturing of biotechnology products. In: Shimasaki C, ed. Biotechnology Entrepreneurship: Starting, Managing, and Leading Biotech Companies. Waltham, MA: Academic Press; 2014:351-385.