Increasing demand drives innovation

There is a saying in the biopharma industry, ‘The product is the process,’ and continuous ‘end-to-end’ manufacturing is one such emerging technology that the FDA is proactively encouraging.1,2

Over the past five years, biologic medicines have accounted for over one in four of all FDA new drug approvals.3 The prevalence and increasing demand for these complex, life-changing medications has helped fuel innovation in manufacturing technologies, including the paradigm shift to continuous ‘end-to-end’ production.4

* As of April 2019

People Behind the Promise

Get industry insiders’ perspectives on relevant topics with this regular video feature.

Meet Mark Langston, Head of Marketing, Executive Director, Biosimilars at Boehringer Ingelheim, and hear him discuss Managing Complexity in Biopharma Manufacturing.

“At Boehringer Ingelheim, the management of complexity comes from our ability to run a full service, from end-to-end manufacturing.”
“At Boehringer Ingelheim, the management of complexity comes from our ability to run a full service, from end-to-end manufacturing.”

People Behind the Promise
is a regular feature of BIOSIMILAR PERSPECTIVES

Future topics and speakers include:

Manufacturers, Payers,
and the Biosimilar Market
with Tom Koenig, Executive Director, Biosimilar
Market Access at Boehringer Ingelheim
Biosimilars and Sustainability
of the Healthcare System
with Molly Burich, Director of Public
Policy: Biosimilars and Reimbursement
at Boehringer Ingelheim
Biopharma Innovation and
Boehringer Ingelheim Fremont Expansion
with Jens Vogel, PhD, President & CEO
Boehringer Ingelheim, Fremont, Inc


End-to-end: A paradigm shift in production

The Complexity of an Airplane Versus a Bicycle

Biologic medicines are made up of large and highly complex molecules—and can be 800 times larger than a typical small-molecule drug, like aspirin.6 And unlike small-molecule drugs that are produced through predictable chemical synthesis, biologics are grown in living cells, which can add a level of complexity analogous to an airplane vs a bicycle.6,7

Further, a typical manufacturing process for a traditional medicine might include 40 to 50 critical tests, while a biologic might undergo 250 or more.12

What Is ‘End-to-End’ Production?

For over 50 years, the biopharma industry has relied on traditional ‘batch’ production. With ‘batch’ production, a set amount of raw material is processed at a time with discrete steps.2 ‘End-to-end,’ on the other hand, is the process of manufacturing a pharmaceutical product from start (ie, raw material) to finish (eg, filled autoinjectors and syringes, in final dosage form) in a fully continuous mode.2

The concept of ‘end-to-end’ is not unique to biopharma; it has also been employed in other industries, including food service and specialty chemicals.4 The holistic view of continuous ‘end-to-end’ manufacturing has led to the reexamination of the other biopharma manufacturing paradigms, including the breaking down of traditional operational silos (eg, engineering, production, and quality). The trend is toward a more integrated multidisciplinary approach.4
“[‘End-to-end’] saves time, reduces the likelihood for human error, and can respond more nimbly to market changes … [and] may reduce the likelihood of drug shortages.” 2
Sau (Larry) Lee, PhD, Deputy Director, Center for Drug Evaluation and Research

Boehringer Ingelheim: 35 Years’ Experience and $217 Million Commitment7

With over 35 years' experience as a contract manufacturer of biologics, Boehringer Ingelheim is one of the industry leaders in the move to continuous 'end-to-end' production. "We are running a fully integrated biotech operation, and we have all functions of the biopharmaceutical value chain right here at the site," says Jens Vogel, PhD, President & CEO of Boehringer Ingelheim’s Fremont facility. "We're investing about $217 million into expanding our capacity and capabilities."

What Does ‘End-to-End’ Mean for You?2,4

Bottom Line: The Patient

The advantages achieved with manufacturing innovations—quality, sustainability andconsistency of production, scalability of process, and potential cost containment—go well beyond the industry. At the end of the day, the patient remains the primary beneficiary, with greater resources available to focus on unmet healthcare needs.4

Catch up on what you may have missed

BIosimilar Perspectives Issue #1:
  1. 1. Biotechnology Innovation Organization. How do drugs and biologics differ?  Accessed April 23, 2019.
  2. 2. Lee S. Modernizing the way drugs are made: a transition to continuous manufacturing. April 2019. US Food & Drug Administration. Accessed April 23, 2019.
  3. 3. US Food & Drug Administration website. New Molecular Entity (NME) Drug and New Biologic Approvals. developmentapprovalprocess/howdrugsaredevelopedandapproved/drugandbiologicapprovalreports/ndaandblaapprovalreports/ucm373420.htm. Accessed April 23, 2019.
  4. 4. Jacoby R, Pernenkil L, Harutunian S, Heim M, Sabad A. Advanced biopharmaceutical manufacturing: an evolution underway. Deloitte. May  2015. Accessed April 23, 2019.
  5. 5. US Food & Drug Administration website. Purple Book: Lists of Licensed Biological Products with Reference Product Exclusivity and Biosimilarity  or Interchangeability Evaluations. ApprovalApplications/TherapeuticBiologicApplications/Biosimilars/UCM412398.pdf. Accessed April 23, 2019.
  6. 6. US Food & Drug Administration website. Biological Product Definitions. Process/HowDrugsareDevelopedandApproved/ApprovalApplications/TherapeuticBiologicApplications/Biosimilars/UCM581282.pdf.  Accessed April 23, 2019.
  7. 7. Data on file. Boehringer Ingelheim. Biosimilars video.
  8. 8. Generics and Biosimilars Initiative. Gabi online. Small molecule versus biological drugs. Small-molecule-versus-biological-drugs. Accessed May 6, 2019.
  9. 9. Blackstone EA, Fuhr JP Jr. The economics of biosimilars. Am Health Drug Benefits. 2013;6(8):469-478.
  10. 10. Ryan AM. Frontiers in nonclinical drug development: biosimilars. Vet Pathol. 2015;52(2):419-426.
  11. 11. Rugo HS, Linton KM, Cervi P, Rosenberg JA, Jacobs I. A clinician’s guide to biosimilars in oncology. Cancer Treat Rev. 2016;46:73-79.
  12. 12. Zezza D, Seamon K, Garnick R, et al. Biologics: can there be abbreviated applications, generics, or follow-on products? BioPharm Intl.  2003;16(7):1-6.