Vincent added that the development and adoption of stable producer cell lines is due to an anticipated challenge for the market: “As interest in cell and gene therapy grows, and the viral vector industry matures, a tightening of the regulations surrounding their manufacturing can be expected.
“Regulations are predicted to impact the use of serum in producer cell growth, as it cannot be guaranteed to be consistent in composition. Adherent 293T cells are hard to grow without foetal bovine serum (FBS) but there are currently not many serum-free media available to grow adherent cells. As a result, lentiviral vector manufacturers will need to start looking for alternative options, such as stable producer cell lines.”
Speed to market
As mentioned by Choi, speed to market now represents a significant challenge for drug developers. According to the US Food and Drug Administration (FDA)’s latest report, 74 percent (34 out of 50) of the novel drugs approved by FDA in 2021 used some form of expedited development or review pathway, specifically Fast Track Designation (36 percent, n=18), Breakthrough Therapy Designation (28 percent, n=14), Priority Review (68 percent, n=34), and/or Accelerated Approval (28 percent, n=14).5
“The increasing pressure for speed to market is at odds with transfer delays as projects move between sites or companies to perform subsequent processes across the supply chain. These delays have been worsened by the effects of COVID-19. The ability to obviate these delays will continue to be a pivotal criterion in selecting a manufacturing partner,” commented Choi.
Frank Kogelberg, Director of Business Development, Contract Manufacturing at Baxter, also emphasised the importance of reducing transfer delays in the report by CPhI and Baxter.2
Skilled labour shortage
Vincent highlighted: “A key factor that will continue to impact biopharma manufacturing in the next year and beyond is the limited availability of skilled labour. Although some of the problems surrounding labour shortages could be solved using automation, the fundamental issue will remain. Preparing workers for the STEM (science, technology, engineering and mathematics) industries will require further funding in the education sector – and any territory (city, state or nation) ready to solve this challenge will be poised to dominate the industry.”
Poorly soluble HPAPIs
According to Lonza CHI’s Rose Mary Casados, Senior Director of Product Management Marketing, the primary challenge facing the manufacturing industry is delivering oral solid dosage (OSD) formulations containing increasingly poorly water-soluble highly potent active pharmaceutical ingredients (HPAPIs). Casados explained: “Treating cancer remains a key area of focus for all of global pharma and continues to drive a tremendous amount of development… Many oncology products use HPAPIs and innovators, and their contract development partners have seen an increase in the number of global development projects involving HPAPIs.”
Lonza predicts that advanced formulation and manufacturing techniques for HPAPI compounds will become better understood and integrated earlier in development through 2022, with innovations in capsule materials and engineering being particularly influential. Casados stated: “Manufacturers are addressing the challenges of HPAPI drug delivery and production by integrating new formulation and drug substance processing methods including lipid-based formulations (LBFs) and amorphous solid dispersions (ASDs).
“The need to deliver HPAPI and other complex compounds now under development is contributing to a shift towards encapsulating formulations in hydroxypropyl methylcellulose (HPMC). If an API is sensitive to water and/or formulated as an ASD, HPMC capsules can help control the effects of water relative to the API and formulation stability.”
Flexibility in manufacturing
Lynn Allen, Vice President of Business Development at MedPharm Ltd, explained how the rise of drug development for orphan and rare diseases is impacting the sector, increasing the importance of flexibility in manufacturing. “As drug development becomes more specified in the target indication, so does the patient population. End markets for orphan drugs or drugs that target specific subsets of a patient population reduce the size of a market for a product. This in turn reduces the size of manufactured batch requirements,” she stated. According to Allen, these smaller batch manufacturing requirements “have led many developers to (use) mid-size and small-tier CMOs who have the scale of equipment suited to meet the demands of a smaller patient population.”
Final thoughts
By no means is this article a comprehensive review of all challenges faced by pharma and biopharma in the year to come. In fact, other concerns raised by the industry included the re-opening of EU pharmaceutical legislation this year and the continued use of virtual site inspections by regulators, which we ran out of space to cover here.
The challenges facing pharmaceutical and biopharmaceutical manufacturing in 2022 are varied, from formulation and delivery challenges to skilled labour shortages and shortened timelines. One potential solution for these hurdles is the integration of advanced technologies. According to Casados, such technologies enable drugs to be manufactured more efficiently and compliantly, and at a lower cost: “Pharma is accelerating its digital Industry 4.0 transformation in pursuit of better cGMP [current good manufacturing practice] compliance. The pressure to adopt advanced information and data technologies across the enterprise will not abate and the digitalisation trend will have significant impact on operational expenses and cost-of-goods accounting for years to come… Advanced, automated, data-controlled processes will certainly be part of the industry’s digitally enhanced future.”
References
- GlobalData, 2021. COVID-19: Contract Pharmaceutical Development and Manufacturing Relationships. [online]. Available at:https://store.globaldata.com/report/gdps0038mar--coronavirus-disease-2019-covid-19-vaccines-and-drugs-contract-pharmaceutical-development-and-manufacturing-relationships/
- CPhI, 2021. Pharma Trends 2022. [online] CPhI, pp.6-7, 16. Available at https://www.cphi-online.com/cphi-pharma-trends-2022-report-page000541.html?utm_source=Docu&utm_medium=News%20Page&utm_campaign=PharmaTrends2022 [Accessed 10 January 2022].
- mRNA therapeutics clinical pipeline by therapy area worldwide 2021 | Statista [Internet]. Statista. 2021 [cited 10 January 2022]. Available from: https://www.statista.com/statistics/1262846/clinical-pipeline-of-mrna-therapeutics-by-therapy-area-worldwide/
- Ferreira M, Cabral E, Coroadinha A. Progress and Perspectives in the Development of Lentiviral Vector Producer Cells. Biotechnology Journal [Internet]. 2020 [cited 10 January 2022];16(1):2000017. Available from: https://www.fda.gov/drugs/new-drugs-fda-cders-new-molecular-entities-and-new-therapeutic-biological-products/novel-drug-approvals-2021https://doi.org/10.1002/biot.202000017
- FDA’s Center for Drug Evaluation and Research. Advancing Health Through Innovation: New Drug Therapy Approvals 2021 [Internet]. US Food and Drug Administration (FDA); 2022 pp. 11-12. Available from: https://www.fda.gov/drugs/new-drugs-fda-cders-new-molecular-entities-and-new-therapeutic-biological-products/novel-drug-approvals-2021