Pharmaceuticals: Regulatory Affairs
some cases additional data may be required to complete the risk assessment.
Materials vs Component Testing Historically, many component suppliers have referenced USP <661> for non-specific physicochemical testing of plastic resins or components but this is now largely considered outdated. The USP <661> chapter was revised with emphasis on resin characterization and container closure requirements, but the March 1, 2019 <665>chapter still emphasized that plastic resins used in the manufacture of components should first be tested per the resins testing requirements described in <661.1>.
Given substantial feedback that this may increase the testing burden on a large number of already qualified components, USP made the decision to decouple the materials testing requirements for the 2020 <665> chapter, keeping the focus and requirements solely on component testing.
For the high pH solvent, USP continues to standardize on pH 10 as a reasonable typical worst-case pH, whereas BioPhorum continues to require a 0.5 N NaOH (~pH 13.5) solvent. USP does allow for the use of 0.1 N NaOH, but only for cases where the drug manufacturing process fluid exceeds pH 10, meaning that in most cases, a pH 10 solvent profile will be expected for high-risk components. The rationale for the USP pH 10 requirement was that (i) pH 10 would cover most pharmaceutical applications where the process fluid could lead to leachables that persist in the process stream, (ii) limited data suggested that 0.5N NaOH (pH ~13.5) may lead to considerably different or worse profiles than pH 10, and (iii) that a standard requirement for pH compatibility at pH ~13.5 could disadvantage innovative new plastics that would be perfectly suited for most
Given substantial feedback that this may increase the testing burden on a large number of already qualified components, USP made the decision to decouple the materials testing requirements for the 2020 <665> chapter, keeping the focus and requirements solely on component testing
useful solvent to simplify many risk assessments. Hence many suppliers, such as Pall Biotech, will provide water extractables profiles for high-value components to simplify component risk assessment and qualification.
Silicone and elastomeric materials
BioPhorum guidance generally applies to all fluid-contact, polymeric materials in single-use bioprocess components, including elastomeric materials.
pharmaceutical applications at pH less than or equal to 10. Component manufacturers adopting the full BioPhorum protocol can expect to see a pH 10 dataset to satisfy the USP requirements in addition to the BioPhorum pH 10 solvent where these are compatible.
Water extraction profiles
Water extraction profiles are not a requirement for USP <665> but continue to be a requirement per BioPhorum.
USP is designed to identify the minimum solvent portfolio that covers a broad range of applications, and argues that extractables compounds are adequately profiled through polar extraction of a low and high pH extraction solution, making an additional requirement for a polar extractables profile in relatively neutral water largely redundant. BioPhorum, in contrast,
conducted a limited-scope review of chromatographic peak data shared by suppliers in 2019, and was unable to reach a conclusion that water profiles were redundant. In addition, the group felt that water profiles provided a highly
Although silicone and elastomeric materials are generally amenable to the characterization testing prescribed by USP <665>, they are not directly within scope of the chapter on ‘plastic’ components. USP has historically considered elastomers in the context of those used for injectables (chapter <381>) and is conscious to avoid conflicting chapters on the same materials. It is, however, expected that USP will focus on developing standards for silicone components in its 2020-2025 cycle.
Achieving bioprocess success Every bioprocess requires a great deal of planning and documentation. Regardless of whether an end user chooses to implement traditional or single- use technologies or systems, the end user takes on a great deal of responsibility in creating the process chain, and it is imperative to ensure that the chosen components (and ultimately, systems) have been reviewed for integrity and meet the needs of the process for the life of the process. Over time, suppliers have taken greater ownership of this responsibility by generating valuable, actionable data that aligns with the latest best practices and standards. As a supplier committed to supporting standards that enhance transparency and streamline the risk assessment process, Pall Biotech has created an online Regulatory Portal(https:// www.pall.co
regulatory). This free reference is actively updated to offer valuable information to industry members in addition to actively engaging with other suppliers and industry partners to collate comprehensive data and make it available to industry. When suppliers take part in these efforts, it becomes easier for end users to ensure the integrity of the components and systems that play such a pivotal role in process success.
REFERENCES 1. BioPlan Associates, Inc., “Report and Survey of Biopharmaceutical Manufacturing Capacity and Production”, 2020.
2. W. Ding, G. Madsen, E. Mahajan, S. O’Connor and K. Wong, “Standarddized Extractables Testing Protocol for Single- Use Systems in Biomanufacturing”, Pharmaceutical Engineering (ISPE), 2014.
3. United States Pharmacopoeia Forum, “Plastic Materials, Components, and Systems Used in the Manufacturing of Pharmaceutical Drug Products and Biopharmaceutical Drug Substances and Products” (PF) 44 (3), 2019, and United States Pharmacopoeia Forum” <665> Plastic Materials, Components, and Systems Used in the Manufacturing of Pharmaceutical Drug Products and Biopharmaceutical Drug Substances and Products” (PF) 46 (5), 2020.
4. B. Scott, G. Madsen, S. Ullsten, G. Dale, P. Wang, K. Wong, and J. Hathcock, “BioPhorum Best Practices Guide for Extractables Testing of Polymeric Single-Use Components Used in Biopharmaceutical Manufacturing” BioPhorum, 2020.
5. S. Ullsten, H. Hong, J. Hathcock, F. Sexton, C. Worsoe, K. Wong and S. K. Mohanvelu, “Biopharm Asia, Inc.,” 11 June 2020. [Online]. Available: https://biopharma-asia. com/webinars/final-revised-version- of-biophorum-extractable-testing- recommendation-part-2/.
6. BioPhorum, “BioPhorum Extractables Portal”, [Online]. Available: https://www. biophorum.co
m/. [Accessed 30-Aug- 2020].
7. P. Biotech. [Online]. Available: file:///C:/ Users/bwill/Downloads/SME_E_n_L%20_ RPSCEL_01_Rev_1.2_27Nov2019_ FINAL.pdf
James Hathcock, PhD Senior Director of The Regulatory and Validation Consulting Team Pall Corporation E: email@example.com
m W: www.pall.co
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