Examination of the regulatory frameworks applicable to biologic drugs (including stem cells and their progeny) in Europe, the U.S., and Australia: part II--a method of software documentary analysis

Abstract

A wide range of regulatory standards applicable to production and use of tissues, cells, and other biologics (or biologicals), as advanced therapies, indicates considerable interest in the regulation of these products. The objective of this study was to analyze and compare high-tier documents within the Australian, European, and U.S. biologic drug regulatory environments using qualitative methodology. Eighteen high-tier documents from the European Medicines Agency (EMA), U.S. Food and Drug Administration (FDA), and Therapeutic Goods Administration (TGA) regulatory frameworks were subject to automated text analysis. Selected documents were consistent with the legal requirements for manufacturing and use of biologic drugs in humans and fall into six different categories. Concepts, themes, and their co-occurrence were identified and compared. The most frequent concepts in TGA, FDA, and EMA frameworks were "biological," "product," and "medicinal," respectively. This was consistent with the previous manual terminology search. Good Manufacturing Practice documents, across frameworks, identified "quality" and "appropriate" as main concepts, whereas in Good Clinical Practice (GCP) documents it was "clinical," followed by "trial," "subjects," "sponsor," and "data." GCP documents displayed considerably higher concordance between different regulatory frameworks, as demonstrated by a smaller number of concepts, similar size, and similar distance between them. Although high-tier documents often use different terminology, they share concepts and themes. This paper may be a modest contribution to the recognition of similarities and differences between analyzed regulatory documents. It may also fill the literature gap and provide some foundation for future comparative research of biologic drug regulations on a global level.

Figure 1.

Concept maps. (A–C): Concepts identified in individual regulatory frameworks' documents: European Medicines Agency documents (A), FDA documents (B), and TGA documents (C). (D–F): Concepts identified in documents across regulatory frameworks: Good Manufacturing Practice (GMP) (1) documents (D), GMP (2) documents (E), and Good Clinical Practice documents (F). For a list of the specific documents in each group, see Table 1. Abbreviations: API, Active Pharmaceutical Ingredients; CFR, Code of Federal Regulations; FDA, Food and Drug Administration; FR, Federal Regulations; TGA, Therapeutic Goods Administration.

Figure 2.

Concept clouds and themes. (A–C): Concept clouds identified by the software in documents across regulatory frameworks: Good Manufacturing Practice (GMP) (1) documents (A), GMP (2) documents (B), and Good Clinical Practice (GCP) documents (C). (D–F): Concept clouds identified in individual regulatory frameworks' documents (D, E) and overlay of themes (F) identified by the software across regulatory frameworks in GCP documents: European Medicines Agency documents (D), TGA documents (E), and GCP documents related concepts and themes (overlay of words is a reflection of the concepts' closeness) (F). For a list of the specific documents in each group, see Table 1. Abbreviations: API, Active Pharmaceutical Ingredients; ARTG, Australian Register of Therapeutic Goods; EC, Ethics Committee; IEC, Institutional (Independent) Ethics Committee; IRB, Institutional Review Board; TGA, Therapeutic Goods Administration.

Figure 3.

Correlation of concepts across data corpus. Pairs of concepts correlation (co-occurrence) identified by the software across the entire data corpus for the Food and Drug Administration documents (A), Therapeutic Goods Administration documents (B), European Medicines Agency (C), Good Manufacturing Practice (GMP) (1) (D) and GMP (2) documents (E), and Good Clinical Practice document analysis (F). Colored slices on the graph present relative frequencies of the key co-occurring concepts. For a list of the specific documents in each group, see Table 1. Abbreviations: API, Active Pharmaceutical Ingredients; FR, Federal Regulations; IEC, Institutional Ethics Committee; TGA, Therapeutic Goods Administration.

Figure 4.

Most frequent themes and concepts. Most frequent themes and their concepts identified by the software in FDA documents (overlay of words is a reflection of concepts' closeness) (A), European Medicines Agency documents (B), and Therapeutic Goods Administration documents (presented here as an example of a strong contextual similarity) (C). For a list of the specific documents in each group, see Table 1. Abbreviations: ARTG, Australian Register of Therapeutic Goods; CFR, Code of Federal Regulations; FDA, Food and Drug Administration; HCT, human cell and tissues.