Point-of-Care Manufacture: Regulatory Opportunities and Challenges for Advanced Biotherapeutics

On 29 June 2021, UCL’s Future Targeted Healthcare Manufacturing Hub (FTHMH) held an online workshop to discuss the concepts and rationale of a new point-of-care (POC) manufacturing regulatory framework in development by the UK’s Medicines and Healthcare products Regulatory Agency (MHRA). The proposal, which seeks to address the unique challenges of manufacturing healthcare products at, (or close to), the POC, is anticipated for publication and public consultation in summer 2021

The UK’s emerging regulatory framework for point-of-care manufacture: insights from a workshop on advanced therapies

Point-of-care (POC) manufacture can be defined as the production of therapies in clinical settings or units close to hospitals and patients. This approach is becoming increasingly via- ble due to the emergence of flexible manufacturing technologies. Expecting an increase in this kind of production, the UK’s regulatory agency, the Medicines and Healthcare products Regulatory Agency (MHRA) is proposing a regulatory framework specifically designed for POC manufacture. To discuss the challenges of POC manufacture and the MHRA’s pro- posal, the EPSRC Future Targeted Healthcare Manufacturing Hub (FTHMH) organized a workshop drawing insights from specialists in cell and gene therapy manufacture. Through presentations and discussion roundtables, the workshop highlighted the challenges for the UK and other countries implementing POC manufacture. The workshop attendees stressed four main issues: quality control; standardization and equipment use; availability of qualified personnel; and the challenges to be met by hospitals participating in POC manufacture systems. This commentary provides a summary of the points discussed in this workshop

A Bichromatic Incidence Bound and an Application

We prove a new, tight upper bound on the number of incidences between points and hyperplanes in Euclidean d-space. Given n points, of which k are colored red, there are O_d(m^{2/3}k^{2/3}n^{(d-2)/3} + kn^{d-2} + m) incidences between the k red points and m hyperplanes spanned by all n points provided that m = \Omega(n^{d-2}). For the monochromatic case k = n, this was proved by Agarwal and Aronov. We use this incidence bound to prove that a set of n points, no more than n-k of which lie on any plane or two lines, spans \Omega(nk^2) planes. We also provide an infinite family of counterexamples to a conjecture of Purdy's on the number of hyperplanes spanned by a set of points in dimensions higher than 3, and present new conjectures not subject to the counterexample.Comment: 12 page

Simultaneous Embeddings with Few Bends and Crossings

A simultaneous embedding with fixed edges (SEFE) of two planar graphs $R$ and $B$ is a pair of plane drawings of $R$ and $B$ that coincide when restricted to the common vertices and edges of $R$ and $B$. We show that whenever $R$ and $B$ admit a SEFE, they also admit a SEFE in which every edge is a polygonal curve with few bends and every pair of edges has few crossings. Specifically: (1) if $R$ and $B$ are trees then one bend per edge and four crossings per edge pair suffice (and one bend per edge is sometimes necessary), (2) if $R$ is a planar graph and $B$ is a tree then six bends per edge and eight crossings per edge pair suffice, and (3) if $R$ and $B$ are planar graphs then six bends per edge and sixteen crossings per edge pair suffice. Our results improve on a paper by Grilli et al. (GD'14), which proves that nine bends per edge suffice, and on a paper by Chan et al. (GD'14), which proves that twenty-four crossings per edge pair suffice.Comment: Full version of the paper "Simultaneous Embeddings with Few Bends and Crossings" accepted at GD '1

On the Number of Facets of Three-Dimensional Dirichlet Stereohedra III: Full Cubic Groups

We are interested in the maximum possible number of facets that Dirichlet stereohedra for three-dimensional crystallographic groups can have. The problem for non-cubic groups was studied in previous papers by D. Bochis and the second author (Discrete Comput. Geom. 25:3 (2001), 419-444, and Beitr. Algebra Geom., 47:1 (2006), 89-120). This paper deals with ''full'' cubic groups, while ''quarter'' cubic groups are left for a subsequent paper. Here, ''full'' and ''quarter'' refers to the recent classification of three-dimensional crystallographic groups by Conway, Delgado-Friedrichs, Huson and Thurston (math.MG/9911185, Beitr. Algebra Geom. 42.2 (2001), 475-507). Our main result in this paper is that Dirichlet stereohedra for any of the 27 full groups cannot have more than 25 facets. We also find stereohedra with 17 facets for one of these groups.Comment: 28 pages, 12 figures. Changes from v1: apart of some editing (mostly at the end of the introduction) and addition of references, an appendix has been added, which analyzes the case where the base point does not have trivial stabilize

Mortality Measurement Matters: Improving Data Collection and Estimation Methods for Child and Adult Mortality

Colin Mathers and Ties Boerma discuss three research articles in PLoS Medicine that address the measurement and analysis of child and adult mortality data collected through death registration, censuses, and household surveys