Investment performance of the South African biotechnology industry and potential financing models

Thesis (M.M. (Finance & Investment)--University of the Witwatersrand, Faculty of Commerce, Law and Management, Wits Business School, 2016.The biotech sector is highly specialized, with long development time lines, high risk and high investment financing requirement, however with high returns. At a global scale, the USA and Europe are the most important markets, accounting for half of the global biotech patents. In 2012, the USA held 46.6% of the global sales in this sector with the European Union at 28.5%, Japan at 8.4% and BRICS at 3.4%. Much of the growth (29.3%) is however, expected in emerging markets. The South African government has invested an amount of approximately R1 billion in the period from 2003 to 2011 in the Biotechnology start-ups. It is not clear whether a return on this investment has been realized. Thus, the aim of this work is to investigate what is the investment performance of the South African Biotechnology industry, what funding models have been used and suggest models that would be appropriate for Biotechnology start-ups to result in an improved investment performance. The methods applied included reviewing various published journal articles, industry reports and lastly having structured expert interviews with major funders in the South African Biotechnology industry that is, the IDC, TIA, the dti and DST. The findings indicate that when compared to the development markets, the composition of the SA biotechnology sector lags behind in terms of the number of companies that are in existence, publically listed companies, revenue generated by companies in this sector and number of jobs created. It is evident that although government funding and percentage national GDP spend on R&D in this sector is on par with that of India and Brazil, the lack of private sector funding is much more pronounced in South Africa. In addition, the market size, industry revenues and profits generated in SA are much less than those of its emerging market counterparts. Furthermore, in addition to the financing environment that is not broad enough, there are critical structural elements such as the involvement of universities, alliances with large corporates and the role of the stock market in raising capital that need to be addressed. It is thus, suggested that the South African government reviews its current funding models in an effort to realize a return on its investments. Two models are proposed in this work. Firstly, government-private sector matching funds linked to an incubator and secondly, increasing the pool of funds by accessing patient capital and structuring it as VC –type fund. These models have been very successful in yielding returns in other markets and improving the impact of the sector.DH201

Evaluation of the impact of reliance on the regulatory performance in the South African Health Products Regulatory Authority: implications for African regulatory authorities

© 2023 The Author(s). This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY), https://creativecommons.org/licenses/by/4.0/Introduction: The World Health Organization (WHO) advocates the use of reliance practices to enable national regulatory authorities (NRAs) to improve patients’ access to medicines. This study considered whether reliance review translates into swifter medicine authorization. Methods: Abridged review outcomes were examined for New Chemical Entity (NCE) and generic applications to the South African Health Products Regulatory Authority (SAHPRA) in Chemistry, Manufacturing and Controls (CMC) and clinical/bioequivalence (BE), as well as overall NCE authorization times. Results: SAHPRA NCE CMC review time was 91 days (abridged) vs. 179 days (full), applicant response time was 34 vs. 105 days, respectively, and there was a >2-fold time reduction for abridged vs. full CMC review (125 vs. 284 days). There was a 99-day decrease in clinical approval time through an abridged review (230 vs. 329 days) and a decrease in marketing authorization time for NCE abridged assessment (446 vs. 619 days). SAHPRA review time for generic applications was 97 days (abridged) vs. 191 days (full); applicant response time was 26 days (abridged) vs. 81 days (full) and there was a >2-fold time reduction for CMC and BE abridged vs. full review (122 vs. 272 days). Conclusion: These results clearly support World Health Organization recommendations for the use of reliance-based regulatory review to expedite the worldwide availability of safe, effective and needed medications.Peer reviewe

South African Regulatory Authority: The Impact of Reliance on the Review Process Leading to Improved Patient Access

Background: The aims of this study were to compare the overall regulatory review timelines achieved by the South African Health Products Regulatory Authority (SAHPRA) in 2020 to the timelines historically achieved by the Medicines Control Council (MCC). This study also aimed to evaluate the regulatory review processes and the good review practices that have been implemented by SAHPRA to support the assessment of new chemical entities and generic product applications for market authorization in the business-as-usual and backlog process streams. Methods: A questionnaire was completed and verified by SAHPRA to describe the structure of the organization, the resources available, the process for regulatory review of new chemical entities and generic products and the level of implementation of good review practices and regulatory decision-making practices for market authorization. Data were collected and analyzed on the overall approval timelines for new chemical entities and generic products registered by SAHPRA in 2020 in the business-as-usual and backlog process streams. Results: A full, independent scientific review was conducted for all new chemical entities and generic product applications in the business-as-usual stream. Facilitated regulatory pathways were introduced for the review of new chemical entities and generic products in the backlog stream. As a result, the timelines for approval of applications in the backlog stream were 68% quicker for both new chemical entities and generics, using facilitated regulatory pathways, such as abridged and verification review models. Conclusion: The comparisons made through this study provided insight into the improvements that have been made through the establishment of SAHPRA and the transition in 2018 from the MCC. The re-engineered processes that have been developed and implemented by SAHPRA to address the backlog in the review of the applications for market authorization have demonstrated a decrease in the overall median approval times. The expansion of these processes into the routine review of medical products will contribute to the enhanced regulatory performance of SAHPRA and patients’ access to new medicines.Peer reviewe

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Preclinical assessment of 68Ga‐PSMA‐617 entrapped in a microemulsion delivery system for applications in prostate cancer PET/CT imaging

Please read abstract in the article.NTeMBI, Grant/Award Number: N/A; Carl and Emily Fuchs Foundationhttp://wileyonlinelibrary.com/journal/jlcr2020-06-15hj2020Nuclear Medicin

Spray-Dried, Nanoencapsulated, Multi-Drug Anti-Tuberculosis Therapy Aimed at OnceWeekly Administration for the Duration of Treatment

Research Article published by MDPIAiming to improve the treatment outcomes of current daily tuberculosis (TB) chemotherapy over several months, we investigated whether nanoencapsulation of existing drugs would allow decreasing the treatment frequency to weekly, thereby ultimately improving patient compliance. Nanoencapsulation of three first-line anti-TB drugs was achieved by a unique, scalable spray-drying technology forming free-flowing powders in the nanometer range with encapsulation e ciencies of 82, 75, and 62% respectively for rifampicin, pyrazinamide, and isoniazid. In a pre-clinical study on TB infected mice, we demonstrate that the encapsulated drugs, administered once weekly for nine weeks, showed comparable e cacy to daily treatment with free drugs over the same experimental period. Both treatment approaches had equivalent outcomes for resolution of inflammation associated with the infection of lungs and spleens. These results demonstrate how scalable technology could be used to manufacture nanoencapsulated drugs. The formulations may be used to reduce the oral dose frequency from daily to once weekly in order to treat uncomplicated TB

In vivo/in vitro pharmacokinetic and pharmacodynamic study of spray-dried poly-(dl-lactic-co-glycolic) acid nanoparticles encapsulating rifampicin and isoniazid.

Research Article published by Elsevier B.V.Poly-(dl-lactic-co-glycolic) acid (PLGA) nanoparticles were prepared by a double emulsion solvent evaporation spray-drying technique and coated with polyethylene glycol (PEG 1% v/v). The PLGA nanoparticles had a small size (229±7.6 to 382±23.9nm), uniform size distribution and positive zeta potential (+12.45±4.53mV). In vitro/in vivo assays were performed to evaluate the pharmacokinetic (PK) and pharmacodynamic (PD) performance of these nanoparticles following nanoencapsulation of the anti-tuberculosis drugs rifampicin (RIF) and isoniazid (INH). The results demonstrated the potential for the reduction in protein binding of these drugs by protection in the polymer core. Furthermore, in vitro efficacy was demonstrated using Mycobacterium tuberculosis (M. tb.) (strain H37Rv). Sustained drug release over seven days were observed for these drugs following once-off oral administration in mice with subsequent drug distribution of up to 10 days in the liver and lungs for RIF and INH, respectively. It was concluded by these studies combined with our previous reports that spray-dried PLGA nanoparticles demonstrate potential for the improvement of tuberculosis chemotherapy by nanoencapsulation of anti-tuberculosis drugs

Mycolic acids, a promising mycobacterial ligand for targeting of nanoencapsulated drugs in tuberculosis

Research Article published by ElsevierThe appearance of drug-resistant strains of Mycobacterium tuberculosis (Mtb) poses a great challenge to the development of novel treatment programmes to combat tuberculosis. Since innovative nanotechnologiesmight alleviate the limitations of current therapies, we have designed a new nanoformulation for use as an anti-TB drug delivery system. It consists of incorporating mycobacterial cellwallmycolic acids (MA) as targeting ligands into a drug-encapsulating Poly DL-lactic-co-glycolic acid polymer (PLGA), via a double emulsion solvent evaporation technique. Bonemarrow-derivedmousemacrophages, either uninfected or infectedwith differentmycobacterial strains (Mycobacterium avium, Mycobacterium bovis BCG or Mtb), were exposed to encapsulated isoniazid-PLGA nanoparticles (NPs) using MA as a targeting ligand. The fate of the NPs was monitored by electron microscopy. Our study showed that i) the inclusion of MA in the nanoformulations resulted in their expression on the outer surface and a significant increase in phagocytic uptake of the NPs; ii) nanoparticle-containing phagosomes were rapidly processed into phagolysosomes, whether MA had been included or not; and iii) nanoparticlecontaining phagolysosomes did not fuse with non-matured mycobacterium-containing phagosomes, but fusion events with mycobacterium-containing phagolysosomes were clearly observed