PHARMACY MANUFACTURE AND QUALITY CONTROL OF MEDICINAL PREPARATIONS ABROAD

The purpose of this work was to study foreign experience in pharmacy manufacture and quality control of medicinal preparations (MP). Scientific literature and internet sources analysis, the author's own observations from 2005 to 2020 were made. It has been established that pharmacy manufacture of MPs abroad is carried out for the special needs of patients when pharmaceutical industry cannot produce them for various reasons. There are various approaches to standardization of the number of manufacturing pharmacies abroad: from complete prohibition of pharmacy manufacture of medicinal preparations in Portugal to mandatory license requirement in Austria and Germany. To manufacture medicinal preparations at a pharmacy the laboratory is established where necessary equipment, inventory, pharmaceutical substances and excipients are placed and the technological process is carried out. Pharmacy manufacture of sterile medicinal preparations is conducted under aseptic conditions in a specially equipped room or in a laminar-airflow cabinet. MPs must not be registered in most countries of the world. In the US and the European Union (EU) medicinal preparations are classified into medicines for immediate use and for prolonged storage. Expiration date must be stated for prolonged storage medicinal preparations, a dossier is made for them in the EU pharmacies. Pharmacies in most countries of the world manufacture medicinal preparations from tablets and capsules. Much attention abroad is given to ensure the quality of pharmacy manufacture of medicinal preparations: in the US, pharmacy manufacture of medicinal preparations is carried out in accordance with the requirements of Pharmacopoeia, in the EU according to the EU Council Resolution. A number of countries have developed guidelines or standard operational procedures for pharmacy manufacture of medicinal preparations. Constant training and assessment of employees’ competencies engaged in pharmacy manufacture of medicinal preparations is performed.

“In the Exercise of a Sound Discretion, Who, of This Class of Persons, Shall Have a Right to the License…”: Family, Race, and Firearms in Antebellum North Carolina

In 1841, North Carolina passed a law requiring free black people to acquire firearm licenses from their county court. This essay argues that the license requirement forced free black people to rely on their families’ support to access firearms, which sits contrary to the “individual right” framework that firearms are often viewed through. Family members helped free black people to construct racial identities, highlight trustworthiness, connect individuals to patrons and professional networks, and manage legal fees, all in pursuit of firearm access. This essay contributes to our understanding of antebellum black families and their connections to their broader interracial communities.

Occupational Licensure and Entrepreneurs: The Case of Tax Preparers in the United States

The authors examine the relationship between entrepreneurship and occupational licensure using data on the universe of more than 700,000 tax preparers in the United States. Prior research suggests that occupational licensure has negative effects on entrepreneurship because it increases the costs of operating a business. By contrast, the authors argue that licensure may allow entrepreneurs to signal quality and enhance their legitimacy. States that require tax preparers to be licensed have higher average rates of entrepreneurship—approximated by tax practice ownership—and, in high-income ZIP codes, more demand for paid preparer services. In the analysis of the introduction of a federal license requirement in tax preparation in 2013, voluntary early adoption of the license by preparers predicts higher chances of survival in the industry. Entrepreneurs are less likely to adopt the license early than are non-entrepreneurs, unless they lack other state-level credentials. Results thus suggest that licensure represents a trade-off for entrepreneurs between the costs of obtaining a license and the benefits of signaling quality and legitimacy.

Leveraging Elsevier’s Creative Commons License Requirement to Undermine Embargo

In the last round of author-sharing policy revisions, Elsevier created a labyrinthine title-by-title embargo structure requiring embargoes from 12 to 48 months for authors sharing via institutional repository (IR), while permitting immediate sharing via an author’s personal website or blog. At the same time, all prepublication versions are to bear a Creative Commons-Attribution-Noncommercial-No Derivatives (CC-BY-NC-ND) license. At the time this policy was announced, it was criticized by many in the scholarly communication community as overly complicated and restrictive. However, this CC licensing requirement creates an avenue for subverting an embargo in the IR to achieve quicker and wider open distribution of the author’s accepted manuscript (AAM). To wit, authors may post an appropriately licensed copy on their personal site or blog, at which point the author’s host institution may deposit without an embargo in the IR, not through the license granted in the publication agreement, but through the CC license on the author’s version, which the sharing policy mandates. This article outlines the background and rationale of the issue and discusses the benefits, workflows, and remaining questions.

Exploiting Elsevier's CC License Requirement to Subvert Embargo

In the last round of author sharing policy revisions, Elsevier created a labyrinthine title-by-title embargo structure requiring embargoes from 12-48 months for author sharing via institutional repository (IR), while permitting immediate sharing via author's personal website or blog. At the same time, all pre-publication versions are to bear a Creative Commons-Attribution-Noncommercial-No Derivatives (CC-BY-NC-ND) license. At the time this policy was announced, it was rightly criticized by many in the scholarly communication community as overly complicated and unnecessary. However, this CC licensing requirement creates an avenue for subverting the embargo in the IR to achieve quicker open distribution of the author's accepted manuscript. In short, authors may post an appropriately licensed copy on their personal site, at which point we may deposit without embargo in the IR, not through the license granted in the publication agreement, but through the CC license on the author's version, which the sharing policy mandates. This poster outlines this issue, our experimentation with application, and engages viewers in questions regarding its potential risks, benefits, and workflows.For more information, including supplementary notes, see http://hdl.handle.net/1808/24107 .

Epidermal growth factor receptor (EGFR) as a predictive and prognostic marker in patients with advanced colorectal cancer (aCRC): The MRC COIN trial experience.

359 Background: KRAS mutation has been shown to be a more effective (though negative) biomarker for selection of patients for EGFR targeted therapy in aCRC. However, positive EGFR immunohistochemistry (IHC) remains a license requirement and was an inclusion criterion in most trials to date. The MRC COIN trial recruited 2445 pts into 3 arms of oxaliplatin + fluoropyrimidine +/- cetuximab without prior EGFR assessment. This trial provides a unique opportunity to definitively examine the role of EGFR IHC as prognostic and predictive marker and potentially the evidence required to remove this assessment from the license for this drug. Methods: Formalin-fixed paraffin embedded (FFPE) tissue was stained retrospectively for EGFR using Dako kit in a national reference lab. Results were assessed by 3 reviewers (BJ, SS, RA) using digital imaging software in a blinded fashion, then by BJ/SS providing consensus for discrepancies. EGFR scoring was assessed as a prognostic variable in association with selected patient, tumor and biochemical data. Cut off points examined for +ve vs -ve tumours, in terms of total tumour cells demonstrating membrane staining, were: 0% vs >0%; <10% vs ≥10%; <20% vs ≥20%. Results: EGFR IHC was adequately assessed for 1621 pts (66% of randomised), 22% were negative (0%) and 78% positive (>0%), balanced across arms. EGFR was not prognostic for PFS within KRAS wt pts at the standardized cut off point 0% vs >0% HR=1.11 95% CI 0.91-1.36 p=0.31 but was at <10% vs ≥10% (HR=1.27 95% CI 1.07-1.52 p=0.008) this was robust to other prognostic variables. No effect was seen for overall response or survival. There was no prognostic effect for the KRAS mutant group. In the 1065 assessable pts randomised to +/- cetuximab, no evidence of EGFR IHC as a predictive marker for response or survival outcomes was observed for the addition of cetuximab to chemotherapy (OS HR=1.11 95% CI 0.70-1.75 p=0.66; PFS HR=0.95 95% CI 0.64-1.43 p=0.82). Conclusions: Extensive assessment of samples from this trial suggest a role for EGFR IHC as a prognostic marker in KRAS wt aCRC but refute the predictive value embedded within the licence for cetuximab used in combination with chemo in first-line therapy. [Table: see text]