4.1. Literature Review: The PRISMA Method

The PRISMA method (Preferred Reporting Items for Systematic Reviews and Meta-Analysis), chosen for the analysis of the literature referenced in this publication, is a systematic, explicit, replicable methodology for the identification, selection and evaluation of articles relevant to the research topic and the collection of data from the studies included in the review. The process, carefully stated in the guidelines, follows a four-step diagram that uses a funnel system to help researchers optimize the reporting system and select relevant publications for study [73]. The steps carried out are shown schematically in Figure 11. This type of approach therefore minimizes bias, thus providing reliable results from which to draw conclusions [74].

PRISMA Flow Diagram. Schematic view of the diagram followed when applying the PRISMA method with the number of items selected for each step [73].

In order to diversify the publications found as much as possible, three different databases were selected for the initial search: Pubmed, Scopus and ScienceDirect. Scopus is the most comprehensive citation and abstract database which, with over 25,000 titles in both journals and books, provides a comprehensive view of world research, not only in science, technology and medicine, but also in the humanities, arts and social sciences [75]. On the other hand, ScienceDirect is dedicated to scientific and medical research. It therefore constitutes a less extensive but equally valid repository, enabling access to 2500 scientific journals, many of which are open access, and 39,000 books [76]. Finally, the selection of contributions in food and pharmaceutical fields is supported by Pubmed. This database includes more than 30 million citations, primarily in the medical and related fields such as biological sciences, behavioral sciences, and biomedical engineering [77]. The use of repositories that allow access to articles on marine biotechnology with different but comparable criteria has therefore led to the collection of a broad spectrum of sources in a uniform, easily replicable manner.

The keywords used as search terms were a combination of the terms “drugs”, “food”, “pharmaceutical application” or “nutraceutical application” with the term “marine biotechnology” or the variant “blue biotechnology”. The search focused on the literature produced (articles, reviews, book chapters) from 2010 to April 2020, identified by the occurrence of keywords in the title or abstract, and keywords chosen by the authors of the publication or used by the system to catalogue articles in the database.

Following an initial screening, 1883 publications were identified, including 481 in Pubmed, 1232 in Scopus and 170 in ScienceDirect, as shown in Table 6.

Articles initially selected for each search term from each database.

The articles selected were screened according to the funnel approach recommended by the PRISMA method.

The removal of duplicates, i.e., identical articles taken from different databases or with different search terms, led to a total number of 1258 articles, which were subjected to further selection as a result of

The next step consisted of a first-level of screening based on a rapid reading of the title and abstract of the articles. This highlighted 560 non-relevant publications that were mainly concerned with applications other than those of the research topic or made no reference to the marine environment. Some were also eliminated because they referred to another topic altogether: for example, the term “blue” led to the identification of a number of articles that referred to the use methylene blue or other blue reagents for experimental use but were actually focused on a totally different field and could not be considered relevant to the objective of this analysis. However, the search term “blue” still had to be included, because it enabled the selection of significant articles that would never have been found using the variant “marine”.

The 702 articles obtained from these first steps were then read more thoroughly, and a further 78 publications were discarded. There were a number of reasons for this elimination, but they were mainly related to the articles being too general in terms of the source, with no recognizable precise focus on the marine environment, or a lack of application for the organisms described and analyzed in the article. Albeit to a lesser extent, other articles were discarded, in spite of the initial filter, for the following reasons: the text was not written in English; the main application on which the article focused was neither pharmaceutical nor food, or was not biotechnological; the type of publication was different from those selected; the publication, especially in the case of book chapters, was a simple, very general presentation of marine biotechnologies and was not useful for understanding the progress of the research. Table 7 shows the number of articles discarded for each reason.

Articles discarded in the second screening phase for each reason.

The funnel screening process resulted in the selection of 620 publications for inclusion in a qualitative and quantitative analysis.

More specifically, from a quantitative point of view, we chose to make a temporal assessment, dividing the articles according to the year of publication, and a geographical assessment, analyzing the origin of the first author. We also decided to rank the journals according to which had published the most on the topic in question.

On the other hand, the qualitative analysis highlighted, for each article selected, the organization used to obtain a given product or to which the application was addressed, and the analysis or production technique used. The publications were also divided into three categories according to the problems faced by the sector that the stated technologies and products were aiming to resolve: the discovery of new products, increasing yields and large-volume production, and sustainability.

Taken as a whole, this data gives a detailed picture of the state of research in marine biotechnology for pharmaceutical and food applications, making it possible to identify both established and innovative technologies to overcome the main challenges faced by the sector.