The safety of biological preparations. Part 2. Safety issues of biosimilars
Bibliographic record
Abstract
The use of the reduced scheme in preclinical and clinical studies of «biosimilars» requires special attention to the safety issues. During the process of the marketing authorization of biosimilars in 2013-2015 the countries with advanced regulatory and pharmacovigilance systems (USA, Canada and EU countries), the most contentious debates were provoked by the issues of extrapolation of the results of the research of a biosimilar infliximab (TNFα-specific monoclonal antibodies). EMA made the decision that the results of the efficacy and safety studies of infliximab, obtained in adult patients with rheumatoid disease, can be extrapolated to the indications for the treatment of inflammatory bowel disease (Crohn’s disease and ulcerative colitis in adults and in children). Several medical associations such as the Association of Gastroenterologists and the Association of Pediatricians believe that this extrapolation is not justified. Health Canada also made a conclusion that the extrapolation is not justified and did not approve the use of the mentioned preparation for the treatment of Crohn’s disease and ulcerative colitis. There is still an ongoing hot discussion on the issue of interchangeability of an original medicine and a biosimilar. Given that the safety of a biosimilar has been studied before obtaining marketing authorization not to the fullest extent, usually safety studies continue after obtaining marketing authorization for a few more years. If there is an interchange of medicines, then it is not possible to objectively evaluate the safety of a biosimilar. In the countries with poor regulatory and pharmacovigilance system not only «biosimilars» are in drug circulation system, but also other medicines registered under the reduced studies scheme, but not in full compliance with the principles of «biosimilarity». The quality of these medicines does not always meet the standards, as evidenced by numerous studies. WHO is concerned about the quality of the mentioned medicines and suggests to call them «non-innovators» and establish a separate group, and claimed that the sponsors were invited for a certain period of time to provide the evidence of the high quality of these medicines.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.014 | 0.017 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.002 |
| Bibliometrics | 0.002 | 0.001 |
| Science and technology studies | 0.001 | 0.008 |
| Scholarly communication | 0.005 | 0.004 |
| Open science | 0.002 | 0.003 |
| Research integrity | 0.011 | 0.009 |
| Insufficient payload (model declined to judge) | 0.007 | 0.004 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".