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Browsing by study line "Teollisuusfarmasia"

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  • Sinnemaa, Olivia (2022)
    The package leaflet (PL) is a technical document sheet included in medicine packages to provide guidance on safety and rational use of medicines for the user. The EU is increasingly encouraging the adoption of digital product information, which in time should be seen as the basic medicine information. The outdated package leaflet has for a long time been criticized by both patients and pharmaceutical operators. As a result, it is important to map the perspectives of various pharmaceutical operators on the electronic package leaflet. The aim of the study was to gain broader knowledge and deeper understanding of what opportunities and challenges the electronic package leaflet entails from the perspective of different pharmaceutical operators, and whether there are differences between opinions of the pharmaceutical operators. The study also sought to find out how the electronic package leaflet compared with the printed current leaflet from an environmental perspective. The study was conducted as a questionnaire e-survey, whose target groups were companies in the pharmaceutical industry, The Finnish Medical Agency (Fimea) and hospital pharmacies / departmental pharmacists. The material was collected over a three-week period in April 2022. The data was analysed both quantitatively and qualitatively. Based on the results of the study, it emerged that 55 experts, broadly across the pharmaceutical field, took part in the study. According to the pharmaceutical operators, the main opportunities of the electronic package leaflet were its ease of use and environmental friendliness. Patient safety, which is always a focal point when discussing medicines, would also increase as the users would have access to the most up-to-date medicine information (75 %, n = 41). In addition, the QR code on the medicine packages could be utilized when introducing ePL. The challenges, however, mainly concerned the user's lack of internet connectivity and incompetence in the use of e-services. Although pharmaceutical operators are of different opinion on the electronic package leaflet, it is highlighted that the majority of respondents (69 %, n = 38) believe that ePL would be an improvement and a more environmentally friendly alternative than the current printed leaflet. The study shown that there are differences in the perspectives on ePL between different pharmaceutical operators. The varying opinions on the electronic package leaflet depends on the respondent's position in the pharmaceutical sector. Despite the disagreement, the majority believe that ePL would be a positive development and a prerequisite for achieving the challenges of the future.
  • Jansson, Teresa (2019)
    Conditional reimbursement was introduced in Finland in January 2017 as a temporary addition in the Finnish Health Insurance Act. An agreement can be made between a marketing authorisation holder (MAH) and the Pharmaceuticals Pricing Board. Conditional reimbursement status can be allowed for a medicinal product if the drug is addressing unmet medical need and there are uncertainties associated to the medicinal product considering i.e. therapeutic value or cost-effectiveness, when traditional reimbursement procedures are not suitable. Risk-sharing is an essential part of the agreements and the results are monitored. Types of agreements are divided into financial- and performance-based agreements. Conditional reimbursement in Finland has not yet been studied in a large extent since its introduction. The aim of this study was to create an overview of the medicinal products with conditional reimbursement in Finland, how the unmet medical need is addressed, and which treatment options are available. Also, benefits and risks of the different stakeholders of risk-sharing agreements (RSA), why these agreements are worth to implement, earlier experiences from the European Economic Area (EEA) countries and what pharmaceutical companies should consider prior to negotiations were investigated. A document analysis was performed for investigating the medicinal products with conditional reimbursement status in Finland. A systematic literature review was conducted for collecting information and earlier experiences of RSAs and managed entry agreements (MEA) in the EEA-countries. On February 1st, 2019 there was 19 medicinal products with conditional reimbursement in Finland. These drugs are successfully addressing unmet medical need. All stakeholders of RSAs encounter benefits and risks of these agreements but the MAH is the one carrying the largest responsibilities and risks. Risk-sharing agreements gained in popularity since the early 2000s in the EEA-countries. There is no golden standard for types of agreements made but MEAs are enshrined in legislation in most countries. The pharmaceutical company should as early as possible start shaping details and collect information of the product for which conditional reimbursement will be proposed to. Negotiations might be challenging, but the aim is an agreement in which both the MAH and the payer are content with. Finland is following a similar trend as other EEA-countries, since most of the medicinal products with conditional reimbursement are oncology medicines. The use of the drugs has been limited through reimbursement number codes for certain patients who are most likely to benefit from the treatment. Rationales for introducing RSAs in EEA-countries were similar, e.g. working with finite resources, improving access, reducing uncertainty and prices, managing budget impact and improving cost-effectiveness. It seems like Finland is unique by the temporary introduction of conditional reimbursement in legislation and in other countries it has been introduced as permanent. Starting the preparations early for negotiations could save time and resources. When a RSA is made and the medicinal product shows the benefits expected, this is the ideal situation where all stakeholders benefit.
  • Ukkonen, Anni (2020)
    The package leaflet (“leaflet”) is a technical document included in medicine packages to provide information about the medicinal product to the user. With the EU now encouraging the adoption of eHealth, it can be assumed that written medicine information would be included in the digitalisation process. Medicine users’ views on electronic forms of medicine information should be assessed before any changes can be made, but so far there is very little data on this. The aim of this study was to find out what kind of leaflet medicine users would prefer and how they would feel about an electronic leaflet. The main aim was to find out if there is a difference in preferences between different types of medicine users and between medicine users of different ages in the provision of a package leaflet. The study also sought to find out if the current leaflet is being read by medicine users. This study was conducted by carrying out a survey to pharmacy customers over the age of 16 collecting prescription medication(s) for themselves (n = 110). The data was collected at one retail pharmacy in Helsinki, Finland during July 2020. The data was analysed quantitatively. This study found that medicine users generally feel positively about an electronic leaflet (liked by 63%) and many are open to idea of an electronic leaflet (75%). The majority (88%) could see positives in using an electronic leaflet, regardless of leaflet preferences. The study did not find a difference between new and repeat medicine users in the preference for a particular leaflet format, but age is correlated with the preference for a particular leaflet type, with younger medicine users wanting an electronic leaflet as often as older medicine users want a printed leaflet. Having the leaflet appear in My Kanta pages after the medication has been dispensed was found to be the most popular way to receive an electronic leaflet. This study also found that there is a difference between new and repeat medicine users when it comes to reading the leaflet after a medication has been dispensed. With the current printed leaflet 81% of repeat medicine users and 38% of new medicine users do not read it. The most common reason given for not reading the leaflet was that the participant had read it before and did not feel the need to read it again. According to this study, medicine users, especially younger medicine users, feel positively about the idea of an electronic leaflet, which is encouraging for the future of an electronic leaflet. The results are in line with prior research, but also suggest that more medicine users feel positively about the idea of an electronic leaflet than before. The leaflet reading behaviours of medicine users also highlight the need for a system, where a medicine user can be alerted to any changes in the leaflet, which is something only an electronic system could do.
  • Puranen, Pinja (2023)
    Medical devices play a crucial role in healthcare, yet their importance is underscored by the potential for adverse events that can lead to serious consequences for patients and users. As a result, manufacturers of medical devices are required to actively monitor the safety and performance of their devices after placing them on the market. In response to incidents involving medical devices and their safety, the European Union Medical Device Regulation (MDR) came into force in May 2021, bringing more emphasis to the post-market surveillance (PMS) of medical devices. In this study, the current state of the post-market surveillance system of medical device manufacturers in Finland was investigated by conducting an online questionnaire in 2023. A total of 30 medical device companies participated in the questionnaire for a return rate of 17%. The dataset included manufacturers of different sizes, producing medical devices of all risk classes. To identify differences in the use of post-market surveillance data sources between different types of companies, the two-sided non-parametric Kruskal-Wallis-Test was used. The rest of the data was analysed using descriptive analysis. The post-market surveillance data sources with the highest reported intensity of use included customer complaints and feedback, production monitoring, and regulatory intelligence monitoring, while Post Market Clinical Follow-up and health services research were used significantly less. Significant differences between manufacturers of different device risk classes were identified for three data sources; manufacturers of higher risk class devices were found to utilize these data sources to a higher extent than manufacturers of low-risk devices. The manufacturers of medical devices seem to utilise reactive post-market surveillance data consistently to a high extent. On the other hand, the results suggest that proactive post-market surveillance methods remain underutilised despite the introduction of the MDR. Medical device manufacturers also use post-market surveillance data sources to different extents, in particular with respect to the medical device risk class. Overall, the results indicate that the MDR is bringing more emphasis on post-market surveillance, which in turn has increased the workload of medical device manufacturers.
  • Ollinkangas, Joni (2022)
    The problems caused by hypromellose in sterile filtration of ophthalmic products in the pharmaceutical industry were investigated. The research project was performed at NextPharma Oy's ophthalmics manufacturing facility in Tampere during the autumn of 2020. Hypromellose is an excipient commonly used in ophthalmic products as a viscosity enhancer to prolong the contact time of the preparation on the eye surface. In the ophthalmics compounding process, hypromellose is first dispersed by slowly sprinkling it into a hot solution and thoroughly mixing, after which the solution is cooled to room temperature. During cooling, the hypromellose dissolves and gels, increasing the viscosity of the solution. Incomplete dispersion or dissolution of hypromellose during the manufacturing process can slow down the filtration rate or even clog the filter completely due to undissolved hypromellose polymer material. Hypromellose is an industrially produced cellulose derivative that often contains some amounts of unreacted cellulose and other sparingly soluble polymer particles as impurities, which can also cause problems in filtration processes. Sterile filtration is a commonly used sterilization method for ophthalmic products, in which the prepared bulk solution is filtered through a 0.1 to 0.2 µm pore size filter membrane into a sterile receiving vessel. Due to the very small pore size, sterile filters are easily clogged if the solution contains poorly dissolved material. The purpose of this work was to collect additional information on the possible causes of clogging caused by hypromellose and to determine whether the filterability of a solution containing hypromellose can be improved by optimizing the manufacturing process parameters. The design of experiments was prepared, creating a two-level full-factorial test matrix without replicates and with three centre points. Four different process parameters were used (mixing time, mixing speed, dispersion temperature, and cooling temperature). Minimum and maximum levels for the parameters were obtained in the initial tests, after which the test solutions were prepared and filtered in a randomized order according to the test matrix. The aim of the screening was to find out which parameters were affecting the filterability and what would be their optimal combination that would maximize the filtration rate and the yield of filtration. Finally, the optimized parameters were used to test different batches of hypromellose, comparing the results to previous filtration tests. Additionally, an alternative hypromellose dispersion method was tested to minimize the amount of insoluble material remained during the dispersion and cooling steps. Of the parameters tested, mixing speed was the least significant, while cooling temperature had the most effect on the filtration results. The solutions with lower cooling temperature had better filtration results, which may be due to reduced aggregation of hypromellose due to increased hydration of the polymer chains. The temperature behaviour of hypromellose solutions could be an interesting subject for further investigation. Longer mixing times and higher dispersion temperatures produced slightly better filtration results on average, but the differences were not statistically significant. Most challenging in the study was controlling the temperature and mixing of the solutions, and the retention of insoluble hypromellose material at the walls of the compounding vessel. The alternative dispersion method gave promising preliminary results, but the method still requires further testing. It would be important to also find the root cause of the filter clogging mechanism e.g., by further analysing the clogged filter membrane. The study provided additional useful information of the behaviour of hypromellose solutions in solution preparations and during sterile filtration, which has been helpful in solving production problems.
  • Kekkonen, Kati (2020)
    Background. Critical thinking skills, which are an aspect of generic skills, are related to the success students have in their university studies and working life after graduation. When it is considered whether the current degree programs and education systems support sufficiently the development of the skillset needed in the future working life of a university student, one can focus on examining the development of critical thinking skills of a student. Due to the lack of scientific studies on critical thinking, research should be done on the field of pharmacy to gather information on the critical thinking skills of master of pharmacy students and to determine, if the master’s degree program in pharmacy is generating the kind of professionals needed in the working life. Aim. The main goal is to study the level of critical thinking skills possessed by students in the beginning of their Master of Pharmacy studies. Combining the theoretical background and empirical study is considered in choosing a suitable method for the study. The method chosen for the study has to be applicable to determining a student’s ability to interpret, analyse and evaluate information, based on which a student consciously arrives on a conclusion while taking into consideration the context and different point of views of students. In addition to studying critical thinking skills, the aim is to analyse the students’ quality of argumentation and the use of references in comprising quality arguments. Methods. The studied set of students comprised of 17 students on their first year in the Master of Pharmacy program in University of Helsinki. The study was performed using a constructed-response task which was based on a real-life problem and was composed of three statements the students had to address utilizing the provided materials. When answering an open question, a student has to be able to analyse, evaluate and synthesize information from different sources. Based on this process, the student must demonstrate in their own words the relevance of the processed information and to construct a coherent essay that also utilizes the provided sources appropriately. The critical thinking skills of the students were evaluated from three aspects: the relevance of the content, processing of information and augmentation. A table for evaluation and classification of the data was created based on the literature study on critical thinking. According to the table, the studied material was divided into three categories. Category 1 entailed students with essays showing the lowest level of critical thinking skills while category 3 entailed students with essays showing the highest level of critical thinking skills. Results and conclusions. A deficiency in the level of critical thinking and argumentation skills possessed by the students was found, which has been encountered in previous studies, as well. All in all, only three out of the studied 17 students, showed impressive critical thinking skills. Most of the student (82%) showed defective argumentation, and more than half (65%) had problems with referencing. In addition, all but one student struggled in utilizing the information gathered from the reference materials. Based on the results, it is important to focus on developing the critical thinking skills of the students in the master’s program in pharmacy. To further study the matter, the same study should be performed on students at the end of their master’s studies to determine if the teaching and evaluation methods in the master’s program in pharmacy are sufficient in developing adequate critical thinking skills
  • Ylinen, Tuike (2019)
    Pharmaceutical industry is supervised by several competent authorities. These authorities all over the world inspect manufacturers in order to make sure they comply with the Good Manufacturing Practice (GMP) guidelines and produce quality products. If non-compliance with the guidelines is detected, the authorities can revoke manufacturing licenses and deny access of the products. Recent trend in pharmaceutical industry is that the Active Pharmaceutical Ingredient (API) manufacturing is concentrated in few factories. If this kind of manufacturer is declared non-compliant and is therefore unable to supply an API, it can lead to drug shortages. This research aimed to find out what kind of quality problems occur in API manufacturing. Because of the concentration trend, it is important to understand what kind of problems the manufacturers do struggle with to prevent any risk for shortages. This research aimed also to determine how much the quality problems in API manufacturing can impact on drug shortages. Also, the number and location of these non-compliance cases were investigated. The chosen time frame was 2016-2018. Several databases were used as information sources in this research. These databases are maintained by the authorities in the U.S. and Europe and they contain information about the inspections and the GMP deficiencies they have found during these inspections. With the information collected from the databases, an inductive content analysis was conducted to determine the reasons for non-compliance with GMP in API manufacturing. Other information (e.g. locations, names of APIs) was also collected from the databases and analysed to answer the rest of the research questions. Results show that the biggest problem areas in API manufacturing were data integrity and analytical testing. Other problems relating to documentation occurred also. The amount of these cases was quite stable, and the relative proportion declined during the time period. Comparison between the list of APIs and drug shortage databases showed that even over 30% of the non-compliant APIs were later in shortage. The effect was greater in Finland than in the U.S. Therefore, it was concluded that the most significant GMP deficiencies in API manufacturing were poor data integrity and inappropriate analytical testing procedures. Secondly, the number of non-compliance cases in API manufacturing has not increased during this time, but these problems may have had an impact on drug availability problems.
  • Liimatta, Janne (2021)
    During co-processing, magnesium stearate can induce surface coating on carrier particles in powders which contain at least one other component in addition to magnesium stearate. Magnesium stearate is sometimes added to powder mixtures as it is known to have beneficial effects on powder characteristics, such as physical and chemical stability, and flowability. In order to fully optimize and control the coating/mixing process, it is necessary to be able to characterize the quality of surface coating. Various methods can be used in determining the coating of powder particles. They can roughly be divided into two different categories: direct and indirect methods. For example, spectrophotometric instruments, which are used to visually express the element distribution on particle surface, are considered direct methods. Indirect methods include methods in which coating parameters are inferred using other properties such as water sorption and powder flowability. Principally direct methods have been used in previous studies to determine the quality of coating. Therefore, the area of interest was especially to study indirect methods and compare them to results obtained using direct methods. Having knowledge of the suitability of indirect methods would be interesting as they might have many benefits compared to direct methods, such as quicker analysis speed and cost-efficiency. The aim of the study was to examine the suitability of direct and indirect methods in studying the surface of powders containing magnesium stearate and active pharmaceutical ingredients (APIs) or lactose, more closely how magnesium stearate was placed on carrier particles as well as the uniformity and the thickness of coating layer. The used methods were selected using literature and own consideration while taking the available equipment into account. The powders containing API (d50 < 10 μm) or lactose (d50 > 80 μm) with magnesium stearate had substantially differing characteristics and thus behaved differently. Therefore, there were differences in the suitability of analytical methods in determining surface of powders. Powders containing lactose and magnesium stearate were able to be examined using direct methods (SEM-EDS and ToF-SIMS) and several indirect methods. Samples with API and magnesium stearate were able to be studied with fewer methods. Validation of the suitability of these methods need more research. However, according to the results from this study, it is probable that surface characterization of studied co-particles can be achieved with direct, but also with indirect methods.
  • Korhonen, Pia (2023)
    Purpose: Growth hormone deficiency (GHD) is treated with daily injections of growth hormone (GH). Daily injections may cause burden to patients and to family, that may decrease treatment adherence and may result poor treatment outcome. The aim of this study was to study growth hormone treatment burden in Finland and to identify possible treatment challenges and what preferences caregivers have for growth hormone treatment (GHT). Research methods and data: Anonymous semi-structured survey was conducted in 50 pharmacies across Finland. Potential responders were identified when they came to buy growth hormone product and they were requested to complete the survey with tablet computer. Survey consisted of questions including subject characteristics, treatment background, parent satisfaction to treatment, treatment expectations, decision-making process, compliance and non-compliance reasons, and parent preferences. Survey was conducted between June 2021 and April 2022. Results: Total 79 persons responded to survey. All responders were satisfied with current treatment, 79.5% were very satisfied and 29.5% were quite satisfied. 25.6% responded that they don’t have any challenges with the treatment and 74.4% reported at least one challenge. Most common challenges were injection (35.9%), storage requirements (35.8%) and high price (16.7%). Most common reasons for missing a dose were travel or sleep overs (57.7%), forgot to take medicine (30.8%) and medicine runs out (19.8%). Parents described best and most effective GHT in their own words to be with less frequent dosing (25.6%), storage in room temperature (24.4%) and easy-to use device (23.1%). Conclusions: All caregivers were satisfied with the treatment. However nearly 75% of the responders identified treatment-related challenges. The most frequently reported challenge was the mode of administration (injection). When describing optimal GHT, the wish for less frequent dosing interval was the most often mentioned. Data from this survey can provide support in selection the optimal type of GHT for pediatric and adolescent patients.
  • Ainonen, Aleksi (2020)
    Tiivistelmä/Referat – Abstract Background: Biotin is marketed specifically for its hair and nail growth-promoting effects, and its use has become more common in recent years. High doses of 100 mg biotin have also been used to treat MS. There are no high-dose oral products on the Finnish pharmaceutical market. Biotin 100 mg tablets are not available on the global pharmaceutical market either. The University Pharmacy manufactures 100 mg biotin capsules for hospital use. Manual manufacturing of biotin capsules is a resource-intensive process. The physicotechnical properties of biotin such as crystal properties, flowability, hygroscopicity, true density and compressibility properties have not been previously published in the literature. Objectives: The aim of the thesis work was to investigate whether high-dose biotin tablets can be manufactured as an industrial-scale process. To support product development decision-making, the aim of the master's thesis was also to explore the physicotechnical properties of biotin. The main goal was to develop a method for the direct compression of biotin tablets, but also to study the applicability of the wet granulation method. Methods: The crystal form of the raw materials was examined by X-ray powder diffractometer, particle size and particle size distribution by laser velocimeter, and compression behavior by tabletability tests as well as Heckel analysis. The flowability of the raw materials was studied by bulk and tapped density measurements. The production of biotin tablets was studied with six test batches, two of which were high shear wet granulated and four were direct compression processes. The tablets were subjected to European Pharmacopoeia quality tests such as friability, disintegration, and dissolution tests. Results: The particle size distribution of the biotin grade used in the tablets was wide, with an average particle size of 58 μm. Biotin crystals are flaky in shape. Biotin used was the α-crystalline form and its crystalline form did not change as a result of high shear wet granulation. The flow of the biotin grade was extremely poor. Biotin was not found to be particularly hygroscopic. Biotin is brittle, and when compressed, it forms by fragmenting. Pure biotin cannot be compressed into a stable tablet, as even tablets made with high compression forces will form a lid from which the tablet will easily crumble. Biotin sticks to tablet machine’s punches and causes problems in the ejection phase due to high frictional forces. Test batches of the high shear wet granulation process were successful on both eccentric and rotary tablet machine. Two batches of direct compression tests performed on rotary tablet machines had to be stopped after the powder mass got stuck in tablet machine’s hopper. Biotin tablet’s dissolution was slow for all the manufactured batches, with an average of 63-73 % biotin dissolution at 45 min time point. Conclusions: Main property to be optimized for biotin tablet formulations proved to be mass flowability. High shear wet granulation improved significantly flowability. Weight variance of the tablets in the wet granulation batches was also very small. Biotin’s slow dissolution from the tablets was another significant challenge for all the test batches. Further development of biotin tablets should therefore focus on investigating, which measures accelerate biotin tablet’s dissolution. Product development would particularly benefit from the development of a more efficient, ultra-high performance liquid chromatography method for dose analysis of biotin tablets. Wet granulation test batches should be manufactured at different process parameter levels with different excipients and excipient concentrations. Design of experiments statistical approach should be utilized for these further studies so that factor interactions could be detected, and the manufacturing process and drug product could be efficiently optimized.
  • Hemminki, Nelli (2024)
    Tablets are solid medicinal products that are produced by compressing tablet mass in a tablet press. The reproducible and reliable functionality of the manufacturing process, facilities and equipment used in the manufacturing process of medicinal products must be validated. There must be a marketing authorisation for the sale of medicinal products, and pharmaceutical companies must comply with current legislation, Good Manufacturing Practices, and other binding guidelines. After marketing authorisation, certain changes, such as significant changes related to the manufacturing process or raw materials, must be notified to the competent authority by means of a variation application. Depending on the extent of the change, a revalidation and/or a regulatory approval before implementing the change may be required, which makes manufacturing process modification slow, expensive, and laborious. However, the pressure to enhance pharmaceutical manufacturing processes and reduce costs is prevailing. In this study, Lean Six Sigma methods were applied to enhance the manufacturing process of a tablet product. The study was divided into two parts. In the first part of the study, the objective was to investigate the manufacturing process of a tablet product X and to identify improvement actions that would make the manufacturing process of the tablet product X more efficient by achieving material and time savings. In addition, improvement actions were prioritized based on the benefits achieved by the improvement actions and the difficulty of implementation. The second part of the study was based on the improvement action selected from the first part of the study. The objective of the second part of the study was to investigate the factors influencing the amount of mass loss during tableting and how the amount of mass loss can be influenced. In this study, mass loss during tableting referred to the dusty mass inside the tablet press during tableting, which is removed from the tablet press to the equipment dedusting system. The purpose of the practical experiment conducted in the tablet production, which was part of the second part of the study, was to investigate how the magnitude of the exhaust airflow and fan power of the equipment dedusting system affects the amount of mass loss generated during tableting. Based on the experiment, adjusting the power of the equipment dedusting system can affect the amount of mass loss generated during tableting. However, further studies are needed to ensure that no dusty mass remains in the piping of the dedusting system or in tablet press at low exhaust airflow and fan power values during tableting. If the results are applied to other tablet products, the effect of a different formulation on powder dusting should be considered. Adequate dedusting during tableting is important so that the dusty mass inside the tablet press is removed as intended, facilitating the cleaning of the tablet press after tableting and reducing the risk of cross-contamination and exposure of workers to dust. The conclusion of this study is that Lean Six Sigma methods can be used more extensively to enhance the manufacturing processes of both tablet products and other pharmaceutical dosage forms and to reduce loss generated during the manufacturing process without revalidation or changes to a valid marketing authorisation.
  • Parhiala, Minna (2020)
    Suomessa on otettu käyttöön nykyiset lääketurvatoiminnot asteittain vuodesta 2012 lähtien. Merkittävimmät muutokset lainsäädännössä olivat haittavaikutuksen määritelmän muutos sekä erityisen turvallisuuprofiilin lääkkeiden asettaminen lisäseurannan piiriin. Haittavaikutusten spontaani ilmoittaminen on edelleen ensisijainen menetelmä lääkkeen turvallisuustietojen keräämiseksi lääkkeen markkinoille saattamisen jälkeisessä vaiheessa. Vaikka spontaani haittavaikutusilmoitusjärjestelmä on ollut olemassa jo 1960-luvulta, on haittavaikutusten aliraportointi valitettavan yleistä. Tämän tutkielman tavoitteena oli arvioida tietoja, kokemuksia ja asenteita lääkkeiden haittavaikutusten ilmoittamisesta, nykyisestä lääketurvalainsäädännöstä sekä lääkkeiden lisäseurannasta ja mustasta kärkikolmiosta terveydenhuollon ammattilaisten keskuudessa Suomessa. Lääkärit (n = 38), sairaanhoitajat (n = 45), farmaseutit (n = 115) ja proviisorit (n = 36) vastasivat verkkokyselyyn. Aineisto analysoitiin osin aineistolähtöisen ja osin teoriaohjaavan sisällönanalyysin avulla. Tutkimuksen teoriasidonnaisena viitekehyksenä toimi Rogersin diffuusioteoria. Tämä pro gradu -tutkielma paljasti joitain eroja haittavaikutusilmoituksiin liittyvissä teidoissa ja asenteissa terveydenhuollon ammattilaisten välillä. Suurin osa vastaajista koki tietävänsä lääkkeiden lisäseurannasta. Lisäseurannasta ennestään tienneiden joukossa, musta kärkikolmio symboli oli paremmin farmasistien (> 84,5%) tiedossa verrattuna lääkäreihin (45,2%) ja sairaanhoitajiin (32,4%). Lääkäreillä oli enemmän kokemusta, mutta vähemmän tietoa haittavaikutusten ilmoittamisesta kuin muilla terveydenhuollon ammattilaisilla. Suurin osa terveydenhuollon ammattilaisista ei muuttanut työskentelytapojaan lisäseurannassa olevien lääkkeiden kohdalla. Tämä tutkielma tuo esiin sen, että terveydenhuollon ammattilaisilla on riittävät tiedot haittavaikutusilmoitusten tekoon, mutta raportoinnin monimutkaisuuden, huonon saatavuuden ja ilmoitusten tekoon rohkaisemattomuuden takia ilmoituksia tehdään vähän. Tulevaisuudessa tietoisuutta lisäseurannan alaisista lääkkeistä on parannettava sekä raportointiprosessia yksinkertaistettava ja tuotava helpommin saataville.
  • Jormanainen, Miika (2021)
    Pharmaceutical industry is in a process of adopting new technologies due to the growing interest towards the continuous manufacturing approach. However, while the continuous wet granulation process with twin-screw granulator (TSG) has been studied widely, there has been less focus on subsequent continuous granule drying process. As a result, truly continuous granule drying device has not been available for a long time. However, L.B. Bohle has introduced a horizontal truly continuous fluid bed dryer (CFBD) in form of a perforated belt. In such system the wet granules are transported via vibration along the bed without actual fluidization while the hot air dries the granules. Accordingly, Bohle QbCon-25 fully integrated powder-to-tablet system facilitates the combination of a TSG and CFBD. However, the combination is relatively new and only few studies using these methods are available. Aim of this study was to experimentally evaluate the novel Bohle’s CFBD and elucidate the effect of formulation and process parameters of TSG and CFBD on granule residual water content. Additionally, the granules were characterized by their size distribution and bulk and tapped densities. Granule temperature and residence time in the dryer was determined with CubiSens mini sensors. In total 84 wet granulation trials in design of experiments setup were performed and multiple linear regression (MLR) model was used to investigate the effects of different process parameters on granule loss-on-drying (LoD) response. As a result, formulation microcrystalline cellulose (MCC) amount and all studied process parameters of TSG and CFBD showed significant effect on drying result indicating a robust manufacturing process. The increase in the amount of MCC in the formulation as well as the increase in L/S ratio and line rate in the wet granulation was reflected in a higher residual water content in dried granules. However, with increased drying time, airflow rate and inlet air temperature the granule residual water content decreased. The most influential process parameter affecting the granule residual water content was the used L/S ratio. In contrast, the material acceleration which corresponds to the granule drying time was the most significant process parameter of the CFBD affecting the granule residual water. However, the material acceleration did not only correspond to the material residence time in the dryer, but also to the thickness of the granule bed in the dryer. This indicated that the material acceleration is a critical process parameter of the CFBD. However, the thickness of the granule bed could not be measured in real time in this study. Additionally, at intense drying conditions granules showed a very dry outcome and further studies are required to elucidate the operational limit of the CFBD device. Furthermore, the vibration during the drying phase did not have an effect on granule size or the bulk and tapped densities. Material behavior in system was plug-flow like and mean material residence time in the CFBD was only 40 seconds with the middle material acceleration setting. Moreover, the temperature of the granules rose close to the process air temperature, but only for a very short time. Additionally, the used process settings in wet granulation affected the granule temperature, however, the most influential factor on the granule temperature was the used inlet air temperature. Overall, Bohle QbCon25 manufacturing system with TSG and CFBD showed high suitability to wet granulate and dry the produced granules with a uniform residual water content up to 20 kg/h throughput rate without process instability issues.
  • Hämäläinen, Noora (2021)
    Mini-tablets are 1-3 mm in diameter and administered as a single tablet or as a multi-particulate formulation. Mini-tablets are an attractive alternative for conventional solid dosage forms due to the ease of administration and the possibility for combination and individualised drug therapy. In mini-tablet production, good flowability of the formulation is critical as minor variations in die filling can lead to significant changes in mini-tablet weights. In addition, to reduce weight variation, the particle size should not exceed 1/3rd of the die diameter. This study aimed to determine the influence of the granule size on mini-tablet weight variability and content uniformity. The feasibility of direct compression, as well as high-shear wet granulated and roller-compacted formulations, were evaluated. From the nine final formulations manufactured, particle size distribution, Hausner ratio, Carr’s index, angle of repose and flowability were determined. The mini-tablets were made on a rotary tablet press using single punches of 3 mm in diameter. Content uniformity and weight variation of the mini-tablets were determined. The direct compression formulation had the smallest particle size, and the roller-compacted formulation milled through a 1.0 mm and 1.25 mm square screen had the largest particle size. Surprisingly, the RC 0.8 mm grater screen formulation had a very wide particle size distribution and is classified as a very fine blend. The wide particle size distribution might result from a high fill ratio during the milling of the roller-compacted ribbons. The four different high-shear wet granule formulations had a very similar particle size distribution. According to the Hausner ratio and Carr’s index values, the flow properties of the formulations varied between fair and very poor, while according to the angle of repose, the flow properties were between excellent and poor. However, all nine formulations were used to make mini-tablets with acceptable uniformity of mass, mini-tablets were within ± 8 % of the target weight, and none exceeded the 10 % limit set by Ph. Eur. The weight variation is small, as indicated by the low RSD of 1.0-2.9 %. The differences in the weight variation may be attributed to segregation due to particle or granule size and density. This is further supported by the fact that no force feeder or vacuum was utilised in the rotary tablet press, possibly causing re-circulation of the formulation and shearing forces. In addition, the fill level of the feeder might have varied between the nine formulations and affect the weight variation in a way that is not recognised in this study. Only direct compression formulation was within the limits of uniformity of content of single-dose preparations set by Ph. Eur. In the final formulations, the amount of paracetamol was in the HSWG 0.8 mm round screen 98.5 % and in the RC 1.0 mm square screen 97.7 %. These results suggest that the formulations contained an adequate amount of paracetamol, which does not explain why the mini-tablets made from high-shear wet granules did not meet the content uniformity criteria. Furthermore, the weight variation might not entirely explain why high-shear wet granulated formulations performed so poorly in the content uniformity analysis. In summary, that direct compression is a feasible manufacturing method for mini-tablets of 3 mm in diameter. However, further studies are needed on the content uniformity of mini-tablets made using high-shear wet granulated and roller-compacted formulations as these did not meet the content uniformity criterion. In particular, the content uniformity of the mini-tablets made from the high-shear wet granulated formulations was not acceptable, and the reason for this was not identified.
  • Sundberg, Enikö (2024)
    Viimeaikaisten tutkimusten perusteella suun sairauksilla on havaittu olevan vakavia systeemisiä vaikutuksia sekä vaikutuksia yleisterveyteen ja hyvinvointiin. Antiseptisia valmisteita käytetään tulehduksellisten suun sairauksien hoidossa, mutta niillä on todettu riittämätöntä tehoa ja paikallisia sivuvaikutuksia. Antimikrobisia aineita käytetään vakavampien suun tulehdusten hoitoon, mutta ne lisäävät antibioottiresistenssin riskiä ennaltaehkäisevässä ja toistuvassa käytössä. Kaksoisvalohoito vähentää mikrobilääkkeiden ja antiseptisten aineiden tarvetta ja siten haitallisia sivuvaikutuksia. Varsinkin ennaltaehkäisevänä hoitona kaksoisvalon uskotaan aiheuttavan vähemmän haittaa, mutta olevan silti riittävän tehokas estämään tulehduksia. Fotodynaamista hoitoa (PDT) on tutkittu mm. parodontiitin, peri-implantiitin ja suun punajäkälän hoidossa. Satunnaistettu, yhdessä keskuksessa toteutettava kliininen lääketutkimus suunniteltiin ja toteutettiin määrittämään säännöllisesti käytetyn antibakteerisen lääkinnällisen laitteen, Lumoral®-kaksoisvalohoidon, tehoa ja turvallisuutta plakin hallinnassa ja ienterveydessä julkisessa terveydenhuollossa. 40 molempaa sukupuolta edustavaa, 37–77-vuotiasta koehenkilöä, joilla oli diagnosoitu parodontiitin vaihe II tai korkeampi, jotka harjaavat hampaitaan päivittäin ja käyttävät hammaslankaa tai hammasharjaa, satunnaistettiin 1:1 kontrolli- ja tutkimusryhmään. Kaikilta koehenkilöiltä kerättiin aMMP-8 ja mikrobiologiset näytteet ja kliiniset parametrit, kuten PPD, BOP, VPI, sekä lähtötilanteessa että tutkimuksen lopetuskäynnillä. Tutkimusryhmä sai aPD-hoitoa päivittäin noin 5 viikon ajan. aPD-hoito suoritettiin CE-merkityllä Lumorinse®-suuvedellä yhdessä CE-merkityn Lumoral®-valoaplikaattorin kanssa. Suuvettä purskuteltiin minuutin ajan, jonka jälkeen annosteltiin 10 minuutin ajan samanaikaisesti 405 nm aBL ja 810 nm lähi-infrapuna (NIR) LED-valoa, kokonaissäteilyaltistuksen ollessa 40 J/cm2. Seurantakäynnit suoritettiin keskimäärin 7 viikon kuluttua lähtötilanteen arvioinnista, jolloin tutkimusryhmässä oli keskimäärin 8 päivän hoitotauko. Tutkimustulokset viittaavat Lumoral® aPDT -hoidon käytön vähentävän ienverenvuotoa, auttaen hoitamaan tulehduksellisia suusairauksia, kuten parodontiittia, peri-implantiittia ja ientulehdusta. Suurempi hyöty on osoitettu tupakoimattomille henkilöille. Tutkimustulokset viittaavat tupakoimattomien henkilöiden, joilla on diagnosoitu vaiheen II tai III parodontiitti, voivan hyötyä Lumoral® hoidosta arvioitaessa syviä ientaskuja. Tutkimus osoittaa potilaiden, joilla on vaiheen II tai sitä korkeampi parodontiitti ja joilla on jo kohtalaisen hyvät kotihammashoitorutiinit, olevan motivoituneita näkemään ylimääräistä vaivaa hoitonsa parantamiseksi. Lumoral®-hoidon tehokkuuden arviointia syvien ientaskujen paranemisessa varten tarvitaan lisätutkimuksia. Lumoral®-hoidon vaikutusta hammasplakkiin, parodontiitin vaiheeseen ja mikrobiologiseen taakkaan tulee varmistaa lisätutkimuksin. Tupakkatuotteiden vaikutus Lumoral®-hoidon tehoon tulee vahvistaa. Optimaalista käyttötiheyttä ja Lumoral®-hoidon kestoa tulee tutkia lisää. Lumoral®-hoidon hyöty potilailla, joilla on vaikea vaiheen IV ja asteen C parodontiitti, tulee varmistaa kohdennetuin tutkimuksin.
  • Heinonen, Pia (2021)
    Oxygen has been used as a medicine since the 18th century and is widely used as prescription and over-the-counter (OTC) medicine. Especially with global COVID-19 pandemic, which started in 2020, the demand for medicinal oxygen has increased significantly and the quality of medicinal oxygen has become increasingly important. Only few studies have been published on the critical process and quality parameters of gases and their impact on product quality. Because oxygen is classified as a medical product, it must be manufactured in accordance with good manufacturing practices regulations (GMP). One part of EU and other GMP guidelines is mandatory annual product quality review (PQR) which must assess the critical quality and process parameters as well as their trends. The aim of the study was to define the critical process and quality parameters for the medicinal oxygen filling process and to analyze the process control, stability, and capability for annual PQR using process data. Process stability and the state of control of processes were assessed using statistical quality and process management tools, such as the Shewhart control diagram and process capability index. Studied process parameters included vacuum level and pressure measured by the filling equipment. Evaluated quality parameters included analysis pressure, O2 and H2O contents. The results of the study showed that the process is not stable and there was a lot of variation between the parameters. Most variation was detected between different cylinder volumes and filling and analysis ramps in all parameters and between different weekdays in H2O content. However, all parameters remained within the specification limits and the Cpk values of all critical parameters were good. By analyzing the data, many variables that can affect the parameters and add variation to the process data can be identified. Based on the results, the necessary measures to improve and optimize the process and quality was identified. In order to stabilize processes and improve performance, the demonstrable variation in process data should be reduced, for example by harmonizing operating methods. According to the study, it was also possible to assess the revalidations required for the process.
  • Tenhola, Ella (2023)
    Medicine shortages have been an increasing problem in the pharmaceutical industry for several years. While the causes of these shortages have been widely researched, they have been found to be diverse and the root causes are difficult to identify. The pharmaceutical care system has been formed over a long period of time, which has led to a growing problem of shortages for various reasons. This study aims to investigate he views of different pharmaceutical sectors on what reforms to the mandatory reserve supply law could help to prevent and shorten the medicine shortages. The study was conducted through a thematic interview. Abductive analysis and thematic analysis were selected as the method of analysis. The study found that mandatory reserve supply is successful in acting as a buffer against short-term shortages, but that a comprehensive reform of the law would be necessary. According to the study, the reform of the law is linked to a wide range of issues. More flexible processes in regulatory aspects, the profitability of the Finnish market, and hospital procurements are closely related to the mandatory reserve supply law. The reform of the mandatory supply list could bring flexibility to exemptions to maintain lower stock levels by renewing the list of medicines and categorizing them into different groups. The act on public contracts law and the mandatory supply reserve law should be better coordinated to avoid wastage and thus ensure Finland's adequate competitiveness However, it should be noted that ensuring Finland's competitiveness and reducing shortages is not solely the responsibility of the mandatory reserve supply law. It also requires extensive international cooperation and it is also believed that bringing production back to Europe and even to Finland is crucial to shorten medicines shortages.
  • Randén, Sari (2024)
    Jätevedenpuhdistamon käsittelymenetelmät eivät poista kokonaan lääkeaineita jätevedestä. Lääkeainejäämiä jää käsiteltyyn jäteveteen ja siksi niitä löytyy pintavedestä. Vielä ei ole täysin selvää, miten altistuminen lääkeainejäämille vaikuttaa ihmisten terveyteen ja ympäristön hyvinvointiin. Tämän pro gradu -tutkielman tavoitteena oli ensin tunnistaa vesiympäristölle haitallisimmat lääkeaineet ja sen jälkeen selvittää, mitkä olivat haitallisimpien lääkeaineiden käyttömäärät HUSin hoitoyksiköissä vuonna 2021. Tutkimuksen tuloksia on tarkoitus hyödyntää jatkossa HUSissa, kun arvioidaan mahdollisia toimenpiteitä ympäristöriskien vähentämiseksi. Tässä tutkimuksessa ympäristöriskiä mahdollisesti aiheuttavien aineiden arviointi koski lääkeaineita, joita käytettiin ihmisten hoitoon vuonna 2021 Suomessa. Tutkimukseen otettiin mukaan ne lääkeaineet, joista oli saatavilla riittävästi dataa riskiosamäärän laskemiseksi (kun ei otettu huomioon lääkeaineen poistumaa jätevedenpuhdistamolla). Tutkimuksen ulkopuolelle rajattiin lääkeaineiden yhdistelmävalmisteet, eläinlääkkeet, vitamiinit, elektrolyytit, aminohapot, peptidit, proteiinit, hiilihydraatit, lipidit, kasvirohdosvalmisteet ja rokotteet. Riskiosamäärä laskettiin 521 lääkeaineelle. Lääkeaineiden, joiden riskiosamäärä oli suurempi kuin 1, katsottiin aiheuttavan riskiä vesiympäristössä: mitä suurempi oli aineelle laskettu riskiosamäärä, sitä suurempi oli ympäristöriski. 521 lääkeaineesta 39 lääkeaineen riskiosamäärä ylitti raja-arvon 1. Lääkeaineet, joiden riskiosamäärä oli yli 10, olivat ibuprofeeni, dabigatraanieteksilaatti, sulfasalatsiini, estradioli, lerkanidipiini, sertraliini, abirateroni, amoksisilliini, rifaksimiini ja vankomysiini. Näiden kymmenen vesiympäristölle haitallisimmin lääkeaineen kulutus vuonna 2021 HUSissa laskettiin hoitoyksiköittäin, jotta saatiin selville, missä hoitoyksiköissä käytettiin näitä lääkeaineita eniten. Kulutuksen laskennassa ei otettu huomioon hoitoyksiköiden jo olemassa olleita lääkevarastoja, jotka oli hankittu ennen vuotta 2021, eikä lääkehävikkiä (lääkejätettä). Tämän tutkimuksen perusteella puuttuva data oli merkittävin tulosten luotettavuuteen vaikuttava tekijä, koska ne lääkeaineet, joista ei ollut riittävästi dataa käytettävissä, jouduttiin rajaamaan tutkimuksen ulkopuolelle. Siten vesiympäristölle haitallisimpien lääkeaineiden luettelosta saattaa puuttua sinne kuuluvia lääkeaineita. Dataa olisi tarvittu etenkin lääkeaineiden poistumasta jätevedenpuhdistamolla sekä tutkimuksesta poisjääneiden lääkeaineiden kulutuksesta, teoreettisista vuorokausiannoksista ja ennustetuista vaikutuksettomista pitoisuuksista. Koska kaikkia haitallisimpia lääkeaineita ei ole vielä selvitetty, lisää tutkimusta ja työkaluja tarvitaan ongelman ratkaisemiseksi