Browsing by Subject "riskiarvio"

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  • Heinonen, Susanna (Helsingfors universitet, 2010)
    Methods for the assessment of the bioequivalence (BE) of drug products are generally well-documented and the approaches for such studies are described in guidances issued by regulatory authorities throughout the world. While in general, the BE requirements of most regulatory bodies have much in common, in various instances specific issues and approaches may differ. In the literature part of the master's thesis these differences in the selected regulatory BE guidelines (Europe, United States and World Health Organization) was examined and also the scientific reasons behind these differences were considered. It was found that the prime differences were in the BE related issues in which the scientific community are not in agreement (multiple dosing, highly variable drugs, moieties to be measured (parent/metabolite), food effect studies etc.). The differences were also related to drug products that have biopharmaceutical, bioavailability (BA), pharmacokinetic, and pharmacodynamic properties that preclude the use of standard approaches that are outlined in regulatory guidelines. In the future the push for international harmonization of regulatory standards is hopefully leading to worldwide discussions and changes regarding BE and other components of the drug approval process (both new and generic drugs). Expensive in vivo BE studies are usually needed for generic drug products or if a formulation is significantly altered during clinical trials. In this master's thesis a pharmacokinetic model (based on a compartmental absorption and transit model, CAT) was constructed and tested to predict relative BA, to assess the risk of bioinequivalency and to probe properties of drugs suitable for the use of the model. Also the errors and uncertainties related to the model were discussed. GI tract physiology, formulation type and drug solubility, dissolution, absorption and elimination rates were taken into account in this pharmacokinetic simulation model. In the model formulation differences were described by dissolution rate constant (Kd) (calculated from experimental dissolution data) and gastric emptying rate (GE) (varies for different formulations). Hence, when integrated with a pharmacokinetic compartment model it was possible to get predictions of concentration-time profiles of different formulations. Generalised rules in BE assessment were used to estimate the risk of bioinequivalency. The resolution power of the model and the errors related to the model was evaluated by theoretical pharmacokinetic simulations. Generally, the simulations suggested that the model predicts the risk in the BE study most accurately when the drug belongs to the class I/III in the biopharmaceutical classification system (BCS) or to the class II when saturation solubility is not the limiting step in the absorption. Used Kd value is valid if dissolution data is accurate (method discriminative). Also, there has to be enough information about the formulation (type, disintegration, excipients). Otherwise it has to be considered if these factors effect on the resolution power. The weaknesses of the simulation models are assumptions. Hence, when exploring the results it has to be estimated case by case, if they affect on model's ability to separate formulations (reliability of the risk assessment and the ability to predict relative BA). This model is useful tool in formulation development and regulatory applications.
  • Kaunomäki, Jenni (Helsingin yliopisto, 2015)
    Background. The Dynamic Appraisal of Situational Aggression (DASA) is a 7-item rating scale used to predict imminent aggression in psychiatric inpatients. DASA measures the presence of seven behaviors that predict the probability of violence within 24 hours. The purpose of this research was to validate the sensitivity of DASA in a Finnish psychiatric inpatient population, examine the risk decreasing interventions applied after identifying high-risk patients and study which interventions were the most effective in decreasing the DASA score over one day of follow-up. Examinations also took into account the number of interventions needed to decrease the perceived risk of violence. Methods. The data (n = 300) were collected in a naturalistic setting during a six-month period in an acute psychiatric admission ward. Interventions were clustered into four groups by frequency of use: (1) interventions restricted by the Finnish Mental Health Act, (2) PRN-medication, (3) discussion with nursing staff, and (4) other interventions. Associations between interventions and change in DASA scores were examined separately for each intervention and also in a single model adjusted for all other interventions. Results and conclusions. There were 44 incidents in which a patient had been mechanically restrained or secluded. Patients had been rated as potentially violent (DASA ≥ 4) in 61 % (n = 27) of the incidents and non-violent (DASA = 0) in 16 % of the incidents (n = 7). The most frequently used interventions were PRN-medication (33.5 % of all interventions), seclusion (15.8 %) and focused discussion with nurse (10.8 %). Interventions regulated by the Finnish Mental Health Act (seclusion, mechanical restraint, involuntary intramuscular medication, limitation of the freedom of movement, physical restraint, and limitation of contacts), PRN-medication, and discussion with nursing staff were not associated with DASA score the following day. Only the category of "other interventions" (e.g., daily activities) were associated with lower DASA score the following day when examined separately or when adjusted for the use of other concurrent interventions. The results showed that the total DASA score decreased if the patient received one to three interventions. Four or more interventions had no statistical relevance on DASA score the following day. DASA is an effective method to predict imminent aggression in the Finnish psychiatric patient population, even though there remains unpredictable violence that is foreseen through DASA scores. Psychiatric staff tend to use fairly restrictive and coercive methods, but DASA scores were seen to decrease only in individuals who received non-coercive interventions.
  • Viitanen, Elina (2018)
    It is the responsibility of the marketing authorization holder to assure that the safety and integrity of the medicinal products is not jeopardized during any phase of the manufacturing process, including transportation. In the last resort it is the marketing authorization holder´s decision how the transportation of medicinal products is controlled and safe and good quality products provided to the patiens. Transportation of medicinal products in European Union area is regulated by EU Good distribution Practise (GDP) guidelines. There are different characteristics for different modes of transportation. While the air freight is most often the fastest mode of transportation, it is also most vulnerable for temperature excursions during loading and unloading the aircraft. The road transportation can in best case provide swift door to door delivery, in worst case the road transportation can be time consuming with many different intermediate storaging locations and many loading phases. Road transportation is also the riskiest mode of transportation in matter of crime. In general, the cargo is in danger whenever the vehicle is not moving. While sea freight is the slowest mode of transportation, in some cases it can be suitable for use. With sea freight big amounts of cargo can be transported simultaneously and rather safely even very long distances. Both air and sea freight require additional mode of transportation from and to airport and port. This is called multimodal transportation. Ultimately the decision of the mode of transportation is a compromise with pros and cons from the different modes of transportation. Some of the risks related to transportation process can be mitigated with the proper risk management. One risk management tool is risk assessment. In case of transportation, risk assessment provides a wide look of the whole transportation chain. ----- Myyntiluvan haltijan vastuu on varmistaa, ettei lääkevalmisteiden turvallisuus tai koskemattomuus vaarannu missään valmistusketjun vaiheessa, mukaanlukien lääkevalmisteiden kuljetuksen aikana. Viimekädessä myyntiluvan haltija on vastuussa siitä miten lääkevalmisteidenkuljetusta kontrolloidaan, jotta potilaille voidaan tarjota turvallisia ja laadukkaita lääkevalmisteita. Euroopan Unionin alueella lääkkeiden kuljetuksen viranomaisvaatimukset on säädetty lääkkeiden hyvät jakelutavat (GDP) -ohjeistossa. Eri kuljetusmuodoilla on kaikilla omanlaisensa ominaispiirteet. Siinä missä lentorahti on usein nopein kuljetusmuoto, se on erittäin altis lämpötilan vaihteluille lentokoneen lastaus- ja purkuvaiheissa. Maantiekuljetus voi parhaassa tapauksessa olla nopea ovelta- ovelle kuljetus, mutta pahimmassa tapauksessa kuljetukseen kuluu aikaa ja se voi sisältää useita kuorman lastauksia ja purkuja eri välivarastoihin. Maantikuljetus on myös kuljetusmuodoista kaikkein riskialttein rikoksille. Yleisesti voidaan sanoa, että maantiekuljetuksen lasti on vaarassa silloin kun ajoneuvo ei liiku. Vaikka merirahti on hitain kuljetusmuoto, joissain tapauksissa se voi olla tarkoitukseen parhaiten sopiva. Hitaudesta huolimatta, meriteitse saadaan kuljetettua samanaikaisesti suuria tavaramääriä suhteellisen turvallisesti pitkiäkin välimatkoja. Sekä meri- että lentorahdit vaativat toisenlaisen kuljeutusmuodon käyttöä satamasta tai lentokentältä kohteeseen. Täytä kutsutaan monimuoto-kuljetukseksi. Lopulta päätös kuljetusmuodosta on kompromissi eri kuljetusmuotojen hyvien ja huonojen puolien välillä. Joitakin kuljetukseen liittyviä riskejä voidaan pienentää kunnollisella riskien hallinnalla. Yksi riskien hallinnan työkalu on riskiarvio. Kuljetusten riskiarvio antaa kattavan kuvan koko kuljetusketjusta.