Varnost in izzivi pri uporabi novih pomožnih snovi v zdravilih

Staniša, Nika (avtor), Peterlin Mašič, Lucija (mentor)

Uvod: Pomožne snovi so poleg zdravilne učinkovine sestavni del vsakega zdravila. Zaradi pojava novih bolezni, novih tehnologij in potreb po izdelavi inovativnih, novih zdravil, se veča tudi potreba po novih pomožnih snoveh. Ta omogočajo nove načine dostave, izboljšajo komplianco pri bolnikih, povečajo stabilnost zdravilne učinkovine in celo izboljšajo varnost. Farmacevtska podjetja pogosto nerada uvajajo nove pomožne snovi v svoje formulacije, ker po trenutni zakonodaji nove pomožne snovi niso neodvisno ocenjene z varnostnega stališča in je treba dokazati varnost nove pomožne snovi podobno kot varnost nove učinkovine. Namen: Namen magistrske naloge je pregled smernic za vrednotenje varnosti novih pomožnih snovi, analiza omejitev za uporabo novih pomožnih snovi v novih zdravilih, pregled primerov novih pomožnih snovi in pregled vloge Ameriške agencije za hrano in zdravila in Varnostnega odbora mednarodne organizacije proizvajalcev pomožnih snovi pri neodvisni registraciji novih pomožnih snovi. Metode: Za pregled potrebne literature smo uporabili vire dostopne na svetovnem spletu. Uporabili smo znanstvene članke in smernice dostopne na uradnih straneh regulatornih agencij in organizacij FDA, IPEC, EMA in ICH. Uporabili pa smo tudi članke najdene na bazi PubMed in ScienceDirect ter Google pod ključnimi besedami »novel excipients«, »new excipients«, »innovative excipients«, »regulation of novel excipients«, »safety of excipients«, »excipient innovation«, »new vs novel excipient«, »intellectual property of the novel excipient«, »excipient database«, »novel excipients and covid« in podobno. Rezultati in razprava: Na podlagi pregledane literature smo prišli do naslednjih rezultatov: • Smernice o varnosti novih pomožnih snovi, ki jih imata na voljo Ameriška agencija za hrano in zdravila in Varnostni odbor mednarodne organizacije proizvajalcev pomožnih snovi so si med seboj podobne. Obseg študij se razlikuje glede na to za kakšno uporabo je namenjena nova pomožna snov, prav tako pa so študije odvisne od načina aplikacije. Evropska agencija za zdravila posebne smernice za testiranje varnosti novih pomožnih snovi nima, predvideva pa testiranje nove pomožne snovi v sklopu testiranja zdravila, za katerega se predvidevajo zelo podobna testiranja, kot za nove pomožne snovi. • Glavne omejitve in izzivi pri uporabi novih pomožnih snovi v novih zdravilih so regulatorna določila, dokazovanje varnosti, visoki stroški in dolg razvojni čas, nejasna opredelitev termina »nova pomožna snov«, neobstoj seznama novih pomožnih snovi ter varovanje intelektualne lastnine. • V zadnjih tridesetih letih je bilo uvedenih le peščica kemijsko novih pomožnih snovi. Pandemija koronavirusa je raziskovalce prisilila v izdelavo novih pomožnih snovi, ki so omogočile izdelavo učinkovitega in varnega cepiva. • Ameriška agencija za hrano in zdravila in Varnostni odbor mednarodne organizacije proizvajalcev pomožnih snovi poskušata izboljšati položaj novih pomožnih snovi in proizvajalcem olajšati njihovo uporabo in registracijo. Ameriška agencija za hrano in zdravila je v letu 2021 uvedla prostovoljni pilotni program za pregled novih pomožnih snovi, ki naj bi proizvajalcem pomožnih snovi omogočil pregled novih pomožnih snovi pred njihovo uporabo v novih zdravilih in omogočil neodvisno oceno. Varnostni odbor mednarodne organizacije proizvajalcev pomožnih snovi pa je izdal nov varnostni vodnik za farmacevtske pomožne snovi, ki velja globalno in je namenjen zagotavljanju informacij za pomoč pri določanju potrebne količine podatkov o varnosti pri uporabi nove pomožne snovi ob upoštevanju, da je lahko glede na vrsto nove pomožne snovi potrebna različna količina in raven podatkov o varnosti. Sklep: Kljub obstoju velikega števila že poznanih pomožnih snovi, ki prinašajo določene prednosti pri njihovi uporabi, je velika potreba po novih. Da bi spodbudili razvoj novih pomožnih snovi, bodo morali regulatorni organi spremeniti zakonodajo in omogočiti neodvisno oceno varnosti novih pomožnih snovi ter pristopiti na tak način, da se bodo zmanjšale omejitve in izzivi pri njihovi uporabi. Velik napredek v tej smeri bi v prihodnosti lahko predstavljal Pilotni program Ameriške agencije za hrano in zdravila.

• Jezik: Slovenski jezik
• Ključne besede: nove pomožne snovi, varnost, FDA, IPEC, EMA, predklinične študije
• Vrsta gradiva: Magistrsko delo/naloga
• Organizacija: FFA - Fakulteta za farmacijo
• Leto izida: 2023
• PID: 20.500.12556/RUL-147207
• Datum objave v RUL: 25.06.2023

Sekundarni jezik

• Jezik: Angleški jezik
• Naslov: Safety and challenges of using novel excipients in medicines

Izvleček

Introduction: Excipients are, in addition to active substances, an integral part of every medicine. The emergence of new diseases, new technologies, and demand for designing innovative new medicines consequently results in increased demand for excipients. These allow for new delivery routes, enhance compliance with patients, increase the stability of active substances, and even improve safety. Pharmaceutical companies are often reluctant to introduce novel excipients in their formulations, because under current legislation they are not independently assesssed for safety, which means that safe use of a novel excipient has to be validated in a similar way to the safety of a new active substance. Purpose: The purpose of the master thesis is to review guidelines for risk assessment of novel excipients, analyse the restrictions for the use of novel excipients in new medicines, review examples of novel excipients, and assess the role of the US Food and Drug Administration and the International Pharmaceutical Excipient Council in the process of independent registration of novel excipients. Methods: In order to review relevant literature we used sources available on the internet. We consulted academic articles and guidelines available on the official websites of regulatory agencies and organisations FDA, IPEC, EMA, and ICH. Additionally, we explored articles from PubMed, ScienceDirect, and Google that were returned from the search by keywords »novel excipients«, »new excipients«, »innovative excipients«, »regulation of novel excipients«, »safety of excipients«, »excipient innovation«, »new vs novel excipient«, »intellectual property of the novel excipient«, »excipient database«, »novel excipients and Covid« and similar combinations. Results and discussion: Based on the reviewed literature we have come to the following conclusions: • Guidelines on the safety of novel excipients, available at FDA and at IPEC, are rather similar to each other. The scope of the studies varies depending on the intended use of a novel excipient and on the route of administration. The European Medicines Agency does not provide special guidelines for assessing the safety of novel excipients, but envisages testing of novel excipients within the process of testing the medicinal product, which is expected to be very similar to the testing of novel excipients. • The main constraints and challenges for the use of novel excipients in new medicines are regulatory provisions, safety assessment, substantial cost and long development times, vague definition of the notion »novel excipient«, absence of a list of novel excipients, and intellectual property rights. • In the last thirty years only a small number of novel chemical excipients has been introduced. The pandemic of Coronavirus forced researchers to develop new excipients that enabled the production of a safe and effective vaccine. • FDA and IPEC have been trying to improve the situation and make it easier for the producers to use and register novel excipients. FDA has launched a voluntary novel excipient review pilot programme in 2021 to allow excipient manufacturers to review new excipients before they are used in new medicines and to allow for an independent assessment. The International Pharmaceutical Excipient Council has issued a new safety guide for pharmaceutical excipients, which applies globally and is intended to provide information to help determine the amount of safety data required when using a novel excipient, bearing in mind that the amount and level of safety data required may vary depending on the type of novel excipient. Conclusion: Despite the existence of a large number of already known excipients, which bring certain advantages in their use, there is a great need for new ones. In order to encourage the development of novel excipients, regulatory authorities will need to amend legislation to allow for the independent safety assessment of novel excipients and to take a less restrictive and less challenging approach to their use. FDA's pilot programme could be a major step forward in this direction in the future.

• Ključne besede: novel excipients, safety, FDA, IPEC, EMA, pre-clinical studies