Sezione di Tecnologia e Legislazione Farmaceutiche Maria Edvige Sangalli Corso di Laurea Magistrale in Chimica e Tecnologia Farmaceutiche – E25 Fabbricazione Industriale dei Medicinali – 4 CFU

Prof. Andrea Gazzaniga

Brevi riflessioni sul programma finora svolto – 22 Ottobre 2014 Dott. Marco Adami

• Le aziende farmaceutiche operano in un ambiente molto “regolamentato” • I prodotti farmaceutici sono progettati e sviluppati in modo da tener conto i requisiti delle GMPs e di altri sistemi di qualità ad esse correlati, come le GLP (Good Laboratory Practices) e le GCP (Good Clinical Practices) 

G

X

P

Regole G

X

P: Esempi applicativi Discovery CMC IND/IMPD Farmacologia e PK Animale/In-vitro GCP GMP Studi clinici Fase I Fase II Fase III Tossicologia Animale/In-vitro NDA/CTD Registrazione Produzione per il mercato CMC = Chemistry, Manufacture and Control GLP

Good Manufacturing Practice (GMP – NBF)

• • • Parte di Quality Assurance che garantisce che i prodotti medicinali destinati all’uomo siano fabbricati in modo riproducibile e controllati in funzione di standard di qualità appropriati al loro impiego Principi e linee-guida in Directive 2003/94/EC per “medicinal products” e per “investigational medicinal products” La guida per l’interpretazione di questi requisiti si trova in Volume 4 of “The rules governing medicinal products in the European Union”, pubblicato dalla European Commission e relativi Annexes: http://ec.europa.eu/health/documents/eudralex/vol-4/index_en.htm

Il sistema deve essere DOCUMENTATO e MONITORATO

Riflessioni del 22 Ottobre 2014

• • Quante volte nelle lezioni finora svolte abbiamo sentito parlare di

QUALITA’

!

Quante volte abbiamo sentito le azioni che le Aziende farmaceutiche intraprendono per ottenere prodotti medicinali di qualità!

− − − − − − Nuovi “paradigmi” di qualità ICH Q8, Q9, Q10 Risk assessment Specifiche eccipienti e prodotto finito Criterio principale di “sourcing” è la affidabilità di produrre in qualità ….

Ma è davvero tutto sotto controllo?

What the Magazines Say

• • • XXX

recalls

Aranesp (darbepoietin alfa) Prefilled Syringes, which are used to treat anemia caused by kidney failure or chemotherapy. The recall comes due to the potential presence of cellulose and/or polyester particles (PharmTech.com, Aug. 15, 2014).

XXX

recalls

two lots of Dianeal low calcium peritoneal dialysis solution with 2.5% Dextrose 5000 mL, which is used for chronic renal failure patients. The recall is being initiated due to the presence of oxidized stainless steel, garment fiber, and PVC particulate matter (in-Pharma Technologist.com, 18 Aug 2014).

XXX

is recalling

more than 100,000 bottles of Cephalexin capsules because the products were manufactured with active pharmaceutical ingredients (APIs) that were not manufactured with GMPs. Last month XXX recalled a chemotherapy made at an Indian plant, while in May, XXX announced that it would shutter its Detroit, Michigan plant. The company did not respond to a request for comment (in-Pharma Technologist.com, 18 Aug 2014).

What the Magazines Say

• XXX announced on August 8, 2014,

is voluntarily recalling

nine lots of Cubicin (daptomycin for injection) to the user level following complaints of foreign particulate matter in reconstituted vials. The nine lots are in addition to the (

more than 100!

) lots voluntarily recalled by XXX in an August 6, 2014 announcement. In issuing the recall notice of August 6, 2014, XXX said that the voluntary recall of these lots was as a result of an issue with a manufacturing line of one of its suppliers that could result in glass particulate matter in vials (DCAT connect).

• XXX

is recalling

millions of containers of its best-selling Similac infant formula that may be contaminated with insect parts. A company spokesman said XXX uncovered the insects last week in one section of a manufacturing plant in Sturgis, Michigan. “We immediately shut down that one area and began an investigation” (Pharmaceutical Processing, 08/20/2014).