Longetivity and Shelf life of stockpiled antivirals (bulk, packaged) versus Antivirals sold via Pharmacies for private Use

Transcription

1 Stockpiling of Medicinal Products SANCO, 22 February 2008 Longetivity and Shelf life of stockpiled antivirals (bulk, packaged) versus Antivirals sold via Pharmacies for private Use Jean-Louis ROBERT, Ph.D. Head Luxembourg OMCL Laboratoire National de Santé Luxembourg

2 Disclaimer This presentation is made in my capacity of Head of an OMCL.

3 Laboratoire National De Santé (L) Service du Contrôle des Médicaments Governmental Institute, part of the Ministry of Health, Luxembourg Laboratoire National De Santé: Broad activities: food control, medicinal microbiology, hematology, anatomy pathology,. Service du Contrôle des Médicaments. Control of products of chemical origin Member of the European OMCL network; Certified ISO (OMCL network) Activities within EDQM, EMEA, WHO

4 Stability studies Stability studies have to be performed on both the bulk materials (active substance) and the medicinal products in order to demonstrate that the products are within specifications during their time of use (commercialisation( commercialisation). Stability studies are part of the application file for MA and are assessed; the outcome is part of the marketing authorisation (shelf-life life of a medicinal product is defined in the SPC). Stability studies conditions simulate the conditions in Europe: climatic zone I/II Standard conditions: Accelerated studies: 40 C/75%RH (6 months) Long term: 25 C/60%RH or 30 C/65%RH (real time) Other conditions possible: e.g. 5 C 5 C storage in a refrigerator

5 Stability studies Outcome of the stability studies: Active substance: re-test period (date) Medicinal product: shelf-life life Re-test period shelf-life life Specifications: a list of tests and appropriate acceptance criteria (limits, ranges); Stability: limits for degradation products: based on qualification (safety) studies Medicinal product: Release specifications Shelf-life life specifications

6 Problem Statement Is it possible to extend the use of an active substance (bulk) and/or of a medicinal product beyond their re- test period or their official shelf-life? life?

7 Facts Active substance (re-test period/date): no problem. In principle a bulk material can be used indefinitely; the re-test date indicates that, if it has passed this date, then prior to manufacturing of the medicinal product, the bulk material has to be tested: if in compliance with the specifications, this batch can be used. True for chemicals Biological products may be different e.g. active substance not isolated

8 Facts Medicinal product (shelf-life): life): A medicinal product where the shelf-life life has been exceeded, should not be on the market anymore (legal issue). Maximum shelf-life life 5 years!?! The shelf life is based on safety data (qualification of the degradation products), in rare case based on efficacy data In theory, no data are available to show the stability status (degradation) after the validity period. In reality..? A degradation does not start just after the validity period but can usually be detected much in advance A lot of medicinal products are safe for use (administration) long after the official (authorised( authorised) ) validity period

9 Facts The concept to store medicinal products beyond the official shelf-life life is nothing new. During the cold war many countries stored a certain number of medicinal products for 10, 20 years. Periodic retesting confirmed the good stability of these products. Normally they are stored under ideal conditions. It should be understood, the difference between commercialised products and those products intended for use in crisis (pandemic) situations. When extending the use of such products beyond the official shelf-life, life, an evaluation should be made taking into account not only the testing results but also the intrinsic stability of the medicinal product (results from stability studies as provided in the application file)

10 Situation in Luxembourg The following stockpiled products are periodically tested: Potassium Iodide, tablets Tamiflu (Oseltamivir phosphate), capsules Ciprofloxacin tablets Stored in climatic rooms Test parameters (shelf-life life specifications): Appearance Purity testing (degradation products) Assay Dissolution Specifications: Marketing Authorisation dossiers

11 Oseltamivir Phosphate Marketed: Capsules 75 mg Capsules 30 mg, 45 mg Powder for oral suspension 12 mg/ml API magistral formulation: Oral solution: 15 mg oseltamivir base/ml 0.1% sodium benzoate (preservative) Stability: 3 weeks stored at 25 C; 6 weeks stored at 5 C5 Extemporaneous formulations based on commercial capsules (in progress)

12 Directive 2001/83/EC..on the Community Code relating to Medicinal Products for Human Use Art. 5 A A Member State may, in accordance with legislation in force and to fulfill special needs, exclude from the provision of this directive medicinal products supplied in response to a bona fide unsolicited order, formulated in accordance with the specifications of an authorised health care professional and for use by his individual patients on his direct personal responsibility

13 Additional thoughts Batches of medicinal products intended for stockpiling should not have an expiry date on their label! Better to speak about suitable for administration rather than shelf-life Change in legislation?