applying a unique combination of disciplines consulting, preclinical, toxicology,

Transcription

1 NAMSA is a Medical Research Organization (MRO), accelerating product development through integrated laboratory, clinical and consulting services. Driven by our regulatory expertise, NAMSA's MRO Approach plays an important role in translational research, applying a unique combination of disciplines consulting, preclinical, toxicology, microbiology, chemistry, clinical and quality to move client s products through the development process, and continue to provide support through commercialization to post-market requirements, anywhere in the world.

2 Tina Hubbell Technical Advisor, Chemistry NAMSA Tina Hubbell is a Technical Advisor with NAMSA, focusing on Analytical and Chemical testing. She holds a bachelor s degree in chemistry from the University of Toledo. Before coming to NAMSA, Tina worked in an analytical laboratory specializing in chemical separations for volatile organic compounds and ultratrace mercury measurements. She is an active member of the local American Chemical Society chapter and has held Executive committee positions including a two year appointment as Chair. 2

3 Updates to USP <661>: USP <661.1> Plastic Materials of Construction

4 Current: USP 38 <661> Biological Reactivity Contained Studies for Specific Polymers LDPE/HDPE, PP, PET/PETG Identity testing (Infrared/Thermal Analysis) Physiochemical testing (non-specific identification) Nonvolatile Residue Heavy Metals Colorant Extraction Etc. 4

5 Current: USP 38 <661> Physiochemical testing Not polymer specific Comprised of four (4) qualitative/quantitative tests Nonvolatile Residue Heavy Metals USP <231> Residue on Ignition Buffering Capacity 5

6 1661 EVALUATION OF PLASTIC PACKAGING SYSTEMS AND THEIR MATERIALS OF CONSTRUCTION WITH RESPECT TO THEIR USER SAFETY IMPACT Three stage approach 1. USP <661.1> raw material 2. Package system per USP <661.2> 3. Product assessment Two means for characterization of a material of construction is outlined in First: direct testing to compliance with Second: the use of the material with a currently approved finished drug product. Deemed appropriate for pharmaceutical use by the appropriate regulatory. Non-interacting materials (packaging with drug material) are exempt from USP <661.1> and do not need to be wellcharacterized. However, this non-interacting designation must be accepted by the appropriate regulatory authority.

7 New: USP 39 <661.1> Effective May 1, 2016 Title: PLASTIC MATERIALS OF CONSTRUCTION Conducted on individual plastic materials used or combined to form components of the packaging system. 7

8 USP 39 <661.1> continued Designed to better characterize materials used in packaging primary means of ensuring the packaging system is suited for its intended use Safety and efficacy Rationale for use by manufacturer Who is affected? - Raw material manufacturers - Drug manufacturers - Packaging-material suppliers

9 USP 39 <661.1> continued Polymer Specific testing: PE, Polyolefins, PP, PVC, PET/PETG Identity testing New testing: Physicochemical testing Additive identification and quantitation by HPLC and TLC Specific metal identification and quantitation by ICP Requires larger amount of sample (averages about 130g vs. 20g) 9

10 Identity Tests Purpose to properly identify materials to ensure proper characterization testing. Based on comparison with a reference standard. Spectroscopic Properties (Infrared Analysis by FTIR) Thermal Properties (Differential Scanning Calorimetry) USP <891>

11 Physiochemical Tests Aqueous Extractions: UV Absorbance: provides some indication of the chemical nature of organic extractables and also provides a semi-quantitative indication of the levels of organic extractable. Acidity/Alkalinity: provides insight into the acidic/basic extractables. Total Organic Carbon (TOC): reflects the total amount of extracted organic compounds. Rough filter for determining which compounds may have high amount of organic extractables.

12 Tests for Additives POLYETHYLENE, CYCLIC OLEFINS, AND POLYPROPYLENE Phenolic Antioxidants, Non-Phenolic Antioxidants, Amides & Stearates Uses HPLC and TLC identification and quantifications PLASTICIZED POLYVINYL CHLORIDE DEHP, N,N -diacylethylenediamines, epoxidized soya oil, epoxidized linseed oil, Vinyl chloride Uses UV, GC, and TLC identification and quantifications

13 Extractable Metals Acidic and Alkali extractions Characterizes extractable metals Inorganics can be found in materials that are used in polymer manufacturing (activators, colorants, etc.) USP <233> Instrumental methods like Inductively Coupled Plasma-Mass Spectroscopy (ICP-MS) Element list vary for polymer

14 USP 39 <661.1> continued Copolymers and Other Polymers NAMSA stance/recommendations on copolymers and other polymers not noted in USP. Biological reactivity Physiochemical testing Extractable metals Additives by standard UPLC/MS screen. Up to manufacturer/user to justify tests conducted for USP characterization. 14

15 New: USP 39 <661.2> Effective: May Title: PLASTIC PACKAGING SYSTEMS FOR PHARMACEUTICAL USE Physicochemical Testing Biological Reactivity Extractables/Leachables and Risk Assessment based on sound and justifiable scientific principles Consistent with nature, clinical use, perceived safety risk Assumed: dosage form-dependent

16 Thank you. For additional information or to request a proposal, please contact NAMSA: (toll free) (outside of USA) (fax) clientcare@namsa.com