10/19/2011
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IPEC General Update
September 28, 2011
Update Topics
• Meeting schedule for 2012• ICH Q3D update• ExcipientFest 2012• EXCiPACT• EXCiPACT• ANSI NSF 363• NSF• IID update• FDA Spectral Library update
DECEMBER 7TH
BOARD OF TRUSTEE MEETINGWEDNESDAY NIGHT 5:30WEDNESDAY NIGHT 5:30
IPEC Meetings 2012
February May September December
Executive Committee11 ‐ 5
21Tuesday
14Monday
24Monday
3Monday
QbD (am)Exc. Comp (pm)
22Wednesday
15Tuesday
22Tuesday
4Tuesdayp (p ) y y y y
GMP (am)Exc. Comp (pmGeneral Update
23Thursday
16Wednesday
23Wednesday
5Wednesday
QbD (am)Exc. Comp (pm
24Friday
17Thursday
24Thursday
6Thursday
ICH Q3DMetal Impuritiesp
ICH Q3D• Guidance is making progress• To Do List
– Still need data from IPEC members (especially on items with mineral‐based excipients) or other non‐Rx products to help drive realistic metal limits
• Ie toothpaste
• IPEC is planning on a workshop for 2012 to gather and review additional data
• M = each ingredient used to manufacture the dosage form• CM = element concentration in component M (μg/g)• WM = weight of component in the maximum total weight of the drug
product administered in a daily dose (g/day)
( ) ∑ ⋅≥M
MM WCdaygPDE μ
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Metal Permitted Daily Exposure, μg/day Permitted Concentration, μg/g (assuming 10g maximum dose)
As 15 1.5Cd 5 0.5Hg 50 5Pb 10 1Al 5000? 500?Ni 250 25Co 0Sn 0Sb 0Tl 0Ba 0Ag 0Rh 100 10Ru 100 10Ru 100 10Mo 250 25B 0Ir 100 10Os 100 10Se 0Pt 125 12.5Pd 100 10Cr 250 25V 250 25Li 430 43Cu 750 75Mn 2500 250Au 0W ** **
Event History
Europe(Ireland)2007 & 2009US
(Baltimore)2011 Asia
(China) 2012
Americas (Puerto Rico)2001 – 20102012
2012
Development of concept / business plan by EXCiPACTTM GSC April 2011
Cross referenced acceptance of Rx360 and EXiPACTTM by 3.Q. 2011
Trademark protection by 2Q. 2011
EXCiPACTEXCiPACTTMTM CertificationCertificationKey Milestones for Implementation
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p y
Acceptance and acknowledgement by IPEC, CEFIC... by 3Q. 2011
• Base funding completed by 90% by 3Q. 2011
• Hiring of staff, establishement of the advisory board by 1.Q 2012
• Start of operations by 1Q. 2012
EXCiPACTTM - Minimise the Risks, Maximise the Benefits
EXCiPACTTM CertificationThe process and relationship
EXCiPACTTM 3rd Party Audit Organisation
Excipient user
ExcipientSupplier
Supplier passes on audit reportUser can verify audit report and
certificate with EXCiPACTTM
Agreement with supplierProvides audit report
and Certificate
Legal Agreement with3rd party auditOrganisations
Publish list and list of Certificates / validity on website
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g ppExcipient
user
EXCiPACTTM - Minimise the Risks, Maximise the Benefits
ANSI NSF 363 Excipient GMP
• 1st draft written and under review by committee– Dale Carter, Dave Klug, Ann VanMeter, Kathie Ulman Irwin Silverstein Chris Moreton JeffUlman, Irwin Silverstein, Chris Moreton, Jeff Brambora, Ian Moore, Steve Moss, Sidney Goode
• January 2012 – Public Draft published for comments
• 2nd Q 2012 – Final Standard Published
NSF InternationalA Global Leader in Public Health and Safety
Corporate Overview
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A Little History…
• Americans began dining out in the late 1930’s.• State health officials monitored food service establishments
for sanitation using a variety of criteria.• Inconsistent rules and regulations arose, varying from town
to town, state-to-state. Hence…A need for uniform national standards; NSF brings regulators• A need for uniform national standards; NSF brings regulators, industry, consumers and public health officials together.
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Founded in 1944 to Develop Standards, Certify Equipment
• NSF was founded as the National Sanitation Foundation in the University of Michigan’s School of Public Health in 1944.
• Today, we are known as NSF International, with a corporate headquarters in Ann Arbor, MI, USA, and operations in 120 countries.
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• Launch Foodservice Equipment Program
• NSF Testing Labs• Launch Swimming
Pool Safety• Launch Plastic
Piping Program
• NSF-ISR launched
• NSF becomes W.H.O. Collaborating Centre
• NSF Shanghai & NSF Mexico
• Davis Fresh acquired• CMi acquired (UK,
Chile, Peru, Italy, Spain, S. Africa, Czech Republic)
• David Begg & Associates (UK, Boston)
• 80,000 sq. ft lab expansion completed
NSF Growth: Organic and Acquisitions
1944 1970s1980s
2001-2005
2008-2011
1950s1960s 1990s 2006-
2007
• NSF founded Ann Arbor, MI
• Develop National Drinking Water Standards
• Bottled Water Certification
• NSF Brussels, Belgium opens to serve Europe
• Cook and Thurber acquired
• Launch Dietary Supplement Program
• QAI acquired• NSF Brazil open• Deloitte & Touche
Quality Registrar acquired (Canada)
• NSF Thailand & NSF India open
• NSF Surefish • Toy Safety• Trucost partner• NSF Costa Rica• Shanghai Lab• NSF Pharmalytica• AQA International
acquired
Bringing Industry, Regulatory and Consumers Together
USDA, EPA, FDA, HC, State, Local
Food, Water, Consumer Goods Media, Educators,Consumer Groups
Consumers
Regulators
Industry
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Today, NSF is a Global Leader in Public Health and Safety
• Developer of over 72 national consensus standards.• Steadfast ties with key associations and govt. agencies.• A Collaborating Centre for the World Health Organization.• Service provider to thousands of organizations in 120 countries.
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NSF Around the Globe
Americas EMEA AsiaUnited States Belgium Poland ChinaBrazil Czech Republic South Africa IndiaCanada France Spain JapanChile Germany Switzerland South KoreaCosta Rica Greece United Kingdom TaiwanMexico Israel ThailandPeru Italy Turkey
Netherlands Vietnam
NSF International OfficesGlobal Partners
NSF International Offices
Global Partners
Laboratories
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An Unmatched Professional Staff and Facility
• 1,200+ experienced professionals: microbiologists, toxicologists, chemist, engineers and public heath experts.
• 165,000 square feet of state-of-the-art laboratories in Ann Arbor and Shanghai, China, plus partner labs around the world.I ti I f ti T h l biliti• Innovative Information Technology capabilities.
NSF Collaborations
• NSF is a World Health Organization Collaborating Centre for: – Food Safety– Water Safety
• Drinking Water Quality Guidelines• Recreational Water Safety Guidelines
– Indoor Environment– Indoor Environment
• Works closely with International, Federal State and Local Regulators:– FDA– USDA– EPA– U.S. Government/Legislature– And many more…
NSF International Accreditations and Certifications Include
U.S. Canada Europe
ISO 14001 ISO 17025
NSF Capabilities/Services
NSF Core Business Units
NSF
Water Food Safety Sustainability
DietarySupplements
/Pharma
ISR
ConsumerProducts
/PLA/ Toy Safety
Food Safety and Quality Services
• Food Safety Systems through the supply chain– GFSI: SQF, BRC, FSSC 22000, GlobalGAP, IFS– Growers, producers, processors, distributors,
retailers• Produce Safety via NSF Agriculture
– Field evaluations, testing, consulting and training for growers, processors, distributors and retailers
• Other Food Safety Systems:– HACCP, Tesco Nurture, Tesco Nurture Organic, LEAF
• Seafood Safety & Quality via NSF Surefish– Seafood inspection, testing and consulting (MSC, ACC, HACCP).
• Processor Safety & Quality Services through NSF Cook & Thurber – Consulting/auditing for food, beverage, animal feed and packaging
industries.• Organic Certification through QAI
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Food Safety and Quality Services
• Retail Food Safety Services– Customized auditing & consulting for
restaurants, supermarkets and retail foodservice
• Foodservice Equipment Certification• Nonfood Compounds Registrationp g• Beverage Quality Certification
– Bottled water, packaged ice, flavored water and functional beverages to US FDA & EU Regulations
– Food Equipment/Nonfood Compounds Cert
• Food Safety Training and Education Programs– classroom, online, video, live webinars and on-site training
Water and Wastewater Systems – Major Program Areas
NSF developed many public health standards adopted by the US EPA to protect drinking water; and standards promoting pool/spa safety. NSF tests and certifies products to those standards:
• Water Treatment Distribution Components & Chemicals ( S / S 60 61)(NSF/ANSI 60 and 61)
• Mech. Plumbing Devices (faucets, valves) (NSF/ANSI 61, Sec. 9)
• Plastic Piping & Components (NSF/ANSI 14) • Drinking Water Treatment Units (RO, Softeners, filters,
pitchers) (NSF/ANSI Stds 42, 44, 53, 53, 55, 58, 62, 177)• Onsite Wastewater Treatment Devices
(NSF/ANSI Stds 40, 41, 46 and 245) • Recreational Water – Pool/Spa Safety (pumps, drains,
pool covers, filters) (NSF/ANSI 50)
Health Sciences (Dietary Supplements and Pharma)
NSF developed the only American National Standard for for Dietary Supplements in 2001 (NSF/ANSI Standard 173).
Di t S l t C tifi ti P• Dietary Supplement Certification Program– GMP audits; Toxicology, Label & Contaminant Reviews
• Athletic Banned Substance Certification Program: – Adds screening for 140 banned substances to the above– MLB, NFL,PGA, LPGA, NYPD, and Canadian Centre for Ethics in Sport
• NSF Pharmalytica – GLP and GMP Lab• analytical testing, consulting, training, registration and research and development
• DBA (David Begg Associates) - Pharma Training & Consulting• DBA Analytical – Biotech, Tox, GMP training
Toys & Residential Consumer Products Safety; Protocols
• NSF is accredited to test and certify toys and children’s products to the Consumer Product Safety Improvement Act.
• NSF develops protocols and standards for residential kitchen items and other household appliances.
• NSF tests a wide range of consumerNSF tests a wide range of consumer products to verify safety, quality and performance.
Sustainability and ISO/Strategic Registrations
• Sustainability Solutions– GHG verification– Environmental Claims verification– Trucost foot printing (carbon, water)– ISO 14001 (Environmental), R2, RIOS– Sustainable Forestry Initiative Sus a ab e o es y a e– Chain of Custody
• Strategic Registrations (ISO):– ISO 9001 (Quality)– ISO 22000 (Food Safety) – ISO 27000 (Information Security) – ISO 13485 (Medical Devices)– And more!
NSF’s Training and Education: A Cornerstone of NSF’s Health-Based Mission
• NSF’s Training and Education Division has a global network of technical experts available to deliver training around the globe for industry, consumers, regulators and pubic health officials.
• Training forms: online, food safety videos/DVD, guidebooks, live webinars and customized on-site training.
• Topics:– Food Safety & Quality
• Agriculture Producers, Food and Beverage Processing, Organic Certification, Seafood Safety and Quality, Restaurants and Supermarket Food Safety, Hotel and Hospitality Safety
– Sustainability, Social Accountability and Environmental management– Pharmaceuticals & Dietary Supplements Safety– Management Systems/ISO Registration – Drinking Water Systems
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Projects with IPEC –• Host midwest meetings• Partner for training programs• IPEA joint venture for EXCiPACT / ANSI
audits
Inactive Ingredient Database (IID) – Recent Issues affecting ANDA
SponsorsSponsorsDavid R. Schoneker
Vice Chair of Scientific & Regulatory PolicyIPEC Americas
Director of Global Regulatory AffairsColorcon
Email: [email protected]
Issues
• New developments at FDA related to the IID – problems for ANDA Sponsors
• FDA’s Substance Registration System (SRS)
• Impact on the Inactive Ingredient Database
• Example - HPMC Grade Issue
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Impact to the IID Assessment
• The SRS nomenclature is being used to add new item listings in the IID which are grade specific with whatever levels happen to be in the NDA or ANDA which triggers inclusion
• These specific references to the grades are now being used by FDA OGD reviewers as a precedence level when evaluating precedence of use at the Gatekeeper point when a ANDA is filed
• Many times the levels listed for the specific grades are much lower that what has traditionally been used
• ANDA sponsors are getting caught in the middle and don’t always know which listing to reference, especially for materials where they have been using non-grade specific references with higher levels in the past
• Triggering refuse to file letters unless additional safety data is provided
Impact to the IID Assessment
• Many times safety data is not readily available from suppliers or the data is old or for a family of materials rather than specific to a grade
• IPEC Americas is trying to set up a meeting with FDA OGD to discuss solutions to this problemdiscuss solutions to this problem
• FDA has agreed to meet with IPEC. Date is being determined. Should be established soon!
• IPEC Regulatory Affairs Committee will be developing the agenda and speaker list for this meeting on Thursday
Discussion and Questions
FDA Spectral Library CALL TO IPEC
• Butylated Hydroxyanisole
• Gelatin• Povidone• Butylated
H d t l
• Maltodextrin• Sorbitol• Croscarmellose• Microcrystalline
Cellulose
• Calcium Stearate• Hydroxy Propyl
Methyl Cellulose• Shellac• Carboxymethyl
C ll l Hydroxytoluene• Glycerin• Pregelatinized
Starch• Calcium
Phosphate (Dibasic)
• Hydroxy Propyl Cellulose
• Propylene Glycol (liquid and solid) 41
• Starch (Corn)• Crospovidone• Polyethylene
Glycol, liquid and solid
• Stearic Acid• Ethylcellulose• Polysorbate 80 • Talc• Titanium Dioxide
Cellulose • Lactose• Silicon Dioxide• Castor Oil• Magnesium
Stearate• Sodium Starch
Glycolate• Cresol
FDA Spectral Library – Participation Benefits
1. An inspector can make an immediate determination as to whether or not laboratory analysis is necessary by performing a screening test. This approach would reduce delays associated with sending samples to a laboratory.
2. Knowledge that FDA is screening excipients and that excipients are receiving a higher level of scrutiny should provide deterrence and add a layer of difficulty for anyone trying to infiltrate the supply chainfor anyone trying to infiltrate the supply chain.
3. All parties can have an increased level of confidence that the material being identified is indeed from the qualified supplier.
4. Materials that are different from the spectral reference standards can be flagged for additional investigation and, if warranted, subsequently added to the library.
5. All parties will have increased assurance that goods were not tampered with, substituted or otherwise falsified with regard to their origin during distribution.
6. Screening and surveillance activities can enable rapid response to concerns of contamination, adulteration and/or substitution in the supply chain reported to or identified by FDA.
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10/19/2011
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FDA Spectral Library – Participation Benefits
1. An inspector can make an immediate determination as to whether or not laboratory analysis is necessary by performing a screening test. This approach would reduce delays associated with sending samples to a laboratory.
2. Knowledge that FDA is screening excipients and that excipients are receiving a higher level of scrutiny should provide deterrence and add a layer of difficulty for anyone trying to infiltrate the supply chainfor anyone trying to infiltrate the supply chain.
3. All parties can have an increased level of confidence that the material being identified is indeed from the qualified supplier.
4. Materials that are different from the spectral reference standards can be flagged for additional investigation and, if warranted, subsequently added to the library.
5. All parties will have increased assurance that goods were not tampered with, substituted or otherwise falsified with regard to their origin during distribution.
6. Screening and surveillance activities can enable rapid response to concerns of contamination, adulteration and/or substitution in the supply chain reported to or identified by FDA.
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IPEC ‐ FDA QbD Excipient Workshop White Oak ‐ December 5th
9am ‐ Noon
• Speakers– Brian Carlin (FMC)
– Dave Schoneker (Colorcon)
Chris Morton (FinnBrit Consulting)– Chris Morton (FinnBrit Consulting)
– Graham Cook (Pfizer ‐ possibly by videoconference if he cannot attend)
– Tom Schultz (J&J)
– FDA perspective
– Others … other
Agenda
• Introduction to IPEC and IPEC Guideline
• Types and Sources of Excipient Variability
• Performance related properties (compositional and physical)
• Limitations of possible controls in chemical plants
• Communication between maker and user
P d i t ti f i i t• Proper design space expectations for excipients
• Misunderstandings of what types of samples will be available for experimentation
• Concepts for design space development
• Advanced concepts for future improvements
• Panel discussion Q&A