The Future of Excipient Auditing P2: Partnership for Supply Chain Management Monday, June 3, 2013,...
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Transcript of The Future of Excipient Auditing P2: Partnership for Supply Chain Management Monday, June 3, 2013,...
The Future of Excipient Auditing
P2: Partnership for Supply Chain ManagementMonday, June 3, 2013, 3:30 p.m. – 5:30 p.mDale CarterDirector Global Quality, Huber Engineered Materials SilicaImmediate Past Chair – IPEC Americas
www.ipecamericas.org 1
IPEC Offers Excipient Stakeholders a Regional Voice
with Global Influence IPEC Federation• Established in 2009, • based in Belgium / made up of regional IPECSIPEC-Americas• North, South and Middle Americas
Partnership with Sindusfarma (Brazil) and SaFybi (Argentina)
IPEC-Europe• Europe, North Africa, Middle East
IPEC Japan
IPEC China
IPEC India (being formed)
IPEC Americas Provides Balance
• Maker members covering the diversity of excipients
• Distributor members• User members
This combination of members provides the full view of issues surrounding excipients, providing IPEC Americas the unique capability to develop science based guidance and position documents that work.
14
13
IPEC History & Guidance Documents
10
0908
070
6
0504
030
2
010
0
9998
9796
95
93 9
492
91
IPEC Forms
Safety Evaluation of New Excipient USP <1074>
GMP Audit
GMP Rev1
Sig. ChangeUSP <1195> EIP
Excipient GMPUSP <1078>
GMP Audit Dist.Cert. of AnalysisUSP <1080>
EMFGMP Audit Rev
1211
Reg. Affairs Conf.
Reg. Affairs Conf.
Reg. Affairs Conf.
GDPIPEC /PQG GMP
EQ 1IPEC/PQG Audit
EQ 1, 2, 3Pedigree Paper
Sig Change R1EIP TemplateQuality Agree.Composition
CoAEIP Rev1
Reg. Affairs Confer. combines with Excipient Fest
Dist. Audit Guide 2011
Stability Program GuideGlossary for Excipients
The Joint IPEC-PQG Good Manufacturing Practices Guide for Pharmaceutical Excipients 2006
• Basic Quality Management Systems principles plus key processes necessary to ensure production of safe consistent products
• Emphasizes communication between manufacture and user– Significant Change– Certificate of Analysis– Stability
• International in scope• Useful and acceptable to suppliers,
users and regulators
Current State
• IPEC/PQG Guideline is the basis for most audits• Individual company auditors in single or group audits.• Quality of the audit varies with auditor background
and experience.• Excipient manufacturers essentially have the same
audit multiple times. • Numerous audits per year for each excipient
manufacturer.– Drives group audit practice– “Check-box” type approach– One day audit
Excipient GMP Certification Standards2 standards from 1 GMP (2006 IPEC PQG)
• EXCiPACT – – GMP/GDP certification as an Annex to ISO 9001:2008
Quality System Standard – Joint effort of IPEC Europe, European Fine Chemicals
Group, IPEC-Americas, Pharmaceutical Quality Group, and European Association of Chemical Distributors
• NSF/IPEC 363GMP – Good Manufacturing Practices for Pharmaceutical Excipients– Forthcoming ANSI Standard for certification of effective
implementation of excipient GMPs by a manufacturing facility
– For use by companies without ISO 9001 registration– Team of Makers, Users, and Regulatory/Academic/public
DRAFT Feb 8, 2013
Guidelines and Standards
• IPEC PQG GMP Guidelines – No certification option– IPEA Certification done through “SOP # 8” that
converts the IPEC guide into a certification protocol
• EXCiPACT – ISO Annex for GMP Certification – Addition to existing ISO certifications
• NSF/IPEC 363 GMP Standard (4Q 2013)– Stand alone QMS + GMP certification
Standards Development Process
• The IPEC/PQG GMP Guideline is the basis for both EXCiPACT and the ANSI/NSF 363 Standards.
• Both development processes had multiple stakeholders involved. – NSF/IPEC 363 followed ANSI process for consensus
standard
• Great care was taken to have the two standards have identical requirements.
• IPEC Americas and IPEC Europe were represented on both development committees.
Risk Assessment in Excipient GMPs
Procedures and controls implemented in following the IPEC-PQG GMPs have always been the output of risk assessment exercises
Now the justification and thought process to support these controls are documented.
– Documentation facilitates better understanding of GMP controls and helps prevent perpetuation of unfavorable consequence from changes made by the uninformed
So what’s new?
Why is Risk Assessment in NSF 363?
• Challenge in defining a clear and auditable standard that can be applied across the vast diversity of excipient manufacturing processes…
• Attempts to define requirements for one excipient often absurd for another.
• Joint IPEC-PQG GMP Guide for Pharmaceutical Excipients 2006, a source document, addressed differences by presenting various options or points for consideration and in some sections also referred to risk assessment.
NSF/IPEC 363 GMP Documented Risk Assessment Required in sections:
4.3 Change Control
5.5.3 Internal Communication
6.2.3 Hygienic Practices
6.3.1 Buildings and Facilities6.3.2.1 Equipment Construction
6.3.3 Utilities
6.4 Work Environment
7.4.1 Purchasing Process7.5.5.2 Excipient Packaging
Systems
8.3.2 ReworkingDRAFT Feb 8, 2013
Risk Assessment
Identification• The sections of NSF/IPEC 363 requiring risk
assessment preload the process by:– defining the scope or “risk question(s)”, – providing the nature of hazards to be considered, and – pointing to risk controls that may be implemented
Risk Assessment for Excipients differ from that for Food Products
• People can chose other food and be nourished but have no choice in taking the medicine prescribed by their physician
• ICH Q9 definition of “harm” includes everything from Food Risk Assessment plus the additional “damage to health, including the damage that can occur from loss of product quality or availability”
• Failure of a drug batch as the result of an excipient also consumes a good API that is no longer available to the market
Documentation
• Allows an assessment of the results in terms of – the risks to be controlled, – the reasoning and facts leading to the
conclusions, – understanding the risks that were considered
• Provides evidence that– competent people performed exercise– adequate information was available– a standard process was followed– an appropriate assessment was conducted
Can a 3rd party audit
do what a 1st party audit does?• Assess compatibility of supplier with
internal programs• Indentify risk and validate controls• Educate supplier • Enhance communication• Meet regulatory/policy requirements
Nothing in FDA regulations prevents using 3rd party auditors
to evaluate suppliers
Sec. 211.34 Consultants.
• Consultants advising on the manufacture, processing, packing, or holding of drug products shall have sufficient education, training, and experience, or any combination thereof, to advise on the subject for which they are retained. Records shall be maintained stating the name, address, and qualifications of any consultants and the type of service they provide.
Why audit?
• Regulatory expectation / requirement• Understand how well the risks from your
suppliers are mitigated by your internal process/programs
• Confirm the reliability of your supply chain• Collect objective evidence that supports your
confidence in the supplier
Benefits of Audit
• Business intelligence to secure supply chain• Process improvement• Validate assumption• Risk assessment• Continuity of supply• Communication with suppliers
Additional Considerations
Audits help both supplier & customer understand• Language differences exist between the chemical and
pharma industries (e.g. process capability vs. validation)• IPEC Guides help with translation • Environmental health and safety systems address GMP
principles. In the chemical industry, consequence of system failure may be tragic to plant, workers and community– Keeping product in pipes and out of environment may
be same as the control of contamination to keep environment out of product in GMP
Third Party Certifications
• Standards build GMP from a universal QMS foundation whose processes connect well to other systems
• Preparation for certification educates suppliers and provides greater understanding of their own processes
• Using qualified auditors in an IPEA or EXCiPACT certification program provides confidence in the audit results (both regulatory and internal)
• Audit reports provide information from which to ask further questions
• Communication can proceed more effectively through other channels building on certification information– Quality Agreements, shorter site visits, conference calls
22
Excipient GMP Certification
Application Planning Audit
Report ReviewCertificationReview Board
23
IPEA Excipient GMP Certification Program
• Comprehensive Site Audit to Excipient GMPs– Minimum 2-days, 2 auditors, single excipient– Excipient manufacturer decides scope of site audit
• Identifies excipients within scope
– Annual surveillance audit
• Certification Board– 4 Independent Qualified Experts
• Review Application, Audit Report, and CAPA plan to Certify
• Audit Sponsorship– Excipient Maker, or– Excipient User
• Audit sponsors are considered confidential and are not disclosed
NOTE: IPEC-Americas has signed an agreement to sell IPEA auditing
to NSF International
24
ANSI Accredited to ISO/IEC Guide 65, General requirements for bodies operating product certification systems
– FDA requested IPEA become accredited
– Accredited since April 2010
E-mail : [email protected]
www.ipeainc.com
IPEA Certification
NOTE: IPEC-Americas has signed an agreement to sell IPEA auditing
to NSF International
25
Cost of Certification & Reports
• First year certification - $20,000 IPEC members, $22,000 non-members for a single site & single excipient (often including multiple grades).
• Additional excipients or manufacture that includes contract operations are priced according to the additional time required for the on-site audit. Audits with extraordinary travel requirements and related costs may cost slightly higher.
• Annual fee for surveillance audit and recertification is half the price of certification.
• IPEC-Americas member companies receive a 10% discount from all prices unless otherwise posted.
• The Certification Audit Report is available for purchase – $500 for IPEC-Americas member companies – $750 for non-members– Most of the proceeds from report sales are provided as a credit to
the excipient supplier to reduce their annual surveillance cost
Benefits of IPEA Certification
• Security that you have opportunity to review report draft for any factual errors, omissions, and confidential information before report is finalized.
• Confidence that, if needed, any CAPA plans will be included as an addendum to an audit report before a final copy is sent to the Sponsor.
• Quality review of each audit report by IPEA review board who insure consistent and appropriate application of IPEC excipient GMP requirements.
• Opportunity to use audit reports to establish to customers your compliance to appropriate GMP requirements.
• Independent and impartial IPEA assessments help gain customer confidence in your quality system
• Confidential audit reports are never sold without notification and approval of the audited manufacturer . Affords you the opportunity to prevent the report from being sold to a competitor.
Supplier passes on audit reportUser can verify audit report and
certificate with EXCiPACTTM
Association
Agreement with supplierProvides audit reports
and Certificate
Legal Agreement with3rd Party AuditOrganisations
Publish on website lists of Valid Certificates Qualified Auditors
EXCiPACTTM Certification The process and
relationship
EXCiPACTAssociation
3RD Party Audit Organisation
Excipient user
ExcipientSupplier
Excipient user
EXCiPACTTM – minimize risks, maximize benefits
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EXCiPACT™ Certification Current Status
· Two Agreements have been signed with Certifying Bodies· blue inspection / mdc, Stuttgart· SGS
· Pilot Audits have been completed· Discussions are ongoing with other Certifying
Bodies
EXCiPACT™ Certification
EXCiPACTTM - minimise risks, maximise benefits
EXCiPACTTM CertificationCost savings for
stakeholdersCost for EXCiPACT
AuditExcipient Supplier Pharmaceutical
Company
Audit fee ~ $13,000
Certificate fee ~ $7000
Surveillance ~ $7000
Internal cost ~ $8000
Total cash-out~ $35,000
Total cost in 3 years~ $35,000
Reduction by one two-day audit a month, plus one day for preparation, at internal cost incl. of ~ $2500 each, plus ~ $6000 travel expenses per year
~ $37,000 savings per year
Reduction by one two-day audit a month , plus three days for travel and preparation of the report , plus travel expenses, at total cost of ~$22,000
~ $74,000 savings per year
Total Savings in 3 years~ $110,000
Total Savings in 3 years
~ $225,000Total Industry Benefit $75,000 $300,000
Audit Sharing Programs
Other programs have many challenges• Use of Industry auditors
• The Quality of the audit is only as good as the auditor
• Legal complexity • Many excipient manufacturers legal departments will not allow
for sharing of audits.
• Excipient manufacturers fear loss of control of confidential or proprietary information.
• Unlike IPEA or EXCiPACT certified auditors, auditors are not subject to qualification standards.
These are not certification programs
William Dale Carter
Immediate Past Chair IPEC Americas
[email protected] of Global Quality
JM Huber, Engineered Materials – Silica
3100 Cumberland Blvd, Suit 600
Atlanta, GA 30339
Phone 678-247-2735 Acknowledgements:
Kathie Ulman – Dow-Corning
Ann Van Meter - Dow Wolff Cellulosics
Irwin Silverstein – IPEA
Priscilla S. Zawislak - Ashland
Iain Moore - Croda