excipient auditing and ipea certification of excipient auditors

The Role of the American National Standards Institute (ANSI)

1Irwin Silverstein, Ph.D. IPEA32

ANSI Activities American National Standard: Excipient GMP

Accreditation of Product Conformity Bodies

Certification to Excipient GMP


IPEA and IPEC-Americas IPEC-Americas: industry association

that develops, implements, and promotes global use of appropriate quality, safety, and functionality ...

IPEA: provides cGMP audit services to the pharm, chemical, and nutriceutical industries to facilitate the assessment of excipient manufacturers to appropriate GMP requirements.

32 Irwin Silverstein, Ph.D. IPEA 3

Excipient GMPs

IPEC-PQG GMP Guide for Pharmaceutical Excipients

U.S. Pharmacopeia <1078>

WHO good manufacturing practices-starting materials

ANSI American National Standard (2010-2011)

NSF 363 Under development

Draft Q1 2011

Approval mid-2011


ANSI Excipient GMP National StandardAuditable Standard

Development

Open Process to Ensure Level Playing Field

Available for Public Comment

Balanced Review and Approval by Impacted Parties

Consideration of Views and Objections


ANSI Excipient GMP National StandardConsensus Approval

Developed for Public Good

Voluntary Compliance

FDA can adopt an ANSI standard as regulation. FDA has expressed the importance of this

standard.


National Technology Transfer and Advancement Act (1996) NIST to coordinate Federal, State and local

standardization and conformity assessment activities

Agencies adopt private sector standards, particularly those developed by standards developing organizations, wherever possible, in lieu of creating proprietary, non-consensus standards

Goal is to reduce unnecessary government standards that create confusion and add expense for compliance

Irwin Silverstein, Ph.D. IPEA 732

OMB Circular A119 (1993) “Federal Participation in the Development and Use of

Voluntary Consensus Standards and in Conformity Assessment Activities”

Establishes policies for Federal use and participation in consensus standards and on conformity assessment activities

Revised in 1998 to achieve consistency with NTTAA terminology


ANSI Excipient GMP National Standard ANSI Standards Developer Proposes to Write Standard

Committee Assembled

Balance of interests:

Excipient Producer

Excipient Users

General Interest

Public Notice of Standard Development

Public Comment Period

Published in Standards Action

Minimum 30-Days


ANSI Excipient GMP National Standard Consideration of Views and Objections

Resolve or

Notify Objector of Appeals Process

Report objection to ANSI Board of Standards Review (BSR)

Final Approval

Consensus Vote

Demonstrate to ANSI consensus was achieved

Review by ANSI BSR

Affirm ANSI requirements were met

Standard Published


ANSI Excipient GMP National Standard Essentially a rewrite of IPEC-PQG Guide into

Standards format

Should to Shall

Require documented risk analyses

Irwin Silverstein, Ph.D. IPEA 1132

Excipient Certification Accredit to American National Standards Institute

Develop Auditable Standard

IPEC-PQG Excipient GMP

Document the Certification Program

Create Program Administration

Establish Objective Expectations

Create Certification Body

Prepare Quality Manual

Host ANSI Assessment

12Irwin Silverstein, Ph.D. IPEC 12Irwin Silverstein, Ph.D. IPEA32

ANSI Accreditation Application filed July 13, 2009

Application 15 pages

plus 97 pages of supporting details

IPEA To Do List1. Complete internal audit Scheduled for July

2. Contract with applicant

3. Schedule audit

4. Assign audit team

5. Train Certification Board members

6. Assign Certification Board


ANSI Product Conformity Accreditation Accreditation Issues

1. Financial Stability and Resources

Demonstrate independence


ANSI Accreditation Accreditation Issues

2. Conflict of Interest

SOP 11

Voluntarily Disclose:

Employed or Consulted prior 5 years

Employees Immediate Family Member

Significant Financial Interest

Recuse from:

Certification Audit

Certification Audit Report Review

Certification Board



3. Auditor QualificationSOP 2 Education and Experience

Training by IPEA

3-Day Workshop or Expedited 1-Day

Report Writing

Excipient GMP Expectations

Performance Review

Observation of an Audit

Ongoing Review



4. Certification Board

SOP 7

Education and Experience (Preferably Management Level)

Excipient Maker, User or Independent (FDA, USP, Academia)

Training by IPEA

Excipient GMP Certification Program

Excipient GMP Expectations

Performance Review



5. Surveillance

SOPs 9, 17, and 20

Certification for 2 years

Surveillance audit annually

Notification of Change that Impacts GMP Quality System

Incidents that Impact Conformance

Customer Audit or Complaint

Regulatory Inspection

Unauthorized use of the Mark or Certificate


ANSI Accreditation ANSI Assessment

1. Review and accept application

2. Establish assessment team

3. Team reviews documentation.

No records to review.


ANSI Accreditation ANSI Assessment

4. Team witnesses audit

5. Team witnesses Certification Board review

6. Team reviews certification records

7. The Team makes a recommendation to ANSI

8. ANSI Board decides on Accreditation of IPEA


ANSI Accreditation Process

Procedures

Assessment

Application

Evaluation Task Force

Accreditation

APPROVED

Preliminary Application


IPEA ANSI Accreditation

ANSI Assessment

1. Review and accept application

2. Establish assessment team

3. Assessor reviews documentation

Quality Manual

SOPs

Policies

Records

4. Assessor witnesses audit

22

No Findings

No Findings


IPEA ANSI Accreditation

ANSI Assessment

5. Assessor reviews audit report and Board minutes Approved Certification of Grace Davison Curtis Bay: Silicon Dioxide

NF

6. Assessor presents accreditation report to Evaluation Task Group (ETG)

7. ETG recommended accreditation to ANSI Accreditation Board

8.Accreditation Board approved Accreditation of IPEA program


IPEA Certification Auditor Competency and Qualification

Education

Audit Experience (Excipient or Pharmaceutical)√ GMP Auditor √ CQA, ISO Lead Auditor, etc

Personalized Training — Excipient Auditing Workshop

Supervised Qualification Audit

Review of Audit Report by

Audit Supervisor

IPEA Executive Management

Consensus Acceptance by CEO and COO

Ongoing Performance Review


Excipient Certification Board 2-Members each from Maker and User

Community or IndependentReview Audit Report and Findings

Interview Auditor

Assess Adequacy of Quality System

Recommendation Certification or

Correction of Deficiencies


Excipient Certification Audit Verification Excipient is Produced Using Appropriate

Quality System Emphasizing:

Manufacturing

Quality Unit

Packaging, Labeling, and Tamper-Evident Seal

Documentation and Records

Change Control

Audit Duration

Per Excipient: 2 Auditors for 2 Days


Certification Criteria1. No Items Rated “Critical Failure”

2. No Items Rated “Does Not Meet” Unless Interim Action or Implemented CAPA

3. No Section with “Partially Meets” Cumulatively Indicating Noncompliance

4. No impression there is a significant risk that the quality system is inadequate to assure excipient safety and quality.


Excipient GMP Certification Comprehensive Site Audit to Excipient GMPs

Minimum 2-days, 2 auditors

Certify Conformance Issue Certificate

Post to Website

Make audit report available at nominal cost Off-set cost for certification

Certification Status Certified

Certification suspended

Certification withdrawn

16 2828Irwin Silverstein, Ph.D. IPEA32

IPEA Certification Program Oversight

Certification Board

4 Independent Qualified Experts

Review Application and Audit Report to Certify

IPEA Management Board

Internal Audit

IPEA Board of Directors

Annual Program Review

ANSI


30

President and Chief

Executive Officer

Vice President and Chief

Operating Officer

Secretary-

Treasurer

Past Chair

IPEC

Management Committee

IPEA Excipient GMP Conformance

Certification Program

Qualified Auditors

Certification Board

IPEA Staff

Irwin Silverstein, Ph.D. IPEA32

IPEA Certification Process

31

Certified

Application Planning Audit

Report ReviewCertificationReview Board

Irwin Silverstein, Ph.D. IPEA32

Accredited April 2010

First surveillance audit: No nonconformances


excipient auditing and ipea certification of excipient auditors

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