George Bernstein, Ph.D. Double Dragon Consulting Inc.

Transcription

1 THE AMERICAN ASSOCIATION OF HOMEOPATHIC PHARMACISTS George Bernstein, Ph.D. Double Dragon Consulting Inc.

2 1. Introduction 2. Background 3. Validation Master Plan 4. Tips for Success 5. What Do I Need to Show an Auditor? 6. Resources 2

3 Principal with Double Dragon Consulting Ph.D. in Chemical Engineering 20+ years of Pharma experience 20+ years as a consumer of homeopathic products Wide range of experience: Quality Systems Development, Audits, Documentation, Investigations, Remediation Validation Project/Program Management Facility Construction and Commissioning Root Cause Analysis Business Process Re-engineering Our website

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5 Can be summarized as follows: The quality, identity, strength, and purity of products are controlled. Notes Stability testing requirements are limited to compatibility of ingredients [see 21 CFR (c)] Homeopathic products must comply with HPUS and USP requirements. Homeopathic products are no longer excluded from testing for identity and strength. See Federal Register: November 26, 2004 (Volume 69, Number 227)] [Proposed Rules] [Page ] 5

6 There may be instances where testing of a homeopathic product for identity and strength of the active ingredients prior to release for distribution would be appropriate and consistent with protection of the public health. For example, in instances where a product includes an active ingredient that at certain levels could be toxic or otherwise pose a public health concern, finished product testing may be appropriate because the testing could identify a significant manufacturing or labeling error. Since requiring this testing when necessary to protect the public health is consistent with FDA s mandate, we are withdrawing the proposed rule. [Federal Register: November 26, 2004 (Volume 69, Number 227)] [Proposed Rules] [Page ] 6

7 Written proof that you meet cgmp in all aspects of product manufacture The FDA defines validation as Establishing documented evidence which provides a high degree of assurance that a specific process will consistently produce a product meeting its pre-determined specifications and quality attributes." 7

8 Perhaps a better definition is: The activities performed to demonstrate that a given utility, system, process or piece of equipment does what it purports to do. The primary means of accomplishing this end is a documented scientific study designed to determine whether the entity under scrutiny in fact: Meets or exceeds the specifications of its design Is properly built, installed, operated and maintained Is suitable for its intended application Conforms to basic cgmp design and operation criteria Will satisfy the concerns of regulatory agencies Is capable of consistently producing a product that meets all predetermined specifications and quality attributes Will meet the goals established for productivity, safety and quality 8

9 Product quality specifications = good product Things that affect product specifications = high risk Where possible use equipment/materials that reduce risk Create processes that reduce risk Document to show that risk is controlled Validation serves to identify and control the risk to product quality and hence, to public health 9

10 Scope of Validation Activities Facilities/Utilities Analytical instruments and methods Equipment Process Cleaning Computer System Not a one time activity! Can be expensive 10

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12 Validation Master Plan the overall plan for: What to validate How to validate Who is responsible for what What documents to produce IQ Installation Qualification Written documentation of what was installed OQ Operational Qualification Written documentation of how it worked when it was installed PQ Performance Qualification An on-going written history of how it is working 12

13 The Validation Master Plan: Defines the scope of the validation projects Defines roles and responsibilities Describes the facility and processes to be validated Defines the validation approach Defines the key validation activities Defines the deliverables/documents to be generated Defines acceptance criteria and applicable regulatory standards How to handle deviations and non-conformance Gives guidance on how to execute the validation project Defines when re-validation is required (change control) Identifies which systems will be validated and those that cannot (with justification) Personnel training and qualifications 13

14 1. Introduction 2. Validation Objectives 3. Scope (risk items) 4. Definitions 5. Responsibilities (who writes, who approves prior to validation, who executes, who approves final documents) 6. Facility Description 7. Process Description 8. Validation Approach (based on risk) 9. Validation Protocol Preparation (who writes, who approves) 10. Acceptance Criteria (acceptable vs. unacceptable results) 11. Monitoring the Validation Program 12. Deviations and Non-conformance (how documented, how resolved) 13. References 14. Appendices Forms Equipment/Process/ Utilities Matrix 14

15 Identity/Strength Testing May be required in certain instances Raw materials must be identity tested (see HPUS, USP) For high potency products where testing may not be possible, develop robust processes for mixing, serial dilution, succussion, trituration, to reduce risk of ingredient mix-ups. For high potency products, use surrogates to validate cleaning effectiveness (e.g., test for lactose residues, cleaning agent residues, and microbial contamination) For low potency products, test for the actual starting material to validate cleaning effectiveness along with cleaning agent residues and microbial contamination Finished goods must be tested for bioburden contamination, tablet characteristics. Establish a release testing program to verify that product does not contain toxic levels of starting material (confirms adequate mixing) 15

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17 1. There are many right ways to validate and many wrong ways, but no validation is no excuse 2. Something is better than nothing 3. There are VMP templates available on the internet. If you go this route, be sure that you understand what you are doing and why when you draft each section. Defensible Position 17

18 1. A Validation Master Plan a. That is in effect and current b. That has been signed and dated c. That is being followed 2. Documentation (e.g., IQ, OQ, PQ) a. That is consistent with the VMP b. That is current c. That has been signed and dated 3. An understanding of why validation is important 4. A change control program 5. Deviation tracking 18

19 Guidance Documents Guidance for Industry. Process Validation: General Principles and Practices. November U.S. FDA. Quality Risk Management. Q9. November ICH. ISPE ( Basic Principles of Commissioning and Qualification. Training Course. ISPE Application of Commissioning and Qualification. Volume 5: Commissioning and Qualification. March ISPE. Templates that can be purchased online Consultants 19

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