EU GMP ANNEX 1 CHANGES CLARIFICATION AND IMPACT

Transcription

1 1 EU GMP ANNEX 1 CHANGES CLARIFICATION AND IMPACT UNDERSTAND THE PROGRESSION OF REGULATORY THINKING AND HOW TO SUCCESSFULLY IMPLEMENT THE PROPOSED CHANGES BALTIMORE, MD MAY 6TH AND 7TH, 2019 UNIVERSITY OF MARYLAND BIOPARK'S LIFE SCIENCES CONFERENCE CENTER

2 2 How will these changes affect your facility? The Annex 1 revision represents the latest global regulatory thinking in regards to manufacturing medicinal products. This major proposed revision includes input from all PICs member countries including US, Europe and others. THIS REVISION NOW APPLIES TO STERILE, LOW-BIOBURDEN AND TERMINALLY STERILIZED PRODUCTS EU/GMP Annex 1 revision links to ICH Q8, Q9 and Q10. The technical requirements for manufacturing medical products expect the implementation of Quality Risk Management (QRM-ICH Q9) within a Pharmaceutical Quality System (PQS ICH-Q10).This applies across the entire lifecycle of the product as defined in Pharmaceutical Development (ICH Q8). In this two day intensive workshop the following will be addressed: Details related to the changes between the proposed revision to Annex 1 and the 2008 version. Impact of each important change will be addressed with relevant case studies which will have bearing on your facilities, processes and policies Real world risk assessment with pertinent standards and guidances that can provide information on assessing contamination risks Discussion on how to implement the proposed Contamination Control Strategy Microrite s Contamination Control and Microbiology Experts will perform a comparative analysis of the 2008 Annex 1 to the proposed revision of Annex 1. This will be inclusive of statements and recommendations made by regulatory authorities, 483 observations and warning letters, supplemented by Microrite s vast experience in assisting companies in prevention and remediation of contamination. Each of the following sections in the proposed revision of Annex 1 will be discussed with respect to the changes which may affect your facility, process, procedures and policies Scope Principle Pharmaceutical Quality System Personnel Premises Equipment Utilities Production and Specific Technologies Viable and Non-viable Monitoring Quality Control

3 3 EVENT OVERVIEW 1. Scope Expanded scope in the proposed revision of EU GMP Annex I where risk assessment, QRM and contamination control strategy can be applied. The scope extends to non-sterile products, terminally sterilized products as well as low-bioburden products where control of particulate, pyrogen and microbes are required. Understanding the relationship between the various regulatory bodies How the expanded scope can affect GMPs in manufacturing of medicinal products 2. Principle General principles as applied to the manufacture of medicinal products. Introduction of a documented Contamination Control Strategy (CCS) to be implemented across the facility in order to assess the effectiveness of all the control and monitoring measures employed. Key elements of a contamination control strategy as required by the proposed revision Examination of the benefits of a documented contamination control strategy 3. Pharmaceutical Quality System (PQS) Highlighting the specific requirements of the PQS when applied to medicinal products. analysis of this brand new section in the revision which makes reference to specific aspects of sterile product manufacturing. Key points emphasized in this section elude to risk assessment which should not be confined only to manufacturing. Review of the addition of an ongoing risk review process. Mistakes made during risk assessment and improper use of QRM will be discussed through case studies of retroactive risk assessment vs proactive risk assessment FDA 483 observations related to contamination issues and case studies where risk assessment did not address the underlying issues will be shared 4. Personnel Examination of the expanded details regarding personnel, personnel training, aseptic techniques, garment choice and maintenance, and qualification as well as disqualification of personnel participating in aseptic manufacturing. Reasons for current 483s related to compromised gowns Common reasons for human borne contamination and how to mitigate the risk Case studies related to gowning and ergonomics which have led to contamination and inadequate aseptic practices Understanding the guidances for gowning and gloving in order to perform an adequate risk assessment Case studies related to training of manufacturing and laboratory personnel in aseptic manufacturing.

4 4 5. Premises Overview of the changes related to specific needs for premise design and guidance on the qualification of premises. Discussion on the substantial details in the revised version related to cleanroom design, barrier systems, measurement of airflows and air velocity, airflow visualizations, airlocks, pass-throughs, finishes, classification and qualification, disinfection as well as residue removal. Additional details, case histories and observations related to: o Cleanroom design, barrier systems, airflows and airlocks o Inadequate tools utilized for design verification and cleanroom certification flaws o Barrier systems flaws which lead to contamination and data integrity o Cleanroom design and barrier integration flaws not caught during smoke studies o Exploration of airflow patterns that lead to particulate and microbial contamination Case studies related to failed smoke studies-reasons and solutions New details on smoke studies in the proposed Annex 1 revision Common issues with airlocks and pass-throughs with respect to the new information in the Annex 1 revision Classification and Qualification: A probe into Annex 15 o New classification and qualification details in the revision with a breakdown as to why validations fail. Changes to cleaning, disinfection and disinfectant qualification as proposed in the revision o Myths and facts about disinfectants, contact time and residue in relation to new information on disinfection in the Annex 1 revision o Common errors made during disinfectant qualification studies o Importance of material compatibility and interactions between disinfectants and supplies o Importance of supply type and quality in controlling contamination 6. Equipment A summary of the few changes related to design and operation of equipment; cleaning process validation and specific changes to qualification of particle counters. Comparison of equipment sections from the 2008 version and the new draft version Examination of Annex 1 as related to validation Reasons why validated systems fail Common errors made during cleaning validation Microbial aspect of cleaning validation 7. Utilities Evaluation of this new section and added details related to water system design criteria, prevention of microbial adhesion and proliferation, WFI storage tanks, prevention of biofilms, and monitoring inclusive of continuous monitoring. Additionally, discussion on the new verbiage used for clean steam and SIP. An outline of the new section for compressed gases, vacuum systems, and cooling systems. Assessing microbial contamination risk in water systems

5 5 Appraisal of ongoing issues with sampling that may be causing sporadic contamination events Similarities between water system and process equipment contamination Common issues in compressed gas systems 8. Production and specific technologies Examination of the changes made for terminally sterilized products. Elaboration on the new section on aseptic preparations including the new table related to various operations and the grades in which they should be performed. Further details related to transfer of closed containers to lyophilizers and integrity of any transfer devices. Changes to reduction of aseptic manipulations utilizing engineering solutions, validation of hold times, and exposure time of sterilized containers and closures in critical processing zones. Details on container closure integrity instead of utilizing visual inspection solely. Changes to the sterilization section as well as further details on BI s (Biological Indicators), disinfection and transfer process for components that cannot be sterilized. New details in the section on sterilization by moist heat, dry heat, radiation and EtO and well as filtration. Changes to BFS (Blow Fill Seal) technology, lyophilization and closed systems. Probe into the brand new section on single use systems. Discussion of barrier system design issues Synopsis of risk in various barrier devices and aseptic manufacturing Assessment of 483 observations where barrier system, container closures and transfer devices have been the cause of contamination 9. Viable and non-viable environmental and process monitoring Examination of the major expansion of this section related to environmental monitoring, setting of alert levels, and changes to monitoring tables. Additional details on particulate considerations for continuous monitoring and rapid microbiological methods. Major changes to exceeding settle plate limits in Grade A. Use of airflow visualization as well as aerobic and anaerobic monitoring has been mentioned for the first time in this section. Scrutiny of a brand new section labeled Aseptic Process simulation (APS) detailing media fill plan, covering interventions and ensuring that contamination is detectable during reading of media fills. 483 observations related to non-risk based EM programs Common errors in setting up monitoring programs Why is airflow visualization proposed in the Draft GMP Annex 1 for selecting risk based sites Consideration of RABs design related to hard wired sampling sites without understanding airflows Risk mitigation during monitoring: o Media issues o Plans o Trends Risk assessment during non-viable and viable particulate sampling equipment selection Common errors in sampling that can increase failures or mask results Continuous monitoring of risk, to process and product via EM trends Breakdown of Process Simulation Studies

6 6 o Understand common media fill failures o Learning from 483 observations related to media fills o Defining interventions, without understanding airflows-a common error o Personnel comfort, gowning and technique risk o Case studies on avoidable media fill failures o Common issues when monitoring personnel o Assessing factors that can lead to contamination events in the fill line 10. Quality Control (QC) Expanded guidance on the quality control section regarding evaluation of microbial contamination risks in materials, process and microbial reduction strategies as well as testing. Reference to evaluating decontamination of sterility samples. Common laboratory errors that lead to sterility test failures Common challenges in investigating sterility test results GENRAL EVENT TIMELINE AND INFORMATION Event Location: University of Maryland BioPark's Life Sciences Conference Center 801 W. Baltimore Street Baltimore, MD Airport: BWI (Baltimore, Washington Intl., MD) Date: May 6th and 7th, 2019 Registration and Breakfast Lunch Break Questions and answers 8.00 AM to 8.30 AM PM to 1.00 PM 3.00 PM to 3.15 PM 4.15 PM to 5.00 PM Microrite does not have a room block or a preferred hotel for event attendees.

7 7 REGISTRATION INFORMATION Personal Information of One Registrant Last Name: Mr. Ms. Dr. First Name: Job Title: Organization: Mailing Address: Telephone: Fee: $ per attendee (Includes 2 day workshop fee, breakfast, lunch, break, and course Additional Attendees First Name: Last Name: Title: First Name: Last Name: Title: First Name: Last Name: Title: First Name: Last Name: Title: Method of Payment: Credit Card and Check payments only. Attendees can register and make payments on Microrite s website- or complete this form and fax to Check payments must be cleared before the workshop date. If you have any questions regarding payment methods feel free to contact Microrite at or send your enquiry to loechsli@microrite.com. For credit card payment on website, a payment receipt will be considered as confirmation of registration. For credit card information faxed to Microrite an confirmation will be sent with a copy of payment receipt. Please call in due time if confirmation is not received after payment. Cancellation must be received 15 business days prior to the workshop less a 10% service fee, cancellation requests will be accepted via only. service fee,

8 8 PAYMENT INFORMATION Choose One (Place X) VISA Master Card American Express Card Holder s Name Address of Card Holder: Enter firm address for corporate card or personal address for personal Street: City/State: Zip Code: Country: Contact Ph No & Card Number: Expiration(Month/Year): Amount (US Dollars): Signature: Name of Attendee(s) Referred by: Kindly note the name of the company or person that referred you to this workshop. We would like to thank them.

9 9 SPEAKER OVERVIEW Morgan Polen is a subject matter expert on contamination control, airflow visualization and particle monitoring in cleanrooms with over 30 Years of experience in various industries. He is a member of the ISO Technical Committee 209 (Cleanrooms and Associated Controlled Environments) and a board member of IEST and has been instrumental in drafting and editing ISO and other cleanroom related standards. Well versed in the practical implementation of cleanroom standards, regulations and guidelines. A valuable resource in addressing contamination control in critical environments for the electronics, aerospace and healthcare industries. He possesses extensive experience in working on cleanroom projects across the globe and speaking on contamination control and pharmaceutical regulations for particle counting and environmental monitoring. Ziva has over 25 years of academic, research, clinical and industrial experience in microbiology, and quality assurance. Ziva has received her Master s Degree in microbiology with a focus on Mycology and has conducted research on developing microbial Insecticides using entomogenous bacteria and fungi. Her career also includes founding and managing clinical laboratories for Maccabi Medical in Israel. She has trained personnel from various industries in microbiology techniques and methods. She uses her extensive experience to teach why assessing risk of microbial contamination should be in the forefront of any company that has products for human/veterinary use. Currently she is the President and Founder of Microrite, Inc., a California based consulting firm providing consulting and training services to pharmaceuticals, biotechnology, medical devices and in vitro diagnostics in the areas of quality assurance, quality control, microbiology, and validation. MORGAN POLEN- SENIOR CLEANROOM & PARTICULATE CONSULTANT MICRORITE, INC. ZIVA ABRAHAM- CEO MICRORITE, INC.