THE PACMP STRATEGY. March 13-16, 2018

Transcription

1 THE PACMP STRATEGY FDA/Xavier PharmaLink Conference 2018 March 13-16, 2018 Ajay Pazhayattil, Director- Pharmaceutical Development, AvacaPharma Inc., Vienna, VA

2 PACMP ICH PREREQUSITES PACMP STRATEGY IMPLEMENTATION EXAMPLES QUESTIONS BENEFITS

3 ICH Q8- Q12 Q9 QUALITY RISK MANAGMENT Q11 DEVELOPMENT AND MANUFACTURE OF DRUG SUBSTANCE Q8 PHARMACEUTICAL DEVELOPMENT Q10 PHARMACEUTICAL QUALITY SYSTEM Q12 TECHNICAL AND REGULAORY CONSIDERATIONS FOR PHARMACEUTICAL PRODUCT LIFECYCLE MANAGEMENT

4 REGULATORY CONVERGENCE ICH Q10 Knowledge Management Quality Risk Management Management Responsibility Product Lifecycle Management Pharmaceutical Quality System Continual Improvement Performance Monitoring ICH Q8 Quality Target Product Profile Critical Quality Attributes Risk Assessment Design Space- DoE Control Strategy Product Lifecycle Management Continuous Improvement ICH Q11 Critical Quality Attributes Risk Assessment Design Space Control Strategy Process Validation Lifecycle Management ICH Q9 Quality Risk Management Risk Assessment Risk Control Risk Communication Risk Review Risk Management Methods & Statistical Tools FDA PV GUIDANCE PV Lifecycle Risk Assessment Statistical Tools Continued Process Verification Continuous Improvement EMA PIC/S WHO USP

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6 SOLUTION CONVERGENCE

7 PQS IS ALREADY A GMP REQUIREMENT EFFECTIVENESS TOOLS ARE THE NEWEST REQUIREMENT

8 THE RIGHT TIME ICH Q12: TECHNICAL AND REGULAORY CONSIDERATIONS FOR PHARMACEUTICAL PRODUCT LIFECYCLE MANAGEMENT o Facilitate management of post-approval CMC changes in a predictable and efficient manner. o Facilitate reduction in the submissions through increased product and process knowledge. o Reduce unnecessary cost, time burdens on industry and regulators, while assuring that patients haveaccess. o Realize benefit of applying innovative manufacturing technologies on a timely basis. o Enable increased transparency between industry and regulators, MAH and manufacturers, reviewers and inspectors. Accomplished through integrated lifecycle tools and enablers.

9 ACTIVITIES ICH Q12: Provide guidance on a framework to facilitate the management of post-approval Chemistry, Manufacturing and Controls changes in a more predictable and efficient manner across the product lifecycle. Adoption of this new ICH Guideline will promote innovation and continual improvement, and strengthen quality assurance and reliable supply of product, including proactive planning of supply chain adjustments.

10 Q12 o Established Conditions (ECS) o Post Approval Change Management Protocol (PACMP) o Product Lifecycle Management (PLCM) o Pharmaceutical Quality System (PQS) and Change Management o Relationship Between Regulatory Assessment and Inspection o Post-Approval Changes for Marketed Products What do you think of the guidance version currently under public consultation?

11 A LIFECYCLE STRATEGY o Effective application of PACMP, is a strategy for lifecycle change management. o Change Examples: Scale, API change, Equipment change o PACMPs may be accepted by a limited health authorities; however, harmonization of best practices across ICH and some non-ich regions facilitate efficient implementation of post-approval changes for patient benefit. o PACMPs save considerable time and resources and enable a continued supply of drugs to patients while maintaining product quality. o 2 types of PACMP and 2 step approach (submission of changes and submission of results leading to faster review due to familiarization of change and faster implementation)

12 PACMP o PACMP is reviewed and approved by the regulatory authority in advance of execution of the protocol. o PACMP utilized for revision of ECs or reporting categories. o PACMP can address one or more changes for a single product, or address one or more changes to be applied to multiple products. o Before implementing the change, risk assessment provided in the initial submission should be reviewed to ensure that the outcomes of that risk assessment are still valid. o A modification to an approved PACMP such as replacement or revision of a test, study or acceptance criterion would normally require a notification. A modification that more significantly alters the content of the protocol require prior approval.

13 o Supportive data from previous experience PACMP COMPONENTS

14 EXAMPLE EC or Impacted Sections What s changing? Current Filing Category Submission Proposed Category 3.2.P.1 Components and Composition (if capsule shell composition is previously included) 3.2.P.4 Excipients (if relevant detail is previously included) 3.2.P.4.5 Excipients of Human or Animal Origin Replacement of gelatin derived capsule shell with vegetable derived capsule shell US: PAS EU: Do & Tell ROW: Notification to Prior Approval depending on country Provide PACMP as prior approval in each jurisdiction prior to change implementation (tell) US: Annual Report EU: Do & Tell (no change) ROW: Notification Post Distribution (Do & Tell) o The primary risks of changing the capsule shells are reduced stability and/or reduced bioavailability of the Drug Product. o Comparative release testing one batch pre- and post-change at minimum of pilot scale to be included in the PQS and available during inspection. o Multi-point dissolution profile comparing at least 12 capsules of current and changed Drug Product from 1 test and 1 reference product. Compare dissolution profiles using the similarity factor equation. Data will be captured in the PQS. o Real-time stability testing one commercial batch. Data will be available. o Use of the new capsule will be validated following GMP requirements.

15 EXAMPLE EC or Impacted Sections What s changing? Current Filing Category Submission Proposed Category Manufacturing Process Development (3.2.P.2.3) Manufacturing Process and Process Controls (3.2.P.3.3) Controls and Critical Steps and Intermediates (3.2.P.3.4) Process Validation and/or Evaluation (3.2.P.3.5) Batch Analyses (3.2.P.5.4) Stability (all sections within 3.2.P.8) Facilities and Equipment (3.2.A.1) Replacement of Conventional Filler with New Isolator US: PAS (tell & do) EU: Type IB (tell & do) CAN: Notifiable Change (tell & do) Provide PACMP as prior approval in each jurisdiction prior to change implementation (tell) Follow-up with post change commercial lot data as Notification of fulfilled commitment (do & tell) o A thorough risk assessment was completed. o The data from the development studies and engineering runs demonstrated that the filling equipment used for the new Isolator can successfully vials with acceptable accuracy and precision. The physicochemical analysis demonstrated product quality. o The change to the filling process will be assessed via both a comparability study and full process validation (including media fill data) and equipment qualifications. o Process validation will be completed under pre-defined PPQ protocols.

16 RISK BASED o Pharmaceutical cgmp s for the 21st Century. o ICH Expert Working Groups- ICH Q8 and Q9- promoted the use of QbD. o FDA actively applied QbD approach. 2013: QbD was mandatory for ANDAs. o Guidance for Industry: Comparability Protocols for Human Drugs and Biologics: Chemistry, Manufacturing, and Controls Information. o Guidance for Industry: Process Validation: General Principles and Practices o Guidance for Industry: Changes to an Approved NDA or ANDA. a risk based approach based on sound science

17 GLOBAL IMPLEMENTATION o EMA recently published a Questions and Answers document on post approval change management protocols (PACMP) o PMDA established a multi-sectional WG for ICH Q12 o Canada-United States (U.S.) Regulatory Cooperation Council (RCC) was created in February 2011 to better align the two countries regulatory approaches. o In 2011, the FDA and EMA launched a pilot program for parallel assessment of Quality by Design applications. o Communication between regulators: a good start

18 WHAT DO YOU THINK? o Would PACMP encourage continuous improvement projects? Yes No o How often do you experience short supply due to approval delays? Many times a year Every month Never o Did you delay a change due to regulatory complexity? Yes No o How long will it take to process a Major PAC (PAS) without a comparability protocol/pacmp, for PAC submission to approval? 0-3 months 3-6 months 6-12 months >12 months o Do you routinely use comparability protocol? Yes No

19 BENEFITS o Reap the benefit of implementing Q8-11. o Supply chain predictability in a competitive environment. o Risk free move to modern manufacturing technologies. o Minimize regulatory management costs. o Enables effective implementation of continuous improvement projects. o Higher product quality and regulatory compliance. o Opportunity to harmonizeglobal submission practices. o Minimize customer complaints and improve organizational goodwill.

20 NEXT change? Are we ready for the ICH Q12- Public comments Global harmonization- Ongoing Enabling tools and procedures Regulatory framework Lets regularize use of Post Approval Change Management Protocol for the benefit of Patients, Organizations and Regulators

21 REFERENCES o ICH Q12: Technical and Regulatory Considerations for Pharmaceutical Product Lifecycle Management. o Post Approval Changes Requirements for Success, 2017 PDA Japan Annual Meeting, Naheed Sayeed-Desta o ICHQ12 Enabling Change and Innovation Using Companies PQS Effectiveness, ISPE 2017 Annual Meeting, Dr. Simianu. o ICH Q12 Pharmaceutical Lifecycle Management: Current Status and Future Prospectives, CMC StrategyForum Japan 2015, Dr. Kishioka, PDMA o ICHQ12 PACMP: Advantages for Consumers, Regulators and Industry, RAPS May 2017, A. Pazhayattil, N Sayeed-Desta, V. Iyer

22 Disclaimer: The views expressed here are those of the presenter and do not necessarily reflect the company's position, strategies, or opinions