This workshop on co-processed API brought together pharmaceutical researchers, regulatory and materials scientists and manufacturing colleagues from industry, academia, and regulatory agencies on July 13 and 14, 2022, from 8:30 a.m. to 4:30 p.m. (EDT).

This in-person was held at the University of Maryland, Baltimore School of Pharmacy, located at 20 N. Pine St. Baltimore, MD 21202. The event was not recorded. 

This two-day workshop examined recent advances in co-processed API as a technology to improve drug-substance physical-chemical properties and drug product manufacturing process robustness and explore proposals for enabling commercialization of these transformative technologies. Regulatory considerations were also discussed with a focus on regulatory classification, regulatory CMC strategies and CMC documentation supporting the use of this class of materials for clinical studies and commercialization.

This workshop is supported by the Food and Drug Administration (FDA) of the U.S. Department of Health and Human Services (HHS) as part of a financial assistance award U01FD005946 totaling $5,000 with 100 percent funded by FDA/HHS. The contents are those of the author(s) and do not necessarily represent the official views of, nor an endorsement, by FDA/HHS, or the U.S. Government.

Day 1: July 13, 2022
 

M-CERSI Welcome Remarks

Stephen Hoag, Ph.D.
Professor, University of Maryland Baltimore
Slides
Conference Introduction & Workshop Intent Ramesh Sood, Ph.D.
Senior Scientific Advisor, ONDP, OPQ, CDER, FDA

Slides


Session 1: Why Does the Development Pipeline Need Technology Options?
 
The Present and Future of Pharmaceutical Quality Larry Lee, Ph.D.
Deputy Super Office Director of Science, OPQ, FDA

Slides

Need for New Paths to Accelerated Technology Implementation Timothy Watson, Ph.D.
Executive Director and Team Leader for CMC Advisory Office, Pfizer

Slides


Case Studies
 
Emerging Modalities and Compound Development Assessment in Small Molecule Early Development Ahmad Sheikh, Ph.D.
Senior Research Fellow and Head of Solid-State and Computational Chemistry, AbbVie

Slides

Persistent Needle Challenges: A Class of Compounds Preventing Crystallization Routes to Modulate Bulk Powder Properties Patrick McArdle, Ph.D.
Professor, National University of Ireland, Galway

Slides

Overview of Particle Engineering Routes and Pipeline Needs Alastair Florence, Ph.D.
Distinguished Professor and Director of CMAC, University of Strathclyde

Slides


Breakout Sessions
 
1A Discussion Leaders Paresma (Pinky) Patel, Ph.D.
Branch Chief of Division of New Drug API, ONDP, OPQ, CDER, FDA

Luke Schenck
Principal Scientist, Merck & Co., Inc.

Timothy Watson, Ph.D.
Executive Director and Team Leader for CMC Advisory Office, Pfizer

 

2A Discussion Leaders Ramesh Sood, Ph.D.
Senior Scientific Advisor, ONDP, OPQ, CDER, FDA

Jeremy Merritt, Ph.D.
Director in SMDD, Eli Lilly & Co.

Deniz Erdemir, Ph.D.
Associate Scientific Director, Bristol-Myers Squibb

  

3A Discussion Leaders Mohan Sapru, Ph.D.
Branch Chief, New Drug Products Division III, Branch V, ONDP, OPQ, CDER, FDA

Steven Ferguson, Ph.D.
Assistant Professor of Chemical and Bioprocess Engineering, University of College Dublin; Adjunct Assistant Professor School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin; Principal investigator, NIBRT

  


Session 2: Technical Considerations for Designation of Co-Processed API as Drug Substance or Drug Product Intermediate
 
Co-Processed APIs – Scientific and Regulatory Considerations for New Drug Development Rapti Madurawe, Ph.D.
Division Director, OPMA, OPQ, CDER, FDA

Slides

Cobicistat on Silicon Dioxide: Utilizing a Carrier Particle Technology to Solve an API’s Physical Property Limitations Jared Evans, Ph.D.
Senior Director, Drug Substance Regulatory Strategy, Gilead Sciences

Slides


Case Studies
 
Integrated Processing for Co-Processed API Steven Ferguson, Ph.D.
Assistant Professor School of Chemical and Bioprocess Engineering, University of College Dublin; Adjunct Assistant Professor School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin; Principal investigator, NIBRT

Slides

Precipitation Processes to Control Material and Powder Properties of Amorphous Solid Dispersions Derek Frank, Ph.D.
Senior Scientist in Particle Engineering Lab in Process R&D, Merck & Co., Inc.

Slides

Co-Processed API Product and Process Development, Optimization, and Scale-up Nima Yazdanpanah, Ph.D. 
Consultant on Advanced Manufacturing and Modeling and Simulation Applications,
Procegence

Slides

Strategic Considerations in Choosing a Co-Processing Approach San Kiang, Ph.D.
Chief Technology Officer Drug Product, J-Star Research/Porton

Slides

Dry Coating Approach to Enhance API Physical Properties Raimudo Ho, Ph.D.
Principal Research Scientist, Materials Science Center of Excellence Lead, AbbVie, Inc. 

Slides


Breakout Sessions
 
1B Discussion Leaders

Ramesh Sood, Ph.D.
Senior Scientific Advisor, ONDP, OPQ, CDER, FDA

Deniz Erdemir, Ph.D.
Associate Scientific Director, Bristol-Myers Squibb

Luke Schenck
Principal Scientist, Merck & Co., Inc.

  

2B Discussion Leaders Rapti Madurawe, Ph.D.
Divisional Director, OPMA, OPQ, CDER, FDA

Jeremy Merritt, Ph.D.
Director in SMDD, Eli Lilly & Co.

Raimundo Ho, Ph.D.
Principal Research Scientist, AbbVie, Inc.

  

3B Discussion Leaders

Paresma (Pinky) Patel, Ph.D.
Branch Chief of Division of New Drug API, ONDP, OPQ, CDER, FDA

Billie Kline, Ph.D.
Chemical Engineering Senior Fellow, Vertex Pharmaceuticals

Haitao Zhang, Ph.D.
Associate Research Fellow in Chemical Process R&D, Sunovion Pharmaceuticals Inc.

  

 

 

Day 2: July 14, 2022
 

Overview & Introduction

Luke Schenck
Principal Scientist, Merck & Co., Inc.

Stephen Hoag, Ph.D.
Professor, University of Maryland, Baltimore

Ramesh Sood, Ph.D.
Senior Scientific Advisor
Slides

Session 3: Regulatory & Scientific Considerations for Designation of Co-Processed API as Drug Substance or Drug Product Intermediate
 
An FDA Perspective on Regulatory Considerations for Co-Processed APIs Laurie Graham-Eure, Ph.D.
Director, Division of Internal Policies and Programs, OPPQ, OPQ, FDA

Slides

Motivation to Define Co-Processed API as a Drug Substance and Overview of Current Regulatory Landscape

Sharon Page, B.Sc. (Hons)
Director, Global Chemistry, Manufacturing and Controls (GCMC), Pfizer R&D UK Ltd.

Lindsey Saunders Gorka, Ph.D.
Director and Team Leader CMC, Pfizer, Inc.

Slides


Case Studies
 
Excellent CU of Low Dose Direct Compression Tablets Achieved Using Co-Processed API Changquan Calvin Sun, PhD
Professor and Associate Department Head, University of Minnesota

Slides

Treatment of Non-active Components in Co-Processed API: Do Excipients Obscure GMP DS Method Ability to Detect Chemical/Phase Purity

Frank Bernardoni, PhD
Principal Scientist, Analytical R&D, Merck & Co.

Slides

Considerations in Regard to Designation of Active Substance for mRNA Therapeutics

Don Parsons, PhD
Vice President, Early Technical Development and Lipid Nanoparticle Process Development, Moderna

Slides


Breakout Sessions
 
1C Discussion Leaders

Peter Capella, PhD
Director, Div. of Immediate and Modified Release Drug Products, OLDP, OPQ, CDER, FDA 

Luke Schenck
Principal Scientist, Merck & Co., Inc.

 

2C Discussion Leaders

Laurie Graham-Eure, PhD
Director, Division of Internal Policies and Programs, OPPQ, OPQ, FDA


Jeremy Merritt, PhD
Director in SMDD, Eli Lilly & Co.

Deniz Erdemir, PhD
Associate Scientific Director, Bristol-Myers Squibb

  

3C Discussion Leaders

Mohan Sapru, PhD
Branch Chief, New Drug Products Division III, Branch V, ONDP, OPQ, CDER, FDA

Ben Stevens, PhD, MPH
Director CMC Policy and Advocacy, GSK

Llorente Bonaga, PhD
Director, Regulatory Affairs, CMC, Global Regulatory Affairs and Clinical Safety, Merck& Co. USA

  


Session 4: How Might We Advance Global Harmonization?
 
Global Regulatory Harmonization Challenges and Opportunities Mahesh Ramanadham, PharmD, MBA
Deputy Director, OPPQ, OPQ, CDER, FDA

Slides

The Zelboraf Story: Sharing Experiences with Different Drug Substance Designations Cinzia Gazziola, PhD
Pharma Technical Drug Regulatory Affairs Manager, F. Hoffman-La Roche, Switzerland

Slides


Case Studies
 

A Strategy for Co-Processed API as Drug Substance in Early Clinical Studies to Rapidly Inform Tech Feasibility with Critical In Vivo Data

Llorente Bonaga, PhD
Director, Regulatory Affairs, CMC, Global Regulatory Affairs and Clinical Safety, Merck & Co. USA

Slides

Metformin Premix: Challenges Encountered During Reclassification from Co-Processed API Use to Resolve Severe

 

Metformin Agglomeration to Pharmaceutical Intermediate

Dirk Wandscheider, PhD
Laboratory Manager Particle Characterization, EMD Serono/Central Analytical Services Merck KGaA, Darmstadt, Germany

Sandra Masanes Marza
CMC Leader Diabetes, Manufacturing Science & Technology, EMD Serono/Merck KGaA, Darmstadt, Germany

Slides

Opportunities and Challenges to Innovation and Harmonization for Pharmaceutical Quality Manufacturing from Industry Perspective

Timothy Watson, PhD
Executive Director and Team Leader for CMC Advisory Office, Pfizer

Slides


Breakout Sessions
 
1D Discussion Leaders

Mohan Sapru, PhD
Branch Chief, New Drug Products Division III, Branch V, ONDP, OPQ, CDER, FDA

Luke Schenck
Principal Scientist, Merck & Co., Inc.

Ben Stevens, PhD, MPH
Director CMC Policy and Advocacy, GSK

  

2D Discussion Leaders

Peter Capella, PhD
Director, Div. of Immediate and Modified Release Drug Products, OLDP, OPQ, CDER, FDA

Jeremy Merritt, PhD
Director in SMDD, Eli Lilly & Co.

Timothy Watson, PhD
Executive Director and Team Leader for CMC Advisory Office, Pfizer

  

3D Discussion Leaders

Mahesh Ramanadham, PharmD, MBA
Deputy Director, OPPQ, OPQ, CDER, FDA

Llorente Bonaga, PhD
Director, Regulatory Affairs, CMC, Global Regulatory Affairs and Clinical Safety, Merck & Co., Inc.

Cinzia Gazziola, PhD
Pharma Technical Drug Regulatory Affairs Manager, F. Hoffman-La Roche Switzerland

  


Workshop Summation, Review of Breakout Sessions 1–4 for Draft Workshop Proceedings Publication
 
  

Luke Schenck
Principal Scientist, Merck & Co., Inc.

Stephen Hoag, PhD
Professor, University of Maryland, Baltimore

Ramesh Sood, PhD
Senior Scientific Advisor, ONDP, OPQ, CDER, FDA

  

 

 

About this Event

Innovations in synthetic chemistry have resulted in improved potency and efficacy of active pharmaceutical ingredients (API), albeit with added molecular complexity. This complexity often comes with challenging physical-chemical properties that cannot be addressed via conventional drug substance processing and particle design routes and ultimately present manufacturing difficulties to drug substance and drug product operations.

A wealth of opportunities to address challenging physical-chemical properties exist through technologies residing at the drug substance-drug product interface. These technologies involve introduction of non-active components (excipients) during drug substance processing to deliver co-processed API, which may have promising implications that stand to transform pharmaceutical manufacturing. The improved physical-chemical properties that co-processed API offer would streamline drug product processing and expand applicability of continuous drug product operations to a wider portion of the development pipeline. Co-processed API has the potential to reduce variability of API properties, improve quality of drug product, enhance the physical and chemical stability of API and maximize the availability of supplies through simplified and robust manufacturing trains. These benefits in total would drive down pharmaceutical cost, and the improved manufacturing robustness stands to reduce drug shortage risks.

Incorporating non-active components during drug substance processing to improve the robustness of the drug product process represents a marked philosophical change to historically separated drug substance and drug product operations. The spectrum of technologies, which have demonstrated success in academic and industry proof of concept arenas, have had limited commercial application thus far. More effective deployment of co-processed API technologies across commercial manufacturing will require a thoughtful and strategic collaboration among academia, industry and regulatory agencies. A combined industry/academic perspective outlining the case for co-processed API, considerations for broader commercial implementation, and some regulatory proposals can be found here (manuscript).

This workshop will present an overview of the changing development pipeline, the need for innovative approaches to improve manufacturing process robustness and assurance of supply, and outline the challenges and promising opportunities afforded by co-processed API with academic and industrial case studies. Importantly, the workshop will outline regulatory and analytical considerations to advance commercialization of co-processed API with opportunities for discussion between attendees. Case studies on co-processed APIs will be presented. The industrial and academic position paper linked above acknowledges that co-processed API may be best suited to manufacture in drug substance facilities due to the need of solvents (and associated HSE constraints) for the most common co-processing technologies. Hence it was proposed that if these materials are manufactured in drug substance facilities, designation of these materials as drug substances (as opposed to drug product intermediates) may be applicable. The workshop will provide opportunities to discuss implications of such designation. Discussions on spray-dried dispersions, which are also constituted of API and excipients were not discussed in the manuscript as they represent an area of precedence of drug product intermediates. However, for the workshop this stance and definition may be relevant for discussion as well as considerations around blurring the DS-DP boundary in context of end-to-end continuous processing.

The format of the workshop will be designed with plenary talks from key thought leaders in the field of co-processing including presentations from the FDA. Ample time for open discussion in panel discussions and breakout sessions with regulatory agencies and the workshop participants will be held to gain insights into strategies for future commercialization opportunities.

 


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