Industries: Pharma / Biotech

QA/QC Strategy for Biologics and Biopharmaceuticals

Course Director: John Geigert, Ph.D.

Course Description - Course runs 9:00 - 5:00 on Day 1 & Day 2 -- 9:00 - 3:00 on Day 3

In the eyes of regulatory authorities, the quality issues of biologics are definitely different from chemical drugs because of: (1) use of living source materials to produce the biologic, (2) increased complexity of biologic manufacturing processes and (3) increased complexity of the biologic molecules themselves. While chemical drugs can become generics, biologics products are best viewed as biosimilars, and not as bio-generics.

Biologics are highly susceptible to adventitious agent contamination – prions, viruses, mycoplasmas, and bacteria/fungi microbes. Risk control procedures – such as barriers to entry, testing to confirm absence, and inactivation/removal – are essential. Lessons can be learned from reported contaminations of biologic manufacturing processes. Compared to chemical drugs, biologics have a more complex process-related impurity safety profile, especially due to the living system-related impurities (e.g., host cell proteins, host cell DNA).

Extensive physicochemical characterization of protein and monoclonal antibody molecular structure, employing multiple, complementary, as well as orthogonal, state-of-the-art analytical methods is necessary, covering primary amino acid sequence changes (e.g., truncation, deamination, oxidation), post-translational modifications (e.g., glycosylation), and higher order structural changes (e.g., secondary folding, aggregation). Because of the molecular structural complexity of a biologic, including its many possible structural variants, functional activity assays are required that can discern which structures have what amount of potency. While bioassay functional activity assays (i.e., in vivo, in vitro) are required for measuring potency, surrogate (analytical) assays can be used if properly correlated to the bioassays. At times, an assay matrix may even be required. Many manufacturers underestimate the amount of resources and time needed to properly implement these functional activity assays.

This course will help the attendee to develop an effective QA/QC quality risk management strategy for biologics, addressing the quality challenges all the way from Phase 1 clinical studies through commercialization. Guidance from the FDA, EMA and ICH will be discussed. In addition, the differences in managing quality for chemical drugs vs biologics will be examined.

Who Should Attend

This three-day quality assurance (QA) and quality control (QC) training course is designed for management and professional staff involved in, or interested in quality assurance and quality control support for biologics and biopharmaceuticals. This course will be of particular interest to QA and QC personnel and management, Regulatory Affairs, Manufacturing, Process Development and Analytical Development staff, and anyone involved with the biologic and biopharmaceutical industry.

Course Agenda

First Day

Quality Challenges for Biologics Are Different

  • Painting the landscape: biologic, specified biologic, biopharmaceutical, biosimilars, etc.
  • Two different U.S. pharmaceutical laws that impact biologics
  • Biologics are not chemical drugs – 3 major areas
  • How these differences are managed by the regulatory agencies

Criticality of QA/QC Involvement with Biologic Processes

  • Why it is important to have QA/QC involved in the manufacturing process earlier than later
  • Quality does not come cheaply – what is the value of QA/QC in biologic manufacturing
  • Value of QA/QC during clinical development
  • Detecting biologic counterfeits

Developing a Corporate Quality Strategy for Biologics

  • Five (5) key elements of an effective quality risk management strategy for biologics
  • Revolutionary impact of strategic ICH Q8, Q9 and Q10 on biologics
  • Implementation of a clinical phase-appropriate quality strategy
  • Critical importance of inter-company quality agreements for biologics

Second Day

Uniqueness #1 –Challenge of Adventitious Agents

  • Plenty of nightmares for biologic manufacturing – prions, viruses, mycoplasmas, bacteria/fungi
  • Reported prion, viral and mycoplasma contaminations of biologic products
  • Designing an effective risk minimization strategy for these agents
  • Not detected does not mean not present – surprises still happen

Uniqueness #2 –Biological Functional Activity (Potency)

  • Therapeutic functional activity, not content, for biologic strength
  • Functional assay landscape: bioassay, surrogate, assay matrix
  • Clinical phase-appropriate development of potency assays
  • Underestimation of resources needed to optimize and control these assays

Uniqueness #3 –Complexity of Impurity Profiles

  • Comparison of impurity profiles for chemical drugs vs biologics
  • Magnitude of process-and product-related impurities for biologics
  • Applying a quality risk management strategy to the impurity profile of biologics
  • Examples of how to develop the control systems for host cell proteins and protein aggregation

Third Day

Biological Characterization, Release and Stability Testing

  • Know your complex biologic molecule – characterization State of the art testing, fingerprinting Comparison of release/stability testing for chemical drugs vs biologics Clinical phase-appropriate implementation of testing

Challenge of Biologic Specification Setting and Expiry Dating

  • Specification setting for critical quality attributes
  • Regulatory authority recommendations for clinical phase-appropriate setting of specs
  • Examples of 4 types of specs used with biologics
  • Comparison of determining expiry dates for chemical drugs vs biologics

Learning Objectives

At the end of the course you will:

  • Understand the critical importance and underlying principles for the QA/QC of biologics and biopharmaceuticals, and know how these principles differ from those for chemical-origin drug products
  • Be able to develop a clinical-phase appropriate, cost-effective strategy to effectively manage the quality lifecycle through clinical development into commercialization of diverse biologic/biopharmaceutical manufacturing processes and products, including establishing effective inter-company quality agreements with outsourced contractors
  • Have the tools and understanding necessary to adequately address biosafety (adventitious agents), potency (biological functioning bioassays) and impurity profile issues for biologic and biopharmaceutical products; and how to set appropriate and adequate product specifications and expiration dates

Testimonials

"The Course Director has impeccably presented a big load of information over 3 days, showing deep knowledge based on experience. He is a natural communicator, and his commitment to deliver a clear message within a tight time schedule confers him an empathetic character. It has been a pleasure to take this course." Veronica F., QC Supervisor, WGTU, University College London Cancer Institute
"The Course Director showed a clear mastery of this incredibly complex area of product development manufacturing and regulatory compliance. Nice job! Very personable, good content - will take a while for everything to sink in." Dr. Matt H., Scientist QA, Promega
"The course was very effective in presenting regulatory issues. The instructor was very knowledgeable and discussed real-life situations." Steve R., Drug Information Specialist, Organon
"The Course Director put a great deal effort into producing an outstanding course. I would recommend this course to all of my colleagues." Jeffrey M., Sr. Information Technology Analyst, Biogen Idec
"The fact that this company limits the class size allows the Course Director to tailor the material to those in attendance. It was obvious that a lot of preparation went into addressing our needs. Needless to say, the instructor was very experienced and did a great job." Amy C., Genentech
"Probably the most specifically appropriate and pertinent course I have ever attended." Senior Drug Information Manager, Bristol Myers
"This course was much better than others I attended and I would strongly recommend this course to others." Dr. Shahid A., VP of Research & Development, NeoPharm

Frequently Asked Questions

Does the course cover both biologics and biopharmaceuticals in clinical development as well as market-approved?

The course covers the Quality Assurance (QA) and Quality Control (QC) requirements and expectations for biologics and biopharmaceuticals in clinical development (i.e., Phase 1 to Phase 3 studies) as well as those having market approval.

Does the course cover FDA and international concerns?

The course covers all aspects of QA and QC requirements and guidance for biologics and biopharmaceuticals from the FDA, European Medicine Agency (EMA), and International Conference on Harmonisation (ICH).

How does this course differ from the course CMC Regulatory Compliance for Biopharmaceuticals and Biologics™?

This course focuses on all aspects of keen interest to quality assurance and quality control, including control systems and setting of specifications and expiry dating for biologics and biopharmaceuticals. On the other hand, the CMC Regulatory Compliance course systematically covers all aspects of CMC regulatory compliance concerns, including areas of keen interest to regulatory affairs, manufacturing and development for biologics.