Industries: Pharma / Biotech

Active Pharmaceutical Ingredient (API) & Drug Product Specifications – From Clinical Development to Market Approval

Course Director: John Geigert, Ph.D.

Course Description - Course runs 9:00 to 5:00 both days

Specifications for active pharmaceutical ingredients (APIs) and pharmaceutical drug products, both chemical drugs and biologics, are essential for product quality and patient protection. The goals of specification setting are (1) to determine appropriate and safe limits or quantitative ranges during clinical development and (2) to justify specifications for the product to enter the market. One of the most difficult challenges in establishing and subsequently justifying specifications is achieving the appropriate balance among all factors – patient safety and efficacy, scientific data, analytical variability, process knowledge and capability, regulatory requirements, and business issues.

The approach to specification setting and their justification has undergone significant change. Strategic international ICH regulatory guidances have been adopted that are driving the entire pharmaceutical industry, including both chemical drugs and biologics, to a higher standard of performance, including Quality by Design (QbD), Quality Risk Management (QRM) and Pharmaceutical Quality System (PQS).

Therefore, it is most important for a pharmaceutical company to have an effective and regulatory compliant approach to setting specifications that can meet both FDA and EMA requirements and expectations. At each stage of drug development, from Phase 1 through commercialization, the basic question needs to be addressed: ‘What is absolutely necessary for the assigned specification to be successful in getting the chemical drug/biologic through clinical trials and into the market, but without impacting patient safety or creating delays in the program?' Of equal importance is the need to justify which quality attributes do not need an assigned specification. Regulatory compliant deficiencies in assigned specifications have resulted in clinical holds and market approval delays.

This course will help the attendee to establish specifications meeting global regulatory requirements and expectations. Participants will also become effective in justification of specifications.

Who Should Attend

This course is designed for those engaged in R&D, Regulatory Affairs, Quality Assurance and Quality Control who are responsible for activities in the development and manufacture of Active Pharmaceutical Ingredient (API) and Drug Products. Personnel who desire an in-depth knowledge of the critical role of specifications and the importance of USP compendial requirements, FDA regulations and ICH guidelines, as well as the relationship between ICH Guidelines and the Common Technical Document (CTD) will find this course of great value.

This comprehensive three-day course is also beneficial to R&D personnel responsible for the use of specifications in conducting Quality by Design (QbD) development of both API and Drug Products.

The course is also of interest to personnel in all departments who participate in the support of manufacture and release of APIs and Drug Products. This includes development personnel in preparing API and Drug Product under cGMP protocols for clinical and non-clinical use, as well as analytical chemists involved with stability testing, assays, methods development and drug release.

First Day

Why Product Specifications Are Necessary

  • Terminology defined: specification, acceptance criteria, in-process vs release vs shelf life, parametric release, periodic/skip testing, real-time release testing (RTRT)
  • Acceptance criteria vs action limits
  • Strengths, and limitations, of specifications as an effective control system – could mean life or death for a patient

Regulations and Guidances on Product Specifications

  • Regulatory specification requirements – FDA and EMA
  • ICH Q and pharma industry specification setting guidances – similarities and differences between chemical drugs and biologics
  • Handling out-of-specification (OOS) test results

Clinical Phase-Appropriate Specification Assignment

  • Preliminary specifications for early stage clinical development
  • Updated/refined specifications for later stage clinical development
  • Patient safety specifications at market approval level even during clinical development

Required API and Drug Product Specifications

  • Proper foundation for specification assignments
  • Similarities and differences between chemical drugs and biologics in release specifications needed
  • Challenge of regional specifications for a global company

Second Day

Quality by Design (QbD) Applied to Specifications

  • Setting up an effective Specification Committee
  • Strategic ICH guidances: Q8, Q9, Q10
  • Quality by Design (QbD) applied to specification setting – balancing patient safety concerns with manufacturing process performance and regulatory authority expectations

Statistical Approaches to Establishing Specifications:

  • Understanding of basic statistics - mandatory
  • Case examples of establishing patient safety regulatory specifications
  • Case examples of establishing manufacturing process consistency specifications

Preparing CTD Regulatory Submissions on Product Specifications

  • Specifications in Module 2.3 Quality Overall Summary and Module 3 Quality
  • Justification of inclusion and/or exclusion of product specifications
  • Interim regulatory specifications – post-market approval commitments – specification lifecycle

Managing Regulatory Authority Specification Interactions/Inspections

  • Regulatory report card on pharmaceutical specification assignments
  • Case examples of problems with proposed regulatory specifications
  • Inspector interest in assigned specifications – what they want to see and why

Learning Objectives

At the end of the two-day course attendees will:

  • Gain a solid understanding of the regulatory compliance requirements and expectations (FDA, EMA, ICH) for API and drug product specifications, for both chemical drugs and biologics
  • Have the tools and understanding to establish regulatory compliant specifications that are clinical phase-appropriate, incorporating Quality Risk Management (QRM)
  • Understand the ICH Q8, Q9 and Q10 Quality by Design (QbD) approach applied to setting specifications as part of an effective control system
  • Be able to appropriately package specifications and their justification into Module 2.3 and Module 3 of the Common Technical Document (CTD)
  • Learn how to avoid major delays in clinical development or market approval due to ineffective setting of specifications


"The course was laid out very well. For a topic that could have been a little boring, the instructor did an excellent job of keeping the class engaged. Well presented, I would definitely take classes with this instructor again!" Christina N., Specification Associate, Johnson & Johnson
"This course was presented in an interactive manner with adequate real life dos and don'ts examples." Lara, Director of Regulatory Affairs, Nexgen Pharma
"The Course Director shared real-world examples of projects that worked on the industry. This is a great improvement on many other courses. Too often, course work details regulations and theoretical concepts. This course, however, correctly balanced case studies and regulations within the pharmaceutical industry. The instructor had a great amount of experience in several different dosage forms and in several disciplines within the industry." Ted R., Supervisor, BI Roxane Inc.
"The Course Director is very knowledgeable about the subject matter and presented it in a very interesting way. Use of course materials and real life examples were very helpful in explaining the concepts and ideas. The casual and interactive nature of the course was great for getting any questions answered and for encouraging the flow of dialogue and information." Jennifer B., AT Supervisor
"The course was taught phenomenally. Best API training course I have taken. I would highly recommend this to a friend." Susasha D., RA Associate, Teva/Barr
"This course is very informative and the Course Director is very experienced and knowledgeable. I would highly recommend this course to anyone involved with specifications." Syed R., Manager (PD), Incyte Corporation
"This course is very informative. I will be using everything that I learned here for my work, and I learned a lot! Thank you." Natalya S., Associate Director-RA CMC, Daiichi-Sankyo