The Role of ICH and How to Meet Quality Guidelines in API Manufacturing

The International Conference on Harmonization (ICH) celebrated its 30^th year in 2020, and since its inception, it has been committed to “achieving greater harmonization worldwide, to ensure that safe, effective and high quality medicines are developed and registered in the most resource-efficient manner.”

While not a regulatory body, the ICH currently represents all countries interested in establishing unified standards. Members include the U.S. FDA, the European EMA and other drug regulatory authorities and departments of health around the world. Working with its members, the ICH has developed more than 60 guidelines for demonstrating the quality, safety and efficacy of a new product when registering it. The ICH also helps set Electronic Standards for the Transfer of Regulatory Information (ESTRI), from applicant to regulator.

Its guidelines are meant to be used in combination with regional requirements, but are not mandatory.

Why should a Contract Development & Manufacturing Organization (CDMO) follow ICH guidelines?

 In the 1980s before the establishment of the ICH, regulations were different for each country, yet today, when most businesses operate globally in some capacity, adhering to ICH standards helps them comply with regulatory strategy around the world, leading to a more effective path to approvals, wherever they may be.

The harmonized set of guidelines established by the ICH has made drug development and manufacturing far less fragmented. Today when we develop an Active Pharmaceutical Ingredient (API) at Seqens CDMO NA, we strive to meet a standard set of guidelines for safety, quality and efficacy and work to ensure that it is sufficiently free of impurities (ICH recommends that they are 99 percent pure) and consequently safe for patients to take.

The ICH has established a particular set of guidelines for API manufacturing. The ICH guidance Q7 Good Manufacturing Practice Guidance for Active Pharmaceutical Ingredients is intended to provide guidance for meeting GMP for the manufacturing of APIs under an appropriate system for managing quality. It helps ensure that APIs meet the quality and purity

characteristics that they claim to have. ICH Q7 does not apply to steps prior to the introduction of the API starting material, yet, there is an expectation that an appropriate level of controls  for the production of the API starting material will have been taken.

How To Meet ICH Guidelines

Following ICH guidelines requires strict oversight, and developing new drug candidates is a daunting challenge in and of itself. Yet, by taking into consideration the following, CDMOs can more easily achieve them.

1. Prepare in the kilo lab. CDMOs need standard protocols for ensuring that processes are scalable and ready to go to manufacturing.  In the kilo lab, the processes developed are run to determine whether they work on a larger scale prior to being used in the more expensive cGMP suites or scaled up further into a cGMP manufacturing plant.
2. Ensure proper maintenance of equipment.  In order to rid drug candidates of impurities, drug developers need highly sensitive instruments and equipment to filter, isolate and identify impurities.  There should be a regular program for preventative maintenance, as well as a firm cleaning regiment for all instruments and equipment. You should also have a mix of equipment with reactors of different sizes, made of different material to meet varying needs. 
3. Build a team of experienced thinkers. Technical teams that can demonstrate innovative thinking can more easily help you meet industry guidelines, since process chemistry is about solving one problem after another. Most CDMOs need to perform hundreds of individual experiments to see how a process behaves, while tweaking it and changing the parameters constantly to get the desired end result. A highly qualified team can decrease the number of process steps for a product, and increase the overall yield. Let guidelines dictate each project at the outset. Here at Seqens CDMO NA, we begin thinking about ICH guidelines at the very earliest stages of a project. We begin each project by looking ahead to what the FDA or EMA will require so that we can have a better view of what lies ahead and plan our experiments and their documentation accordingly.
4. Understand that Master Batch Records are key. The Master Batch Record (MBR) is the most important part of GMP manufacturing since it contains the details the manufacturing activities for each intermediate and the final API. It also part of the required documentation for compliance with the ICH’s Guidance for Industry, Q7 Good Manufacturing Practice Guidance for Active Pharmaceutical Ingredients. They should be well written, with clear, concise and accurate language that conveys the technical and procedural information necessary to ensure consistent manufacturing that meets all safety, efficacy and quality requirements.

Industry guidance provided by the ICH provides a set of standard best practices toward which all CDMOs should strive toward. By following its guidance, CDMOs, sponsors and government agencies can be assured that critical drugs and the ingredients that go into them are as safe and effective as possible for the people who rely upon them around the world.

For more related articles regarding compliance check out: Avoiding FDA Drug Rescissions or Internal Auditing:  The Belt and Suspenders Approach to Quality.