Drug development, approval, manufacturing, and post-marketing…..Japan’s journey of a pharmaceutical product

Drug development, approval, manufacturing, and post-marketing

• Development of a new drug involves a complicated process that requires a lot of time and enormous amounts of funding. In order to create one drug, you would need to evaluate approximately 700,000 candidates¹⁾. Of them, just one reaches the patients. Here, we will share how a new drug begins its journey, from the research and development of candidate compounds, to a product, to the patients, and how we are involved with drugs once the physician prescribes a drug to patients. We will explain what pharmaceutical companies call “the lifecycle of a drug.”
  ¹⁾ from Japan Pharmaceutical Manufacturers Association DATABOOK 2013

The journey of a pharmaceutical product

1. Basic research

 

• Conduct a research to discover new drug candidate substances and components and create new compounds. Most requires 2 to 3 years. This process also functions as an opportunity to research the yet-to-be-defined mechanisms of diseases, where the basic research conducted may not directly lead to a new drug. Discovering a seed for a new drug is like looking for a piece diamond on the bottom of the deep ocean, where these highly uncertain basic research and drug development research could become the base in identifying several million candidate elements. After this process, a screening method to narrow down potential substances will be developed, and several of the candidate substances move on to the next process.
• There are two types of research, collaborative research and sponsored research, where pharmaceutical companies and others provide funding support.
  The research is conducted after an official contract is exchanged with universities and others.

  Collaborative research：(Joint research expenses in the JPMA Transparency Guideline)

  Research institutions such as universities and investigators of pharmaceutical companies and others conduct a research cooperatively.

  Sponsored research：(Research commissioning expenses in the JPMA Transparency Guideline)

  Sponsors such as pharmaceutical companies entrust research institutions such as universities to conduct the research, where accomplishments are reported to the sponsors.

  

  The journey of a pharmaceutical product

  2. Development

  1) Non-clinical trial

  • CMC: Quality
    CMC stands for Chemistry, Manufacturing and Control. Design and research for manufacturing procedures, specifications and stability tests are carried out.
  • A process to investigate the efficacy and safety of candidate drug compounds. An animal testing is conducted for pharmacokinetics, pharmacological and toxicity tests. The next trials are conducted based on data obtained from this first process. This process takes about 3 to 5 years.
  • The trial is required to be conducted based on GLP for non-clinical trial regarding safety of pharmaceutical products.

  2) Clinical trial

  • The clinical trial is conducted by pharmaceutical companies and others based on the Pharmaceutical Affairs Law, in order to have a new drug approved or to apply for a new indication for an existing drug. Other than clinical trials conducted by pharmaceutical companies with an objective of approval application, there are trials called investigator-led clinical trials which are conducted by physicians and medical institutions for the purpose of the approval application.
  • The trial process investigates the efficacy and safety of the candidate compound on humans. The clinical trial is conducted mainly in 3 steps, Phase I, Phase II and Phase III. This process takes approximately 3 to 10 years. It is required to conduct the trials based on the GCP.

    Phase I trial (human pharmacology study) :

    Confirms mainly the compound’s safety among healthy people

    Phase II trial (exploratory study) :

    Confirms the drug’s administration method and administration amount among a small number of patients

    Phase III trial (confirmatory trial) :

    Confirms the drug’s efficacy and safety among numerous patients

    

The journey of a pharmaceutical product

3. NDA and regulatory approval application

• The various steps in this process are usually conducted by pharmaceutical companies alone. However, at times accomplishments are made through a cooperative effort with universities and medical institutions. In order for cooperative research with universities and medical institutions to steadily progress, and for new drugs to be created as a result, companies sometimes contribute by providing funding to the research. The types of funding provided are presented in the table below. Also, for certain items an example is illustrated and explained in each process within the “product lifecycle,” and is hyperlinked to the cost items of each member companies’ disclosure target within the JPMA‘s “Transparency guideline for the relationship between corporate activities and medical facilities and others.”
• The progress of each process within the “product lifecycle” is managed by adhering to various laws and self-regulations. We will explain the process of drug development that at times is considered complicated, to the manufacturing and distribution of new drugs, and related laws and regulations to adhere to. The following table shows one part of the product lifecycle chart.
  Product lifecycle and requirements overview

 

Terminology: Product lifecycle and related laws

• PAL：Pharmaceutical Affairs Law
  A Law regulating matters related to the manufacturing, distribution, standards and screening, handling and advertising regulation and others for healthcare products, quasi-drugs, cosmetics and medical devices in Japan. (Law No. 145, Aug. 10, 1960).
• GLP：Good Laboratory Practice
  A standard for conducting non-clinical studies on the safety of drugs. It is a standard regarding animal studies in non-clinical studies, particularly regulated for toxicity studies.
• CMC：Chemistry, Manufacturing and Control
  Information regarding Chemistry, Manufacturing and Control. It refers to the integrated concept of researches for drug substance process, drug development, and quality assessment, as well as works related to those researches. The pharmaceutical companies’ CMC includes a wide range of work from non-clinical studies, clinical studies to regulatory approval applications.
• GCP：Good Clinical Practice
  A standards regarding the implementation of clinical trial for pharmaceutical products.
• ICH：International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use
  A project that brings together regulatory authorities in Europe, Japan and the United States. The purpose is to make recommendations on ways to achieve greater harmonisation in the interpretation and application of technical guidelines and requirements for product registration.
• GMP：Good Manufacturing Practice
  A ministry ordinance related to standards for the manufacturing management and quality management of pharmaceutical products and quasi-drugs. It refers to the standard for the manufacturing management and quality management at manufacturing facilities of pharmaceutical products and others.
• PV：Pharmacovigilance
  Activities related to the safety monitoring of pharmaceutical products. It refers to the careful monitoring and continuous surveillance of the safety of an approved product during its life on the market.
• GQP：Good Quality Practice
  A standard on the quality management of pharmaceutical products and others.
• GDP：Good Distribution Practice
  A standard on pharmaceutical product distribution.
• GPSP：Good Post-marketing Study Practice
  A standard on the implementation of the pharmaceutical products’ post-marketing surveillance and study.
• GVP：Good Vigilance Practice
  A standard on the safety management of pharmaceutical products and others after manufacturing and distribution.

 

Sources:

• e-Gov
• Japan Pharmaceutical Manufacturers Association
• Pharmaceutical and Medical Devices Agency
• EFPIA Glossary