Keith Gallicano, Ph.D., Chief Scientific Officer, was invited to present at the Inhalation Drug Delivery Association (IDDA) conference, Beijing, China, April 19-20, 2019. Novum has extensive experience designing, conducting and analyzing inhalation studies using its specialized dosing chamber and is being sought by Chinese industry looking to enter this area. Below is information on the founding of the IDDA, an overview of the IDDA 2019 conference, and a history of asthma and chronic obstructive pulmonary disease (COPD) in China.
Founding of the IDDA1
The IDDA was founded in 2013 in Nanjing, China to promote research and development of inhaled products and improve inhalation technology and inhalation product standards in China. Members of the alliance include people working in inhalation drug research and development, quality monitoring, production enterprises, colleges, universities and institutes. Since 2013, the IDDA has organized three conferences covering topics related to inhalation.
Overview of IDDA 2019 Conference
The 2019 conference focused on bioequivalence studies for orally inhaled drug products (OIDPs) and was co-hosted by the Chinese Society of Particuology Inhalation Particles Committee and Genco Medical Company. More than 200 Chinese delegates attended the conference, with invited speakers from the US (Keith Gallicano, Ph.D. and Yaning Wang, Ph.D., Director, Division of Pharmacometrics, Office of Clinical Pharmacology, CDER, FDA) and Sweden (Bo Olsson, Ph.D., Emmace Consulting). All presentations were in Chinese except those from Drs. Gallicano and Olsson.
Dr. Gallicano’s presentation “Design, conduct, and data analysis of in vivo studies to support bioequivalence evaluation of oral inhalation drug products (OIDPs)” was well received and provided an overview of lung deposition of OIDPs and pharmacokinetic and pharmacodynamic studies to support bioequivalence, with emphasis on the design and data modeling for bronchoprovocation (methacholine challenge) studies of short-acting beta-2 agonists (e.g., albuterol sulfate inhalation aerosol). There is high interest in China on how methacholine challenge studies are conducted, considering the Chinese Food and Drug Administration (CFDA) generally follows the US FDA’s Product Specific Guidances for OIDPs.
Dr. Wang’s presentation “Orally inhaled drug products – regulatory perspective on 505(b)(2) pathway” was important given the lack of understanding of how to file for a 505(b)(2) application, the difficulty to develop generic products for OIDPs, and the preference for Chinese drug companies to seek the 505(b)(2) pathway as an alternative to the generic 505(j) pathway for submission to FDA. He highlighted several case examples of OIDPs that were successfully submitted by the 505(b)(2) pathway, including Teva’s RespiClick® device for dry powder inhalers.
Dr. Olsson’s presentation “How to establish IVIVC of generic inhalation products” provided insight into how likely is a pharmacokinetic bioequivalence study to succeed and when to invest in a pharmacokinetic bioequivalence study. He stressed that the dose is fundamental (delivered dose is not always equal to systemic dose) and biorelevant in vitro methods, such as mouth-throat models, are essential for prediction of lung dose, and concluded that physiologically-based mechanistic modeling can provide in-depth understanding of in-vitro in-vivo correlation (IVIVC) of generic OIDPS.
The Chinese presentations were on the clinical, bioanalytical, regulatory, scientific and technology challenges of bioequivalence studies of OIDPs. In China, most clinical pharmacokinetic studies are conducted in hospital-based clinics and not CROs; there is little practical experience in China with conducting pharmacodynamic bioequivalence studies of OIDPs. Therefore, Chinese pharmaceutical companies are looking for experienced CRO like Novum to help with clinical conduct of pharmacokinetic and pharmacodynamic studies of OIDPs for submission to Chinese and global regulatory agencies.
Asthma and COPD in China
In China, there are multiple, major causes for human respiratory diseases. These include high population in cities, large numbers of people who smoke, use of motor vehicles, rapid industrial expansion, and worsening environmental pollution.1
China’s 27 provinces and four municipalities have a total population of 1.37 billion. There were more than 32 million asthma patients in 2016 and the incidence of asthma in the total population has been increasing at a rate of 4% per year. Among young persons below 14 years of age, 3.7% suffer of asthma.1
The incidence of COPD is very high in China, with more than 80 million patients in 2016. The percentage of the population suffering from COPD is 14% for persons over 40 years of age and 8% for those over 28 years of age.1
Owing to the continuous increase in asthma and COPD disease, there has been an average growth in drug treatment of more than 20% for the past five years. The total inhalation drug market in China was approximately $1.6 billion USD in 2015. Products from GSK, AstraZeneca, Boehringer Ingelheim and other international pharmaceutical companies account for 90% of the total market. In addition, more local pharmaceutical companies are becoming involved in the area.1
The regulatory pathway for approval of OIDPs in China poses a major challenge for local Chinese companies, such that there are very few generic OIDPs approved in China.
- Shen A, Hou S, Wang Z. The Inhalation Drug Delivery Association (IDDA) China. Inhalation. April 2017, pp. 6-7.