Evolution of Clinical Trial Agreement Review in Malaysia Through CRM

To regulate the conduct, relationships, responsibilities, and obligations of the parties involved in the clinical trial, the Clinical Trial Agreement (CTA) must be in place. The parties in a CTA are not usually limited to sponsors or contract research organizations (CROs), but also include institutions and principal investigators. The Malaysian Guideline for Good Clinical Practice, has defined the CTA as“A written, dated, and signed agreement between two or more involved parties that sets out any arrangements on delegation and distribution of tasks and obligations and, if appropriate, on financial matters. The protocol may serve as the basis of a contract.”(1) Read more

Have I Done Enough? – Recruitment and Retention

Read more contents from CRM Bulletin Issue 14. Download here!

The success or failure of a trial strongly lies in the recruitment achievements.  Although clinical trials has been conducted in more than few decades, the recruitment continues to be an immerse challenge for most trials. Investigators enthusiasm for ambitious recruitment targets is often misguided. This is called as “Lasagna Law” where by, investigators overestimate the pool of available patients and at the end of the study fails to deliver the promised target. Read more

Unraveling the Methodology of Risk Based Monitoring

Read more contents from CRM Bulletin Issue 14. Download here!

The growth of clinical research is extraordinary and the number of clinical trials being approved to run is increasing rapidly in the world. Therefore, there is an increase in the complexity of newer trials as well as the cost of monitoring them. This increasing complexity leads to clinical sites generating more errors during data collection, thus causing delays in the data-cleaning process. Furthermore, there is a higher chance for deviations to occur and be unnoticed at a clinical site. These deviations may directly affect patient safety and data integrity, and is in violation of Good Clinical Practice (GCP). Considering this development, most pharmaceutical companies (or sponsors) are moving towards a new monitoring approach called the Risk-Based Monitoring (RBM) model. For RBM to be defined, a comparative analysis needs to be made between RBM and the traditional monitoring model. Read more

Site Selection – What a Sponsor Looks For?

Read more contents from CRM Bulletin Issue 14. Download here!

Clinical research is a process that studies a new treatment effectiveness. While it is a very good opportunity for doctors to study the disease development and treatment, the conduct of clinical research by doctors themselves requires a huge budget. Industry Sponsored Research (ISR) provides a good opportunity for doctors to be involved in new and ground-breaking research that may potentially change the course of treatment globally. The number of clinical research has been increasing over the past 10 years. Almost 50% of all trials registered in clinicaltrial.gov showed that it is conducted in Asia. However, less than 1% of the registered clinical research came to Malaysia. To increase the number of ISR in Malaysia, feasibility process plays an important role. Read more

Malaysia Spearheads Stem Cell Research

Read more contents from CRM Bulletin Issue 14. Download here!

The Ministry of Health (MOH) Ampang Hospital is embarking on a pioneering stem cell research exploring the use of mesenchymal stem cells (MSCs) in acute graft-versus-host-disease (aGVHD). While this innovative treatment has already been approved in several countries, it has so far only been used as salvage therapy after failing steroids and other immunosuppresants, and rarely employed as a front-line therapy. Steroid refractory aGVHD has a dismal prognosis with mortality in excess of 90% and no viable second-line options.1Working in collaboration with Cytopeutics®, a local company with an impressive track record of basic and clinical trials in stem cell, this Phase I-II double blind randomized clinical trial has been approved by the Medical Research Ethics Committee (MREC) and the National Stem Cell Ethics and Research Sub-committee (NSCERT). More centres are expected to participate in the trial locally and abroad including Singapore and Australia. The success of the treatment will provide a real chance of the patient surviving against the odds as well as put Malaysia on the map in the field of stem cell advances. Read more

Kuala Lumpur Sports Medicine Centre (KLSMC) On Stem Cells Research And Therapy

Read more contents from CRM Bulletin Issue 13. Download here!

Articular Cartilage Repair and Regeneration

Articular cartilage is the soft tissues that surround the bones in the knee joint enabling smooth movement of the knee. Anyone who has suffered or is suffering from damaged cartilage will know just how painful it can be. This can also seriously impact their quality of life and daily function. Regeneration of damaged cartilage has long been thought impossible due to the nature of its tissues. The conventional way of treating cartilage damage often involves complex surgery and is limited to small areas. Even so, the success rates were variable and inconsistent. Often the treatments result in the formation of scar tissues, which cause the cartilage to breakdown faster than normal healthy cartilage; and eventually lead to revision of surgery, higher medical care cost, and little to no improvement in quality of life. Read more

My Personal Experience in Conducting Trials in Sabah and Sarawak

By Soon Wen Xian

Soon Wen Xian, a medical graduate of Volgograd State Medical University, is currently a Clinical Research Associate at an international pharmaceutical organization based in Malaysia.


When I was a young boy, Sabah and Sarawak have always had an air of mystery about it. Despite both being the largest and second largest state in Malaysia, I never had a chance to visit them. And that was until I joined the clinical research industry. Read more

CRM’s Quality Improvement Plan

At clinical research sites, Standard Operating Procedures (SOPs) help define the study team standard practices and daily processes to assure execution of study tasks are in accordance with the requirements. SOPs should contain enough detail to guide the study team through a particular procedure and thereby establish uniformity in the everyday functions of each site. Read more

Esketamine Trial – A Success Story in Patient Recruitment

Written by Chan Wei Quan, Site Manager at Janssen

 

Of all the illnesses out there today, which one would you say is the leading cause of disability around the globe? The answer may surprise you.

It’s depression, which affects more than 15 million adults in the U.S. and more than 300 million worldwide, according to the World Health Organization (WHO). It can cause the affected person to suffer greatly and function poorly at work, at school and in the family. At its worst, depression can lead to suicide. Close to 800 000 people die due to suicide every year.

All existing antidepressants work on the same premise by increasing the brain levels of serotonin and/or norepinephrine—neurotransmitters. However, only about half of the patients receive an adequate response from them, which typically takes four to eight weeks or longer for someone to start feeling better. When you are that depressed and possibly on the point of contemplating suicide, 4 to 8 weeks is a long time…. Read more

Biosimilars: Are they generics?

Article contributed by Shaun Lee Chia Choon.

Shaun Lee is an aspiring clinical research professional with an interest in drug safety and development. He graduated with a Masters of Pharmacy qualification from The University of Bath UK and at the time of writing, is a study coordinator at Kuala Lumpur Hospital.


The short answer is no and here is why.

Generics are conventionally small-molecule drugs, commonly produced via synthetic methods. They are interchangeable with the reference innovator products as their approval depends on the fulfilment of regulatory requirements to be both bioequivalent (comparable pharmacokinetics) and pharmaceutically equivalent (identical active substance). In other words, generics are therapeutically equivalent carbon copies of the reference innovator products.

In contrast, biosimilars (or “follow-on protein products” in the United States) are biological products which are highly similar, but not identical, to the reference innovator products for the approved indications. These pharmaceutical products contain active drug substances derived from living systems which are innately highly variable with regards to their post-translational modifications of proteins. In addition, the active substance of biological products generally consists of high molecular weight protein isoforms folded in specific three-dimensional configurations which are highly sensitive to changes. Consequently, there is increased probability of heterogeneity even between biological products of the same active ingredient and hence, a more comprehensive regulatory pathway is required for the approval of biosimilars compared to generic products.

REGULATORY APPROVAL OF BIOSIMILARS

Following the approval of the first biosimilar product (Omnitrope®) by the European Medicines Agency (EMA) in 2006, there have been many updates on the regulatory processes with regards to the approval of future biosimilars.

The United States Food and Drug Administration (FDA) uses a “totality-of-evidence” approach to approve biosimilars whereas the EMA uses a stepwise approach, which is the method adopted by the Malaysian regulatory body. Nevertheless, biosimilars are approved in both approaches upon demonstration of an absence of clinically significant differences in safety, quality and efficacy profile to the reference product. As a result, the approval pathways for biosimilars are generally more simple than novel biological products, with only selected nonclinical and clinical studies which are primarily comparative studies against reference innovator products.

In addition, the Malaysian regulatory authority imposes requirements for robust post marketing safety studies, particularly on the immunogenicity of certain biosimilars. This is in response to reported safety concerns including the development of antibodies that may attenuate the action of the biological product or neutralise the biological activity of endogenous proteins such as in the rare case of antibody-mediated pure red cell aplasia.

Read more contents from CRM Bulletin Issue 11. Download here!

INTERCHANGEABILITY AND SUBSTITUTION POLICIES

Presently, the Malaysian regulatory authority does not permit the interchangeability and automatic substitution of biosimilars and reference products at the pharmacy level. In contrast, automatic substitution by pharmacists is permitted under Section 351(i) of the United States Public Health Service Act once a biosimilar is given an “interchangeable” status by the FDA. This is supported by a recently released draft guidance on the interchangeability of biological products by the FDA in January 2017, in line with the Biologics Price Competition and Innovation Act of 2009. While the EMA pioneered the approval of biosimilars, the agency does not have the authority to decide on the interchangeability status of biological products; this decision resides with the regulatory authorities in individual EU state members.

TAKE HOME MESSAGE

The development of biosimilars has increased treatment options at lower costs, thus, improving the access to medicines for a larger patient pool. However, healthcare professionals should be aware of the regulatory approval pathways and potential differences between biosimilars and the reference innovator products to make an informed treatment decision which is in the best interest of their patients.