CMC development

To develop candidate compounds (such as small molecules and nucleic acids) that are identified in drug discovery into drugs accessible to patients, we need to have technologies for the mass production of active pharmaceutical ingredients (developed in process research), conduct qualitative assessment in analytical research, and develop pharmaceutical formulations. At Nippon Shinyaku, we continue to challenge ourselves to find new solutions in these processes of product development, actively engaging in PLCM mainly through the addition of new indications and dosage forms.

For example, one of our PLCM themes is the extension of product life by using advanced technologies that enable the reformulation of ointments as capsules, injections as tablets, and tablets into a smaller size or fine granular form.

Product development 01

Process research

In process research, we develop synthesis methods and technologies to accommodate the industrial-scale production of candidate compounds that are identified in drug discovery research. Focusing on not only small molecules but also nucleic acids, we also conduct nucleic acid process research. The development of Viltepso, the first nucleic acid drug in Japan, posed a major challenge for us. Yet, this process enabled us to cultivate related technological know-hows, which we hope to mobilize in our R&D activities to develop and launch new nucleic acid drugs in the future.

Product development 02

Analytical research

In analytical research, in preparing regulatory application for manufacturing and marketing approval, we establish methods and criteria for the qualitative assessment and evaluate the quality of developed compounds.
In the research of preparing for the application for the nucleic acid drug Viltepso, we compensated the absence of official guidelines for nucleic acid drugs by developing our own analytical technologies and setting quality standards for APIs and formulations in consultation with the regulatory authorities. We utilize the analytical technologies and related know-hows for manufacturing nucleic acid drugs, which are developed in promoting high-quality pharmaceutical quality control.

Product development 03

Formulation development

Formulation development involves conducting research on dosage forms and the functionality of formulations so that active ingredients can be maximally effective; developing manufacturing processes that achieve the target quality levels in formulations; and designing formulation specifications (including shape, color, and indications) to ensure the ease of use for patients and health care providers.
In the development of Tramal OD (orally disintegrating tablets) indicated for cancer-associated pain or chronic pain, the bitter taste of tramadol hydrochloride, its active ingredient, was masked using a special technology. This feature and its formulation not requiring water are appreciated for the administration to elderly patients, patients with difficulty in swallowing, and patients subjected to restricted water intake.

Product development 04

Product Life Cycle Management (PLCM)

In the pharmaceutical industry, PLCM involves enhancing the product value of a drug by such means as discovering new indications, adding new dosage forms, and improving user convenience. We at Nippon Shinyaku believe that PLCM is as significant as developing epoch-making new drugs because they both aim to meet the needs of the times and society. By responding to the user needs, mainly those of patients, we in fact make a long-term contribution to people’s health and well-being
Nippon Shinyaku is vigorously promoting PLCM using advanced technologies to maximize product value through the addition of new indications and reformulate drugs as orally disintegrating (OD) tablets or tablets into a smaller size, thereby extending product life.

Additional indications of selexipag

Selexipag, the active ingredient of Uptravi, Nippon Shinyaku’s original drug for treating PAH launched in 2016, is also assumed to be effective in treating other diseases. Nippon Shinyaku is currently conducting clinical trials to verify this assumption and add indications of selexipag for three diseases: chronic thromboembolic pulmonary hypertension (CTEPH), for which effective treatment is to widen the pulmonary arteries as in the case of PAH; arteriosclerosis obliterans (ASO); and lumbar spinal stenosis (LSS). We are aiming to add these indications to maximize the value of selexipag.

CTEPH Pulmonary hypertension resulting from thromboembolism that is caused by an organized blood clot obstructing the pulmonary arteries, designated as an intractable disease in Japan. In 2016, Nippon Shinyaku received orphan drug designation from the MHLW for CTEPH indication.
ASO The disease in which blood circulation to the limbs is disturbed because of arteriosclerotic lesions in the extremities, patients typically suffer from intermittent claudication (feeling numbness or pain in the lower limbs while walking, often to the extent of not being able to continue walking, which subsides after a short period of rest). Many patients have advanced systemic arteriosclerosis and have a high fatality rate because of myocardial or cerebral infraction.
LSS Narrowing of the spinal canal covering nerves because of chronic compression from the lumbar bone deformation, among other factors, which in turn presses the cauda equine and nerve roots, hence causing pain in the lower back and limbs and nervous symptoms such as intermittent claudication, as in the case of ASO.

Development of Onetram

Onetram Tablet 100 mg, which was launched by Nippon Shinyaku in 2015 for treating persistent cancer pain and chronic pain, is the first tramadol sustained release tablet in Japan. This drug was developed by applying the unique sustained release technology that was in-licensed from Endo Ventures Limited (Ireland) to tramadol hydrochloride, the active ingredient of Tramal Capsule 25 mg (administered four times per day), which Nippon Shinyaku launched in 2010. The double structure of Onetram comprising the quick-releasing periphery and the center for sustained release ensures the immediacy and durability of efficacy at the same time. With once-a-day administration being highly convenient for patients who require extended pain control, Onetram is expected to improve medication adherence.