Information regarding the Pharmaceutical Affairs Law in Japan and manufacturing

1. Perspective
By Scott M. Wheelwright, PhD and Hiroshi Kosaku
New Opportunities Result from Changes to
Japan’s Pharmaceutical Affairs Law
I n April of this year, modifications to the basic law regu-
lating pharmaceuticals in Japan—the Pharmaceutical
Affairs Law (PAL)—became effective, providing new
pathways for non-Japanese companies to follow in bring-
ing products to market in Japan. The two changes having
the greatest impact on drugs are the introduction of drug
master files (DMF) and the newly-granted permission that
allows marketing firms to outsource all of their manufac-
turing.
Under the new law, non-Japanese firms will be able
to file the entire chemistry, manufacturing and controls
(CMC) section directly with the Ministry of Health,
Labour and Welfare (MHLW), utilizing the DMF system.
In the past, all such data were filed by an in-country
caretaker who played the role of application sponsor. This
could have been a drug company who was the marketing
partner, a local subsidiary of the non-Japanese company
or a distributor with sufficient sophistication to handle roles played by the DMF in the US. And, because the CMC
this task. The in-country caretaker was the submission’s information can now be kept separate from the marketing
ultimate owner and was responsible for the accuracy of the application, other avenues of distribution become available.
data and its translation. Thus, under the former arrange- Instead of requiring a partner with extensive experience in
ment, a company was not able to keep critical data fully manufacturing and regulatory affairs to submit the applica-
confidential from its Japanese partner. Under the new tion for a non-Japanese company, the foreign firm can take
regime, a non-Japanese company can file the CMC data a larger role and enter into a more limited agreement, or
directly with MHLW without risk of compromise by a into agreements with multiple firms, for reaching different
partner. Of course, translation is still required, but this can market segments or for multiple indications.
be performed by a specialist firm who serves as the resi- The second change of note allows Japanese develop-
dent caretaker and submits the actual DMF filing. Such a ment and marketing companies to outsource all or part of
consulting firm can also serve as the interface with MHLW drug substance or product manufacturing. In the past, the
for all communications. Sections of the common technical marketing company was required to perform the manufac-
document (CTD) may form the basis of the DMF. turing, at least fill and finish operations. Now, under the
The benefits and opportunities that arise from this modified PAL, all of this work can be outsourced. One
change include increased confidentiality of proprietary data consequence of this change is that Japanese companies are
and the opportunity to pursue different types of relationships now looking for CMOs outside their organizations, includ-
with Japanese companies than were available in the past. ing offshore. Another outcome is that pharmaceutical
For example, the description of a drug substance or product companies can now split off their manufacturing arms as
manufactured by a contract manufacturing organization separate enterprises. The motivation for this restructuring
(CMO) can be submitted directly to the agency without is to improve their financial profile by divesting a lower-
sharing the information with the Japanese marketing part- return activity so that the remaining business activities
ner or distributor. This means a CMO has greater protec- show a higher collective return. This restructuring of the
tion of confidential material, including such information as industry has already begun with the recent announcement
other products manufactured in their facility, because the by Chugai (the Roche subsidiary in Japan) that they will
details of their operation no longer have to be shared with divest all their manufacturing operations into a separate
the Japanese marketing partner. This is similar to one of the entity by January 2006. This change also opens the way
51
July 2005 Regulatory Affairs Focus

2. Perspective Essentials of RA
for Japanese pharmaceutical companies to combine their eyes glass over when I rave, yet again, about how much I
manufacturing arms with those of other firms to benefit love where I am and what I am doing. It is a crazy place,
from economies of scale. We may see such moves in the this regulatory “Other.” But, as I learn to navigate the
not too distant future. terrain, I am often rewarded with glimpses of scientific
In summary, the introduction of the DMF system and brilliance and remarkable humanity. All in all, “Other” is
the freedom to outsource manufacturing provide benefits a pretty good place to live, and one that welcomes new
and opportunities to non-Japanese companies who move residents. Keep it in mind if you think you might like to
to take advantage of these recent changes in the Japanese relocate to an area that can be a little rocky but offers some
Pharmaceutical Affairs Law. spectacular views.
NOTES
Scott M. Wheelwright, PhD, is the founder and president of Strategic
Manufacturing Worldwide, a consultancy providing manufacturing and devel- 1. http://www.cia.gov/cia/publications/factbook/
opment services to the biotechnology and pharmaceutical industries. He has 2. http://www.ncrr.nih.gov/clinical/crfact.pdf
more than 20 years experience in manufacturing, development, quality and 3. http://www.ncrr.nih.gov/clinical/crguide2004/guide17March2004.pdf
compliance. 4. http://grants.nih.gov/grants/funding/women_min/guidelines_amended_
10_2001.htm
Hiroshi Kosaku is senior director of the regulatory and strategy consultation 5. http://www.aaas.org/spp/rd/nih06p.htm
division at CMIC, a CRO with offices in Japan, Korea and China providing spe- 6. http://www.fda.gov/cder/guidance/959fnl.pdf
cialized assistance in regulatory affairs, clinical testing and market research. He
has over 15 years experience in industry, including several years working on
regulatory affairs projects.
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52 July 2005
Regulatory Affairs Focus