PHARMACEUTICAL VALIDATION: A METHOD? OR MORE

C O N F I D E N T I A L SECTION 01 OF 02 TAIPEI 002078

SIPDIS

STATE FOR EAP/RSP/TC, STATE PASS AIT/W AND USTR FOR KI AND
FREEMAN, USDOC FOR 4431/ITA/MAC/AP/OPB/TAIWAN/MBMORGAN AND
JDUTTON

E.O. 12958: DECL: 05/05/2015
TAGS: ECON ETRD TW
SUBJECT: PHARMACEUTICAL VALIDATION: A METHOD? OR MORE
MADNESS?


Classified By: AIT Director Douglas Paal, Reason 1.4 (b)


1. (U) Summary: Representatives from PhRMA accompanied AIT
to meetings with Taiwan Department of Health (DOH) officials
to discuss pharmaceutical validation issues on April 28. AIT
intervention salvaged a heated exchange between PhRMA,
Taiwan,s Bureau of Food and Drug Analysis (BFDA) and local
pharmaceutical association representatives. BFDA's Risk
Profile Number (RPN) methodology continues to lack
transparency but the meeting eventually led to promises of
useful clarifications of terms. A brief discussion of BFDA
proposed computer validation requirements reassured PhRMA
that Taiwan's requirements should not be too difficult to
meet. In a separate meeting, Taiwan,s Bureau of
Pharmaceutical Affairs (BOPA) agreed to allow PhRMA to
provide input into the draft guidelines for review of Active
Pharmaceutical Ingredients (API) and agreed to extend import
licenses for medical devices in the registration process
until the end of 2005. End Summary.


2. (U) In response to a request by the Pharmaceutical
Research Manufacturers Association (PhRMA) and the
International Research Pharmaceutical Manufacturers
Association (IRPMA),Acting Director General of Taiwan,s
BFDA, Erick Suen called a meeting of pharmaceutical
manufacturers to discuss outstanding validation issues
including the methodology for assigning RPNs and requirements
for computer validation. Cynthia Wang (Merck),Allan Chu
(Eli Lilly),Roy von Kutzleben (Pfizer),and Marie Vodicka
(PhRMA),joined IRPMA's Executive Director Carol Cheng and
AIT Econ and Commercial officers in attending.

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BFDA Wants an RPN Resolution Now
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3. (SBU) Acting DG Suen was eager to reach consensus on
acceptable RPN methodology, used to identify pharmaceutical
manufacturing sites for inspection by Taiwan authorities.
PhRMA was not prepared to agree to any particular
formulations but raised several questions about the apparent
arbitrariness of the scoring and weighting of each factor in
the formula. BFDA attempted to negotiate the scoring of each
factor and was extremely frustrated by PhRMA's reluctance to
bargain. After a brief break that allowed participants to
disengage and consult among themselves, Suen returned and
agreed to hear PhRMA's concerns without insisting on
negotiating compromises in the meeting.


4. (U) BFDA's RPN formula considers four categories: quality
control issues, dosage forms, a Good Manufacturing Process
(GMP) Standard and Regulatory Environment, and the volume of
product distributed in Taiwan. These scores are weighted and
totaled and then used to prioritize manufacturing site
inspections. PhRMA expressed no concerns about scoring or
weighting in the dosage form or volume categories, but had
concerns about the definitions and weighting in the quality
control and regulatory environment categories.

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PhRMA Asks for Clarifications on RPN Categories
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5. (U) Specifically, PhRMA asked for clarification about the
criteria for determining the pharmacovigilance score (based
on BFDA's post-marketing surveillance and distributor
complaints) and a vaguely worded catchall category for
"special situations." PhRMA also requested clarifications on
scoring for those companies that had products recalled. BFDA
responded that the score could be differentiated based on
whether the recall was government mandated or self-initiated
and whether the recall was for quality or safety issues.


6. (U) PhRMA also disagreed with the scoring based on the
regulatory environment of the manufacturing country and
differential based on the type of documentation provided
(full documents vs. the Certificate of Pharmaceutical Product
(CPP) and template),arguing that these factors were
inappropriately scored and violated BFDA's commitment to
ensure that the RPN factors would be risk based. BFDA
countered that a manufacturer's willingness to submit full
documentation was a show of compliance with Taiwan
regulations and should be rewarded, an argument that was
quickly rejected by AIT and PhRMA. BFDA agreed to provide
more detailed explanations of each factor and post them on
the BFDA website.


7. (U) Finally, AIT and PhRMA raised questions about the
weighting for each category. Due to simple mathematical
errors, it appears BFDA's formula unintentionally over
weights the first category. BFDA confirmed its intention is
to weight each category as a fixed percentage of the final
score and promised to review the math.

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Computer Validation Too Easy?
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8. (U) Discussion of computer validation (stage three)
procedures focused on BFDA's creation of a detailed draft
checklist. PhRMA expressed concern that the checklist it had
seen was too detailed and suggested that it would be
impossible for manufacturers to complete. AIT urged BFDA to
remain consistent with the principles of stage one and two
validation and minimize additional required documentation.
BFDA clarified that the checklists were being drafted as an
internal tool only and that manufacturers would not be
required to submit these documents. Suen and his staff
agreed that a description and overview of computer systems
already validated by a competent national authority should
meet Taiwan's requirement. BFDA also requested that PhRMA
prepare a concrete proposal for computer validation
requirements and confirmed that it would be willing to accept
any CPP that includes a GMP certificate issued after computer
certification had been included in the GMP process as
fulfillment of this requirement. BFDA also reminded PhRMA
that manufacturers that volunteer for inspection are exempt
from these requirements.

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BOPA Raises GMP-API
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9. (U) Separately, the PhRMA delegation paid a courtesy call
on Counselor to the Minister of Health, Dr. Hsiao Mei-ling,
and BOPA Director General Dr. Wang Hui-po. Hsiao and Wang
again confirmed that BFDA is the competent Taiwan authority
for all matters related to pharmaceutical validation. They
also raised the issue of BOPA's review of active
pharmaceutical ingredients (API),explaining that API reviews
are conducted by a BOPA-assigned committee. PhRMA noted that
it may not be possible for all manufacturers to provide
requested GMP-API documents since each country has differing
requirements. BOPA agreed to consider any input from PhRMA
as the guidelines are being drafted.

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Good News on Registrating Medical Devices
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10. (U) AIT Econoff took the opportunity to raise a separate
issue regarding registration of medical devices.
Manufacturers and importers are being required to register
all classes of medical products by June 20, 2005 or face
import restrictions. Manufacturers and importers have
expressed concern that BOPA staff will be unable to process
registration applications by the deadline, potentially
barring life-saving devices from Taiwan. BOPA DG Wang said
BOPA recognized the problem and had decided that as long as
manufacturers submitted registration applications by the June
20 deadline, they would not face import restrictions through
the end of 2005.

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Comment: PhRMA Hurting Itself
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11. (C) Comment: PhRMA's frustrating meeting with BFDA was
in significant part a result of PhRMA's lack of coordination
either with BFDA or AIT. PhRMA informed AIT less than a week
before the delegation was scheduled to arrive and made no
effort to involve AIT in scheduling of meetings or setting of
agendas. The parties had widely divergent expectations for
the meeting and it was only the timely intervention of AIT
officials that allowed the parties to return to the table for
what ended up being moderately productive discussions. The
most significant obstacle to progress in resolving
pharmaceutical validation issues has been a lack of reliable
communication between Taiwan,s DOH and PhRMA, all too often
the origin of the problem has been disorganization and an
inability or unwillingness to coordinate on PhRMA's part.
The remaining technical issues involved with RPN calculation
may require some compromise but should not be too difficult
to resolve. To do so, however, will require vastly improved
coordination and communication between PhRMA, AIT and BFDA.
AIT made this point clearly to PhRMA delegates and it
appeared to be understood before they departed.
PAAL