Bureau  Circular No. 008, s. 2006, which lifts the moratorium on the conduct of bioavailability/bioequivalence studies for selected pharmaceutical products, was issued in recognition of the availability of facilities and bioanalytical methods to be used in the conduct of bioequivalence studies.

On the other hand, Bureau Circular No. 2007-005, which implements Administrative Order No. 2005-31 or the Guidelines and Procedure for the Issuance of the Principal Certificate of Product Registration and the Listing of Identical Drug Products based on the Identity of the Manufacturer and Pharmaceutical Formulation, requires the conduct of Bioavailability/bioequivalence studies of drug products that are likewise listed in Bureau Circular No. 008 s. 2006 and are prospectively to be covered by Principal Certificates of Product Registration.

As such, the sudden deluge of applications for Bioavailability/Bioequivalence studies accordingly makes the conduct of studies to be scheduled months apart. This scenario leads to the delay of issuance of Certificates of Product Registration (CPR) and if permitted to continue, this may eventually hinder the government ™s policy to lower the costs of medicines identified in Bureau Circular No. 008, s. 2006, this amendment.


Item II, (A) of Bureau Circular No. 008, s. 2006 on Initial Registration is hereby amended to read as follows:

A. Initial Registration

1. All new and pending applications for initial registration of products listed in Bureau Circular No. 008 s. 2006 which were already scheduled for BA/BE studies and awaiting the results thereof shall be issued a Certificate of Product Registration (CPR) which will be valid only for one (1) year without extension, unless if the BA/BE study cannot be completed within one (1) year from the date of the issuance of the CPR, in which case, only one extension is allowed and only for another year; provided that the applicants shall have fully complied with the following requirements and the same have passed evaluation by the proper division of the Bureau, to wit:

a.  The applicant have completed all other documentary requirements for the purpose;

b. The applicant shall submit proof of payment of the requisite BA/BE studies with the corresponding schedule. The schedule must indicate the date when the study shall be expected to be completed;

c. The applicant shall submit complete data (e.g. graphs, assay methods) of comparative dissolution profiles (reference innovator product versus product to be registered). The dissolution profiles should be performed using the parameters identified in Bureau Circular No. 13-A s. 1999; and

d. The applicant shall execute and submit a duly notarized Affidavit of Undertaking containing the following:

Agreement

i) that in the event the result of the BA/BE study fails, or there has been verified report/s of serious adverse events (serious physical injuries or death) and the proximate cause thereof is the use of the product under study, or there is findings of misrepresentation or falsification by the applicant on the data or any document it tendered with the BA/BE center in connection with the conduct of the study as well as the result submitted with the Bureau, the CPR so issued shall be revoked or cancelled immediately at the instance of the Bureau and delisting of the registration of the product from the database without notice and hearing;

ii) to voluntarily surrender the CPR issued and recall or withdraw voluntarily from the market the product covered by said CPR pursuant to Bureau Circular No. 08 s. 2001;

iii) to indemnify and/or hold BFAD free and harmless against any and all

third party claims and/or actions pertaining to the above incident and action of the applicant;

iv) that the applicant is aware that this Office is not precluded and can, at any time even when an amended CPR is already issued pursuant to paragraph two (2) below, validate and inspect with the BA/BE center the data or any document it tendered with said center in connection with the conduct of the study as well as the results of the study submitted with the Bureau; and

v) that if the CPR expires without securing favorable extension from the Bureau, to voluntarily cease and desist from further manufacturing, importing, exporting, selling, offering for sale, distributing, or transferring the product covered by the CPR.

2. In the event that the BA/BE study is completed within the validity of the CPR, the holder thereof shall submit the result of the study (whether favorable or failed) to this Office within five (5) days from receipt of the same. After determination by this Bureau of the favorable result, the CPR shall be amended immediately in accordance with Item II(C) of Bureau Circular No. 008, s. 2006.

3. Upon the other hand, if the study failed or there is verified report/s of serious adverse events (serious physical injuries or death) and the proximate cause thereof is the use of the product under study, this Office shall immediately revoke the CPR and cause the delisting of the registration of the product from the database without notice and hearing.

4. Also, in the event of any findings of misrepresentation or falsification by the applicant on the data or any document it tendered with the BA/BE center in connection with the conduct of the study as well as the result submitted with the Bureau, this Office shall likewise immediately revoke the CPR or the amended CPR, if already issued, and cause the delisting of the registration of the product from the database without notice and hearing.

5. In any of the preceding instances, the original CPR must be voluntarily surrendered with this Bureau.

6. Failure to cause the submission of the result of the study as directed above shall likewise be a ground for the revocation of the CPR.

7. For purposes of efficient and prompt action of CPR extension, all concerned establishments are enjoined to submit the original CPR one (1) month before the expiry date of the same.

8. In case the CPR expires without securing a favorable extension and the result of the study has not yet been completed and/or submitted, the establishment shall cease and desist from further manufacturing, importing, exporting, selling, offering for sale, distributing, or transferring the product covered by the CPR. If subsequently the result of the BA/BE study was released and the same is favorable to the applicant establishment, the establishment shall apply, if it so wishes, an initial registration attaching the result of the said study, subject to proper evaluation, with the corresponding payment of the applicable fee.

The above guidelines shall also apply to Item III, (2) (c) and (d) of Bureau Circular 2007-005.

B. Renewal Registration

Item II, (B) (1) of Bureau Circular No. 008 s. 2006 on Renewal Registration is hereby amended to read as follows:

1. All applications for renewal registration of drug products listed above which were already scheduled for BA/BE studies and awaiting the results thereof shall be issued a CPR which will be valid only for one (1) year without extension; provided that the applicant shall have fully complied with the requirements listed in Item II, (A), (1) above, except in the case of CPR extension.

2. The provisions in Item II, (A) (2), (3), (4), (5) and (6) above shall also apply.

3. In case the CPR expires and the result of the study has not yet been completed and/or submitted, the establishment, shall cease and desist from further manufacturing, importing, exporting,  selling, offering for sale, distributing, or transferring the product covered by CPR. If subsequently the result of the BA/BE study was released and the same is favorable to the applicant establishment, the establishment shall apply,  if it so wishes, an initial registration attaching the result of said study, subject to proper evaluation, with the corresponding payment of the applicable fee.


Non-compliance with any of the directive above shall be deemed as a violation which should result in punitive and/or administrative sanctions appropriate thereto.


A. BA/BE Centers are required to keep and maintain the records of every BA/BE studies conducted and make it readily available at any time for purposes of inspection, verification, and/or audit by this Bureau.

B. For the above purpose, BA/BE Centers shall not dispose any records relating to BA/BE studies conducted without the written concurrence of this Office.

This Circular shall take effect immediately.

Adopted: 08 Oct. 2007