Chapter II
PROVISIONS FOR STUDY DATA REPORT OF BIOAVAILABILITY/BIOEQUIVALENCE IN DRUG REGISTRATION
Article 7. The generic drugs in conventional dosage forms effecting the whole body
1. The drugs falling into one of the following cases are exempted from reporting bioequivalence study data as registering drug:
a) Intravenous injection drug with the same type of use as injected is the solution in water, with the same pharmaceutical substance and the same concentration with the drug which has been approved;
b) Drug using way of injection different from by intravenous injection with the same using form as injected is the solution in water or in oil, with the same pharmaceutical substance and the same pharmaceutical substance concentration, the same exipient or the type of exipient equivalent to drug which has been approved;
c) The drug is used under the form of solution in water as drinking, with the same pharmaceutical substance and the same pharmaceutical substance concentration with approved drugs with a condition that the excipients contained in drug do not affect the transport of drugs through digestion, absorption, and stability of the pharmaceutical substance in the body.
d) Drug used in aerosol form.
2. The drugs do not fall into the cases prescribed in clause 1 of this Article, containing pharmaceutical substance on the list of pharmaceutical substances required to report bioequivalence study data as registering drug (Annex 2) must report bioequivalence study data as registering.
3. The drug that its formula has a combination of several pharmaceutical substances, including pharmaceutical substances on the list of pharmaceutical substances required to report bioequivalence study data as registering drug (Annex 2), must report bioequivalence study data for such pharmaceutical substances.
4. For different contents of oral use of the same pharmaceutical substance (or the same combination of pharmaceutical substances), the same dosage forms of the same manufacturer, made in the same location, the report of bioequivalence study data of a content can be considered to accept for the remaining contents (usually the contents shall be lower except for the bioequivalence study for higher contents cannot make because of safety reasons) when meeting the following conditions:
a) The being considered contents have the same production process with the content used in bioequivalence study;
b) Formula of dosage of the being considered contents must be the same on composition (excipients and pharmaceutical substance) and the same rate of combination between the compositions or, in the case of pharmaceutical substance account for less than 5% in the formula, the rate of coordination among the remaining compositions in the formula must be similar as compared with the dosage formula of the content used in bioequivalence study;
c) Having a linear relationship between pharmaceutical substance content and absorption ability of pharmaceutical substance into the body in the considered dose (or treatment dose);
d) For the solid oral drugs: In the same conditions of testing the solubility, dissolution diagram of the being considered content must be similar to the contents used in bioequivalence study (based on percentage of pharmaceutical substance released by time). The method of setting, comparisons of dissolution diagram and acceptable limits specified in Annex II- bioavailability/bioequivalence study guideline of ASEAN.
Article 8. The generic drugs in modified release dosage form with full body effects
1. The drugs under package dosage form dissolved in the intestine: applied as for the drug in conventional dosage forms in accordance with provisions in Article 7.
2. The drug containing any pharmaceutical substance in the modified release dosage form not dissolved in the intestine must report bioavailability or bioequivalence study data and/or report appropriate clinical trials the case by case basic as follows:
a) Drug in the modified release dosage form is marketed for the first time intended to replace a drug in the conventional dosage form or the modified release dosage form of different style which has been approved of the same pharmaceutical substance:
- If it has data on a correlation between clinical response (including response to therapy and adverse reactions) and drug concentrations or active metabolites (from pharmaceutical substance for trying) in plasma, required to report bioavailability study data comparing between the drugs need to be tried with respective control drug in conventional dosage form. This obtained comparison bioavailability study data will be used to evaluate the safety and efficacy of drugs in being considered modified release dosage forms. If the obtained pharmacokinetic data in the study is not sufficient to prove the safety and efficacy of being considered drugs, it needs to conduct a proper clinical trial to supplement;
- If it has no available data on a correlation as mentioned above, it must conduct an appropriate clinical trial to determine at the same time the parameters of pharmacokinetics and pharmacodynamics of drugs.
b) Drug in the modified release dosage form intended to be equivalent to a drug in modified release dosage form of the same type which has been approved: required to report bioequivalence study data of drugs compared with corresponding control drug which are considered for the equivalent design.
3. The generic drugs in extended-release dosage form of oral use:
a) Apart from the provisions applied generally to the drug in modified release dosage form not dissolved in the intestine mentioned in clause 2 of this Article, required to supplement the report of research data on the effects of food to bioavailability of the drug.
b) For the drugs have different contents of the same pharmaceutical substance (or the same combination of pharmaceutical substances) in this dosage form, may be considered acceptable bioequivalence study report data of the high content for the lower content in the case satisfying the following conditions:
- As the capsule form containing the same type of particle that difference on the contents of pharmaceutical substance in the capsule obtained by adjusting the amount (or volume) of particles in the capsule or:
As the tablet form of the same pharmaceutical substance -release mechanism, with the dosage formula similar to the ingredients (excipients and pharmaceutical substance) and with the same rate of combination of these ingredients in the formula;
- The being considered contents are of the same manufacturer, made in the same location and same process of preparation with a content used in bioequivalence study;
- Having a linear relationship between pharmaceutical substance content and absorption ability of pharmaceutical substance into the body in the considered dose (or treatment dose);
- In the same conditions of testing the solubility, the dissolution diagram of the being considered content must be similar to the content used in the bioequivalence study (based on the percentage of pharmaceutical substance released by time ). The methods of setting, comparison of the dissolution diagram and acceptable limits specified in Annex II- bioavailability/bioequivalence study guideline of ASEAN.
Article 9. The changes for drugs approved
1. Changes in recipe or dosage processes that affect the bioavailability of the drug:
a) For invention drug: requirements to report bioequivalence study data of drugs have changed compared with the control drug as invention drugs with the formula and process of dosage which has been approved;
b) For generic drugs: requirements to report bioequivalence study data of drugs have changed compared with the control drug used in bioequivalence studies of drugs which has been approved.
2. Relocation of production (unchanged preparation recipe and process of preparation) requirements to report similar data of solubility of the drug is produced at the new location compared to manufactured drugs at the former place approved. Similar evaluation method of solubility and acceptable limits is specified in Annex II- study guidance of bioavailability/bioequivalence of ASEAN.
Article 10. The process and procedures for receiving records
Report of bioavailability/bioequivalence study data is part of drug registration dossier, which was received at the Drug Administration of Vietnam under the provisions of Circular No.22/2009/TT-BYT dated 24/11/2009 of the Health Ministry provided for medicine registration.
Tìm kiếm
Thông tư 08/2010/TT-BYT hướng dẫn báo cáo số liệu nghiên cứu sinh khả dụng/ tương đương sinh học trong đăng ký thuốc do Bộ Y tế ban hành (Bản Word)