Mr. TANAKA Katsuya(田中 克哉) Section Chief, Pharmaceutical Evaluation Division, Pharmaceutical Safety and Environmental Health Bureau, Ministry of Health, Labour and Welfare (MHLW) Feb 5 th , 2020 4th India -Japan Medical Products Regulatory Symposium Regulatory system on Generic drugs in Japan 4th India - Japan Medical Products Regulation Symposium 2019 1
21
Embed
Regulatory system on Generic drugs in Japan · •The following tests are also considered generally applicable to generic drugs. -Limits of the content of the ingredient(s) and/or
This document is posted to help you gain knowledge. Please leave a comment to let me know what you think about it! Share it to your friends and learn new things together.
Pharmaceutical Safety and Environmental Health Bureau,
Ministry of Health, Labour and Welfare (MHLW)
Feb 5th, 2020
4th India -Japan Medical Products Regulatory Symposium
Regulatory system on Generic drugs in Japan
4th India - Japan Medical Products Regulation Symposium 2019 1
Contents
• Introduction of Review Points and BE Guidelines
• Overview of Japan’s Strategy for promoting the use of Generic Drugs
24th India - Japan Medical Products Regulation Symposium 2019
Contents
• Introduction of Review Points and BE Guidelines
• Overview of Japan’s Strategy for promoting the use of Generic Drugs
34th India - Japan Medical Products Regulation Symposium 2019
・Expiration of re-examination period of the original product
・No valid patent (substance/utility patent for the active ingredient) at the time of
approval
・Warranty of equivalent quality and bioequivalence to the original product
Requirements for application/approval of generic drugs
Comparing with the original, brand drug, generic drug have the same:
・API (active pharmaceutical ingredients)
・Strengths
・Route of administration
・Dosage form
・Dose and administration and Indications
What are generic drugs?
About generic drugs
44th India - Japan Medical Products Regulation Symposium 2019
Documents Originator Generic
a. Origin or background of discovery, condition of use in foreign countries
1 Origin or background of discovery ○ ×
2 Conditions of use overseas ○ ×
3 Special characteristics, comparisons with other drugs etc. ○ ×
b. Manufacturing methods, specification and test methods
1 Chemical/physical characteristics and structure property ○ ×
2 Manufacturing methods ○ △
3 Specification and test methods ○ ○
c. Stability1 Long-term storage tests ○ ×
2 Tests under severe conditions ○ ×
3 Accelerated tests ○ ○
d. Pharmacological action1 Tests to support efficacy ○ ×
2 Secondary pharmacology, safety pharmacology ○ ×
3 Other pharmacology △ ×
e. Absorption, distribution, metabolism, and excretion
1 Absorption ○ ×
2 Distribution ○ ×
3 Metabolism ○ ×
4 Excretion ○ ×
5 Bioequivalency × ○
6 Other pharmacokinetics △ ×
f. Acute/sub acute/chronic toxicity, teratogenicity, and other type of toxicity
1 Single dose toxicity ○ ×
2 Repeated dose toxicity ○ ×
3 Genotoxicity ○ ×
4 Carcinogenecity △ ×
5 Reproductive toxicity ○ ×
6 Local irritation △ ×
7 Other toxicity △ ×
g. Clinical trials 1 Results of clinical trials ○ ×
h. Package inserts 1 Points to consider of package inserts ○ ○
Note) ○ means necessary, × means not necessary, and △ means to depend on each product
Requirements of data in application in Japan
54th India - Japan Medical Products Regulation Symposium 2019
1. Specifications and analytical procedures
• Specifications are one part of a total control strategy for the drug substance and drug product designed to ensure product quality and consistency (ICH Q6A guideline).
• The following tests are also considered generally applicable to generic drugs.
- Limits of the content of the ingredient(s) and/or the unit of potency, Description, Identification tests, Specific physical and/or chemical values, Purity tests, Water or loss on drying, Residue on ignition, Assay, and so on.
Points of quality review
4th India - Japan Medical Products Regulation Symposium 2019 6
1. Specifications and analytical procedures (continued)
• Assay
• Set acceptance criteria assuring the equal efficacy and safety based on the batch data and stability data, etc.
• Impurities
• Equal or tighter acceptance criteria than that of
the original drug in principle.
• Review based on ICH guidelines (Q3A, Q3B, Q3C) about impurities which are not detected in the original drug.
Points of quality review
74th India - Japan Medical Products Regulation Symposium 2019
2. Manufacturing processes
The Marketing Approval Document includes all processes from starting material(s) to packaging process.
• Starting materials
• Intermediates
• Critical steps
• In-process control
• Container closure system, and so on
• An applicant should demonstrate that the manufacturing process is capable of consistently producing drug substance and drug product of the intended quality.
Points of quality review
84th India - Japan Medical Products Regulation Symposium 2019
3. Stability
• An applicant should submit 6 months of accelerated stability data.
- at 40 ℃, RH 75%, 3 lots, for 6 months
• In some cases, the applicant should also submit the following stability data at the time of submission.
Long-term storage tests
- at 25 ℃, RH 60%, 3 lots, for 12 months at least
Tests under severe conditions
- photostability, etc.
Points of quality review
94th India - Japan Medical Products Regulation Symposium 2019
4.Bioequivalence
• Assure therapeutic equivalence of a generic drug to the original drug.
• Compare the bioavailability between a generic drug and the original drug.
TimeP
lasm
a level of
dru
g
Points of quality review
104th India - Japan Medical Products Regulation Symposium 2019
• Guideline for Bioequivalence Studies of Generic Products + Q&A (February 29, 2012)
– Q&A has not been denied the possibility of acceptance of foreign subjects BE data.
– Japanese research group has summarized the consideration from the scientific view point to cope with BE study (including acceptance of foreign subjects data).
Summary:
− The target of BE studies is to detect differences between formulations, and the influence that the racial difference bring to the result could be considered to be small.
− Foreign BE studies are acceptable as a rule in light of the current guideline concept.
− However, if there is a significant difference between the dissolution rates of the standard formulation and the investigational formulation, it is necessary to conduct BE studies for Japanese who are subject to administration.
− The standard formulation should be the brand name product that is approved and distributed in the Japanese domestic market.
Foreign subjects BE study data
114th India - Japan Medical Products Regulation Symposium 2019