✦ 스마트 요약
Circular No. 04/2010/TT-BYT guides the sampling of medicines to determine their quality, applicable to agencies, organizations, and individuals related to this activity. The Circular provides detailed regulations on conditions, procedures, and sampling processes for raw materials, semi-finished products, finished products, and packaging materials, with the aim of ensuring medicine quality.
적용 범위
Agencies, organizations, and individuals involved in the sampling of medicines, particularly pharmaceutical production and trading enterprises; samplers; state management and inspection agencies for medicine quality.
핵심 사항
- Samplers must meet requirements regarding qualifications and legal responsibility (Article 3).
- The amount of samples taken depends on testing requirements and quality standards, at least sufficient for three analyses (Article 9).
- Sampling principles must be supervised and recorded fully, without mixing samples showing different signs (Article 10).
- Costs for sampling medicines are implemented according to the provisions of the Law on Product Quality and Safety 2007 (Article 8).
- Sampling schemes are based on the homogeneity and origin of the batch of raw materials (Article 16).
🌐 이 문서의 사회적 영향
- Positive impact: Ensuring medicine quality, enhancing public health safety.
- Negative impact: Increased costs for businesses during the sampling and testing process.
❓ 자주 묻는 질문
What requirements must samplers meet?
Samplers must be inspectors, specialized pharmaceutical quality control officers, or members of inspection teams established by state management and inspection agencies for medicine quality (Article 3).
How much sample should be taken?
The amount of samples taken depends on testing requirements and quality standards, at least sufficient for three analyses or must be enough to perform tests ensuring accurate results (Article 9).
What does the cost of sampling medicines include?
The cost of sampling medicines for quality testing is implemented according to the provisions of Article 37, Article 41, and Article 58 of the Law on Product Quality and Safety 2007 (Article 8).
On what basis is the sampling scheme determined?
Sampling schemes are based on the homogeneity and origin of the batch of raw materials. There are three schemes: n, p, r, each with its own formulas (Article 16).
Who is responsible for implementing this Circular?
The Director of the Drug Administration Department is responsible for guiding the implementation of this Circular. The Heads of the Ministry of Health's Office, the Inspectorate of the Ministry of Health, the Science and Training Department, the Director of the Drug Administration Department, and the Directors of drug testing institutes bear the responsibility for enforcement (Article 18).
전문
CIRCULAR
Guidelines for sampling medicines to determine quality
Pursuant to Decree No. 188/2007/NĐ-CP dated December 27, 2007 of the Government on the functions, tasks, powers, and organizational structure of the Ministry of Health;
Pursuant to the Drug Law dated June 14, 2005;
Pursuant to the Law on Product Quality and Goods dated November 21, 2007;
Pursuant to Decree No. 79/2006/NĐ-CP dated August 9, 2006 of the Government detailing the implementation of certain provisions of the Medicine Law;
Pursuant to Decree No. 132/2008/NĐ-CP dated December 31, 2008 of the Government detailing the implementation of certain provisions of the Law on Product Quality and Goods;
The Ministry of Health provides guidelines for sampling medicines to determine quality as follows:
PART I
GENERAL PROVISIONS
Article 1. Scope of Regulation and Applicability
Article 1. This Circular guides the procedures, formalities, and conditions for sampling medicines (finished products, raw materials, and excipients) to determine quality.
Article 2. This Circular applies to agencies, organizations, and individuals related to medicine sampling activities and pharmaceutical production and trading enterprises involved in such activities.
Article 3. In production and trading activities, entities may apply appropriate contents of this Circular to take samples for testing at various stages of production, storage, internal delivery, or between entities. Based on the provisions of this Circular, the head of the entity may establish specific regulations on sampling medicines in accordance with good manufacturing practices and good storage practices at the entity.
Article 2. Interpretation of Terms
The terms in this Circular are understood as follows:
1. Sampling medicines: Refers to technical operations aimed at collecting a certain quantity of medicine (finished products, raw materials, and packaging materials) representative of the actual quality status of a batch of medicines for determining the quality of medicines.
2. Production batch: A defined quantity of medicine (finished product, raw material, and packaging material) processed in a single process or a series of processes and having uniformity.
3. Sampling unit: A separate part of a production batch such as each intact or non-intact package, box, or container selected for sampling.
4. Initial sample: A quantity of medicine directly taken from a part-position within a sampling unit. Depending on the purpose of sampling and the requirements for quality testing, the quantity of medicine in the initial sample must be sufficient to create an analytical sample and a retention sample.
5. Individual sample: A medicine sample formed by thoroughly mixing initial samples taken from a sampling unit.
6. Common sample (Final sample): A medicine sample formed by mixing some or all individual samples together, used to create an analytical sample and a retention sample. (If it is a solid powder, it can be ground and mixed together, if it is liquid, it can be mixed together, or if it is pre-dosed units, they can be placed next to each other).
7. Analytical sample: A portion of the common sample used for analysis in the laboratory. The quantity of medicine in the analytical sample must be sufficient to perform all tests according to the quality standards.
8. Retention sample: A portion of the common sample retained for retesting when necessary. The quantity of medicine in the retention sample must be at least equal to that of the analytical sample.
9. Sampler: The person responsible for performing sampling operations.
10. Sampling diagram: A diagram describing the position, number of units, and/or quantity of raw materials to be collected.
Chapter II
CONDITIONS FOR SAMPLING MEDICINES
Article 3. Conditions for samplers
Samplers must meet the following requirements:
Clause 1. The sampler must be a drug inspector, a specialized pharmaceutical quality control officer, or a member of a state inspection team established by the competent authority for quality control of medicines.
Clause 2. The sampler must be an employee knowledgeable about drug analysis or testing, familiar with legal documents on medicine quality management, legal procedures, and sampling techniques.
Clause 3. The sampler must be trained in relevant techniques and regulations, and must wear appropriate protective clothing when taking samples.
Article 4. Powers and responsibilities of the sampler
1. When performing their duties, the sampler must present the inspection officer card or quality control inspector card, or the introduction letter/determination to establish the inspection team issued by the head of the management agency or state quality control agency for drugs.
2. The sampler has the right to request the drug sample source to present relevant files and documents related to the origin, quantity, and quality of the batch of drugs being sampled, and to make decisions on sampling methods, number of samples for analysis, and samples for storage during the sampling process.
3. The sampler has the right to take any batch or package within a batch of drugs if there is suspicion about its quality.
4. The drug sampler shall be responsible under the law for technical operations and legal procedures during the sampling, transportation, and transfer of samples to the testing agency.
Article 5. Sampling Location
Drug sampling must be carried out in a separate area that meets hygiene requirements (cleanliness level) and specific technical requirements for each type of sample (temperature, humidity, light, sterility...), avoiding risks of contamination, cross-contamination, and changes in the quality of the collected sample as well as the remaining portion of the drug after sampling.
For sterile drug raw materials, sampling must be conducted in a clean, sterile area.
Article 6. Sampling Tools
Sampling tools and sample containers must be made of inert, clean materials suitable for the characteristics of each type of sample, ensuring they do not affect the quality of the sample, do not introduce impurities causing contamination or cross-contamination, and must ensure safety for the sampler (See Appendix 2).
Article 7. Transportation and Transfer of Samples
1. After completing the sampling, the sampler or inspection team must promptly transfer the collected samples along with the sampling record to the testing agency. In special cases, samples may be sent to the testing agency via postal service, but the storage conditions of the samples to be sent must be clearly noted.
2. Collected drug samples must be packed in appropriate packaging and transported using suitable means to ensure the samples are stored according to regulations, preventing damage or breakage during transportation. Special attention should be given to samples requiring specific storage conditions such as vaccines or biological products used for treatment and diagnosis.
3. If necessary, the inspection team may encode the samples to ensure certain confidential information before transferring them to the testing agency.
Article 8. Costs of Drug Sampling
The costs of drug sampling for quality testing are implemented according to Articles 37, 41, and 58 of the Product and Goods Quality Law 2007 and other relevant regulations.
Chapter III
PROCEDURE FOR SAMPLING AND SAMPLING OPERATIONS
Article 9. Quantity of Samples to Be Taken
1. The quantity of samples required for analysis and storage is calculated based on the testing requirements, applicable drug quality standards, and the testing method of the sample, but must be at least sufficient for three analyses or must be sufficient to perform tests to obtain accurate and reliable results.
2. Typically, two samples (one for analysis and one for storage at the testing agency) are taken from each production batch. In special cases, more than two samples for analysis and storage may be taken to ensure sufficient samples for testing and storage at relevant agencies and organizations.
Article 10. Sampling operations:
1. Principles of sampling:
- Depending on the inspection purpose and each type of product, the sampler decides to choose an appropriate sampling method.
- The sampling process must be supervised and fully recorded. All signs of inconsistency and damage to the drug and packaging materials must be recorded.
- The sampling procedure must ensure that inconsistencies in each sampled unit and in the entire batch of drugs can be promptly detected. Inconsistencies include differences in shape, size, or color of crystalline, granular, or powdered solid particles; moisture layers on hygroscopic substances; sedimentation of solid drug components in liquid or semi-solid preparations; layer separation in liquid preparations.
- Samples taken from parts with different signs or from packages suspected of having quality issues of the batch should not be mixed or combined, as this mixing would obscure signs of contamination, low content, or other quality issues. Separate samples must be created from these parts and packages.
- For finished drug products, the sampling process must consider official tests and supplementary tests for each drug form (for example, tablets or intravenous solutions). Supplementary tests include tests to identify counterfeit drugs, adulterated drugs, and drugs containing unauthorized substances.
- Drugs removed directly from packaging should not be recombined with drugs still in packaging.
2. Sampling sequence:
- Physically inspect the batch: separate by product type and production batch, further isolate boxes showing signs of damage or poor hygiene for inspection and separate sampling. Discard packaging units without labels.
- From the product batch, take out sampling units, open packaging to obtain initial samples and immediately reseal the opened packages. The quantity of raw material in the initial sample must be sufficient to prepare subsequent samples.
- Mix the initial samples into individual samples for each sampling unit.
- Mix the individual samples into a common sample.
- Create the final sample: from the common sample, take equal portions to form the final sample consisting of the analysis sample and the retention sample.
3. Analysis samples and retention samples must be placed in containers, sealed tightly, and labeled. The label of the sample container must clearly state the drug name, manufacturer's name, production batch code, expiration date, box number sampled, sampling location, quantity of sample taken (if the sample is narcotic, psychotropic, precursor, or radioactive drug raw materials, the quantity must be written in words), sampling date, and storage conditions consistent with the sampling record.
4. After completing the sampling, all participants in the sampling must seal the samples to ensure their safety during transportation from the sampling site to the receiving site. The sealing of the sample must clearly indicate the sampling date and have at least the signature of the sampler and the representative of the sampled entity.
If necessary, the remaining portion after sampling must also be sealed to prevent drug substitution.
5. Establish a sampling record: the sampling record must clearly state the batch number, sampling date, sampling location, storage conditions, any additional observations and abnormalities during the sampling process, and have at least the name and signature of the sampler and the representative of the sampled entity.
If the quality inspection team conducts the sampling, there must also be the signature of the Inspection Team Leader.
If the representative of the sampled entity does not sign the record, then the record must have the signatures of the sampler and the witness.
This record must be made in at least three copies: one copy retained at the sampled entity, one copy retained at the testing agency, and one copy retained at the regulatory and quality control agency (refer to Appendix 1).
6. Specific procedures for conducting sampling steps refer to Appendix 3.
Article 11. Sampling of raw materials for drugs.
1. In case there is only one package of raw material:
a) For solid raw material sampling: Take initial samples from different positions in the container (top, middle, and bottom). If the initial samples do not show any perceptual differences, mix all initial samples to form a separate sample.
b) For liquid or semi-solid raw material sampling: If they are not uniform, they must be mixed thoroughly before sampling. For example, if a liquid preparation separates into layers, it must be stirred evenly before sampling, or if there are sediment particles in the liquid, they must be dissolved or dispersed evenly before sampling, which can be done by warming or stirring thoroughly.
2. In case there are multiple packages in a batch of raw materials:
Depending on the purpose of sampling for inspection, the degree of uniformity, and the quality of the drug batch, select an appropriate sampling method according to Article 16 of this Circular.
Article 12. Sampling of unfinished products that have not been packaged.
These products include powdered drugs, liquid drugs, syrup, ointment, granules, tablets, injections, etc., contained in large packages to be transferred to individual packaging facilities. Each production batch is sampled as follows:
1. If the product batch has only 1-2 packages, open both packages. If the product batch has three or more packages, open three packages. Take at least three initial samples from different positions in each package.
2. Mix the initial samples together to form a common sample, then create a final sample consisting of an analysis sample and a retention sample.
Article 13. Sampling of packaging materials.
Sampling of packaging materials is carried out according to the provisions of Article 16 of this Circular.
Article 14. Sampling of finished drugs.
1. Sampling of finished drugs for quality testing or monitoring:
a) Sampling should follow the principle of random sampling and must be taken from different positions within the batch.
b) Based on the drug quality standards, the quantity of drugs to be sampled should be sufficient for testing and retaining samples. In cases where there is insufficient information to accurately calculate the required quantity of drugs, refer to the minimum quantity of finished drugs to be sampled as stipulated in Appendix 5 of this Circular.
c) The sampling procedure is based on the guidelines provided in Appendix 3 of this Circular.
2. Sampling for sensory inspection upon drug importation: The quantity of samples taken for sensory inspection is regulated in Appendix 4 of this Circular.
Article 15. Sampling of medicinal herbs.
Medicinal herbs or partially processed medicinal herbs, including animals, plants (dried medicinal plants and parts of plants), and minerals, are considered non-uniform raw materials and should be sampled according to Article 16, Scheme r of this Circular.
Article 16. Sampling schemes for initial raw materials and packaging materials.
1. Before conducting sampling, the sampler must check the integrity and level of damage of the containers, and the uniformity of the product inside each sampling unit.
2. Sampling may be conducted according to one of the three sampling schemes listed in Table 1 below.
Table 1: Values of n, p, or r for N units of packages*
|
Value of n, p, r
|
Value of N
|
||
|
Scheme n
|
Scheme p
|
Scheme r
|
|
|
2
|
Up to 3
|
Up to 25
|
Up to 2
|
|
3
|
4 - 6
|
25 – 56
|
3 – 4
|
|
4
|
7 – 13
|
57 – 100
|
5 – 7
|
|
5
|
14 – 20
|
101 – 156
|
8 – 11
|
|
6
|
21 – 30
|
157 - 225
|
12 – 16
|
|
7
|
31 – 42
|
|
17 – 22
|
|
8
|
43 – 56
|
|
23 – 28
|
|
9
|
57 – 72
|
|
29 – 36
|
|
10
|
73 - 90
|
|
37 - 44
|
a) Scheme n
Use "Scheme n" when the batch of raw materials to be sampled is considered uniform and supplied from a defined source. Samples can be taken from any part of the raw material container (usually from the top layer). "Scheme n" is based on the formula n = 1 + , with N being the number of units of packages in the batch. The minimum number of units to be sampled n is obtained by simple rounding. From these n randomly selected units, take initial samples, which are stored in separate sample containers. If the initial samples taken do not raise any perceptual or qualitative doubts, the initial samples are mixed uniformly to form a separate and common sample for analysis and retention according to the general procedure.
b) Scheme p
Use "scheme p" when the batch of raw materials is considered uniform, from a defined source, and the main purpose is qualitative testing. "Scheme p" is based on the formula p = 0.4 , with N being the number of units of packages in the batch. The value of p is obtained by rounding up to the next highest integer. Initial samples are taken from each of the N units of packages in the batch and stored in separate sample containers. These initial samples are inspected for sensory and qualitative characteristics. If the results are satisfactory, p common samples are formed by appropriately mixing the initial samples for retention or analysis (if necessary).
c) Scheme r
Use "scheme r" when the batch of raw materials is suspected to be non-uniform and/or received from an undefined source, or when the initial raw materials are partially processed medicinal herbs. This scheme is based on the formula r = 1.5 , with N being the number of units of packages in the product batch. The value of r is obtained by rounding up to the next highest integer.
Initial samples are taken from each of the N units of packages and stored in separate sample containers. These initial samples are inspected for sensory and qualitative characteristics. If the results are satisfactory, r samples are randomly selected for separate testing. If the test results are consistent, the retention samples can be combined into one retention sample.
3. For sampling of initial raw materials for qualitative purposes, production facilities that do not apply the above schemes shall follow the "Good Manufacturing Practice for Drugs" (GMP-WHO) guidelines recommended by the World Health Organization.
Chapter IV
IMPLEMENTING PROVISIONS
Article 17. Effective Date
This Circular takes effect 45 days from the date of issuance.
Repeal Decision No. 262/BYT-QĐ dated February 23, 1995 of the Minister of Health regarding the issuance of the "Regulations on Sampling Drugs to Determine Quality".
Article 18. Responsibility for Implementation
1. The Director of the Drug Administration Department is responsible for guiding the implementation of this Circular.
2. The Heads: Office Director of the Ministry of Health, Inspector General of the Ministry of Health, Head of the Science and Training Department, Director of the Drug Administration Department, Director of the Central Institute for Pharmaceutical Inspection, Director of the Ho Chi Minh City Institute for Pharmaceutical Inspection, Director of the National Institute for Vaccine and Biomedical Product Control, Directors of Provincial Health Departments, Health Chiefs of sectors, and Heads of related units are responsible for implementing this Circular.
3. During the implementation process, if there are difficulties or obstacles, organizations and individuals are requested to promptly report to the Ministry of Health (Drug Administration Department) for consideration and resolution./.
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Luật Chất lượng sản phẩm, hàng hoá số 05/2007/QH12
발효 중
04/2010/TT-BYT
Circular No. 04/2010/TT-BYT guides the sampling of medicines to determine their quality.
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