Medical network - on March 17, according to the drug production quality management standard (revised in 2010) "the three hundred and tenth regulation, on March 16, the CFDA biochemical drugs in the appendix, as" drug production quality management standard (revised in 2010), form a complete set of documents, shall be implemented as of September 1, 2017.
Biochemical drugs appendix
The first chapter the scope
Referred to in article 1 of this appendix biochemical drugs refers to the animal's organs, tissues, body fluids, secretions, integrated by pretreatment, extraction, separation and purification of safe, effective and quality control of drugs. Mainly includes: protein, polypeptide, amino acid and its derivatives, nucleotides and its derivatives, grease, polysaccharide, enzyme and coenzyme (not including biological products products listed in the appendix).
In article 2 of this appendix is suitable for the pretreatment, extraction, separation and purification of raw materials, such as the preparation of raw materials (concentrate) and its preparation and quality control process.
The acquisition process should comply with the relevant provisions of the state of raw materials, pharmaceutical production enterprise shall and quality supervision and control of its source.
Article 3 the organization comes from people, urine products according to this appendix shall prevail.
The second chapter, the original,
Article 4 shall establish perfect quality management system, based on the principles of quality risk management, combining with the characteristics of variety and clear from raw material acquisition to the quality of the finished product release in different stages of the management responsibility, ensure that the product is safe and effective, the quality control.
Article 5 of the biochemical drugs has the following characteristics, to improve the quality of the sources of the raw materials and intermediate inspection of the special products, production process, control:
(a) biochemical drugs production involves the extraction of organs, tissues, body fluids, secretions, separation and purification process, such as uneven raw material itself has a sex.
(2) the quality control of biochemical drugs usually adopt biological analysis technology, than the physical and chemical measurement with greater variability.
(3) of the raw materials and intermediate products in the process of production is a good medium for pollution microorganism growth, pathogenic microorganisms in raw material on product quality and production environment there is a big risk.
The third chapter personnel
Article 6 to engage in biochemical drugs production, quality assurance, quality control, procurement and other related personnel (including cleaning, maintenance personnel) shall be based on the product and its production is engaged in the production operation related laws and regulations on a regular basis, professional knowledge, health, and basic knowledge of microbiology and safety requirements and other aspects of training and assessment, and incorporated into the individual training files.
Article 7, head, head of the production management, quality management and quality of the authorized person should have corresponding professional knowledge (e.g., microbiology, biology, immunology, pharmacy, biological, pharmaceutical, biochemical, etc.), and can earnestly perform their duties in the production and quality management. Personnel engaged in supplier audit, should know the animal species, breeding, slaughtering, quarantine, acquisition and its raw material storage transportation and so on related knowledge, and can effectively in the process of supplier management and audit to perform their duties.
Article 8 to evaluate the biological safety of produced variety, according to the evaluation results, the operator of the production, maintenance, inspection, management personnel should take the necessary safety protection measures.
Article 9. Under normal circumstances, the workers from the former raw materials processing regions through to have inactivated products and other products processing area. If you can't avoid this through, must be based on the principles of quality risk management to prevent pollution control measures.
The fourth chapter of plant and equipment
Article 10 the biochemical drugs production environment and plant facilities and equipment should not pollution caused by the raw materials, intermediate products and finished products; Air cleanliness level should be adapted to the usage of our products and production operation.
Article 11 the workshop should be set to prevent insects and other animals into the facilities. Especially used for processing animal organs, organizations or body fluids or secretions of the operation area should be equipped with effective insect rat measures, and to assess its effectiveness.
Article 12 raw materials acquisition of plant facilities and equipment should conform to the requirements of the product corresponding characteristics, health management and relevant regulations of the state, and separated from pharmaceutical production area.
Article 13 should combine product potential risk, technological requirements and characteristics of different stages of production, set up corresponding production operation area of the environment control requirements, should as far as possible to reduce the product (or materials) is the risk of microbial contamination.
Article 14 in the process of production should be based on product features, process, factors such as intended use and equipment, using the means of risk assessment, to adopt corresponding prevention error, cross contamination, safety protection measures, such as using a special plant and equipment, periodic mode of production, the use of closed systems. If use exposure container or equipment operation, should avoid pollution measures. Difficult to clean the equipment or components should be dedicated. Biochemical drugs to remove/inactivated virus before the process steps, shoulds not be Shared with other animal origin of drug equipment and facilities, and inevitable, proper measures to prevent cross contamination.
Article 15 raw material pretreatment should be dedicated area, raw materials (concentrate) preparation and preparation production areas should be strictly separated. Raw materials (concentrate) preparation and preparation production and purification of air-conditioning systems should be set independently.
Article 16 the pretreatment of raw materials and the extraction, purification equipment, instruments, pipe, valve and container, including the sampling equipment should be clean, corrosion resistant, easy cleaning or disinfection, and according to the product characteristics and process control requirements for effective cleaning or disinfection process.
Article 17 the use of frozen or refrigerated facilities clean area, cleaning and maintenance should not clean area environment pollution.
Article 18 the materials and products used for storage of frozen or refrigerated facilities should have the measures to prevent emergencies happen, avoid the material and product quality is affected.
The fifth chapter virus removal/inactivated and validation
Article 19 should be based on risk control principle, combining with the variety characteristics and sources of raw materials, adopting effectively remove/inactivated virus process steps and methods. To remove/inactivated virus at the same time, don't have a bad effect to improve the quality of products.
Article 20 the removal/inactivated virus production process should be effective and verified, when the production process is changed, should reassess the applicability of the validation, when necessary to validate.
Article 21 the inactivated virus removal/process validation can be reference to the relevant virus removal/inactivated methods and guidelines and related regulations.
Article 22 the virus removal methods/inactivated virus challenge in the validation of the test shall be used for production of plant facilities and equipment.
Article 23 the inactivated virus removal/validation does not take the place of raw material and production process quality management requirements.
The sixth chapter of supply chain management
Article 24 of the enterprise shall, according to the universality of biochemical drugs supply chain and complexity, the effective traceability system based on the principles of quality risk management and control measures, and each link of the supply chain requirements should be defined in a file. Companies and suppliers must sign a quality assurance agreement, clear the corresponding quality responsibility, require suppliers reference appendix management.
Article 25 to biochemical drugs strictly control the sources of the raw materials, raw materials should be derived from the epidemic area, and considering the condition of source of an epidemic.
(a) raw materials should be derived from healthy animals, included in the management of inspection and quarantine animal raw materials from the quarantine inspection shall be healthy animals.
(2) from the people of the organization or urine, the gathering shall specify the collection methods and requirements.
(3) should be regularly collecting animal epidemic information source area, the quality risk assessment. When your disease risk, the corresponding quality control measures should be taken.
(4) should be established according to the raw material characteristics and principles of risk control traceability system and record accordingly.
Article 26 the organs, tissues, body fluids, secretions, raw materials, such as collecting unit shall be made in accordance with the relevant national qualifications.
Article 27 of the quality management department should set up the supplier's quality management files based on the characteristics of variety, shall at least include: supplier qualification, scale, quality agreement, raw materials of animal origin, species, age, after the sampling position and method, preservation method and validity, etc.
Article 28 shall periodically for raw materials supplier on-site audit. Focuses on the supply chain of each link quality control, to ensure that suppliers provide controllable, stable product quality, and quality audit report.
Article 29 in response to each batch of receiving inspection of raw materials, and have corresponding record:
(a) the supplier in accordance with approval by the department of quality management;
(2) raw material with the quarantine certificate in accordance with the goods;
(3) the packaging are in conformity with the physical, identify content should comply with the supplier archives related content;
(4) the outer packing should be complete without damage;
(5) the special requirement of storage temperature, the temperature should be confirmed when receiving; Entire carriage of temperature monitoring records shall be complete traceability, the temperature is always in line with the requirements of quality control.
Article 30. The raw materials, intermediates, packaging material or container during storage and transportation should not affect the product quality, and its direct contact should be at least as to meet the requirements of food packaging materials, packaging materials suppliers and the material should be relatively fixed.
Article 31 the cold storage and cold chain transport equipment should be identified. Raw material storage conditions, storage time, transportation conditions, such as after confirmation, to ensure product quality.
Chapter 7 production management
Article 32 the effective measures should be taken to avoid different species or same species of different organs, tissues, body fluids, secretions in the confusion and mistakes in the process of collection, transport and storage, pollution, cross contamination.
Response to article 33 of the biochemical drugs raw materials, intermediates, raw materials (concentrate) for batch number or serial number management, to ensure the traceability of production process.
Article 34 should combine product characteristics, try to reduce the production process of microorganism and its related metabolites such as pollution, cross contamination.
(a) should be according to the product properties and storage conditions specified time interval between different production stages of production, shorten the time interval of different production stage as much as possible.
(2) intermediate products, raw materials (concentrate) storage time should be defined and validated.
(3) the raw materials, intermediate products, raw materials (concentrate) should not be repeated freezing and thawing, should be validated when necessary, to ensure the quality of the products are not affected.
(4) after the production of equipment and containers should be within the prescribed time limit for cleaning, disinfection or sterilization.
(5) direct contact with the intermediate product, raw material (concentrate) of packaging containers, equipment cleaning, disinfection or sterilization after should avoid pollution again. Extraction, separation and purification of raw materials of all sorts of equipment, containers, between different products and different batches should be clean and disinfect.
(6) the same equipment generally shall not be used for different products or the same product at different stages of inactivated virus removal/operation. If using the same equipment, proper cleaning or disinfection measures should be taken to prevent the virus by equipment or environment by the previous operation to the subsequent purification operation.
Article 35 a by-product of the production or waste should be timely out of production area, production environment and equipment to prevent pollution.
Article 36 shall take necessary measures to prevent the virus after remove or inactivate products contaminated; Have been virus removal/inactivated treatment products and has not yet been products should have clear distinctions and identification, and the appropriate method should be adopted to prevent confusion and mistakes.
Article 37 chromatography and ultrafiltration steps, if any, used for purification of chromatography separation column and the ultrafiltration device should be dedicated. The same column chromatography separation and ultrafiltration device shall not be applied to the various stages of production. Should have file regulation chromatography column and the ultrafiltration device of an acceptable standard, operating conditions and regeneration process, service life, cleaning or sanitizing program, process monitoring parameters, etc.
Article 38 a solvent used in the production use to be recovered, such as recycling procedures should be established and its use that meet the needs of quality standards. Recycled solvent reuse may not produce unfavorable influences on product quality and safety.
Chapter 8 quality management
Article 39 shall be in accordance with the "pharmacopoeia of the People's Republic of China" and the approval of the state food and drug administration of quality standard of biochemical drugs raw materials, auxiliary materials, intermediates, raw materials (concentrate) and finished product inspection. Unable to set the standard, the enterprise should be appropriate internal control quality standards are established according to the varieties of quality risk, increase the freshness, microbial limit should be considered when necessary, bacterial endotoxin or pyrogen, abnormal toxicity, step-down material, such as exogenous factor check project.
Article 40 the raw material source of biochemical drugs should be relatively stable, and shall specify the animal species and organs. When necessary for raw materials of animal species were identified, such as PCR method, etc.), sample should be representative.
Article 41 the biochemical drugs release of raw materials should include a complete track record of raw materials, raw materials into the management of inspection and quarantine animals should be healthy animals from the quarantine inspection.
Article 42 of the raw materials, auxiliary materials, intermediates, raw materials (concentrate) of inspection should be completed in the appropriate production stage, when inspection cycle is long, can for subsequent process, first for inspection qualified rear can release the finished product.
Article 43 when necessary, intermediates, raw materials (concentrate) should be sample, so as to meet the needs of detection or intermediate control confirmed, sample quantity should be enough, and stored under appropriate conditions, to facilitate quality traceability.
Chapter ix the art language
Article 44 the following term meaning is:
(a) raw material: used in pharmaceutical production of animal organs, tissues, body fluids, secretions, and people's organizations, urine, such as starting material, not including accessories.
(2) raw materials acquisition, from the supplier audit qualified units, collection of animal organs, tissues, body fluids, secretions, and organization, the process of urine.
(3) before treatment: the medicinal part of raw materials of freezing and thawing, cutting, picking, washing and the subsequent processing such as mixing, centrifugal, freezing and thawing process.
(4) intermediates, raw materials before processing products, convenient for quality control.
(5) raw materials (concentrate) : intermediates by extraction, purification, virus removal/inactivated, the indicators meet the requirements of quality standard products.
(6) virus removal/inactivated: will remove or inactivate viruses from the product to ensure safe process.
(7) : the supply chain from raw material acquisition to make the process of intermediate products. |
