1 Chemical products such as sodium hydroxide and sodium bisulfite have passed the inspection according to pharmacopoeia standards, but can they be put into production immediately? If not, what procedures do you need to go through as paving materials? If it is sent to the provincial inspection office, is it necessary to send only one batch or batch for inspection? In addition, under the condition that the equipment, methods and production processes are unchanged, is it enough to do the cleaning verification only once or every year? Thank you.

A: Raw materials used in the production of APIs are relatively loose, but the raw and auxiliary materials of preparations are already in the Pharmacopoeia, which must be medicinal grade or products with approval number. Products that are not in the Pharmacopoeia can be used in edible grade, but they must have product quality standards. Other products are implemented according to the provisions of the Pharmacopoeia. Any verification must be done three times before it is statistically significant.

2 Our company is preparing to apply for GMP certification in the paste workshop. According to the requirements of (3) self-inspection of drug production management and quality management in the application and review of "good manufacturing practice Certification Management Measures" (including the general situation of enterprises, historical evolution, production and quality management, changes in software and hardware conditions of re-certified enterprises at the expiration of the certificate, and corrections of unqualified items in the previous certification), does it mean that there must be "corrections of unqualified items in the previous certification" in the self-inspection content?

A: Yes, there must be the previous inspection and rectification of all drug supervision departments, including the last certification.

3 We need to design the spray workshop now. Is the spray workshop a non-sterile preparation? The cleanliness level of the production environment should be 1 thousand? Or 1 thousand?

Answer: Spray is usually a non-sterile preparation. If it is for external use, it can be used for non-traumatic skin, with a grade of 3,. If it is used for traumatic skin or oral administration, it needs a grade of more than 1,.

4 If the pharmaceutical production license is uniformly renewed, will the original dosage forms in the production range fail to pass GMP certification, and the range that failed to pass GMP certification will be deleted from the production range when it is renewed? (For example, the original certificate stated large capacity, small capacity, oral preparation and freeze-dried powder. But now only small capacity and oral preparation have passed GMP certificate. So, is it only small capacity and oral preparation written in the production scope when the certificate is renewed? )

A: If the large-volume injection is in the old range, the range will be cancelled according to the regulations, and the new range will be retained.

5 Is there a limit on the number and time of retrospective re-verification?

A: There is no time limit, but there is a time requirement. Usually, the re-verification is stipulated as one year, and the high-efficiency filtration of equipment with relatively high risks, such as air conditioning system, is usually stipulated as half a year.

6 GMP stipulates that the dosage should be 1% of the prescription. How should we understand this? Here, 1% feeding means: 1. After conversion according to the content, moisture and conversion of the main medicine of the raw materials, each time it is converted into 1% feeding? That is, if my raw material content is 99%, should my dosage be: prescription/99%? In this case, the specific feeding weight should be changed every time. 2. All raw materials that meet the quality standards of APIs are treated as 1%, and the prescription amount is given. In this case, the feeding amount is fixed every time. Excuse me, which understanding should be more accurate?

Answer: The first operation is more suitable for the production requirements, because the product specifications in production are usually content specifications. For example, the content of the main drug in a tablet is taken as the specification, and the raw materials are required to be fed according to the converted 1% theory, so that the product specifications can meet the requirements. The produced drug has the original uniformity, content and potency, quality and purity of the product. The drug prepared according to the prescription is guaranteed to have an active ingredient content of not less than 1%. Here, 1% feeding means: 1. After conversion according to the content, moisture and conversion of the main medicine of the raw materials, each time it is converted into 1% feeding? That is, if my raw material content is 99%, should my dosage be: prescription/99%? In this case, the specific feeding weight should be changed every time. 2. All raw materials that meet the quality standards of APIs are treated as 1%, and the prescription quantity is given. In this case, the feeding quantity is fixed every time. What kind of understanding should be more accurate? < P > A: The first operation is more suitable for production requirements, because the product specification in production is usually the content specification, such as tablets, and the converted 1 is used as the specification. Only the specifications of the produced products can meet the requirements. The produced drugs have the original uniformity, content, potency, quality and purity of this product. For the drugs prepared according to the prescription, the content of active ingredients should be guaranteed to be no less than 1% of the marked amount or the specified amount.

8 Can the aluminum barrels for sterile APIs be reused? Why?

A: It can't be reused. The recycled products don't meet GMP requirements, and on the other hand, there is a great quality management risk for aseptic products.

9 How to define the materials managed according to the label category except labels and instructions? Can packaging materials (such as large boxes and aluminum foils) with only name, specification and trademark but no usage and dosage be managed without labeling materials?

A: Small boxes also belong to materials managed according to labels. Large boxes and unprinted aluminum foils can be managed according to ordinary materials.

Is it necessary to have a general batch production instruction for p>1 batches of production records? Our company can't give a general batch number at the beginning, but there is a general batch packaging instruction when batch packaging records are made. In this case, what should we do in actual production? Is it the production instruction under each process, or is it traditional to give a batch number before production, or just sort out the relevant process records of the final batch number and bind them with batch packaging records to form a batch production record?

Your company's operation is inconsistent with GMP requirements and does not meet the requirements. Without batch production instructions, you can't produce, without batch number, you can't have batch instructions, which is not in line with the specifications. You need to continue to study laws and regulations and training.

11 Can the purchased Chinese medicine material management department be used as a specimen after being identified by the Chinese medicine factory? What qualifications must the person in charge of the identification of Chinese medicine specimens have? Our employees have a bachelor's degree in Chinese medicine, but their professional title is engineer. Does he have specific qualifications for the identification of Chinese medicine specimens?

A: At present, there is no clear regulation on the specimens used in enterprises, which can be considered suitable by experienced old pharmacists and Chinese medicine engineers and technicians.

12 Do overseas companies (the United States) need to pass the GMP certification in China in addition to the fda certification in the United States (after the completion, all the drugs they produce will be sold to the United States, not sold and used in China)!

a: pharmaceutical manufacturers who have obtained China's pharmaceutical production license must pass GMP certification in China, and the raw material factories that go out as intermediates will be decided by the enterprises according to the situation.

13 When building off-site workshops, the time for proposing to change the production license should be before applying for factory acceptance, after factory acceptance, or before applying for substitute materials production.

A: Apply at the same time when applying for acceptance. After passing the inspection, it will be changed by the drug supervision department according to law.

14 Our company has purchased a batch of raw materials, and the components and contents are in line with the national standards. However, the internal and external packaging labels are not marked with the product approval number. After investigation, the factory has indeed produced this batch of raw materials. What should be done with this raw material?

A: How is the supplier evaluation standard and inspection system of your factory formulated? If it doesn't meet the requirements, it can be returned.

15 There has been no guidance from the state on the determination of drug production date and batch number, and enterprises have various practices. The production date adopts the feeding date or intermediate date or finished product date, and the batch number adopts the feeding date or intermediate date or finished product date or serial number. My personal opinion is that because the determination of product validity is calculated from the finished product date when the product is registered, and the validity on the production package is calculated according to the production date, I think the production date should be calculated.

A: Batch: a drug prepared with a limited number of raw materials and packaging materials or by a single process or a series of processes, which is homogeneous. Sometimes it is necessary to divide the batch into a certain number of sub-batches, and these sub-batches are finally merged into a homogeneous final drug batch. In the case of terminal sterilization, the batch is determined by the capacity of the sterilization cabinet. In continuous production, the drug batch must correspond to the production-defined process. In line with the requirements of homogeneity, batch can be defined as a fixed quantity or a quantity produced in a fixed time. Batch number: the combination of clear numbers and words that uniquely identify the characteristics of a batch in labels, batch records and corresponding analysis certificates. The batch is related to the production date, but not necessarily, and can be carried out by serial number. However, the production date is relatively strict, and the production date is usually the same. The production date of APIs is based on the fine drying and packaging date. The date of preparation is the production date, and biological products are usually a continuous production process, so it is difficult to distinguish raw materials from preparations. Generally, the date of purified active substances is the production date. The above is a reference, and the key is to investigate the stability test of products to ensure the safety of drugs.

16 Some accessories imported as chemical raw materials are better than domestic pharmaceutical-grade accessories, and the factory inspection is also carried out according to China Pharmacopoeia, which meets the requirements.

A: Imported auxiliary materials can only be used after obtaining the import registration certificate.

17 Our company is going to carry out the construction of GMP workshop. Do you want to set up a project? If yes, there is no relevant provision in your bureau's work guide. If no, how to handle the GMP preliminary examination?

a: the project has been cancelled, and professional design-construction-acceptance-certification-production.

18 how long is the validity period of food raw materials? Where can I find the expiration date of raw materials for health food such as oil, pigment, extract and plant powder?

A: Food standards are under the control of technical supervisors, and you can ask them.

19 The license renewal information of our company has been reported, but now the enterprise type of our company's business license has been changed from the original "joint venture" to "limited liability company". What should I do if the pharmaceutical production license is changed?

A: Apply for changes according to normal procedures.

2 I would like to ask: How can the equipment for producing sterile APIs, such as dryers, be cleaned to meet aseptic requirements?

A: There are many cleaning methods. However, the equipment that comes into direct contact with drugs must be sterilized after cleaning.

21 If one pharmaceutical manufacturer entrusts another to produce a drug, can the entrusting party still produce it?

A: If it meets the GMP requirements and obtains the certificate, it can also be produced.

22 At present, there is a plaster production enterprise in Henan, but it is Jianzihao and has not obtained the qualification of drug registration and production. I want to set up a production enterprise in Guangdong to produce this plaster product. What should I do?

A: Drug registration should be done first.

23 When should I apply for changing the production license for adding workshops outside the factory, and what materials should I prepare?

A: After completing the construction of new workshops, For the application requirements, please refer to "Changes of Pharmaceutical Production License" in the service guide of our bureau.

24 Does the quality management department fulfill the responsibility of evaluating the quality stability of raw materials, intermediate products and finished products, and provide data for determining the storage period of materials and the validity period of drugs? At least one batch of each variety is reserved for quality stability evaluation every year. What are the specific requirements of the above-mentioned "quality stability evaluation"? Is it necessary to do the test like "long-term stability test"? Or can we just do "accelerated stability test"? Or can a new stability evaluation scheme be set in addition to the two?

Answer: Like the long-term stability test, it is an important duty of quality management to evaluate the stability of products, including the evaluation of appearance, content and related substances, and provide data for the expiration date of drugs.

25 Does the expiration date of raw materials start from the production date of the raw material manufacturer until the preparation manufacturer puts it into production? Do I need to consider the expiration date of the preparation? In addition, our company has some seasonal varieties, and the last batch of remaining raw materials is about 5% more or less than the amount required by the process regulations. Can you put them in at one time? (strengthen verification in the general mixing process)

A: 1. According to the current laws and regulations, the period of validity is counted as the date of preparation feeding, and other issues do not need to be considered. 2. How to implement the 2.SOP.

Can the work clothes with a grade of 26, be degraded (for example, in a clean area with a grade of 3,) for cleaning, disinfection and sorting?

Answer: 1. Laundry rooms for cleaning, sorting and storing work clothes used in different clean areas should be set up. 2.3,-level clean work clothes can be washed, dried and sorted in non-clean room (area) laundry rooms. 3.1,-level and above (including 1,-level) clean work clothes should be washed and cleaned in clean room (area). The work clothes used in the aseptic operation area above the level of should be washed in the laundry room of the level of 1,, and then sent to the aseptic area for operation after sterilization.

27 Now, due to the expansion of production scale, we plan to set aside a part in the warehouse area and establish a packaging workshop according to the requirements of internal packaging. I wonder if this violates GMP requirements and can it be implemented?

A: The certified workshop must be produced according to the declared floor plan. If there is any change that affects the production and products, it must be reformed when the production is stopped, and it needs to be re-certified if necessary.

28 Excuse me, our company is building an off-site workshop. Should we apply for the change of production license or GMP certification first?

A: Apply for the change of production license first. Later, I applied for GMP certification.

29 Our factory is a manufacturer of APIs. We planned to carry out GMP certification of four API varieties at the end of December this year, so we are preparing materials to change the license first. However, according to the unified deployment of the factory, the certification time may be postponed to January 26, when the license has been renewed, my question is: when the four API varieties apply for renewal materials, Our factory has reported as a new production scope, so does the new license include the production scope of these four varieties? If not, shall we apply for GMP certification next year with the old license or wait until we get a new license? If we get a new license, it may be too late to apply for change. What should we do?

Answer: If it is a variety that has just obtained the document number this year, it can be a new variety, and the new license will be retained. Otherwise, it will be handled according to the provisions of the document.