Oral liquid bottle aluminum cap is a kind of medicine packaging material used in conjunction with oral liquid bottle. It is widely used in the packaging of oral liquid and oral solution for its good sealing performance and convenient portability. The registered name is oral liquid bottle aluminum-plastic combination cap , Oral liquid bottles are easy to puncture aluminum caps (referred to as oral liquid bottle aluminum caps in the text), some large-volume pharmaceutical manufacturers consume tens of millions of aluminum caps a month. The following author takes this very commonly used pharmaceutical packaging material as an example to discuss some problems and suggestions that are difficult to regulate in accordance with the current pharmaceutical packaging material laws, regulations and standards in the daily supervision of pharmaceutical packaging materials:
     
Problem 1: The outer packaging label of the aluminum cap of the oral liquid bottle does not match the actual state:
     
The aluminum caps of oral liquid bottles used in drug packaging are not used independently. Anyone who has taken oral liquids knows that a rubber stopper or cushion must be added between the aluminum cap and the medicine. The rubber stopper (pad) plays The main function of isolation and sealing. At present, medical aluminum caps and medical rubber plugs (pads) are used as two different packaging materials that directly contact drugs. The state independently issues registration certificates for pharmaceutical packaging materials. According to this management, pharmaceutical manufacturers should separately Purchased by the enterprise and used in the filling room. However, in the production operation of oral liquid, due to technical and cost factors, it is impossible for pharmaceutical companies to purchase aluminum caps from aluminum cap manufacturers separately, and to purchase rubber plug pads from rubber plug (pad) manufacturers and then assemble them together for packaging. Oral liquid. The current common practice is: pharmaceutical factories directly purchase aluminum caps that have been assembled with rubber plugs (pads), and pharmaceutical packaging material manufacturers provide oral liquid aluminum caps with different materials according to market demand. (Pad), there are latex, silicone rubber, etc., then the assembly process of the inner plug and the aluminum cap is actually completed in the aluminum cap manufacturer. This aluminum cap is already a composite product of two pharmaceutical packaging materials when it leaves the factory. According to the "Administrative Measures for Packaging Materials and Containers in Direct Contact with Drugs" (Bureau Order No. 13), the medicinal rubber plugs used in aluminum caps must also have the "Medicine Packaging Materials Registration Certificate", which meets the relevant standards. Oral liquid aluminum cap manufacturers often only obtain the "Medicine Packaging Material Registration Certificate" for the aluminum cap. The inner plug is purchased from outside, and only the product name, batch number and corresponding drug packaging material registration certificate are marked on the outer packaging of the product at the factory. Number, resulting in inconsistency with the actual sales status of the finished product, and the legal identity of the inner plug cannot be traced back.

In addition, law enforcement officers also found a lot of oral liquid aluminum cap products lined with natural rubber plugs in the finished product warehouse of an aluminum cap manufacturer. The outer packaging was also marked with the registration number of the drug packaging material, but the rubber plug was not indicated. Material, and natural rubber stoppers due to unstable chemical properties, as early as 2005 have been included in the national compulsory list of pharmaceutical packaging materials. Although the company explained that they are all sold to health care products and food manufacturers, there is no difference between the outer packaging and the aluminum covers sold to drug manufacturers, and the hidden dangers of mixing into drug manufacturers cannot be ruled out.
In fact, not only the aluminum caps of oral liquid bottles, but also the outer packaging labels of most pharmaceutical packaging materials have problems with incomplete identification content to varying degrees. For example, only one certificate is used to replace the label, the name of the label is inconsistent with the registration certificate of the pharmaceutical packaging material, Incomplete production batch numbers or production dates, no execution standards, no expiration date, no expiration date, etc. Some companies, in order to save costs, produce different types of pharmaceutical packaging materials that use the same outer packaging, and all pharmaceutical packaging materials obtained The registration certificate numbers are all printed on the outer packaging and recycled.
Analysis: The current "Administrative Measures on Packaging Materials and Containers in Direct Contact with Drugs", "General Rules for Assessment", and national standards for pharmaceutical packaging materials do not specify the content of packaging labels for pharmaceutical packaging materials, but are formulated by the company itself, which leads to packaging An important factor that is confused and cannot be used as an indicator.
     
Question 2: The quality control of the composite aluminum cover lined with rubber plug pad:
     
The aluminum cap is registered as an independent pharmaceutical packaging material. The declared production procedure only contains the production content of the aluminum cap, and the assembly process without rubber plug pads. Naturally, there is no content to detect rubber plug pads in the quality standard. The aluminum cap leaves the factory. At that time, the manufacturer only issued a report on the inspection according to the quality standard of the aluminum cover, and there was no guarantee of whether the quality inspection index of the inner rubber plug (pad) was qualified. As a terminal for the use of pharmaceutical packaging materials-most pharmaceutical manufacturers and preparation rooms of medical institutions do not have sufficient pharmaceutical packaging material inspection capabilities. The quality control of purchased pharmaceutical packaging materials mainly depends on the supplier’s qualified inspection report. According to the internal control standards for oral liquid aluminum caps formulated by pharmaceutical factories, generally only the appearance, specifications, dimensions, and microbiological limits of the aluminum caps are regulated, but there are no test items for the inner rubber plug (pad). . According to the requirements of GMP, before purchasing aluminum caps, pharmaceutical manufacturers will ask suppliers for the registration certificates of aluminum caps and inner plugs and other relevant qualifications, but whether the aluminum caps purchased each time are equipped with legal, Qualified medicinal rubber plugs (pads) often lack monitoring and inspection capabilities. The incomplete packaging label of oral liquid aluminum caps is also one of the reasons. At the same time, aluminum cap manufacturers are relatively loose in the management of the purchase, use, and delivery of rubber plugs (pads). The in and out have not been inspected. They believe that "the rubber plugs (pads) are not our products" and do not need to be responsible for their quality. , Resulting in vacuum and blind spots in the quality control of medicinal rubber stoppers (pads) during production, circulation and use.

Analysis: The "Drug Administration Law" and the "Administrative Measures on Packaging Materials and Containers in Direct Contact with Drugs" stipulate that pharmaceutical manufacturers and medical institutions that prepare pharmaceutical preparations must not use pharmaceutical packaging materials that do not conform to national standards. For the use of unqualified pharmaceutical packaging materials, the (food) drug regulatory authority shall order the suspension of use and impose a fine of 10,000 yuan up to 30,000 yuan, and the (food) drug regulatory authority shall supervise and handle the pharmaceutical packaging materials that have been produced or imported. . For the use of unqualified pharmaceutical packaging materials, the (food) drug supervision and administration department shall order the suspension of use and impose a fine of 10,000 yuan up to 30,000 yuan. The packaging materials for packaged drugs shall be immediately taken back and the (food) drug The supervision and management department supervises the handling. However, in actual supervision work, the drug supervision department lacks corresponding technical support and judgment basis for whether it meets the "statutory standards" and whether it is "unqualified". After the promulgation and implementation of the new YBB series of national standards, the issued "Registration Certificate for Pharmaceutical Packaging Materials" did not require changes, which brought difficulties to supervision, especially for composite pharmaceutical bags with aluminum caps for oral liquids lined with rubber plugs (pads) Material, lack of applicable legal standards. Moreover, the current coverage of supervision and sampling of pharmaceutical packaging materials is far from enough. The "Administrative Measures on Packaging Materials and Containers in Direct Contact with Drugs" stipulate that the national and provincial drug regulatory agencies organize random inspections on the production and use of pharmaceutical packaging materials. Because there is no authority for supervision and sampling, the basic supervision department that undertakes the main daily supervision work is still unable to carry out this work, and the basis, means and strength of supervision are insufficient. Sometimes drug quality problems (such as excessive moisture, bacteria contamination, etc.) caused by unqualified pharmaceutical packaging materials are often "paid" by pharmaceutical manufacturers, resulting in a lack of motivation and sense of urgency to actively improve product quality and inspection capabilities. , Is not conducive to clarifying quality responsibility and strengthening quality awareness.
     
Problem three, material management is chaotic, production, quality inspection, and sales records are incomplete, and process management is not standardized
     
Due to the particularity of the rubber stopper (pad) in the production process of the oral liquid aluminum cover, it is neither used as a raw material nor an intermediate product, but is equivalent to the part of the finished product. According to the production process regulations of the aluminum cover, there is no rubber stopper assembly. For the content of (pad), most aluminum cover manufacturers have not formulated relevant management systems for rubber plugs (pads), and have not established records of purchase, use, and inspection. The relevant content cannot be reflected in the batch production and sales records, so the aluminum cover It is difficult to trace the source and quantity of all rubber plugs (pads) used in the production site and records of enterprises.

In daily supervision, we also found that some aluminum cap manufacturers purchase raw materials such as silicone rubber and entrust rubber stopper (pad) manufacturers to process them in order to reduce costs, and then return them to be used as lining rubber stoppers (pads) to fill oral liquid aluminum. It is cancelled and sold to pharmaceutical manufacturers. Since the current national laws and regulations have not made clear deterministic provisions and approval procedures for the entrusted processing of pharmaceutical packaging materials, there is no basis for handling such behavior, but if it is not regulated, it will inevitably affect the pharmaceutical packaging materials. Quality in turn has a negative impact on the quality of medicines.

Analysis: Although the production quality management requirements for each link of the entire production process are stipulated in the "General Rules for the Assessment of Pharmaceutical Packaging Materials Production Site", the implementation of the "General Rules for Assessment" is mainly reflected in the pre-licensing supervision, only for pharmaceutical packaging materials Enterprises are binding when applying for registration and re-registration of pharmaceutical packaging materials. The state has not yet formulated the "Measures for the Supervision and Administration of the Production of Pharmaceutical Packaging Materials." For post-licensing supervision, the primary drug regulatory authorities have no practical supervision and inspection procedures and standards. If the supervisory authority finds that the company violates the General Principles or even does not comply with the standard inspection, that is, serious behaviors such as sales, etc., it can only be persuasion, education, and no penalty clauses, so the regulatory effect is not obvious.

Medicine packaging materials are an inseparable part of medicines, which accompany the whole process of medicine production, circulation and use. However, due to the quality problems of some pharmaceutical packaging materials, some harmful substances in the packaging materials may cause the medicine to dissolve or react with some components in the medicine to directly affect the quality of the medicine. Therefore, the quality of the medicine packaging material is directly related to the quality of the medicine. It is related to the safety of the people's medication. However, compared with drug quality management, the current quality management of pharmaceutical packaging materials in my country is obviously lagging behind, and some problems in the production process have seriously affected the quality of pharmaceutical packaging materials. These problems have their own reasons, such as the small scale of the industry, low-quality employees, weak quality management system, and poor self-discipline. The company is the first responsible person, but sound laws and regulations and effective supervision are also two indispensable aspects. At present, due to the imperfect legal system of pharmaceutical packaging materials, the imperfect relevant standards and the system that is not compatible with actual production Defects, the status quo that cannot be followed or started in supervision can also not be ignored.

A few suggestions:

1. Revise the "Measures for the Administration of Packaging Materials and Containers in Direct Contact with Drugs", or formulate the "Measures for the Supervision and Administration of the Production of Pharmaceutical Packaging Materials" as soon as possible, appropriately increase the content of supervision and inspection, and strengthen the supervision and inspection of the production quality system of pharmaceutical packaging companies. Make daily supervision scientific, standardized, and procedural, and promote the improvement of enterprise quality management.

1. Strengthen post-licensing supervision, clarify that after obtaining the "Registration Certificate of Pharmaceutical Packaging Materials", the company does not follow the requirements of the "General Rules for On-site Inspection and Acceptance of Pharmaceutical Packaging Materials" to organize production and increase the corresponding administrative penalty clauses. To change the situation where the basic drug regulatory departments cannot start when they encounter the problems of repeated reforms and repeated violations in the production and quality management of enterprises.

2. Clearly stipulate the contents of packaging and labeling of medicine packaging materials, which can be regulated with reference to the packaging of medicines.

3. Promote the GMP certification system for pharmaceutical packaging materials when conditions are met. With the completion of pharmaceutical GMP certification, the requirements of pharmaceutical manufacturers for pharmaceutical packaging materials will be further improved, which puts forward higher requirements for the standardized management of pharmaceutical packaging materials manufacturers. In order to establish a pharmaceutical packaging material quality management system that is compatible with pharmaceutical production, the state should implement a GMP certification system for pharmaceutical packaging material manufacturers to ensure the quality of pharmaceutical packaging materials and meet the needs of pharmaceutical packaging.

2. Improve the registration standards for pharmaceutical packaging materials based on actual conditions, and determine the principle of batch division based on actual product conditions. Take oral liquid aluminum-plastic composite caps and oral liquid easy-stab aluminum caps as an example, which has been extended in the production chain. The final product (that can be directly applied to the state of drug packaging) can be registered and standards can be formulated, such as oral liquid Standards for aluminum-plastic composite caps and oral liquid perforable aluminum caps should include the content of testing rubber plugs (pads). Manufacturers responsible for the production of aluminum caps should incorporate the assembly process of rubber plugs (pads) into the production process regulations. The purchased rubber plugs (Padding) As a raw material for management, review, and acceptance, the requisition record is included in the batch production record of the aluminum cover. The source, qualification, and batch number of the rubber plug (pad) used in each batch of products should be traceable.

3. Organize and carry out the quality supervision and sampling inspection of pharmaceutical packaging materials. The supervision and sampling inspection of the quality of pharmaceutical packaging materials shall be included in the daily sampling inspection work, and the sampling inspection of pharmaceutical packaging materials shall be increased. Establish a technical force compatible with the supervision of pharmaceutical packaging materials to keep product quality under control from the source.

4. Integrate with the implementation of drug GMP, urge drug manufacturers and other drug packaging material use terminals to strengthen the qualification review of the drug packaging material supplier, especially to carry out on-site inspections around the other party’s quality management system, strict acceptance procedures, increase testing items, and get stuck Export of unqualified pharmaceutical packaging materials by upstream companies.

5. Strengthen the self-discipline awareness of enterprises in production according to law. The drug regulatory department should strengthen the supervision of the laws, regulations and rules of the company, such as the Drug Administration Law, the Implementation Regulations of the Drug Administration Law, the Management Measures for Packaging Materials and Containers Directly Contacting Drugs, and the General Rules for the Assessment of Pharmaceutical Packaging Materials Production Sites. Training to effectively raise the awareness of enterprises to produce according to law. At the same time, companies must strengthen the training of employees, closely integrate the actual operation of the job, carry out targeted training, and cultivate technical backbones in production and inspection, so as to improve employees' quality management awareness and job standard operation capabilities. Administrative guidance measures such as credit rating assessment and establishment of industry associations can also be adopted to guide enterprises to strive for brand creation, standardize development, and become bigger and stronger.