Glass packaging: Starting from the conversion to medium boron

  November 8th is the beginning of winter season. The seminar on the impact of pharmaceutical glass packaging on drug quality and market, sponsored by the China Medical Packaging Association, was held in Cangzhou, Hebei Province. Except for a few pharmaceutical packaging material experts, more than 160 attendees all came from over 60 pharmaceutical companies.

It is rare for pharmaceutical companies to be so concerned about the dynamics and progress of upstream suppliers in the packaging field. However, in the eyes of the pharmaceutical representatives present, it is quite normal. Behind the rarity and normalcy lies an increasingly pressing event in the pharmaceutical industry: the approval of the association between excipients, packaging materials, and drugs.

The Opinions of the State Council on Reforming the Drug and Medical Device Evaluation and Approval System (Guofa [2015] No. 44) specify that drug and pharmaceutical packaging materials, as well as pharmaceutical excipients, shall be subject to associated approval. The separate approval of pharmaceutical packaging materials and pharmaceutical excipients shall be changed to simultaneous evaluation and approval when approving drug registration applications. At the same time, implement the applicant's main responsibility.

With the endorsement of Document No. 44, it is necessary for pharmaceutical production enterprises, especially high-risk injection production enterprises and glass packaging production enterprises, to strengthen interaction and pay attention to the packaging material technology market.

The advantages of Zhongboron are fully demonstrated　　

The neutral penicillin bottle used by Cornell Pharmaceutical is made of neutral borosilicate glass (referred to as neutral glass). The consensus among pharmaceutical packaging material experts has long been that neutral glass, due to its good chemical stability, low alkali leaching, and water resistance, is particularly suitable for drugs that are slightly acidic, alkaline, and pH sensitive. Therefore, neutral glass is widely used in injection packaging in developed countries, and countries such as Russia and India are also vigorously promoting it. However, in China, most injection glass packaging still uses low borosilicate glass. According to data provided by Yuan Chunmei, a senior engineer at the Beijing Institute of Drug Packaging Materials Inspection, only 1% of the over 600 registration certificates for injection packaging bottles in China are produced using neutral glass tubes. The safety risks associated with injections have long been recognized by drug regulatory authorities and the industry.

In 2012, a sample of 111 batches of injection pharmaceutical glass packaging materials from the former Beijing Municipal Medical Products Administration found that "a few glass packaging materials had water resistance on the inner surface, 121 ℃ particle method water resistance, and other inspection data close to the critical value of the standard; a few glass ampoules had fracture force inspection results close to the critical boundary of the standard, indicating quality hazards".

Industry insiders point out that the situation in Beijing is actually widespread throughout the country. Clinically, it has been found that some glass bottle injections may lose their activity within the expiration date and are prone to detachment, white spots, etc. Direct injection into the blood can cause problems such as capillary blockage and granuloma. In severe cases, debris may even embed into brain blood vessels, endangering life. These glass bottles are made of low borosilicate glass or lower end sodium calcium glass.

Against this background, on November 8, 2012, the former National Food and Drug Administration issued a notice on strengthening the supervision and management of pharmaceutical glass packaging injection drugs ([2012] No. 132). The notice requires that for biological products, slightly acidic or alkaline, and pH sensitive injections, pharmaceutical glass or other suitable packaging materials with 121 ℃ particle method water resistance of level 1 and internal surface water resistance of level HC1 should be selected. And neutral glass is precisely the medicinal glass that meets the above requirements.

Three years have passed, and boron has not yet become the mainstream of injection packaging. Behind the quality issues of injections, there are still frequent shadows of low-end packaging materials: In July this year, the dobutamine hydrochloride injection sold by Liuzhou Pharmaceutical and produced by Zhejiang Ruixin Pharmaceutical contained glass debris, which was recognized by the Liuzhou Food and Drug Administration in Guangxi as a substandard drug; In October of that year, the revised pharmaceutical industry was also punished by the Chengdu Food and Drug Administration for using substandard drug packaging materials such as low borosilicate glass controlled oral liquid bottles.

Market knot to be resolved　　

Zhao Ting, General Manager of Shandong Fangming Pharmaceutical Group Co., Ltd., pointed out that 95% of glass packaged injections in China use low borosilicate glass or sodium calcium glass, and in clinical practice, 95% of small capacity injections are priced at only one to two cents per tube. If their packaging is changed to medium borosilicate glass, the cost will basically double. There are many manufacturers of small capacity injections, and the competition is very fierce. Unless they are recognized in drug bidding and allow injections packaged in neutral glass to gain a price advantage in market access, Liangbi will inevitably be expelled. He also proposed specific suggestions for the conversion of injection packaging from low boron to medium boron: the country should formulate policies and the industry should promote it step by step, such as first stipulating the conversion of injections with pH values within a certain range; Each province's bidding should also give pharmaceutical companies using neutral glass packaging a certain proportion of markup rights. "The policies of various management departments need to cooperate with each other, the use of neutral glass can be implemented, and the quality and safety level of injections can be improved." Zhao Ting emphasized.

Compatibility with drugs, reasonable cost-effectiveness, and policy coordination support are essential in the process of transitioning from low boron drugs to medium boron. Representatives from pharmaceutical companies have also raised the challenge of explaining how using more expensive packaging materials can bring greater profits under the situation of medical insurance cost control, which is not only for pharmaceutical companies but also for pharmaceutical packaging material companies.

Reform promotes transformation　　

In addition to factors such as market and price, another constraint for pharmaceutical companies to upgrade their pharmaceutical packaging materials is their lack of understanding and concern about approval.

As with previous seminars, the China Pharmaceutical Packaging Association actively builds a platform for communication among pharmaceutical companies, packaging material companies, and drug regulatory agencies. Authoritative figures are invited to answer questions and clarify doubts for enterprises. What is a formulation? Formulations are active ingredients, excipients, and packaging materials. We hope that enterprises can pay attention to drug registration reform, including related approvals. After the reform, the responsibility and pressure of pharmaceutical companies will inevitably increase. Packaging materials will affect the stability of drug quality. Some injections may pass factory testing, but in reality, they are no longer qualified within the expiration date due to the interaction between the drug solution and glass. If it is indeed believed that neutral glass is better than low boron drug glass, pharmaceutical companies should start early and replace it early A drug regulatory official suggested to the company at the meeting. Cai Hong, Secretary General of the Pharmaceutical Packaging Association, pointed out that in the 13th Five Year Plan, the association hopes to convert water needle glass packaging from low boron to medium boron. The reason is that liquid formulations are high-risk products, and strong acid and alkali biological products are more sensitive. To promote the smooth transition from low boron drug glass to neutral drug glass, on the one hand, we need to seek policy support; On the other hand, enterprises need to be less wait-and-see and hesitant, contribute more wisdom, voice more opinions, and provide more suggestions.

As the only Chinese member of the Packaging, Storage and Transportation Committee of the United States Pharmacopoeia Commission, Gao Yonghua, Deputy Secretary General of the Pharmaceutical Packaging Association, introduced the requirements and standards of US regulatory agencies for pharmaceutical packaging materials, as well as the key points and methods for pharmaceutical companies to audit suppliers. She suggests that in the current reform of the drug evaluation and approval system, pharmaceutical companies will become the main responsible party for drug quality. They should have a deep understanding of the characteristics and production process of packaging materials as soon as possible, conduct extractable substance research and compatibility tests, and choose packaging that is suitable for specific drugs (1-on-1); On the basis of complying with national mandatory standards, develop suitable protocol (contract) standards (referring to Chinese Pharmacopoeia, YBB, ISO and association standards); To meet the requirement of safe and reliable drug quality, it is recommended to use neutral borosilicate glass material for water injection; Pharmaceutical companies conduct thorough audits of packaging material suppliers, communicate fully with suppliers, handle changes properly, and ensure continuous acquisition of packaging products that meet quality requirements.