Thermal stability and storage of human insulin

医学 糖尿病 人口 胰岛素 制冷 人胰岛素 冷链 环境卫生 环境科学 业务 内科学 生物 食品科学 工程类 内分泌学 机械工程
作者
Bernd Richter,Brenda Bongaerts,Maria‐Inti Metzendorf
出处
期刊:The Cochrane library [Elsevier]
卷期号:2023 (11) 被引量:5
标识
DOI:10.1002/14651858.cd015385.pub2
摘要

Background Health authorities stress the temperature sensitivity of human insulin, advising protection from heat and freezing, with manufacturers suggesting low‐temperature storage for intact vials, and once opened, storage at room temperature for four to six weeks, though usage time and maximum temperature recommendations vary. For human insulin, the recommendations of current shelf life in use may range from 10 to 45 days, and the maximum temperature in use varies between 25 °C and 37 °C. Optimal cold‐chain management of human insulin from manufacturing until the point of delivery to people with diabetes should always be maintained, and people with diabetes and access to reliable refrigeration should follow manufacturers' recommendations. However, a growing segment of the diabetes‐affected global population resides in challenging environments, confronting prolonged exposure to extreme heat due to the climate crisis, all while grappling with limited access to refrigeration. Objectives To analyse the effects of storing human insulin above or below the manufacturers' recommended insulin temperature storage range or advised usage time, or both, after dispensing human insulin to people with diabetes. Search methods We used standard, extensive Cochrane search methods. The latest search date was 12 July 2023. Selection criteria We included clinical and laboratory studies investigating the storage of human insulin above or below manufacturers' recommended temperature storage range, advised usage time, or both. Data collection and analysis We used standard Cochrane methods. We used GRADE to assess the certainty of evidence for the clinical study. Most information emerged from in vitro studies, mainly from pharmaceutical companies. There is no validated risk of bias and certainty of evidence rating for in vitro studies. We thus presented a narrative summary of the results. Main results We included 17 eligible studies (22 articles) and additional information from pharmaceutical companies. Pilot clinical study One pilot clinical study investigated temperature conditions for insulin stored for six weeks in an unglazed clay pot with temperatures ranging between 25 °C and 27 °C. The mean fall in plasma glucose in eight healthy volunteers after clay pot‐stored insulin injection was comparable to refrigerator‐stored insulin injection (very low‐certainty evidence). In‐vitro studies Nine, three and four laboratory studies investigated storage conditions for insulin vials, insulin cartridges/pens and prefilled plastic syringes, respectively. The included studies reported numerous methods, laboratory measurements and storage conditions. Three studies on prefilled syringes investigating insulin potency at 4 °C up to 23 °C for up to 28 days showed no clinically relevant loss of insulin activity. Nine studies examined unopened vials and cartridges. In studies with no clinically relevant loss of insulin activity for human short‐acting insulin (SAI), intermediate‐acting insulin (IAI) and mixed insulin (MI) temperatures ranged between 28.9 °C and 37 °C for up to four months. Two studies reported up to 18% loss of insulin activity after one week to 28 days at 37 °C. Four studies examined opened vials and cartridges at up to 37 °C for up to 12 weeks, indicating no clinically relevant reduction in insulin activity. Two studies analysed storage conditions for oscillating temperatures ranging between 25 °C and 37 °C for up to 12 weeks and observed no loss of insulin activity for SAI, IAI and MI. Four studies, two on vials (including one on opened vials), and two on prefilled syringes, investigated sterility and reported no microbial contamination. Data from pharmaceutical companies Four manufacturers (BIOTON, Eli Lilly and Company, Novo Nordisk and Sanofi) provided previously unreleased human insulin thermostability data mostly referring to unopened containers (vials, cartridges). We could not include the data from Sanofi because the company announced the permanent discontinuation of the production of human insulins Insuman Rapid, Basal and Comb 25. BIOTON provided data on SAI after one, three and six months at 25 °C: all investigated parameters were within reference values, and, compared to baseline, loss of insulin activity was 1.1%, 1.0% and 1.7%, respectively. Eli Lilly and Company provided summary data: at below 25 °C or 30 °C SAI/IAI/MI could be stored for up to 25 days or 12 days, respectively. Thereafter, patient in‐use was possible for up to 28 days. Novo Nordisk provided extensive data: compared to baseline, after three and six months at 25 °C, loss of SAI activity was 1.8% and 3.2% to 3.5%, respectively. Loss of IAI activity was 1.2% to 1.9% after three months and 2.0% to 2.3% after six months. Compared to baseline, after one, two and three months at 37 °C, loss of SAI activity was 2.2% to 2.8%, 5.7% and 8.3% to 8.6%, respectively. Loss IAI activity was 1.4% to 1.8%, 3.0% to 3.8% and 4.7% to 5.3%, respectively. There was no relevant increase in insulin degradation products observed. Up to six months at 25 °C and up to two months at 37 °C high molecular weight proteins were within specifications. Appearance, visible particles or macroscopy, particulate matter, zinc, pH, metacresol and phenol complied with specifications. There were no data for cold environmental conditions and insulin pumps. Authors' conclusions Under difficult living conditions, pharmaceutical companies' data indicate that it is possible to store unopened SAI and IAI vials and cartridges at up to 25 °C for a maximum of six months and at up to 37 °C for a maximum of two months without a clinically relevant loss of insulin potency. Also, oscillating temperatures between 25 °C and 37 °C for up to three months result in no loss of insulin activity for SAI, IAI and MI. In addition, ambient temperature can be lowered by use of simple cooling devices such as clay pots for insulin storage. Clinical studies on opened and unopened insulin containers should be performed to measure insulin potency and stability after varying storage conditions. Furthermore, more data are needed on MI, insulin pumps, sterility and cold climate conditions.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
芋圆Z.完成签到,获得积分10
刚刚
赵亚伟发布了新的文献求助10
1秒前
ZZZ完成签到,获得积分10
3秒前
栗子完成签到 ,获得积分10
5秒前
等待的盼波完成签到,获得积分10
5秒前
CAOHOU应助嘟嘟请让一让采纳,获得10
5秒前
5秒前
天天向上完成签到,获得积分10
5秒前
野原小龙虾完成签到,获得积分10
6秒前
time完成签到,获得积分10
6秒前
6秒前
阿绿发布了新的文献求助10
10秒前
11秒前
11秒前
雨柏完成签到 ,获得积分10
11秒前
wanci应助qwe1108采纳,获得10
12秒前
明天过后完成签到,获得积分10
14秒前
jin完成签到,获得积分10
15秒前
yhy完成签到 ,获得积分10
16秒前
黑色卡布奇诺完成签到,获得积分20
16秒前
tanglu发布了新的文献求助10
16秒前
可爱的函函应助梁大海采纳,获得10
16秒前
成就绮琴完成签到 ,获得积分10
17秒前
xicifish完成签到,获得积分10
17秒前
目光之澄完成签到,获得积分10
18秒前
wanci应助研友_ndDPBn采纳,获得10
18秒前
耍酷的白梦完成签到,获得积分10
19秒前
miracle完成签到 ,获得积分10
20秒前
coding完成签到,获得积分10
21秒前
22秒前
犹豫水蓝完成签到,获得积分10
23秒前
yin完成签到,获得积分10
23秒前
JUGG完成签到,获得积分10
23秒前
CipherSage应助阿湫采纳,获得10
24秒前
FIN应助手机采纳,获得20
24秒前
星辰大海应助东黎采纳,获得10
24秒前
量子星尘发布了新的文献求助10
24秒前
wujingshuai完成签到,获得积分10
25秒前
少年完成签到,获得积分10
25秒前
星辰大海应助ficus_min采纳,获得10
26秒前
高分求助中
【提示信息,请勿应助】关于scihub 10000
Les Mantodea de Guyane: Insecta, Polyneoptera [The Mantids of French Guiana] 3000
徐淮辽南地区新元古代叠层石及生物地层 3000
The Mother of All Tableaux: Order, Equivalence, and Geometry in the Large-scale Structure of Optimality Theory 3000
Global Eyelash Assessment scale (GEA) 1000
Picture Books with Same-sex Parented Families: Unintentional Censorship 550
Research on Disturbance Rejection Control Algorithm for Aerial Operation Robots 500
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 4038524
求助须知:如何正确求助?哪些是违规求助? 3576221
关于积分的说明 11374737
捐赠科研通 3305912
什么是DOI,文献DOI怎么找? 1819354
邀请新用户注册赠送积分活动 892688
科研通“疑难数据库(出版商)”最低求助积分说明 815048