安全第一–对于人类和环境

高活性物质需要特别安全的生产工艺。使用密闭和WiP(在位水洗)系统保障了操作人员的健康。使用WiP可以更快地进行产品转换。在WiP机器上安装一个密闭包装,可以在加工高活性颗粒时提供全新的可能性。

安全–如何运作

观察WiP和密闭流程是如何提高生产力和安全性的。

Containment Guard
“密闭防护”

绝对可靠的密闭防护在高效活性药物成分药品生产中越来越重要(HPAPI)。其目的是可靠地保护患者免受交叉污染的风险,并在操作人员使用机器处理高活性物质时排除所有风险。为了应对这些挑战,我们开发了Containment Guard密闭防护系统,同时在生产过程中保障您的效率。该系统包括:

  • 符合SMEPAC指南(大气颗粒浓度标准化测量)测量标准的测试过程。
  • 压片密闭方案的技术开发基础。

安全在于七个循环

有关测试过程的所有信息

测量过程
毫不费力就能达到精确测量

测量方法基于SMEPAC指南。其由密闭补充,以涵盖其他实用方面:

  • 定位测量探头
  • 操作人员的位置
  • 样本数量
  • 机器操作模式
  • 故障或错误期间的系统性能
  • 包括加工设备在内的系统总性能计算

实现专门针对密闭压片系统的可重复评估成为可能。

基于OEB级别的证书
菲特压片机在施瓦岑贝克的客户中心特殊试验室里进行此项测试。测试成功后,压片机将收到密闭证书。证书级别基于OEB级别和/或相应的PDE值。

1090i WiP
精心构思的清洁概念

可更换转台和高效清洁概念确保1090i WIP的高生产率。它们使产品快速转换和缩短停机时间成为可能。在密闭版本中,1090i WiP具有一把手动喷枪和一个吸尘喷嘴。格拉特的进料系统支持无污染给料。

2090i WiP
低冲击、转换快

生产过程极快:2090i WiP中的可清洗压力室确保产品快速转换和缩短停机时间。在密闭版本中,2090i WiP具有一把手动喷枪和一个吸尘喷嘴。进料系统支持无污染给料。

3090i WiP
安全快速的大批量生产

在大批量生产过程中,3090i WiP双出料旋转式压片机在确保了生产效率的同时,也减轻了操作人员的压力。3090i WiP借助自动预洗等设备,可以完全集成到过程自动化中。在不同形状和尺寸的产品之间可以迅速改变。原料通过密闭版本中的进料系统给入。材料容器可以以完全无污染的方式进行安装和移除。

Capsule filling machine FE75 and FE75

具有可选密闭选项的FE55
操作人员和环境安全

作为一个制造商,你是否越来越多地生产高活性物质?然后你可以依靠低粉尘生产提供的安全保障。FE55的可选密闭选项提供了一个高效的平台。

具有可选密闭选项的FE75
大输出,高安全

当您不希望在安全方面做出任何妥协的情况下又对输出提出最大要求时,FE75是您正确的选择。

技术参数

此概述显示适合您需求的合适的密闭或WiP解决方案。

型号

冲头数(最大)

压片产量(最大)

机器尺寸(毫米)

最大药片直径(毫米)

重量(千克)

FE55 密闭 87 626,400 1,306 x 1,306 x 2,048 25 mm 约3,800
FE75 密闭 115 1,656,000 1,463 x 1,463 x 2,046 25 mm 约5,500
1090i WiP 30 216,000 960 x 960 x 2,034 25 mm 约2,000
2090i WiP 45 324,000 1,220 x 1,220 x 2,022 25 mm 约3,500
3090i WiP 75 1,080,000 1,390 x 1,390 x 2,024 25 mm 约4,800

了解更多关于
密闭

如有任何疑问,请随时与我们联系。我们将携手使您的生产更加高效、更具创新、更易盈利。

您只需给我们拨打电话或发送电子邮件。

Global Sales
Fette Compacting GmbH 
Grabauer Str. 24 
21493 Schwarzenbek 
Deutschland

电话   +49 4151 12 0
电子邮箱   tablet@fette-compacting.com

  • FE55 密闭包装
    名称 FE55 密闭包装
    大小 744 KB
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  • Title Brochure Containment English
    Containment Guard
    名称 Containment Guard
    大小 6 MB
    数量 1
    类型 pdf

密闭趋势档案

随着制药技术的发展,密闭防御的需求不断增长。
The future of Containment

密闭的未来

密闭专家Richard Denk的论文

Containment technologies have progressed in leaps and bounds over the last few decades. At the same time, operator protection requirements have risen due to new, highly potent and highly hazardous active ingredients. Richard Denk analyzed what that means for future technological developments as part of an expert group set up by the International Society for Pharmaceutical Engineering (ISPE). A look at the future of containment.

I have been passionate about containment for almost 20 years. I first came across the subject at an ISPE conference in the USA in 1996. Some time later, I became an active member of the US ISPE Containment Group, which I subsequently co-chaired for several years. During this time, a number of fundamental ISPE guidelines were initiated, such as the Standardized Measurement Of Equipment Particulate Containment (SMEPAC) covering maximum levels for containment systems. In 2008, the time was right to set up a regional ISPE containment group for Germany, Austria and Switzerland. I have been chairing this expert group ever since – something I love doing.

Three major containment trends

Containment technologies have developed more and more over the last 20 years. New technologies for safe and efficient pharmaceutical production have constantly emerged. But will that continue to happen over the next few years? How will the world of pharmaceuticals change in the foreseeable future and what does that mean for containment moving forwards? We have discussed these issues at length within the German/Austrian/Swiss ISPE group and talked to numerous industry representatives. This formed the basis for the Pharma 2025 initiative, within which we are also considering the question of containment. In short, as have identified three main focal points:

1. Process-integrated containment will replace adapted containment. The production process will merge with containment. This will enable optimum containment production with the smallest possible footprint. As a consequence, there will be fewer contaminated surfaces, resulting in considerable advantages for cleaning and refitting. Should it become possible to create a small, self-enclosed clean room inside the containment area, the GMP environment for this process could also be simplified. There have already been several initial developments along these lines – for example in the packaging of tablets and capsules.

2. Single-use systems will be another focal point over the next ten years. Disposable technologies have a major advantage in that the manufacturing process can be adapted quickly and easily to containment requirements. These systems offer the greatest advantages for relatively small production quantities and the field of research and development. Single-use technologies are also worth considering if the product being manufactured changes frequently or highly flexible process management is needed. Examples of such systems include disposable liners and single-use isolators for the transportation and pharmaceutical processing of highly potent substances. The biotech industry is also increasingly replacing stainless steel systems with single-use technologies.

3. Continuous manufacturing will play an important role for the production of high-potency or highly hazardous active pharmaceutical ingredients. Continuous manufacturing has a number of advantages over batch production: the process equipment is more compact, meaning it has a smaller surface to be cleaned. The processes are also linked with one another or several process stages are completed by a single machine. This makes for fewer containment interfaces.

We will continue to examine these trends in depth within the ISPE Containment Expert Group over the coming years.

Food for thought: containment pyramid and handbook

When I developed the containment pyramid about 15 years ago (see diagram), it had five levels with corresponding limits. Now, some of the substances in use are so highly potent or highly hazardous that we have added a sixth tier. This category is for products with a maximum particulate contamination level of less than 200 nanograms per cubic meter. Even more efficient containment systems will be needed in the future to comply with such low limits.

We compiled our latest containment findings in the ISPE group and used them to develop a containment handbook specifically for pharmaceutical production. The book will be available from ISPE from late September 2015. It is designed to serve as a guideline and reference work for users in the pharmaceutical industry on all containment issues – from the basics to system life cycles.

Personally, I have no doubt that there are many more changes to come in the field of containment over the next ten years. It will be interesting to see how things develop.

By Richard Denk,
Chair of the ISPE Containment Expert Group (Germany, Austria, Switzerland),
Sales Manager Containment der SKAN AG,
Author at Maas & Peither GMP-Verlag

Highly-active substances

高活性物质

波恩大学制药技术教授Karl G. Wagner访谈录

Prof. Dr. Wagner, what makes an API highly potent?
Two aspects need to be considered when answering that question. One is the desired effect of a drug within the body. In this respect, a substance is considered highly potent is it is biologically effective at a dose of no more than 150 micrograms per kilo of body weight. The other aspect is operator exposure during pharmaceutical processing, which is defined in the OEL figures. In this context, APIs with a workplace concentration of 10 micrograms per cubic meter of air or less are rated as highly potent.

Which therapies are highly potent substances used for?
There are substances that are effective at extremely low doses in every therapeutic area. However, key application areas include highly toxic cytostatic drugs for cancer therapies and hormones for contraception, HRT, and numerous other uses.

What is the significance of HPAPIs for new drugs?

Due to their genesis, new API molecules are becoming more and more selective and active. This is also necessary, so that manufacturers can develop drugs that offer an advantage over the existing standard therapy, which is crucial for them to be approved.

Which fields of research are driving the development of high-dose drugs?
As the biochemical processes in the body are very well understood, we now know where most receptors – the targets for drug therapy – are located. The high-potency approach came about because we are increasingly able to design the right molecule keys for the receptors with the help of computer-aided simulations. After all, there is a key for each receptor which fits that particular lock perfectly. A picklock might work too, but this is more of a rough and ready approach which won’t operate the lock mechanism so smoothly. In the field of solids, however, we still often face the problem of low bioavailability when high-potency substances are administered orally.

What causes this low bioavailability?
Due to their high receptor affinity, most new chemical entities (NCEs) have low water solubility, which limits their absorption in the gastrointestinal tract. In this case, suitable formulation concepts need to be found. New biological entities (NBEs) suffer from another problem: our bodies are programmed to break down proteins and peptides as food. Outwitting this program is very complicated.

How can this problem be solved in solids production for biopharmaceuticals?

Personally, I think it might be possible to protect the protein by encasing it. Simply coating a tablet is not enough though. The substance needs to be made of into extremely fine particles – just a few micrometers or even nanometers. These then have to be used to generate miniparticles, which need to be encapsulated to protect them from enzymes and stomach acid. The casing also has to have an affinity with the mucous membrane in the intestine so that the particle can embed itself there in a targeted fashion and the active ingredient can penetrate the wall of the intestine. Scientists are already able to produce such particles.  The challenge lies in finding the right shell. It is particularly difficult to subsequently put the particles in a solid form that enables them to disperse again as effective individual particles following administration. A lot of research still needs to be done here in the coming years and decades.

How is knowledge shared with pharmaceutical manufacturers?

There’s still a huge gap here. In my view, it would be constructive for pharmaceutical manufacturers to set up a cross-industry initiative to statistically analyze toxicological data with safety factors, OELs, and data from occupational health investigations. This would enable researchers and users to interact much better and tackle current challenges more effectively.

 

(Photo: ©markusblanke - iStock)

Cross-contamination – A challenge for tableting

交叉污染——压片面临的挑战

菲特的商品

Pharmaceutical production increasingly involves the use of highly-active ingredients. This is also accompanied by increased demands on containment. Cross-contamination in particular becomes a risk for patient safety and product quality. But what requirements actually apply here and what technologies offer effective protection during tableting?

HPAPIs (High Potency Active Pharmaceutical Ingredients) remain a growth driver for the pharmaceutical industry. By 2022, the HPAPI market is likely to grow from 11 billion euro (2014) to 24 billion euro, according to a forecast by Grand View Research. This will mainly be attributable to advances in tumor therapy and hormone treatment. But patent expiration will also mean that manufacturers of generic products will increasingly enter the market.

This development will also be accompanied by increased requirements on manufacturing processes. Pharmaceutical manufacturers will be obliged to adjust to more frequent product changes involving highly-active substances, whereby this will be accompanied by a general risk that active substance residue in the plant is transferred to other products. The tolerances for such cross-contamination are however practically zero in the case of HPAPIs.

Evaluating the risks of cross-contamination

The regulatory authorities have also set their sights on the issue of cross-contamination which likewise appears several times in chapters 3 and 5 of the EU GMP Guidelines revised in 2015. These chapters emphasize the responsibility of companies when it comes to undertaking toxicological analyses and comprehensive risk management against cross-contamination.

However, the toxicological analysis is a challenge for many companies. To date, for example, standard practice involved specifying one-thousandth of the therapeutic dose as the maximum value for tolerable residue. The general rule that maximum ten PPM (Parts Per Million) of another product could be contained in a medicinal product also applied. In the case of HPAPIs, however, new approaches are required which consider the individual active agents. An alternative approach is represented by the PDE value (Permitted Daily Exposure, also ADE value, Acceptable Daily Exposure) which defines the dose which most likely does not display any adverse effects when someone is exposed to it all their life. Information for the calculation of such limits, users can derive for example from the Annex 1 of the EU GMP Guidelines. Having said that, the expertise for such limits still needs to be developed in many companies.

Protecting against cross-contamination in tableting

In order to satisfy the requirements on contamination protection in production, suitable technological concepts are vital. "Comprehensive containment with Wash-in-Place facilities is the best protection against cross-contamination", explains Jörg Gierds, Senior Product Manager at Fette Compacting. "As a machine manufacturer, we work intensively on such systems which can be fully integrated in the process flow, whereby contamination risks lurk in every pipe and seal. For this reason, all machine components must be designed so as to prevent residue from arising in the first place as well as being fully washable."

Nowhere for production residue to hide

In order to minimize the risk of cross-contamination, Fette Compacting has realized special design concepts which start as soon as the plant is set up, as Gierds outlines: "For example, we have designed the pipe system to be very transparent in washable tablet presses. As a general rule, pipes are difficult to examine for residue on the inside which is why we use a single-pipe piping system, which directs the water via a single, easy-to-control line through the plant."

Inside the tablet press, product loss can be particularly prevalent where machine components intersect, e.g. valves, seals and welded connections. In its capacity as a process apparatus, a tablet press is under a certain degree of pressure. This means that powder can even reach places you would never imagine it to be. Consequently, all components need to be coordinated even more precisely and their transfer points continuous. These requirements can be satisfied using double-flap valves and hollow-profile seals, for example. A WiP Center ensures optimal hygienic results for washable systems by Fette Compacting, whereby product residue is practically eliminated thanks to a combination of diaphragm valves and orbital welded pipes.

Safe, automatic washing

Where encapsulated plants are involved, individual components must be recorded and washed by a single program. The washing programs for the Fette Compacting WiP and Containment tablet presses can be configured and programmed accordingly depending on the respective product. A special rotation and spray jet design ensures that the cleaning agent reaches every area of the process chamber. Even the dust extraction pipes can be washed, preventing particles from falling back into the machine. In addition, tight spaces which are difficult to access can be rinsed using a manual spray gun.

On the basis of these concepts, users can also press highly-active agents safely and efficiently. Ultimately, cross-contamination is then no longer an acute risk but rather a calculable aspect of prevention.