In India, majority of the Pharma manufacturing facilities handle multiple products and 80% of the facilities manufacture Oral Solid Dosage forms, i.e. Tablets and Capsules. These products share common equipment in the facilities thus increasing the potential for cross contamination. Therefore, every manufacturing process has to be followed by an efficient cleaning procedure and it is imperative to have a well-defined and validated cleaning system in place in order to prevent the cross contamination of the products.
Two important aspects to be considered for achieving efficient cleaning include:
- Selection of Equipment Design: The design of the equipment should be such that it lends itself for easy cleaning such as smooth impervious surface and good material of construction like polished stainless steel that can withstand cleaning with various detergents and solvents.
- Use of automated tailor-made Cleaning Systems for consistency in cleaning of the equipment.
Western countries also use the same technologies as used in India. In India, experts pinpoint that the pharma company decides what level of cleaning is required and how to go about it. SOPs are laid down accordingly based on the available methods and technologies.
Technologies and Trends
Clean-In-Place system (CIP) is highly desirable and most of the drug manufacturing equipment nowadays has this system in place. The cleaning procedure is inbuilt. There are standalone or external equipment – known as COP equipment, in which all parts of the equipment can be dismantled for application of cleaning procedures.
For each and every equipment, it is important to identify hard to reach and hard to clean surfaces. If the part can be dismantled that should be the first preference, if not, suitable modification to the cleaning procedure is required that may include use of specially designed tools such as long handle brushes, use of pressure guns with specially designed spray nozzles etc.
Says S. M. Mudda, Director – Technical & Operations, Micro Labs, Bangalore, Out of the four major sources of cross contamination i.e. Airborne Transfer, Mix-up, Mechanical Transfer and Chemical Residue from the equipment, the residue from previous product entering into another product inadvertently beyond unacceptable limits poses a major challenge for cleaning of the equipment in a multi-product facility. You require an efficient cleaning system which is automated and validated one to ensure that you are able to clean the equipment to the desired level consistently. However if you do it manually, consistency in cleaning may not always be possible.”
The global trend therefore, besides having a CIP, is to lay emphasis on designing GMP-compliant equipment. Design of the equipment is such that there are no hard to clean areas. There is no possibility of retention of residue also. The material is of stainless steel and the equipment has polished surfaces and good engineering design.
Cleaning Work Flow in Drug manufacturing unit
Echoing similar views, YA Chowdary, Executive Vice-President-Operations, Medreich Limited, Bangalore, says, Cleaning of the equipment in a pharmaceutical industry plays a very important role in eliminating the cross contamination. In order to ensure proper cleaning of the equipment, one should develop a suitable cleaning method which can remove the traces of the previous product and validate the cleaning method to verify the adopted method is capable of giving expected results.
An appropriate cleaning method need to be developed for the cleaning of the equipment based on the type and the design of the equipment. Though the equipment cleaning procedure may differ between two batches of the same product and between two different products, we are mainly discussing about the cleaning of equipment between one product to another product. Let us take an example of a cleaning procedure of an equipment and validation of it. Rapid Mixing Granulator (RMG) is an equipment used mainly in the manufacturing of tablet dosage forms. To clean the equipment, initially the equipment is dismantled and the removable parts are separated from the machine.
The parts and the equipment are initially cleaned with raw water from a high pressure jet to remove the adhered material. Later the equipment and the parts are cleaned by using a cleaning agent – 0.1% Sodium Lauryl Sulphate (which is a food grade material and widely used as a pharmaceutical excipient in the formulations) with a scrubber. Usually the cleaning agent selected should be easily removable, food grade and the detergent used should give information to derive the acceptable limit based on scientific rationale. After the completion of the cleaning with the cleaning agent, the machine & the parts are thoroughly cleaned with adequate raw water with high pressure jet to remove any traces of the cleaning agent. Some times even hot water is also used for these purposes. Once the equipment is thoroughly cleaned finally the parts and the entire equipment is cleaned with purified water. This purified water is made through Reverse osmosis / De-ionization techniques to meet the pharmacopoeial standards. The same procedure is used to clean the entire area and the surface of the machine. Finally the equipment is dried with a reusable non shredding cloth. Dupont is one of the leading manufacturer of the cloth.
Clean steam is used in the pharmaceutical industries in processes where the steam or its condensate can come into contact with a pharmaceutical or medical product and cause contamination. In such cases, steam from a conventional boiler (often called utility or plant steam) is unsuitable because it may contain boiler additives, rust or other undesirable materials. The use of clean steam is determined by the rules of Good Manufacturing Practice (GMP). These are general rules applicable to pharmaceutical manufacture, detailed in the Code of Federal Regulations. They do not provide any specific recommendation regarding steam, but do present the general requirements of facilities, systems, equipment and operation needed to prevent contamination of pharmaceutical products during their manufacture.
The main use of clean steam in manufacturing is for the sterilization of products or, more usually, equipment. Steam cleaning (sterilization) can be done in a set up which is compatible with heat. There are restrictions that design of the set up should cater to the temperature because when steam is used, the temperature of the room may go up to 80-90OC. “Being a part of the CIP, steam cleaning is also required to bring down microbial load in some manufacturing units, where all dosage forms are manufactured,” Mudda adds.