Amidst reports of doubtful credibility of manufacturing standards followed by some of the pharma companies in the country, particularly with reference to Ranbaxy, Hospira and Wockhardt, topics like Good Manufacturing Practices and proper cleaning standards have gained more prominence than ever.
Despite the fact that India enjoys a unique position of low cost manufacturing and highest quality medicine, there is also a requirement for continuous monitoring of quality related aspects with cleaning in pharma facilities as a major thrust area.
Cleaning of pharma machinery
Cleaning of the equipment in pharmaceutical industry plays an 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 needs to be developed for cleaning based on the type and the design of the equipment. What is being discussed here is the cleaning process of the equipment after the manufacture of one product and switching over to another product.
A case in point is 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.
Cleaning protocols and standards
The parts and 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 and 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 this purpose. After the equipment is thoroughly cleaned , 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 this cloth.
Steam cleaning
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 manufacturers as 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.
Maintaining hygiene
Different companies use different methods for cleaning & sanitizing of their facility/equipment. Hydrogen Peroxide or Ozone and Sodium Hypochlorite are used to sanitize the facility and equipment. These reagents cleanses the equipment based on the ability to generate nascent oxygen and chloride ion, which effectively controls microbial contamination. Cleansing agents like Sodium Lauryl Sulphate (SLS) is required for eliminating the previous product residue. The main purpose is to keep microbial load / cross contamination under control.
Taking the aspect of hygiene into consideration, experts pinpoint that the quality of the environmental conditions depends on the basic hygiene levels followed in the facility. If the area of the facility is cleaned on a day- to- day basis with detergents, solvents, solutions and mopping of the floor is carried out with suitable disinfectants, the microbial quality of that particular area is taken care of . Fumigation and other customized solutions are also available in the market, which helps reduce contamination by microbial growth.
Some experts however do not recommend use of any chemical during cleaning because cleaning validation study is done after the cleaning process.
Sampling techniques and testing methods
The equipment should be visually clean and it can be confirmed by physical verification. However, more scientific and quantifiable methods of sampling such as sampling by swab and rinse water samples are used in the industry.
These samples are tested for determining the residue of the previous product by validated analytical methods capable of detecting low level residues.
Cleaning validation of equipment
Once the equipment cleaning method is developed, the cleaning method needs to be validated. Cleaning validation is a procedure to establish the documented evidence that the cleaning method used to clean the equipment is capable of removing the traces of the previous product, to a level below the acceptance criteria.
This is mainly because visually one may not be able to see the residual matter. But when a sample is taken from the product's contact surface and analyzed chemically, traces may be found.
Cleanroom setting
Once the equipment and the area is cleaned and ready to start the activity, it is important to check the conditions that are required to perform the manufacturing activity in the area. For example, capsule and tablets manufacturing area requires controlled temperature and humidity conditions. These conditions are very important to maintain the quality and the stability of the product being manufactured.
Emerging trends in cleaning equipment
There are some equipment which are Cleaning in Place (CIP ) because the personnel cannot afford to move the equipment because of their heavy nature. Equipment like Rapid Mixing Granulator (RMG) and Fluid Bed Drier (FBD) are CIP equipment. Meshes and other storage bins are considered as the Cleaning Out of Place (COP) ones. They can be removed and cleaned separately in the dedicated washing areas. There are equipment available to clean these removable parts and the storage bins, which can be programmed for the washing cycles. However, such cleaning of the equipment also requires validation.
There are several washing equipment available in the market which are both indigenous as well as imported ones. However, the indigenous ones are value for money products with good performance and efficiency.
Need of the hour
The need of the hour is to develop good design in equipment, good design of CIP equipment and validated automated cleaning procedures so that cleaning is done efficiently in Indian pharma manufacturing units.
While the Government is making claims that India's pharmaceutical sector is a highly regulated one and the fact that its exports are strictly guided by various regulatory regimes of the importing countries, there is a need to spruce up the cleaning facilities in the pharma manufacturing units.