The pharmaceutical industry is driven by national and international regulations to market their products in domestic and global markets for the need of patients. The international Pharmacopeia or National Compendium is setting the standards for the quality of drug products for their intended use. Interestingly, the regulations and Pharmacopeia standards are applicable and covered for raw materials, excipients, APIs, packaging materials and drug products.
Apart from these items, there are many items which are directly or indirectly used in manufacturing activities to influence the quality of pharmaceutical products. These items are so called consumables or miscellaneous materials. There were no defined requirements issued by any regulatory agency so far for the qualitative and quantitative composition, the tests to be carried out on these consumables materials as a guidance for pharmaceutical industry.
The objective of this article is to bring basic understanding and requirements for some of the key items used in pharmaceutical manufacturing activities.
Basic understanding on contamination
In pharmaceutical industry, the product and processes must be kept clean and uncontaminated. Contaminants in the manufacturing environment include basically anything that is harmful to the process or product.
Product contaminants can be divided into three major categories such as particulate contaminants (viable and non-viable particles); chemical contaminants (all other contaminants that are not solid); physical risk factors (for example, temperature, humidity, pressure, radiation, static electricity, vibrations, etc).
What is consumables?
Key materials which are used in support of manufacturing or which is coming in contact with the product during manufacturing that may not become part of final product.
The consumables can be classified into three categories based on their applications:
Direct quality impacting: Consumables which will have direct contact with product and directly affect the quality, purity, strength and safety of the final product. Examples are product filters, product contact tubing and process gases, polyethylene bags etc.
Indirect quality impacting: Consumables which do not come into direct contact with the product and may affect the quality, purity, strength and safety of the product. Examples are gloves, garments, lubricants, wipes/mops, etc.
Non-quality impacting: Consumables which will not affect the quality, purity, strength and safety of the product. Examples are engineering tools and housekeeping items, etc.
Quality impacting consumables
Product/process filters: Filters are widely used in fluid passage through their pores, retaining particles too large to fit through their apertures. Since sterilizing grade filters are a critical part of any aseptic process, a significant amount of testing and documentation is conducted to support the suitability of filters use. The filters include: Polyvinylidine fluoride (PVDF)/Polytetrafluoroethylene (PTFE)/ Polyester/Polypropylene.
Product/process tubing: Silicone tubing is widely used in the pharmaceutical applications since it is safe and did not contain plasticizers or other additives that could leach into a drug product and cause toxicological issues. Silicone tubing is highly flexible and tear resistant, making it a good choice for transporting fluids between tanks, or for use in filling machines. Peroxide-cured materials have better pump life and reduced spallation relative to standard platinum catalyzed tubing.
Process gases: Pharmaceutical industries use compressed gases in a wide range of applications including chemical synthesis, controlled atmosphere and blanketing, cell cultivation, chilling /freezing, etc. Gas suppliers can describe the quality of gases as either ‘industrial” or “pharmaceutical”. Gas should be purchased according to an agreed specification and delivered with a ‘certificate of conformity/certificate of analysis’ depending on the criticality of operations.
Cleanroom garments: The IEST published the latest revision of IEST-RP-CC003.3, “Garment Considerations for Cleanrooms and Other Controlled Environments” in 2003. It outlines all aspects of cleanroom garment systems, including the recommended components and construction of cleanroom garments and testing of the cleanroom reusable apparel used in cleanrooms. Some of the most common tests and the standards applicable to those tests are:
- Grab tensile, MVTR, Air permeability, Pore size and abrasion tests
- Flammability, surface resistivity, Static electricity decay and bacterial filtration efficiency
Cleanroom disinfectants: The choice of a disinfectant is critical for a pharmaceutical cleanroom not only because of potential losses due to contaminated product but also because of user safety as well as room turnaround. Biocides used in cleanrooms are subject to FDA and USP guidelines, which classify them, describe their mechanism of action and efficiency to get the disinfection process validated. The specific standard to regulate cleanroom disinfectants is USP 29 NF-24 <1072>.
Cleanroom mops/wipes: Pharmaceutical mopping systems need to be effective at removing both non-viable and viable contamination, capable of applying a disinfectant or detergent, suitable for autoclaving or sterilization. If a poor choice of mop is made which is difficult or uncomfortable to use and quickly leads to operator fatigue, then a robust bio-decontamination programme will not be achieved.
Pharmaceutical lubricants: The lubricants used in the manufacture of pharmaceutical products and pharmaceutical packaging must be food approved. To make manufacturing processes more reliable, H1 lubricants should be used exclusively. The allowable lubricant contamination constituted by the FDA is 10 parts per million.
Pharmaceutical gloves: The recent past regulatory citations and warning letters revealed that major pharmaceutical companies in India had serious non-compliance in handling gloves into their receipt, testing, storage and issuance to production use. Gloves are tested to determine the Acceptable Quality Level (AQL) of the product as per ISO 2859-1. Surgical glove manufacturers also are required to meet the current Good Manufacturing Practices (cGMP) regulation for medical devices (21 CFR 820), which includes establishing and maintaining control procedures to ensure that the gloves' specified design requirements consistently are met.
ConclusionIt is important to understand the application of consumables and criticality in usage of them in production and quality control aspects to define their pre-determined quality attributes. Though these consumables are not a part of product composition, it is playing an important role in minimizing the contamination into the drug products. Hence, it is a right time to start the implementation of consumable management in pharmaceutical industry to meet product quality and safety requirements.
(Author is associate director of Corporate Quality Assurance,
Mylan Laboratories Ltd, Bilekahalli, Bannerghatta Road, Bangalore-76)