by Marcel Dion, Director of Marketing for Washing and Steam Sterilization Systems in the Life Sciences Division of STERIS Corporation and Matt Hofacre, responsible for global applications team with STERIS Life Sciences Capital Equipment Solutions

Non-GMP or GMP Washers and Sterilizers: How to Choose article is featured in the November/December 2015 issue of Pharmaceutical Engineering®.

This three part series will present the standards and guidelines typically used by manufacturers to design and build GMP washers and sterilizers. It describes the characteristics that differentiate GMP from regular laboratory equipment.  In part one we will cover:

  • What are GMPs?
  • What are the GMPs for washers and sterilizers?

Automated washing systems and steam sterilizers (autoclaves) are often used in research and drug-manufacturing facilities to clean and sterilize a variety of items. Washers use water, cleaning agents, and mechanical action to remove residues from soiled laboratory and manufacturing-component surfaces. Sterilizers use steam to deactivate biological waste, sterilize cleaned laboratory and drug-manufacturing components, or terminally sterilize drug products.

Since a wide range of washers and sterilizers designed for various applications is available on the market today, the following questions are often raised:

  • What is a GMP washer?
  • How do you describe a GMP sterilizer?
  • Why are GMP washers and sterilizers so much more expensive than laboratory units?
  • What are the most significant differences between the GMP washers and sterilizers?
  • Why does it take more time to procure a GMP unit?
  • When do I need to consider a GMP system instead of a non-GMP system?
  • Can I turn my existing regular equipment into a GMP system?

These are all good questions!

What Are GMPs?

GMP stands for “good manufacturing practice,” a standard that is observed in regulated pharmaceutical-manufacturing facilities. GMP is also often used, rightly or wrongly, as a qualifier when describing pieces of equipment, such as the washers and steam sterilizers that are used in these facilities.

This article highlights the standards and guidelines typically used by manufacturers to design and build GMP washers and sterilizers. It describes the characteristics that differentiate GMP from regular laboratory equipment. Finally, a side-by-side comparison summarizes the main differences between the two types of equipment and describes typical applications for each.

cGMP

The US Food and Drug Administration (FDA) ensures the quality of drug products by carefully monitoring drug manufacturers’ compliance with its current Good Manufacturing Practice (cGMP) regulations. These contain the minimum requirements for the methods, facilities, and controls used in the manufacturing, processing, and packing of a drug product. The regulations make sure that a product is safe for use and that it has the ingredients and strength it claims to have.1

One can see that the word “manufacturing” in GMP actually refers to the production of food, drug products, and active pharmaceutical products; it does not refer to equipment. So, the term “GMP washers and sterilizers” could be somewhat misleading. “Pharmaceutical-grade washers and sterilizers” is perhaps a more appropriate term, so it will be used throughout the rest of this article.

GMPs for pharmaceutical-grade washers and sterilizers

FDA cGMP regulations for finished pharmaceuticals are provided in the Code of Federal Regulations (CFR), Title 21, parts 2102 and 211.3 Unfortunately, the regulations provide limited information concerning the way equipment used for this application should be designed and manufactured. However, four sections in subpart D of Part 211 do refer specifically to equipment:

Section 211.63—Equipment design, size, and location: “Equipment used in the manufacture, processing, packing, or holding of a drug product shall be of appropriate design, adequate size, and suitably located to facilitate operations for its intended use and for its cleaning and maintenance.”

Section 211.65—Equipment construction: “Equipment shall be constructed so that surfaces that contact components, in-process materials, or drug products shall not be reactive, additive, or absorptive so as to alter the safety, identity, strength, quality, or purity of the drug product.”

Section 211.67—Equipment cleaning and maintenance: This section covers mostly maintenance aspects, and does not provide much information concerning the design of the equipment itself.

Section 211.68—Automatic, mechanical, and electronic equipment: “Equipment used in the manufacture, processing, packing, or holding of a drug product shall be routinely calibrated, inspected, or checked according to a written program designed to assure proper performance. Written records of those calibration checks and inspections shall be maintained.”

In short, the FDA regulations provide general guidelines and few specific details related to the design and manufacture of equipment for the pharmaceutical industry. Therefore, manufacturers of such equipment must rely on other standards and guidelines, such as the American Society of Mechanical Engineers Bioprocessing Equipment (ASME-BPE) standard and the International Society for Pharmaceutical Engineering (ISPE) good automated manufacturing practice (GAMP®) guidelines.

The BPE standard is intended for design, materials, construction, inspection, and testing of vessels, piping, and related accessories— such as pumps, valves, and fittings—for use in the biopharmaceutical industry.5 GAMP® 5: A Risk-Based Approach to Compliant GxP Computerized Systems, published by ISPE, provides guidance on achieving compliant computerized systems that are fit for intended use in an efficient and effective manner.10

Other health care sterilization references, such as British Standard EN285,11 UK Department of Health HTM 201012 (now CFPP 01-01),13 and ISO 17665,14 are also commonly applied in pharmaceutical applications. These standards do contain some basic information on machine construction, performance, and testing requirements. Many pharmaceutical-grade units comply with elements of these standards.

Read part two which covers Pharmaceutical Grade vs. Laboratory Washers and Sterilizers and the five categories of characteristics:

  • Manufacturer’s quality assurance program
  • Mechanical design
  • Process monitoring
  • Control and software system
  • Design, manufacturing, and qualification documentation

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In March, the ISPE Training Institute will be conducting a Facilities, Systems & Equipment training focusing on the tools for implementing a sustainable approach to a risk-based C&Q program, integrating the new C&Q program into existing quality systems, Quality Assurance and Engineering Management Systems and defining organizational capabilities to support the new C&Q program   Sign up today!

References:
1. US Food and Drug Administration. “Drug Applications and Current Good Manufacturing Practice (cGMP) Regulations. 17 December 2014. http://www.fda.gov/drugs/developmentapprovalprocess/manufacturing/ucm090016.htm.
2. ———. Code of Federal Regulations, Title 21, Part 210. “Current Good Manufacturing Practice in Manufacturinwg, Processing, Packing, or Holding of Drugs; General.” 21 August 2015. http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=210.1.
3. ———. Code of Federal Regulations, Title 21, Part 211. “Current Good Manufacturing Practice for Finished Pharmaceuticals.” 21 August 2015. https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfCFR/CFRSearch.cfm?CFRPart=211.
5. American Society of Mechanical Engineers, Bioprocess Equipment Group. ASME BPE—2014 Bioprocessing Equipment. 2014. p. ix.
10. International Society for Pharmaceutical Engineering. GAMP® 5: A Risk-Based Approach to Compliant GxP Computerized Systems. February 2008. http://www.ispe.org/gamp-5.
11. British Standards Institution. EN285:2006A2:2009. “Sterilization. Steam Sterilizers. Large Sterilizers.” http://shop.bsigroup.com/ProductDetail/?pid=000000000030192330.
12. UK Department of Health. NHS Estates. “Health Technical Memorandum 2010: Sterilisation.” 1994. http://www.isopharm.co.uk/validation-engineer/htm-2010.
13. UK Department of Health. “Choice Framework for Local Policy and Procedures 01-01—Management and Decontamination of Surgical instruments (Medical Devices) Used in Acute Care. Part A: The Formulation of Local Policy and Choices.” http://www.his.org.uk/files/3113/7908/4699/CFPP_01_01_A_Management_and_decontamination_of_surgical_instruments_medical_devices_used_in_acute_care._Part_A_The_formulation_of_local_policy_and_choices.pdf.
14. International Organization for Standardization. “ISO 17665-1:2006. Sterilization of Health Care Products—Moist Heat—Part 1: Requirements for the Development, Validation and Routine Control of a Sterilization Process for Medical Devices.” http://www.iso.org/iso/catalogue_detail.htm?csnumber=43187.

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