Standardization News

Various ASTM International technical committees contribute to healthcare with standards that improve care delivery, support medical research and drug development, enhance product manufacturing, and more.

Terry Woods, Ph.D., is leader of the Solid Mechanics Laboratory at the U.S. Food and Drug Administration’s Center for Devices and Radiological Health in Silver Spring, Maryland. She puts it this way: “ASTM’s a neutral playing field where all stakeholders can get to know and trust each other; it’s a good place to collaborate and work together.”

Here’s a look at some results of those stakeholders’ important work.

Safety and Magnetic Resonance

The committee on medical and surgical materials and devices (F04) includes more than 900 professionals from some 30 countries responsible for over 300 standards that help patients worldwide.

One important contribution is to safety in the magnetic resonance environment. MR imaging, or MRI, with its non-invasive, non-radiation imaging capabilities, have provided a new view of the human body. With its use, medical professionals can see part or all of the human body and better detect problem conditions or disease.

Because of the powerful magnets used, MRI also comes with safety hazards such as issues for patients who have metallic implants.

Standards from F04 help assess MRI safety. Standard F2503 (practice for marking medical devices and other items for safety in the magnetic resonance environment) “defines how you label things. But to label it you need to know how to test it,” says Woods, a long-time member of the F04 committee who launched the work on MR standards.

Tests that support the labeling include:

• Test method for measurement of magnetically induced displacement force on medical devices in the magnetic resonance environment (F2052),
• Test method for evaluation of MR image artifacts from passive implants (F2119),
• Test method for measurement of magnetically induced torque on medical devices in the magnetic resonance environment (F2213), and
• Test method for measurement of radio frequency induced heating on or near passive implants during magnetic resonance imaging (F2182).
• The F04 committee also defines terminology (F2503) used internationally to label devices and other items for safety in the MR environment.

Tissue Engineering

In July, a new leukemia therapy — one made using a patient’s own cells — gained recommendation for approval by a U.S. Food and Drug Administration advisory committee. The therapy (CTL109) is a treatment for an acute form of childhood/young adult leukemia.

“It’s a huge breakthrough,” says Carl Simon, Ph.D., a project leader in the Biomaterials Group at the U.S. National Institute for Standards and Technology, and chair of the subcommittee on cells and tissue-engineered constructs for TEMPs (F04.43). And while this is only one product, Simon adds that it blazes a trail for similar approaches.

CTL109 is a treatment in regenerative medicine, or TEMPs — tissue engineered medical products – that have been developing since the 1980s. Overall, says Simon, “The purpose is to coax the natural body to regenerate tissue.”

As described by the U.S. National Institute of Biomedical Imaging and Bioengineering at the National Institutes of Health, tissue engineering involves:

• Cells from the patient, stem cells, or lab cell lines;
• An environment such as a scaffold, from natural or synthetic materials, to support the cells;
• Biomolecules, such as growth factors, to help the cells be healthy and productive; and
• Physical and mechanical forces to help cell development.

Tissue engineered products can vary from skin replacement and grafts to cartilage and small arteries. Supporting the process and its parts are over 40 standards from the F04 TEMPs subcommittees. The standards address biomaterials and biomolecules, cells and tissue engineered constructs, TEMPs assessment, adventitious agents, and cell signaling. The newest addition to the TEMPs standards is a guide for TEMPs for knee meniscus surgery (F3223). Those who produce, deliver, and regulate TEMPs can refer to the standard to help assess options for meniscus repair or reconstruction.

The standards provide guidance on what one should think about for a product, says Simon, and while “these are not regulatory documents, they may have regulatory implications.” TEMPs standards are used in applications to the U.S. Food and Drug Administration. Several more proposed standards are underway to further TEMPs use in vascular grafts, cartilage, heart valves, and more.

Medical Device Cleaning

A rising interest in reusable medical devices has brought along with it an interest in standards from F04 that support their cleaning. Stephen Spiegelberg, Ph.D., president of Cambridge Polymer Group and a member since 1998, says that there are two overriding questions:

• How do you know a device is clean?
• What are acceptable cleanliness levels? 

For example, like a cooking pan with dried food bits on it, a device that has dried before cleaning will be harder to clean than one that has not.

The subcommittee on material test methods (F04.15) is tackling these questions. One recently approved standard will help the medical industry prepare artificial test soils – blood, feces, and other biological matter – that can simulate device contamination. In this way, manufacturers that make reusable devices such as surgical instruments and pumps can test their cleanliness.

Also underway are a number of other standards related to cleaning devices:

• Characterizing the performance of brushes designed to clean the internal channel of a medical device (WK53082);
• Using a force tester to evaluate the performance of a brush part designed to clean the external surfaces of a medical device (WK57049);
• Application of test soil for the validation testing of device reprocessing instructions (WK57707);
  Determination of effectiveness of cleaning processes for reusable medical instruments using a microbiologic method (simulated use test) (WK59761); and
• A guide for methods of extraction of test soils for the validation of cleaning methods for reusable medical devices (WK60064).

These standards will allow someone to say, “Here’s how I test this, and the results will be reliable,” says Spiegelberg. That will provide both regulators and manufacturers with an understanding of what will make a device safe for use and reuse.

Pharmaceutical and Biopharmaceutical Manufacturing

“You have to build quality into the process,” says Graham Cook, Ph.D., senior director of process knowledge/quality by design at Pfizer.

And while Cook was speaking more about the committee’s focus on pharmaceutical and biopharmaceutical manufacturing (E55), that applies to all of the group’s work. The committee, which is responsible for over 20 standards, works on efficiency and consistency in processes and systems. 

Key among E55 standards is the guide for specification, design, and verification of pharmaceutical and biopharmaceutical manufacturing systems and equipment (E2500). It offers a streamlined approach to being sure that the systems and equipment are fit for intended use. For continuous manufacturing — which offers reduced lead time and planning, plus a more streamlined process — the guide for the application of continuous processing in the pharmaceutical industry (E2968) provides concepts and principles to consider.

Other standards support biopharmaceutical manufacture, especially with regard to viral clearance validation and single-use systems as well standards of general interest to the industry.

The committee counts pharmaceutical manufacturers, suppliers, service providers, and regulatory representatives among its members. Industry representation is broadening, with additional members from other countries becoming involved. 

Ferdinando Aspesi, senior partner at Bridge Associates International LLC and E55 vice chairman, says that “the committee will continue supporting industry innovation in small and large molecule manufacturing.”

Cook says, “Pharmaceuticals is a highly regulated industry, with a complex and fragmented set of differing regulatory agencies and requirements. International consensus standards, such as those developed within ASTM E55, have the potential to support manufacturing by providing globally accepted standards that complement the regulatory framework.” E55, through its outreach and work with regulatory representatives, is working toward the standards’ broader use.

Radiation Processing: Sterile Medical Products

You head to a doctor’s office or clinic for a shot, but first the gloved nurse swabs your arm with an alcohol wipe. Afterward, a small bandage may cover the spot. The gloves and the syringe, along with the bandage, have all been sterilized to prevent problems such as infection.

The sterilization of medical devices and pharmaceutical products, as well as consumer and food products, is done using a variety of processes, depending on the product. One of these methods is radiation processing, which is a controlled application of gamma rays, electrons, or X-rays to kill the microorganisms that might be present.

“The goal is to deliver high quality products that medical professionals can trust,” says John Logar, senior director of aseptic processing and terminal sterilization at Johnson & Johnson. Logar currently chairs the ASTM International committee on radiation processing (E61) and works on the more than 30 standards overseen by the group.

E61 standards cover subjects such as qualifying and monitoring radiation sterilization processes, calibration and use of dosimeters, procedures for measuring radiation absorbed dose, and more. The standards are recommended by the U.S. Food and Drug Administration and referenced in multiple standards from the International Organization for Standardization (ISO). In particular, ISO 11137- 3, Sterilization of Healthcare Products – Radiation – Part 3: Guidance on Dosimetric Aspects, includes more than a dozen E61 standards that support the end user in meeting the ISO 11137-3 requirements.

Logar notes that E61 has worked with ISO for many years through a pilot program that became official in 2006, to reduce duplication of effort and provide guidance about how to use radiation processing to sterilize medical products sold around the world. Through the agreement, a standard goes through both the E61 and responsible ISO committees for approval.

E61 now aims to develop new standards on assessing the quality of irradiation equipment through standard validation and re-validation activities and industry- established acceptance criteria. These standards will provide another level of guidance to the end user in assuring consistency in irradiation equipment capability across the industry. The ultimate goals continue: quality processes, safe products, better patient care.

Medical Gloves: Ensuring Quality

It’s a familiar sight: a doctor or nurse practitioner or phlebotomist walks into the treatment area, washes his or her hands, and puts on a pair of gloves. The gloves come in different sizes and different colors, and their box may sit on a cart or slid into a wall dispenser. Medical practices together use billions of them each year.
A key point about these gloves is the use of standards from an ASTM International technical committee on rubber and rubber-like materials (D11). The responsible subcommittee, consumer rubber products (D11.40), includes a group focused on medical gloves, which oversees more than a dozen standards. The standards specify rubber and nitrile medical gloves, among others, and help manufacturers and testers check for things like residual powder or holes.

Among the standards are:

• Specification for rubber surgical gloves (D3577), which includes tests for sterility, dimensions, tensile strength, elongation, protein content, and more;
• Test method for detection of holes in medical gloves (D5151), designed to evaluate product samples
• Test method for residual powder on medical gloves (D6124), because it’s all right to have powder on some medical gloves but not on others;
• Practice for the assessment of resistance of medical gloves to permeation by chemotherapy drugs (D6978), to help compare medical glove materials and how well they resist chemotherapy drug permeation;
• Practice for determination of expiration dating for medical gloves (D7160), with accelerated stability and real time aging tests; and more.

“All of the standards have their place,” says Margaret Stephens, “If they didn’t, they’d be replaced.” Stephens, who leads the medical gloves group, is a quality specialist for Medline Industries. In her job, she works with factories all over the world that make the gloves.

Stephens says that the standards are internationally used. And she notes that gloves imported into the United States have to meet U.S. Food and Drug Administration requirements and that means ASTM standards cited by FDA.

The group currently is working on a specification for polyethylene gloves for medical applications (WK49857) and another for chemotherapy gloves (WK49858). All those interested are encouraged to participate. “If I don’t participate, I don’t have a say,” Stephens says. “The requirements we do together level the playing field.”