Time is money. Reducing time-to-market, particularly in the product development cycle, is always a top priority for any business. The use of ASTM standards in the healthcare packaging industry has gone a long way toward increasing productivity and reducing costs in this highly regulated sector.

ASTM Committees D10 on Packaging and F02 on Flexible Barrier Materials have been active for several years developing and maintaining standard test methods, practices and guides for the packaging industry. Subcommittees D10.32 on Consumer, Pharmaceutical and Medical Packaging and F02.60 on Medical Device Packaging cover the standardization of healthcare packaging, developing standards that comply with the U. S. Food and Drug Administration.

Medical device packaging standards are particularly useful for companies that declare conformance to recognized consensus standards, while pharmaceutical packaging standards provide a reduced regulatory burden and stability requirements without compromising the safety of the drug product.

In 1997, the FDA’s Center for Devices and Radiological Health implemented the recognition and use of consensus standards pursuant to the FDA’s Modernization Act, stating that conformance to recognized consensus standards may be used to satisfy premarket product review requirements. Manufacturers applying for a premarket notification, investigational development exemption application, or premarket approval application may declare conformity to recognized consensus standards in lieu of submitting data to fulfill the regulatory requirements. This eliminates, in most cases, the need to review the actual test data for those aspects of the device addressed by the standard. The FDA expects review times will decrease because the process for providing and reviewing safety and effectiveness evidence for new medical devices is more efficient. Additionally, the resolution of issues or questions can be very time consuming for the FDA and the device manufacturer. The use of recognized consensus standards can often eliminate the need for resolution on questionable issues.

Standards: Regulatory and Manufacturer Confidence
One of the primary FDA considerations in new product applications is the ability to sterilize the product and maintain that sterility until the time of use. Medical device packaging allows for and provides that requirement. Therefore, the packaging is part of new medical device applications and is reviewed by the FDA. Manufacturers may declare conformity to recognized consensus standards for packaging. This is where Subcommittee F02.60 has played a significant role with their standards development process.

In 1997, the American National Standards Institute had adopted the International Organization for Standardization’s ISO 11607, “Packaging for terminally sterilized medical devices.” This standard established the requirements for packaging materials, package design and the packaging process for sterile medical devices. At the time this standard was adopted, there were very few standardized test methods to demonstrate conformance with the requirements of the standard. It was at this time that the FDA recognized ANSI/AAMI/ISO 11607 as a consensus standard applicable for companies to declare conformity. In addition, notified bodies conducting third party assessments for CE marking compliance to the European Union’s Medical Device Directive were also using ISO 11607 for packaging conformance and approval.

Subcommittee F02.60 set out on a course of action to develop and standardize all test methods and practices applicable for conformance to ANSI/AAMI/ISO 11607 requirements. Package integrity test methods were the least standardized. In accordance with FDA guidance on test method acceptance, all standard test methods for package integrity were to include identified levels of sensitivity (how small a hole or leak the test method could reliably detect), packaging materials and types of packages applicable for the method, and, of course precision and bias statements derived from round-robin testing. The FDA and the international standard require that the test methods used to demonstrate conformance be validated.

With sensitivity identified and a P&B established, users of the ASTM test methods had a high degree of confidence and a starting place for validation. Companies knew what packages and materials were applicable for their purpose and did not have to spend the extra time to develop the
sensitivity requirement. Their test method validation simply required duplication of sensitivity and demonstrated repeatability and reliability in finding defectives.

Applying for recognition of these ASTM standards by FDA’s CDRH was the next phase. Since all test methods, practices and guides developed by F02.60 were in support of a consensus standard already recognized by CDRH, there was no difficulty in getting all applicable ASTM standards recognized. Currently there are 14 ASTM medical device packaging standards recognized with all new standards approved within the last six months pending recognition.

So what does this mean for manufacturers applying for new medical device approvals? By declaring conformance to recognized consensus standards, test methods, test method protocols, and, in some cases, test data do not need to be submitted to the FDA as part of their application. The FDA has a high degree of confidence that the methods used reliably demonstrate that the materials and package will provide sterility maintenance and thus a safe and effective medical device.

The ISO 11607 packaging standard is undergoing a
revision to harmonize it with European norms on medical device packaging. Several of the European packaging standards have required test methods to demonstrate conformity to the standard. ASTM International will play a role in standardizing the normative, required, test methods through its consensus process. Many of these test methods have not undergone any conformation of reliability and repeatability. This work will provide manufacturers selling product in the European Union, as well as EU-based companies, with standardized methods of conformity.

Different Approaches for Different Requirements
Because of the differences among the FDA Centers for Drugs, Biologics and Devices, Subcommittee D10.32 on Consumer, Pharmaceutical and Medical Packaging has taken a different approach. FDA’s Center for Drug Evaluation and Research has several guidance documents specifically listing appropriate material and container requirements and testing necessary to demonstrate drug safety and efficacy in new product applications.

These requirements are laid out in CDER’s Guidance
for Industry — Container Closure Systems for Packaging Human Drugs and Biologics, May 1999. Additionally, requirements for new drug applications are very specific. Once the drug, and therefore, the package, is approved, requirements for post approval changes come into effect. At the present time, FDA guidance is being drafted for “packaging post-approval changes,” known as PACPAC. PACPAC will address qualification, stability and filing requirements for post approval changes on container closure systems for human drug and biological products. It is anticipated that this guidance will reduce the regulatory burden and stability requirements without compromising product safety.

Pharmaceutical packaging test methods will be needed to demonstrate “as-good-or-better-than” properties of the package for drug safety. Scientifically sound and reliable test methods will be required to demonstrate equivalence with the currently approved package. These test methods and their results will provide the necessary documentation to show that expensive, long-term stability may not be necessary and the documentation needed for prior FDA approval may not be required or significantly reduced.

This is the current task for the D10.32 PACPAC task group to identify and develop the appropriate material, container and integrity test methods that FDA will accept. Industry and packaging experts have developed a list of anticipated test methods they believe are needed to accommodate post approval changes. These areas include product protection from temperature, light, moisture and air; compatibility with the drug dosage form; safety of the drug from packaging material leaching toxic substances; and performance of the package as it refers to its ability to function in the manner for which it is designed.

Even though healthcare packaging has been emphasized within these two subcommittees, it must be noted that other divisions and subcommittees of D10 and F02 have also played significant and supporting roles for the development of relevant standards applicable to the regulatory review process.

The consensus standards approach saves all parties time and money in the regulatory approval process. Product development cycle time and regulatory review time can be reduced, bringing new products to the market sooner. Package development productivity is increased with applicable and reliable ASTM standards available. Less time is spent developing rationales and validating “in-house” test methods. Conformity assessments for international market approvals become standardized with clearly defined requirements.

ASTM International’s role in healthcare packaging has made, and will continue to make, an indelible mark on pharmaceutical and medical device products for sale in the United States, Europe and the rest of the world by standardizing test methods, practices and guides for the packaging of ethical and consumer pharmaceuticals and sterile medical devices. The esteem in which ASTM International is held and its process of implementing and managing consensus standards works well for regulatory bodies worldwide. //

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