Healthpack Conference 2015 Design Validation and Sampling for Thermoformed Packaging. Elizabeth Nugent Vice President of European Sales

Transcription

1 Healthpack Conference 2015 Design Validation and Sampling for Thermoformed Packaging Elizabeth Nugent Vice President of European Sales

2 Introduction Design Validation and Sampling for Packaging. Why it is important to determine risk when choosing sample size. Certain factors often dismissed in design packaging validations, leading to failures. Why it is important to understand the design inputs pertaining to specific design failure modes How understanding inputs yields robust designs.

3 Background The rise in hospital-acquired infections in recent years has brought attention from many healthcare professionals Handling procedures, hospital hygiene practices have all been scrutinized. The Centers for Disease Control and Prevention (CDC) indicate that a number of microbes have been implicated as causing these infections through the years. These include: Staphylococcus aureus. Enterobacteriaceae. Pseudomonas aeruginosa.

4 Background CDC also suggests that increases in hospital infections can be linked with the organisms becoming more resistant. The most likely source of hospital infections relates to handling and hygiene procedures of the healthcare providers and hospitals. Medical device and Pharmaceutical manufacturers are doing their part to ensure that device packages and their contents do not contribute to increasing infection rates. As a result, the integrity testing and risk assessment of medical device packaging is critical.

5 Background Medical device manufacturers are required to package devices so that they withstand the rigors of shipping and arrive at the point of use in a safe and functional condition. Additionally, they must employ testing protocols that provide objective evidence that the process will produce an expected outcome.

6 Background At the same time, the industry faces immense pressures regarding the cost of healthcare. The medical device industry faces an increasing level of expectation that must be delivered at a reduced cost. As a result choosing the appropriate sample size and testing protocols to validate the processes can be a daunting task. The best approach includes considering risks and understanding the risks with choosing too many or too few samples.

7 Why it is important to determine risk when choosing sample size. Risky Approach: The biggest concern is patient harm. Inadequate package testing employing too few samples can lead to: - Product recalls, - Damage to company reputation, - Lawsuits, increased - FDA scrutiny - Decreased stock prices. Within the hospital, questionable products can lead to delays in the operating room and a lack of confidence in the product.

8 Why it is important to determine risk when choosing sample size. The Risk of Being Too Conservative. When a manufacturer employs an excessive level of test severity or the result can delay the introduction of an otherwise beneficial device. Such a delay means that superior treatments are not available as quickly as possible. An overly cautious approach can also yield excessive waste and increased disposal costs, both of which are associated with over packaging. Excessively high standards result in loss of opportunities to reduce the cost of healthcare.

9 Why it is important to determine risk when choosing sample size. Appropriate level of risk approach 21 CFR 820, does not require a specific risk management system, it does require risk analysis where appropriate in design validation ISO is recognized by FDA as a system that employs riskbased decision making and an analysis of potential risks associated with an unexpected outcome. Through careful consideration of risk, including cost and benefit, positive outcomes can be maximized. Balancing these issues comes into focus in choosing an appropriate sample size when validating your processes.

10 Why it is important to determine risk when choosing sample size. Important factors to be considered when determining an appropriate sample size include; - Possible risks associated with a given failure, - Likelihood of the failure, - Relevant consequences associated with the failure - and any relevant sterile barrier system history.

11 Why it is important to determine risk when choosing sample size. The QSR dictates that manufacturers establish methods and controls to ensure that processes are validated with a high degree of assurance. This regulation applies to packaging processes and, consequently, to the integrity of packages. There is no mention of an acceptable quality level (AQL) in current government documents. FDA broadly defines what must be done, leaving details up to device manufacturers.

12 Why it is important to determine risk when choosing sample size. Manufacturers of medical devices use a variety of techniques to determine suitable sample sizes. Some are often inappropriate. Sample-size justifications that have been inherited in this way may reflect historical judgments made years before the broad application of statistical methods and statistical process control. Arbitrarily picked sizes tend to be round numbers, such as n = 10 or n = 30. Thirty is a particularly popular one, as many people believe it to be the magical, statistically valid sample size.

13 Why it is important to determine risk when choosing sample size. Consider a lot of 50 units; by sampling n = 30, 60% of the total population produced has been sampled. If the sample were pulled appropriately (i.e., throughout the run), and the process were in control, some reasonable assumptions can be made about the portion of the population that was not sampled. But now consider sampling n = 30 in a lot of 2 million units. Another way of dispelling the n = 30 approach is to determine what confidence is obtained if a sample size of 30 is used for pass-fail data. Without context, such as considering lot size or risk factors associated with a failure, is not a sound approach.

14 Why it is important to determine risk when choosing sample size. Finally, in some circumstances, uninformed companies may limit sample sizes based on the assumption that producing and testing units would be too expensive. The effect to the company of just one inaccurate conclusion that compromises the integrity of a sterile barrier system and results in a recall or harms a patient far surpasses the incremental costs of testing additional units.

15 Choice of sampling plan The proper sampling plan must be selected based on whether the data are attribute or variable. Regardless of the type of data, using plans like the ASTM standards generally requires an AQL. An AQL is user defined. In other words, customers determine the acceptable level of product quality, or the numbers of failures they are willing to accept. Another sound statistical approach is for companies to determine their own sample size, based on confidence intervals.

16 Choice of Sampling Plan This is not as difficult as it sounds. The confidence level required will be chosen based on an understanding of the risks associated with a failure, the history of the product, the likelihood of a failure, etc. The greater the level of confidence needed, the larger the number of samples required, and the more certainty exists regarding the population being produced. Sample size can be calculated for both attribute and variable data. These calculations require manufacturers to have examined, and challenged, their processes to understand the inherent variability.

17 Packaging for terminally sterilized Medical devices - Part 2 The international standard EN ISO 11607, part 2, describes the validation of the packaging process. It serves as the basis for the drafting of this guideline which should be understood as an orientation aid for the successful implementation of validation in reprocessing practice. The international standard EN ISO 11607, part 2, serves as the basis for the drafting of this guideline which should be understood as an orientation aid for the successful implementation of validation in reprocessing practice.

18 Factors often overlooked in design packaging validations Why is Packaging almost as important as the device itself? Packaging plays a key role in safely delivering specialized treatment to patients. Most single use sterilized medical devices can be opened with a high degree of confidence that it has remained sterile throughout storage, handling, and transportation. Regulatory authorities recognize the critical nature of sterile barrier or primary package by considering them components or accessories to the medical device.

19 Factors often overlooked in design packaging validations Validating on the cheap. Many people in manufacturing are unaware of the need to test their packaging, or the existence of the ISO standards and the fact that these standards are being used by the FDA and the European Community. They try to validate the packaging on the cheap without using sound, scientific practices. In a rush to market companies risk non-compliance with regulations, or worse yet, they risk unknowingly let suspect devices reach patients.

20 Factors often overlooked in design packaging validations Validating on the cheap. The time to properly validate a full-package system depends on the product s shelf life and its expiration date. For example, it usually takes three to six months to go from package concept to final qualification for a one-year shelf life. The validation schedule should also allow for unexpected events, such as finding pin holes in the packaging after a test.

21 Factors often overlooked in design packaging validations Loss of Sterility This is the most common defect in medical packaging and can happen from fractured thermoforms along with pinholes, slits, cuts, and tears in pouch packages. These defects come from handling (or mishandling) Vibrations during transportation Storage, and impact caused by dropping.

22 Factors often overlooked in design packaging validations. Big pouches into small cartons Pinhole defects in pouches can be reduced by inserting the pouch into a carton without folding, wrinkling or creasing the ends. Pinholes occur at the junctures of the creases and folds when they are vibrated, causing the intersection to be worked. This effect is exacerbated by making complex folds of the pouch causing a very concentrated point of stress at the juncture of the materials. This can be circumvented by using secondary packages.

23 Factors often overlooked in design packaging validations No prequalification Diving into validation. Cutting corners to trim time is short-sighted and usually backfires by extending development schedules. A few common prequalification tests that should be used to detect potential design and manufacturing problems include seal strength and include seal strength and integrity tests on manufactured packages.

24 Factors often overlooked in design packaging validations No prequalification Another test used to prequalify package-product compatibility is dynamic testing associated with transportation and handling. Most sterile medical-device packages do not typically lose sterility simply sitting on a shelf. Failures often stem from events in manufacturing, during shipping to the sterilization facility, or during distribution.

25 Factors often overlooked in design packaging validations Not planning for failure Should you test just one product in one package? Or four products in a box? To determine the worst-case scenario, it is necessary to decide the most common shipping configuration before validating the package. In this way, other package configurations of the same or similar products may be covered by one validation. In fact, a few ISO guidelines work to device manufacturers benefit. For example, a provision allows validating families of packaged products rather than individual configurations.

26 Factors often overlooked in design packaging validations Incorrect Material Using the wrong package type or material for the product. Some examples Fracturing of thermoform trays as a result of using the wrong plastic material for the intended product (for instance, if the product mass is too great for the impact resistance of plastic). The thermoform design is also critical to ensure that the product is held in place firmly so that a loose product is not jettisoned through the tray lid and fracturing of the plastic doesn t occur from the insideout.

27 Factors often overlooked in design packaging validations Not recognizing Tyvek separation as a false-positive Seal integrity tested routinely using bubble and dye-leak methods, was sheet separation of the porous web of Tyvek. In integrity tests, this sheet separation appears as false-positive when the material is bent, folded, or wrinkled. This phenomenon does not change the sterile barrier performance of the material and that any leakage of air or dye solution is only along the transverse direction of the material and not between the Tyvek and poly material. Suspect false-positive, require review under high magnification to determine the cause of the leakage.

28 Factors often overlooked in design packaging validations Performing aging at high test temperatures Attempts to reduce costs and time, some manufacturers decide to accelerate the shelf life or expiration date studies to unrealistic and indefensible limits Temperatures over 65 C are indefensible based on the rationale typically used to justify accelerated aging protocols. Real time aging can be performed; however, products are often obsolete by the time a three-year expiration date is validated.

29 Factors often overlooked in design packaging validations Performing aging at high test temperatures The FDA does not require expiration dating for products without components with a defined effective life, while European Directives imply that all sterile medical devices must have an expiration date. Temperature selection for the accelerated aging study should avoid unrealistic failure conditions, such as deformation due to melting.

30 Factors often overlooked in design packaging validations Ignoring human factors To understand use-related hazards, it is necessary to have an accurate and complete understanding of how a device and packaging will be used. Understanding and optimizing how people interact with technology is the subject of human factors engineering (HFE) and usability engineering (UE). HFE/UE considerations that are important to the development of medical devices include three major components of the deviceuser system:

31 Factors often overlooked in design packaging validations (1) device users, (2) device use environments and (3) device user interfaces.

32 Factors often overlooked in design packaging validations Not developing protocols Before working on a validation, write a protocol. It provides a blueprint for how testing will be done Validation qualifies the materials and processes that make the complete package. If one process is not right, the entire system breaks down and the manufacturer risks harm to patients.

33 Factors often overlooked in design packaging validations Wrong sample size Many factors play a role in determining sample size including what type of test it is (e.g. quantitative/variables or qualitative/attributes); What is the sample population; How many samples are available for testing; What are the economics; and what are the risk factors (e.g. confidence intervals).

34 Summary As critical as packaging is some companies occasionally Don t take it seriously Think about it too late in the design cycle Try to save money Or inappropriate materials. Avoid these mistakes and plan well in advance to develop and validate your packaging using a risk based approach.

35 Summary Today we talked about a practical approach to Packaging Design Validation and discussed some of the risks associated to decisions on sample size and validation approach I hope this helps you when conducting your next packaging validation Thank You

36 Questions